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  • American Meteorological Society (AMS)
  • Annual Reviews
  • Cambridge University Press
  • 2005-2009  (2,529)
  • 1980-1984
  • 1950-1954
  • 2005  (2,529)
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Years
  • 2005-2009  (2,529)
  • 1980-1984
  • 1950-1954
Year
  • 1
    Unknown
    Cambridge, U.K ; New York, N.Y : Cambridge University Press
    Keywords: Cellular telephone services industry ; Electronic books ; Mobile communication systems, Economic aspects ; Wireless communication systems, Economic aspects
    Pages: 1 v. (various pagings)
    ISBN: 0-511-11564-4
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  • 2
    Unknown
    Cambridge ; New York : Cambridge University Press
    Keywords: Shakespeare, William, Tragedies ; Electronic books ; Identity (Psychology) in literature ; Tragedy ; Violence in literature
    Pages: ix, 228 p.
    ISBN: 0-511-11352-8
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  • 3
    Unknown
    New York : Cambridge University Press
    Keywords: Capital market ; Electronic books ; Futures market ; Stock exchanges
    Pages: 1 v. (various pagings)
    ISBN: 0-511-11580-6
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  • 4
    Keywords: Developing countries, Economic policy. ; Federal government, Developing countries.
    Pages: xi, 276 p.
    ISBN: 0-511-11566-0
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  • 5
    Unknown
    Cambridge ; New York : Cambridge University Press
    Keywords: Dynamics. ; Kinematics.
    Pages: x, 374 p.
    Edition: 3rd ed
    ISBN: 0-511-11583-0
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  • 6
    Unknown
    Cambridge ; New York : Cambridge University Press
    Keywords: Shakespeare, William, Language ; Shakespeare, William, Romeo and Juliet ; Shakespeare, William, Stage history, 1950- ; Shakespeare, William, Stage history, England, London ; Electronic books ; English language, Pronunciation, Early modern, 1500-1700 ; Globe Theatre (London, England : 1996- )
    Pages: xviii, 188 p.
    ISBN: 0-511-11364-1
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  • 7
    Unknown
    Cambridge, U.K ; New York : Cambridge University Press
    Keywords: Electronic books ; Religion, Study and teaching (Higher) ; Theology, Study and teaching (Higher)
    Pages: xvii, 230 p.
    ISBN: 0-511-11355-2
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  • 8
    Unknown
    Cambridge [England] ; New York : Cambridge University Press
    Keywords: Engineering mathematics, Data processing. ; Numerical analysis, Data processing. ; MATLAB.
    Pages: viii, 426 p.
    ISBN: 0-511-12811-8
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  • 9
    Unknown
    New York : Cambridge University Press
    Keywords: Materials, Mechanical properties.
    Pages: xx, 425 p.
    ISBN: 0-511-11575-X
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  • 10
    Unknown
    Cambridge, UK ; New York : Cambridge University Press
    Keywords: Autonomy (Psychology) ; Electronic books ; Ethics, Modern
    Notes: Planning agency, autonomous agency / Michael E. Bratman -- Autonomy without free will / Bernard Berofsky -- Autonomy and the paradox of self-creation : infinite regresses, finite selves, and the limits of authenticity / Robert Noggle -- Agnostic autonomism revisited / Alfred R. Mele -- Feminist intuitions and the normative substance of autonomy / Paul Benson -- Autonomy and personal integration / Laura Waddell Ekstrom -- Responsibility, applied ethics, and complex autonomy theories / Nomy Arpaly -- Autonomy and free agency / Marina A.L. Oshana -- The relationship between autonomous and morally responsible agency / Michael McKenna -- Alternative possibilities, personal autonomy, and moral responsibility / Ishtiyaque Haji -- Freedom within reason / Susan Wolf -- Procedural autonomy and liberal legitimacy / John Christman -- The concept of autonomy in bioethics : an unwarranted fall from grace / Thomas May -- Who deserves autonomy, and whose autonomy deserves respect? / Tom L. Beauchamp -- Autonomy, diminished life, and the threshold for use / R.G. Frey
    Pages: ix, 350 p.
    ISBN: 0-511-08224-X
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  • 11
    Unknown
    Cambridge, UK ; New York : Cambridge University Press
    Keywords: Kant, Immanuel,, 1724-1804. ; Causation.
    Pages: xi, 451 p.
    ISBN: 0-511-08217-7
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  • 12
    Unknown
    Cambridge, UK ; New York : Cambridge University Press
    Keywords: Monte Carlo method. ; Statistical physics.
    Pages: xv, 432 p.
    Edition: 2nd ed
    ISBN: 0-511-13098-8
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  • 13
    Unknown
    Cambridge ; New York : Cambridge University Press
    Keywords: Equality. ; Minorities. ; Minorities, Civil rights. ; Multiculturalism. ; Social conflict. ; Social groups.
    Pages: xii, 390 p.
    ISBN: 0-511-08065-4
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  • 14
    Unknown
    Cambridge, UK ; New York : Cambridge University Press
    Keywords: Frege, Gottlob,, 1848-1925.
    Notes: Biography -- Function and argument -- Sense and reference -- Frege's Begriffsschrift theory of identity -- Concept and object -- Names and descriptions -- Existence -- Thought, truth value and assertion -- Indirect reference -- Through the quotation marks
    Pages: xix, 226 p.
    ISBN: 0-511-10977-6
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  • 15
    Unknown
    Cambridge : Cambridge University Press
    Keywords: Space time codes.
    Pages: 1 v. (various pagings)
    ISBN: 0-511-11562-8
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  • 16
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2000. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 403 (2000): 37-65, doi:10.1017/S0022112099006916.
    Description: The dynamics of expanding domes of isothermal lava are studied by treating the lava as a viscoplastic material with the Herschel–Bulkley constitutive law. Thin-layer theory is developed for radially symmetric extrusions onto horizontal plates. This provides an evolution equation for the thickness of the fluid that can be used to model expanding isothermal lava domes. Numerical and analytical solutions are derived that explore the effects of yield stress, shear thinning and basal sliding on the dome evolution. The results are briefly compared with an experimental study. It is found that it is difficult to unravel the combined effects of shear thinning and yield stress; this may prove important to studies that attempt to infer yield stress from morphology of flowing lava.
    Description: The financial support of an EPSRC Advanced Fellowship is gratefully acknowledged by R.V. C. N. J. B. was partially supported by the NSF Grant OCE-9616017 and an EPSRC Visiting Fellowship Grant GR/M50409.
    Keywords: Isothermal lava domes
    Repository Name: Woods Hole Open Access Server
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  • 17
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Parasitology 128 (2004): 577-584, doi:10.1017/S0031182004005025.
    Description: Human serum high-density lipoprotein (HDL) is necessary and sufficient for the short-term maintenance of Plasmodium falciparum in in vitro culture. However, at high concentrations it is toxic to the parasite. A heat-labile component is apparently responsible for the stage-specific toxicity to parasites within infected erythrocytes 12–42 h after invasion, i.e. during trophozoite maturation. The effects of HDL on parasite metabolism (as determined by nucleic acid synthesis) are evident at about 30 h after invasion. Parasites treated with HDL show gross abnormalities by light and electron microscopy.
    Description: Professor Hajduk was supported by NIH. Professor Day was supported by a Research Leave Fellowship from The Wellcome Trust. Dr Imrie and Ms Carter were supported by Programme Grant funding awarded to Professor Day from The Wellcome Trust. Dr Ferguson was supported by an equipment grant from The Wellcome Trust.
    Keywords: Plasmodium falciparum ; High density lipoprotein
    Repository Name: Woods Hole Open Access Server
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  • 18
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Geological Magazine 141 (2004): 195-207, doi:10.1017/S001675680400891X.
    Description: Because magmatism associated with subduction is thought to be the principal source for continental crust generation, assessing the relative contribution of pre-existing (subducted and assimilated) continental material to arc magmatism in accreted arcs is important to understanding the origin of continental crust. We present a detailed Nd isotopic stratigraphy for volcanic and volcaniclastic formations from the South Mayo Trough, an accreted oceanic arc exposed in the western Irish Caledonides. These units span an arc–continent collision event, the Grampian (Taconic) Orogeny, in which an intra-oceanic island arc was accreted onto the passive continental margin of Laurentia starting at [similar] 475 Ma (Arenig). The stratigraphy corresponding to pre-, syn- and post-collisional volcanism reveals a progression of [varepsilon]Nd(t) from strongly positive values, consistent with melt derivation almost exclusively from oceanic mantle beneath the arc, to strongly negative values, indicating incorporation of continental material into the melt. Using [varepsilon]Nd(t) values of meta-sediments that represent the Laurentian passive margin and accretionary prism, we are able to quantify the relative proportions of continent-derived melt at various stages of arc formation and accretion. Mass balance calculations show that mantle-derived magmatism contributes substantially to melt production during all stages of arc–continent collision, never accounting for less than 21% of the total. This implies that a significant addition of new, rather than recycled, continental crust can accompany arc–continent collision and continental arc magmatism.
    Keywords: Grampian Orogeny ; Western Ireland ; Continental crust ; Nd isotopes ; Laurentia ; Iapetus Ocean
    Repository Name: Woods Hole Open Access Server
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  • 19
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2003. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 28 (2003): 521-558, doi:10.1146/annurev.energy.28.011503.163443.
    Description: Agriculture and industrial development have led to inadvertent changes in the natural carbon cycle. As a consequence, concentrations of carbon dioxide and other greenhouse gases have increased in the atmosphere and may lead to changes in climate. The current challenge facing society is to develop options for future management of the carbon cycle. A variety of approaches has been suggested: direct reduction of emissions, deliberate manipulation of the natural carbon cycle to enhance sequestration, and capture and isolation of carbon from fossil fuel use. Policy development to date has laid out some of the general principles to which carbon management should adhere. These are summarized as: how much carbon is stored, by what means, and for how long. To successfully manage carbon for climate purposes requires increased understanding of carbon cycle dynamics and improvement in the scientific capabilities available for measurement as well as for policy needs. The specific needs for scientific information to underpin carbon cycle management decisions are not yet broadly known. A stronger dialogue between decision makers and scientists must be developed to foster improved application of scientific knowledge to decisions. This review focuses on the current knowledge of the carbon cycle, carbon measurement capabilities (with an emphasis on the continental scale) and the relevance of carbon cycle science to carbon sequestration goals.
    Description: The National Center for Atmospheric Research is supported by the National Science Foundation.
    Keywords: Carbon sequestration ; Measurement techniques ; Climate ; Kyoto protocol
    Repository Name: Woods Hole Open Access Server
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  • 20
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 516 (2004): 83-113, doi:10.1017/S0022112004000473.
    Description: Oceanic observations indicate that abyssal mixing tends to be localized to regions of rough topography. How localized mixing interacts with the ambient fluid in a stratified, rotating system is an open question. To gain insight into this complicated process laboratory experiments are used to explore the interaction of mechanically induced boundary mixing and an interior body of linearly stratified rotating fluid. Turbulence is generated by a single vertically oscillating horizontal bar of finite horizontal extent, located at mid-depth along the tank wall. The turbulence forms a region of mixed fluid which quickly reaches a steady-state height and collapses into the interior. The mixed-layer thickness, $h_m\,{\sim}\,\gamma ({\omega}/{N})^{1/2}$, is spatially uniform and independent of the Coriolis frequency $f$. $N$ is the initial buoyancy frequency, $\omega$ is the bar oscillation frequency, and $\gamma\,{\approx}\,1$ cm is an empirical constant determined by the bar geometry. Surprisingly, the export of mixed fluid does not occur as a boundary current along the tank perimeter. Rather, mixed fluid intrudes directly into the interior as a radial front of uniform height, advancing with a speed comparable to a gravity current. The volume of mixed fluid grows linearly with time, $V\,{\propto}\,({N}/{f})^{3/2}h_m^3 \textit{ft}$, and is independent of the lateral extent of the mixing bar. Entrainment into the turbulent zone occurs principally through horizontal flows at the level of the mixing that appear to eliminate export by a geostrophic boundary flow. The circulation patterns suggest a model of unmixed fluid laterally entrained at velocity $u_e \,{\sim}\,Nh_m $ into the open sides of a turbulent zone with height $h_{m}$ and a length, perpendicular to the boundary, proportional to $L_f \,{\equiv}\,\gamma ({\omega}/{f})^{1/2}$. Here $L_{f}$ is an equilibrium length scale associated with rotational control of bar-generated turbulence. The model flux of exported mixed fluid $Q\,{\sim}\,h_m L_f u_e$ is constant and in agreement with the experiments.
    Description: This work was supported by the Ocean Ventures Fund, the Westcott Fund and the WHOI Academic Programs Office. Financial support was also provided by the National Science Foundation through grant OCE-9616949.
    Keywords: Abyssal mixing ; Stratified rotating system
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  • 21
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 506 (2004): 217-244, doi:10.1017/S0022112004008572.
    Description: The effect of both vertical and horizontal components of the Earth's rotation on plumes during deep convection in the ocean is studied. In the laboratory, the misalignment, characterized by the angle $\alpha$, between the buoyancy force (‘effective’ free-fall acceleration ${\bm g}_e$) and the rotation axis ${\bm \Omega}$ is produced by using the centrifugal force: an experimental tank was placed at a large distance from the centre of the turntable. The mathematical analogy between the laboratory model and the oceanic environment is presented. For $\alpha\,{=}\,30^\circ$, a number of laboratory experiments spanning a wide range of the buoyancy flux parameter, and correspondingly Reynolds number, is used to illustrate the development of the convective plume from a point source in regimes ranging from weakly to highly turbulent. New features of the flow, as compared to $\alpha\,{=}\,0$, are documented and explained. The incoming heavier dyed fluid jet disintegrates into fast-sinking coherent blobs (in a low-Reynolds-number regime) or turbulent billows (in a high-Reynolds-number regime) and a more diffuse cloud of highly diluted dyed water. An analysis of the forces acting on an ellipsoid moving in a rotating fluid with the main balance including the buoyancy, Coriolis forces, and the hydrodynamic reaction due to generation of inertial waves correctly predicts the trajectory of a descending blob. It also explains the tendency of the plume to develop in the direction intermediate between ${\bm g}_e$ and ${\bm \Omega}$ and to shift ‘eastward’ (lagging the rotation of the centrifuge) if the plume is envisaged as an ensemble of blobs. The stretching of the highly diluted dyed water along the absolute vorticity tubes with simultaneous shearing by horizontal quasi-two-dimensional flow produces conspicuous tilted structures or tilted Taylor ‘ink walls’. The misalignment between ${\bm g}_e$ and ${\bm \Omega}$ enhances the turbulent mixing and development of tilted structures by breaking the symmetry and producing motions directed away from the rotation axis. We argue that the conditions at the sites of ocean deep convection are favourable for the development of tilted structures because of the smallness of the Rossby number and an extreme homogenization of the mixed layer. We hypothesize that the homogenized sublayers observed within actively convecting regions in the ocean may not be horizontal, but in fact analogous to the tilted ‘ink walls’ observed in the laboratory experiments and that they represent the internal structure of a plume on horizontal scales smaller than its depth.
    Description: This work was supported by a grant from The Andrew W. Mellon Foundation Endowed Fund for Innovative Research and by the National Science Foundation grant OCE-0116910.
    Keywords: Convective plumes
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  • 22
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2000. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 404 (2000):117-149, doi:10.1017/S0022112099007065.
    Description: In order to gain insight into the hydraulics of rotating-channel flow, a set of initial-value problems analogous to Long's towing experiments is considered. Specifically, we calculate the adjustment caused by the introduction of a stationary obstacle into a steady, single-layer flow in a rotating channel of infinite length. Using the semigeostrophic approximation and the assumption of uniform potential vorticity, we predict the critical obstacle height above which upstream influence occurs. This height is a function of the initial Froude number, the ratio of the channel width to an appropriately defined Rossby radius of deformation, and a third parameter governing how the initial volume flux in sidewall boundary layers is partitioned. (In all cases, the latter is held to a fixed value specifying zero flow in the right-hand (facing downstream) boundary layer.) The temporal development of the flow according to the full, two-dimensional shallow water equations is calculated numerically, revealing numerous interesting features such as upstream-propagating shocks and separated rarefying intrusions, downstream hydraulic jumps in both depth and stream width, flow separation, and two types of recirculations. The semigeostrophic prediction of the critical obstacle height proves accurate for relatively narrow channels and moderately accurate for wide channels. Significantly, we find that contact with the left-hand wall (facing downstream) is crucial to most of the interesting and important features. For example, no instances are found of hydraulic control of flow that is separated from the left-hand wall at the sill, despite the fact that such states have been predicted by previous semigeostrophic theories. The calculations result in a series of regime diagrams that should be very helpful for investigators who wish to gain insight into rotating, hydraulically driven flow.
    Description: The authors have been supported by the National Science Foundation through Grants (OCE-9810599 for L.J.P. and K.R.H. and OCE-9711186 for EPC). L.J.P. also received support from the Office of Naval Research under Grant N00014-95-1-0456 and K.R.H. under grant N00014-93-1-0263.
    Keywords: Rotating-channel flow ; Hydraulically driven flow
    Repository Name: Woods Hole Open Access Server
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  • 23
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 514 (2004): 107-119, doi:10.1017/S0022112004000126.
    Description: While acoustic scatter from oceanic turbulence is sensitive to temperature–salinity covariations, there are unfortunately no published measurements of the turbulent temperature–salinity co-spectrum. Several models have been proposed for the form of the co-spectrum of two scalars in turbulence, but they all produce unsatisfactory results when applied to the turbulent scattering equations (either predicting negative scattering cross-sections in some regimes or predicting implausible levels of correlation between temperature and salinity at some scales). A new model is proposed and shown to give physically plausible scattering predictions in all density regimes. High-frequency acoustic data illustrate the importance of the co-spectrum for acoustic scattering, but were collected in a density regime where there is little difference between the co-spectrum models.
    Description: This work was supported by NSERC and by ONR under grant #N00014-93-1-0362.
    Keywords: Oceanic turbulence ; Co-spectrum ; Temperature–salinity covariations
    Repository Name: Woods Hole Open Access Server
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  • 24
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2002. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 452 (2002): 97-121, doi:10.1017/S0022112001006668.
    Description: Buoyancy-driven surface currents were generated in the laboratory by releasing buoyant fluid from a source adjacent to a vertical boundary in a rotating container. Different bottom topographies that simulate both a continental slope and a continental ridge were introduced in the container. The topography modified the flow in comparison with the at bottom case where the current grew in width and depth until it became unstable once to non-axisymmetric disturbances. However, when topography was introduced a second instability of the buoyancy-driven current was observed. The most important parameter describing the flow is the ratio of continental shelf width W to the width L* of the current at the onset of the instability. The values of L* for the first instability, and L*[minus sign]W for the second instability were not influenced by the topography and were 2–6 times the Rossby radius. Thus, the parameter describing the flow can be expressed as the ratio of the width of the continental shelf to the Rossby radius. When this ratio is larger than 2–6 the second instability was observed on the current front. A continental ridge allowed the disturbance to grow to larger amplitude with formation of eddies and fronts, while a gentle continental slope reduced the growth rate and amplitude of the most unstable mode, when compared to the continental ridge topography. When present, eddies did not separate from the main current, and remained near the shelf break. On the other hand, for the largest values of the Rossby radius the first instability was suppressed and the flow was observed to remain stable. A small but significant variation was found in the wavelength of the first instability, which was smaller for a current over topography than over a flat bottom.
    Description: Partial support for C.C. was provided by a TMR fellowship, MAS3-CT96-5017.
    Keywords: Buoyancy-driven currents ; Bottom topography
    Repository Name: Woods Hole Open Access Server
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  • 25
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2002. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 468 (2002): 179-204, doi:10.1017/S0022112002001520.
    Description: A similarity solution to the long-wave shallow-water equations is obtained for a density current (reduced gravity = g[prime prime or minute], Coriolis parameter = f) propagating alongshore (y = 0). The potential vorticity q = f/H1 is uniform in [minus sign][infty infinity] 〈 x [less-than-or-eq, slant] xnose(t), 0 〈 y [less-than-or-eq, slant] L(x, t), and the nose of this advancing potential vorticity front displaces fluid of greater q = f/H0, which is located at L 〈 y 〈 [infty infinity]. If L0 = L([minus sign][infty infinity], t), the nose point with L(xnose(t), t) = 0 moves with velocity Unose = [surd radical]g[prime prime or minute]H0 [phi], where [phi] is a function of H1/H0, f2L20/g[prime prime or minute]H0. The assumptions made in the similarity theory are verified by an initial value solution of the complete reduced-gravity shallow-water equations. The latter also reveal the new effect of a Kelvin shock wave colliding with a potential vorticity front, as is confirmed by a laboratory experiment. Also confirmed is the expansion wave structure of the intrusion, but the observed values of Unose are only in qualitative agreement; the difference is attributed to the presence of small-scale (non-hydrostatic) turbulence in the laboratory experiment but not in the numerical solutions.
    Description: This work is funded by National Science Foundation grants OCE-9726584 & OCE-0092504 (M. E. S.) and OCE-9810599 (K. R. H.).
    Keywords: Potential vorticity front ; Frontal intrusion ; Kelvin wave
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  • 26
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2003. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 481 (2003): 329-353, doi:10.1017/S0022112003004051.
    Description: In this article we investigate time-periodic shear flows in the context of the two-dimensional vorticity equation, which may be applied to describe certain large-scale atmospheric and oceanic flows. The linear stability analyses of both discrete and continuous profiles demonstrate that parametric instability can arise even in this simple model: the oscillations can stabilize (destabilize) an otherwise unstable (stable) shear flow, as in Mathieu's equation (Stoker 1950). Nonlinear simulations of the continuous oscillatory basic state support the predictions from linear theory and, in addition, illustrate the evolution of the instability process and thereby show the structure of the vortices that emerge. The discovery of parametric instability in this model suggests that this mechanism can occur in geophysical shear flows and provides an additional means through which turbulent mixing can be generated in large-scale flows.
    Description: F.P.’s and G.F.’s research was supported by grants from NSF, OPP- 9910052 and OCE-0137023. J.P.’s research is supported in part by a grant from NSF, OCE-9901654.
    Keywords: Time-periodic shear flows ; Parametric instability
    Repository Name: Woods Hole Open Access Server
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  • 27
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 515 (2004): 415-443, doi:10.1017/S0022112004000576.
    Description: The investigation involves the hydraulic behaviour of a dense layer of fluid flowing over an obstacle and subject to entrainment of mass and momentum from a dynamically inactive (but possibly moving) overlying fluid. An approach based on the use of reduced gravity, shallow-water theory with a cross-interface entrainment velocity is compared with numerical simulations based on a model with continuously varying stratification and velocity. The locations of critical flow (hydraulic control) in the continuous model are estimated by observing the direction of propagation of small-amplitude long-wave disturbances introduced into the flow field. Although some of the trends predicted by the shallow-water model are observed in the continuous model, the agreement between the interface profiles and the position of critical flow is quantitatively poor. A reformulation of the equations governing the continuous flow suggests that the reduced gravity model systematically underestimates inertia and overestimates buoyancy. These differences are quantified by shape coefficients that measure the vertical non-uniformities of the density and horizontal velocity that arise, in part, by incomplete mixing of entrained mass and momentum over the lower-layer depth. Under conditions of self-similarity (as in Wood's similarity solution) the shape coefficients are constant and the formulation determines a new criterion for and location of critical flow. This location generally lies upstream of the critical section predicted by the reduced-gravity model. Self-similarity is not observed in the numerically generated flow, but the observed critical section continues to lie upstream of the location predicted by the reduced gravity model. The factors influencing this result are explored.
    Description: M. H. N. would like to thank the Danish Natural Science Research Council for financial support. L. P. and K. H. were supported by the Office of Naval Research under grant N00014-1-01-0167 and by the National Science Foundation under grant OCE-0132903.
    Keywords: Hydraulic behaviour ; Reduced gravity model
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  • 28
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    Cambridge University Press
    Publication Date: 2022-05-25
    Description: Author Posting. © Cambridge University Press, 2001. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 437 (2001): 301-323, doi:10.1017/S0022112001004402.
    Description: Laboratory and numerical experiments are used to study flow of a uniform-density fluid on the [beta]-plane around a thin zonally elongated island (or ridge segment in the abyss). This orientation is chosen specifically to highlight the roles of the zonal boundary layer dynamics in controlling the circulation around the island. There are examples of deep ocean topography that fall into this category which make the work directly applicable to oceanic flows. Linear theory for the transport around the island and the flow structure is based on a modification of the Island Rule (Pedlosky et al. 1997; Pratt & Pedlosky 1999). The linear solution gives a north–south symmetric flow around the island with novel features, including stagnation points which divide the zonal boundary layers into eastward and westward flowing zones, and a western boundary layer of vanishing length, and zonal jets. Laboratory experiments agree with the linear theory for small degrees of nonlinearity, as measured by the ratio of the inertial to Munk boundary layer scales. With increasing nonlinearity the north–south symmetry is broken. The southern stagnation point (for anticyclonic forcing) moves to the eastern tip of the island. The flow rounding the eastern tip from the northern side of the island now separates from the island. Time-dependence emerges and recirculation cells develop on the northern side of the island. Mean transport around the island is relatively unaffected by nonlinearity and given to within 20% by the modified Island Rule. Numerical solutions of the shallow water equations are in close agreement with the laboratory results. The transition from zonal to meridional island orientation occurs for island inclinations from zonal greater than about 20°.
    Description: This work was supported by the National Science Foundation (Grant Number OCE96-16949).
    Keywords: Zonal boundary layer dynamics ; Island Rule
    Repository Name: Woods Hole Open Access Server
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    Publication Date: 2022-05-25
    Description: First published online as a Review in Advance on October 24, 2005. (Some corrections may occur before final publication online and in print)
    Description: Author Posting. © Annual Reviews, 2005. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Physiology 68 (2006): 22.1-22.29, doi:10.1146/annurev.physiol.68.040104.105418.
    Description: Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.
    Description: This work was made possible by support from NIH grants AR38404 and AR46125 as well as the University of Pennsylvania Research Foundation.
    Keywords: Parvalbumin ; Ca2+ release ; Ca2+ uptake ; Cross-bridges ; Adaptation ; Sound production ; Whitman Center
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  • 30
    Publication Date: 2022-05-26
    Description: Author Posting. © Cambridge University Press, 2005. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 536 (2005): 253-283, doi:10.1017/S0022112005004544.
    Description: The generation of a gravity current by the release of a semi-infinite region of buoyant fluid of depth $H$ overlying a deeper, denser and quiescent lower layer in a rotating channel of width $w$ is considered. Previous studies have focused on the characteristics of the gravity current head region and produced relations for the gravity current speed $c_{b}$ and width $w_b$ as a functions of the local current depth along the wall $h_b$, reduced gravity $g^\prime$, and Coriolis frequency $f$. Here, the dam-break problem is solved analytically by the method of characteristics assuming reduced-gravity flow, uniform potential vorticity and a semigeostrophic balance. The solution makes use of a local gravity current speed relation $c_{b} \,{=}\, c_b(h_b,\ldots)$ and a continuity constraint at the head to close the problem. The initial value solution links the local gravity current properties to the initiating dam-break conditions. The flow downstream of the dam consists of a rarefaction joined to a uniform gravity current with width $w_b$ (${\le}\, w$) and depth on the right-hand wall of $h_b$, terminated at the head moving at speed $c_b$. The solution gives $h_b$, $c_b$, $w_b$ and the transport of the boundary current as functions of $w/L_R$, where $L_R \,{=}\, \sqrt{g^\prime H}/f$ is the deformation radius. The semigeostrophic solution compares favourably with numerical solutions of a single-layer shallow-water model that internally develops a leading bore. Existing laboratory experiments are re-analysed and some new experiments are undertaken. Comparisons are also made with a three-dimensional shallow-water model. These show that lateral boundary friction is the primary reason for differences between the experiments and the semigeostrophic theory. The wall no-slip condition is identified as the primary cause of the experimentally observed decrease in gravity current speed with time. A model for the viscous decay is developed and shown to agree with both experimental and numerical model data.
    Description: This work was supported by NSF Grants OCE-0095059 and OCE-0132903.
    Keywords: Gravity current ; Dam-break problem
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  • 31
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    Cambridge University Press
    Publication Date: 2022-05-26
    Description: Author Posting. © Cambridge University Press, 2003. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 490 (2003): 189-215, doi:10.1017/S0022112003005007.
    Description: The baroclinic instability of a zonal current on the beta-plane is studied in the context of the two-layer model when the shear of the basic current is a periodic function of time. The basic shear is contained in a zonal channel and is independent of the meridional direction. The instability properties are studied in the neighbourhood of the classical steady-shear threshold for marginal stability. It is shown that the linear problem shares common features with the behaviour of the well-known Mathieu equation. That is, the oscillatory nature of the shear tends to stabilize an otherwise unstable current while, on the contrary, the oscillation is able to destabilize a current whose time-averaged shear is stable. Indeed, this parametric instability can destabilize a flow that at every instant possesses a shear that is subcritical with respect to the standard stability threshold. This is a new source of growing disturbances. The nonlinear problem is studied in the same near neighbourhood of the marginal curve. When the time-averaged flow is unstable, the presence of the oscillation in the shear produces both periodic finite-amplitude motions and aperiodic behaviour. Generally speaking, the aperiodic behaviour appears when the amplitude of the oscillating shear exceeds a critical value depending on frequency and dissipation. When the time-averaged flow is stable, i.e. subcritical, finite-amplitude aperiodic motion occurs when the amplitude of the oscillating part of the shear is large enough to lift the flow into the unstable domain for at least part of the cycle of oscillation. A particularly interesting phenomenon occurs when the time-averaged flow is stable and the oscillating part is too small to ever render the flow unstable according to the standard criteria. Nevertheless, in this regime parametric instability occurs for ranges of frequency that expand as the amplitude of the oscillating shear increases. The amplitude of the resulting unstable wave is a function of frequency and the magnitude of the oscillating shear. For some ranges of shear amplitude and oscillation frequency there exist multiple solutions. It is suggested that the nature of the response of the finite-amplitude behaviour of the baroclinic waves in the presence of the oscillating mean flow may be indicative of the role of seasonal variability in shaping eddy activity in both the atmosphere and the ocean.
    Description: J.P.’s research is supported in part by a grant from NSF, OCE 9901654.
    Keywords: Baroclinic instability ; Baroclinic waves
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  • 32
    Publication Date: 2022-05-26
    Description: Author Posting. © Cambridge University Press, 2000. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Zygote 8 (2000): 15-24, doi:10.1017/S0967199400000782.
    Description: The physiology of the early embryo may be indicative of embryo vitality and therefore methods for non-invasively monitoring physiological parameters from embryos could improve preimplantation diagnoses. The self-referencing electrophysiological technique is capable of non-invasive measurement of the physiology of individual cells by monitoring the movement of ions and molecules between the cell and the surrounding media. Here we use this technique to monitor gradients of calcium, potassium, oxygen and hydrogen peroxide around individual mouse preimplantation embryos. The calcium-sensitive electrode in self-referencing mode identified a region of elevated calcium concentration ([similar]0.25 pmol) surrounding each embryo. The calcium gradient surrounding embryos was relatively steep, such that the region of elevated calcium extended into the medium only 4 [mu]m from the embryo. By contrast, using an oxygen-sensitive electrode an extensive gradient of reduced dissolved oxygen concentration was measured surrounding the embryo and extended tens of micrometres into the medium. A gradient of neither potassium nor hydrogen peroxide was observed around unperturbed embryos. We also demonstrate that monitoring the physiology of embryos using the self-referencing technique does not compromise their subsequent development. Blastocysts studied with the self-referencing technique implanted and developed to term at the same frequency as did unexamined, control embryos. Therefore, the self-referencing electrode provides a valuable non-invasive technique for studying the physiology and pathophysiology of individual embryos without hindering their subsequent development.
    Description: A portion of this work was funded by an NIH R21 #RR 12718–02 to D.L.K. and P.J.S.S., KO81099 to D.L.K. and NIH P41 RR01395 to P.J.S.S.
    Keywords: Calcium ; Embryo physiology ; Embryo transfer ; Oxygen ; Preimplantation diagnosis
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  • 33
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    Cambridge University Press
    Publication Date: 2022-05-26
    Description: Author Posting. © Cambridge University Press, 2005. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 529 (2005): 71-95, doi:10.1017/S0022112005003393.
    Description: The role of mesoscale oceanic eddies in driving large-scale currents is studied in an eddy-resolving midlatitude double-gyre ocean model. The reference solution is decomposed into large-scale and eddy components in a way which is dynamically consistent with a non-eddy-resolving ocean model. That is, the non-eddy-resolving solution driven by this eddy-forcing history, calculated on the basis of this decomposition, correctly approximates the original flow. The main effect of the eddy forcing on the large-scale flow is to enhance the eastward-jet extension of the subtropical western boundary current. This is an anti-diffusive process, which cannot be represented in terms of turbulent diffusion. It is shown that the eddy-forcing history can be approximated as a space–time correlated, random-forcing process in such a way that the non-eddy-resolving solution correctly approximates the reference solution. Thus, the random-forcing model can potentially replace the diffusion model, which is commonly used to parameterize eddy effects on the large-scale currents. The eddy-forcing statistics are treated as spatially inhomogeneous but stationary, and the dynamical roles of space–time correlations and spatial inhomogeneities are systematically explored. The integral correlation time, oscillations of the space correlations, and inhomogeneity of the variance are found to be particularly important for the flow response.
    Description: Funding for this research was provided by NSF grants OCE 0091836 and OCE 03-44094, by the Royal Society Fellowship, and by WHOI grants 27100056 and 52990035.
    Keywords: Mesoscale oceanic eddies ; Large-scale currents ; Random-forcing model
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  • 34
    Publication Date: 2022-05-26
    Description: Author Posting. © Cambridge University Press, 2002. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 464 (2002): 251-278, doi:10.1017/S0022112002008868.
    Description: The dynamics of buoyant gravity currents in a rotating reference frame is a classical problem relevant to geophysical applications such as river water entering the ocean. However, existing scaling theories are limited to currents propagating along a vertical wall, a situation almost never realized in the ocean. A scaling theory is proposed for the structure (width and depth), nose speed and flow field characteristics of buoyant gravity currents over a sloping bottom as functions of the gravity current transport Q, density anomaly g[prime prime or minute], Coriolis frequency f, and bottom slope [alpha]. The nose propagation speed is cp [similar] cw/ (1 + cw/c[alpha]) and the width of the buoyant gravity current is Wp [similar] cw/ f(1 + cw/c[alpha]), where cw = (2Qg[prime prime or minute] f)1/4 is the nose propagation speed in the vertical wall limit (steep bottom slope) and c[alpha] = [alpha]g/f is the nose propagation speed in the slope-controlled limit (small bottom slope). The key non-dimensional parameter is cw/c[alpha], which indicates whether the bottom slope is steep enough to be considered a vertical wall (cw/c[alpha] [rightward arrow] 0) or approaches the slope-controlled limit (cw/c[alpha] [rightward arrow] [infty infinity]). The scaling theory compares well against a new set of laboratory experiments which span steep to gentle bottom slopes (cw/c[alpha] = 0.11–13.1). Additionally, previous laboratory and numerical model results are reanalysed and shown to support the proposed scaling theory.
    Description: This research was supported by NSF grant OCE-0095059.
    Keywords: Buoyant gravity currents ; Scaling theory ; Sloping bottom
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    Publication Date: 2022-05-26
    Description: Author Posting. © Cambridge University Press, 2003. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of the Marine Biological Association of the UK 83 (2003): 1347-1350, doi:10.1017/S0025315403008798.
    Description: Trophic positions (TP) were estimated for the blue shark (Prionace glauca), shortfin mako (Isurus oxyrinchus), thresher shark (Alopias vulpinus), and basking shark (Cetorhinus maximus) using stable isotope ratios of carbon ([delta]13C) and nitrogen ([delta]15N). The basking shark had the lowest TP (3·1) and [delta]15N value (10·4‰), whereas the thresher shark had the highest values (4·5, 15·2‰). Mako sharks showed considerable variation in TP and isotopic values, possibly due to foraging from both inshore and offshore waters. Thresher sharks were significantly more enriched in [delta]15N than blue sharks and mako sharks, suggesting a different prey base. The [delta]13C values of thresher sharks and mako sharks varied significantly, but neither was significantly different from that of blue sharks. No statistical differences were found between our TP estimations and those derived from published stomach contents analyses, indicating that stable isotope data may be used to estimate the trophic status of sharks.
    Description: This work was supported by National Marine Fisheries Service Grant NA16MF1323 to M.E.L.
    Keywords: Prionace glauca ; Isurus oxyrinchus ; Alopias vulpinus ; Cetorhinus maximus ; Trophic positions
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  • 36
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    Cambridge University Press
    In:  Biased embryos and evolution vol. 74, 1/2, pp. 209-211
    Publication Date: 2024-01-12
    Keywords: evolution ; natural selection ; variation ; developmental bias
    Repository Name: National Museum of Natural History, Netherlands
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  • 37
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    Annual Review of Immunology 23 (2005), S. 161-196 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Our views regarding the origins and functions of splenic marginal zone B cells have changed considerably over the past few years. Perspectives regarding the development and function of these cells vary considerably between investigators studying human and rodent immunology. Marginal zone B cells are now recognized to constitute a distinct naive B lymphoid lineage. Considerable progress has been made regarding the mechanisms involved in marginal zone B cell development in the mouse. Many of the molecular events that participate in the retention of this lineage of B cells in the marginal zone have been identified. Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates.
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  • 38
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    Annual Review of Immunology 23 (2005), S. 487-513 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Helper T (Th) cellĐ??regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cellĐ??B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.
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  • 39
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    Annual Review of Immunology 23 (2005), S. 415-445 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The proliferation and differentiation of lymphocytes are regulated by receptors localized on the cell surface. Engagement of these receptors induces the activation of intracellular signaling proteins that transmit the receptor signals to distinct targets and control the cellular responses. The first signaling proteins to be discovered in higher organisms were the products of oncogenes. For example, the kinases Src and Abelson (Abl) were originally identified as oncogenes and were later characterized as important proteins for signal transduction in various cell types, including lymphocytes. Now, as many cellular signaling molecules have been discovered and ordered into certain pathways, we can better understand why particular signaling proteins are associated with tumorigenesis. In this review, we discuss recent progress in unraveling the molecular mechanisms of signaling pathways that control the proliferation and differentiation of early B cells. We point out the concepts of auto-inhibition and subcellular localization as crucial aspects in the regulation of B cell signaling.
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  • 40
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 683-747 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the disease. The activation of CD4+ autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease. Damage of the target tissue, the central nervous system, is, however, most likely mediated by other components of the immune system, such as antibodies, complement, CD8+ T cells, and factors produced by innate immune cells. Perturbations in immunomodulatory networks that include Th2 cells, regulatory CD4+ T cells, NK cells, and others may in part be responsible for the relapsing-remitting or chronic progressive nature of the disease. However, an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.
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  • 41
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    Annual Review of Immunology 23 (2005), S. 651-682 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: CD8+ T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral TCD8+ responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how TCD8+ are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive TCD8+ in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.
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  • 42
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    Annual Review of Immunology 23 (2005), S. 945-974 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Notch pathway is gaining increasing recognition as a key regulator of developmental choices, differentiation, and function throughout the hematolymphoid system. Notch controls the generation of hematopoietic stem cells during embryonic development and may affect their subsequent homeostasis. Commitment to the T??cell lineage and subsequent stages of early thymopoiesis is critically regulated by Notch. Recent data indicate that Notch can also direct the differentiation and activity of peripheral T and B cells. Thus, the full spectrum of Notch effects is just beginning to be understood. In this review, we discuss this explosion of knowledge as well as current controversies and challenges in the field.
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  • 43
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    Annual Review of Immunology 23 (2005), S. 975-1028 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The conversion of exogenous and endogenous proteins into immunogenic peptides recognized by T lymphocytes involves a series of proteolytic and other enzymatic events culminating in the formation of peptides bound to MHC class I or class II molecules. Although the biochemistry of these events has been studied in detail, only in the past few years has similar information begun to emerge describing the cellular context in which these events take place. This review thus concentrates on the properties of antigen-presenting cells, especially those aspects of their overall organization, regulation, and intracellular transport that both facilitate and modulate the processing of protein antigens. Emphasis is placed on dendritic cells and the specializations that help account for their marked efficiency at antigen processing and presentation both in vitro and, importantly, in vivo. How dendritic cells handle antigens is likely to be as important a determinant of immunogenicity and tolerance as is the nature of the antigens themselves.
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  • 44
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    Annual Review of Immunology 23 (2005), S. 515-548 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also regulate self-tolerance by supporting CD4+CD25+ T regulatory cell homeostasis. CTLA-4 can exert its inhibitory effects in both B7-1/B7-2 dependent and independent fashions. B7-1 and B7-2 can signal bidirectionally by engaging CD28 and CTLA-4 on T cells and by delivering signals into B7-expressing cells. The five new B7 family members, ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1) are expressed on professional antigen-presenting cells as well as on cells within nonlymphoid organs, providing new means for regulating T cell activation and tolerance in peripheral tissues. The new CD28 families members, ICOS, PD-1, and BTLA, are inducibly expressed on T cells, and they have important roles in regulating previously activated T cells. PD-1 and BTLA also are expressed on B cells and may have broader immunoregulatory functions. The ICOS:ICOSL pathway appears to be particularly important for stimulating effector T cell responses and T cellĐ??dependent B cell responses, but it also has an important role in regulating T cell tolerance. In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance. In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential.
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  • 45
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 26 (2005), S. 877-900 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Natural killer T (NKT) cells constitute a conserved T cell sublineage with unique properties, including reactivity for a synthetic glycolipid presented by CD1d, expression of an invariant T cell antigen receptor (TCR) ʼ̛ chain, and unusual requirements for thymic selection. They rapidly produce many cytokines after stimulation and thus influence diverse immune responses and pathogenic processes. Because of intensive research effort, we have learned much about factors promoting the development and survival of NKT cells, regulation of their cytokine production, and the means by which they influence dendritic cells and other cell types. Despite this progress, knowledge of the natural antigen(s) they recognize and their physiologic role remain incomplete. The activation of NKT cells paradoxically can lead either to suppression or stimulation of immune responses, and we cannot predict which will occur. Despite this uncertainty, many investigators are hopeful that immune therapies can be developed based on NKT cell stimulation.
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  • 46
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 549-600 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Tec family tyrosine kinases are now recognized as important mediators of antigen receptor signaling in lymphocytes. Three members of this family, Itk, Rlk, and Tec, are expressed in T cells and activated in response to T cell receptor (TCR) engagement. Although initial studies demonstrated a role for these proteins in TCR-mediated activation of phospholipase C-??, recent data indicate that Tec family kinases also regulate actin cytoskeletal reorganization and cellular adhesion following TCR stimulation. In addition, Tec family kinases are activated downstream of G proteinĐ??coupled chemokine receptors, where they play parallel roles in the regulation of Rho GTPases, cell polarization, adhesion, and migration. In all these systems, however, Tec family kinases are not essential signaling components, but instead function to modulate or amplify signaling pathways. Although they quantitatively reduce proximal signaling, mutations that eliminate Tec family kinases in T cells nonetheless qualitatively alter T cell development and differentiation.
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  • 47
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory antiparasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.
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  • 48
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    Annual Review of Immunology 23 (2005), S. 23-68 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Several members of the tumor necrosis factor receptor (TNFR) family function after initial T cell activation to sustain T cell responses. This review focuses on CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR, all of which can have costimulatory effects on T cells. The effects of these costimulatory TNFR family members can often be functionally, temporally, or spatially segregated from those of CD28 and from each other. The sequential and transient regulation of T cell activation/survival signals by different costimulators may function to allow longevity of the response while maintaining tight control of T cell survival. Depending on the disease condition, stimulation via costimulatory TNF family members can exacerbate or ameliorate disease. Despite these complexities, stimulation or blockade of TNFR family costimulators shows promise for several therapeutic applications, including cancer, infectious disease, transplantation, and autoimmunity.
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    Annual Review of Immunology 23 (2005), S. 447-485 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.
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    Annual Review of Immunology 23 (2005), S. 101-125 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering.
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    Annual Review of Pharmacology 45 (2005), S. 1-25 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The author describes studies that led to the resolution and reconstitution of the cytochrome P450 enzyme system in microsomal membranes. The review indicates how purification and characterization of the cytochromes led to rigorous evidence for multiple isoforms of the oxygenases with distinct chemical and physical properties and different but somewhat overlapping substrate specificities. Present knowledge of the individual steps in the P450 and reductase reaction cycles is summarized, including evidence for the generation of multiple functional oxidants that may contribute to the exceptional diversity of the reactions catalyzed.
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    Annual Review of Pharmacology 45 (2005), S. 51-88 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: This review describes the three mammalian glutathione transferase (GST) families, namely cytosolic, mitochondrial, and microsomal GST, the latter now designated MAPEG. Besides detoxifying electrophilic xenobiotics, such as chemical carcinogens, environmental pollutants, and antitumor agents, these transferases inactivate endogenous ʼ̛,?‚-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. These enzymes are also intimately involved in the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, as well as the degradation of tyrosine. Among their substrates, GSTs conjugate the signaling molecules 15-deoxy-??12,14-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal with glutathione, and consequently they antagonize expression of genes trans-activated by the peroxisome proliferator-activated receptor ?? (PPAR??) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Through metabolism of 15d-PGJ2, GST may enhance gene expression driven by nuclear factor-?”B (NF-?”B). Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease. Polymorphisms in human MAPEG are associated with alterations in lung function and increased risk of myocardial infarction and stroke. Targeted disruption of murine genes has demonstrated that cytosolic GST isoenzymes are broadly cytoprotective, whereas MAPEG proteins have proinflammatory activities. Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products. Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress.
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    Annual Review of Pharmacology 45 (2005), S. 177-202 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The importance of reactive metabolites in the pathogenesis of drug-induced toxicity has been a focus of research interest since pioneering investigations in the 1950s revealed the link between toxic metabolites and chemical carcinogenesis. There is now a great deal of evidence that shows that reactive metabolites are formed from drugs known to cause hepatotoxicity, but how these toxic species initiate and propagate tissue damage is still poorly understood. This review summarizes the evidence for reactive metabolite formation from hepatotoxic drugs, such as acetaminophen, tamoxifen, diclofenac, and troglitazone, and the current hypotheses of how this leads to liver injury. Several hepatic proteins can be modified by reactive metabolites, but this in general equates poorly with the extent of toxicity. Much more important may be the identification of the critical proteins modified by these toxic species and how this alters their function. It is also important to note that the toxicity of reactive metabolites may be mediated by noncovalent binding mechanisms, which may also have profound effects on normal liver physiology. Technological developments in the wake of the genomic revolution now provide unprecedented power to characterize and quantify covalent modification of individual target proteins and their functional consequences; such information should dramatically improve our understanding of drug-induced hepatotoxic reactions.
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    Annual Review of Pharmacology 45 (2005), S. 291-310 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The cytochrome P450 monooxygenases (CYPs) are the dominant enzyme system responsible for xenobiotic detoxification and drug metabolism. Several CYP isoforms exhibit non-Michaelis-Menten, or "atypical," steady state kinetic patterns. The allosteric kinetics confound prediction of drug metabolism and drug-drug interactions, and they challenge the theoretical paradigms of allosterism. Both homotropic and heterotropic ligand effects are now widely documented. It is becoming apparent that multiple ligands can simultaneously bind within the active sites of individual CYPs, and the kinetic parameters change with ligand occupancy. In fact, the functional effect of any specific ligand as an activator or inhibitor can be substrate dependent. Divergent approaches, including kinetic modeling and X-ray crystallography, are providing new information about how multiple ligand binding yields complex CYP kinetics.
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    Annual Review of Pharmacology 45 (2005), S. 335-355 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Recent discoveries of novel and potentially important biological activity have spurred interest in the chemistry and biochemistry of nitroxyl (HNO). It has become clear that, among all the nitrogen oxides, HNO is unique in its chemistry and biology. Currently, the intimate chemical details of the biological actions of HNO are not well understood. Moreover, many of the previously accepted chemical properties of HNO have been recently revised, thus requiring reevaluation of possible mechanisms of biological action. Herein, we review these developments in HNO chemistry and biology.
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    Annual Review of Pharmacology 45 (2005), S. 385-412 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Adenosine and its receptors have been the topic of many recent reviews ( 1Đ??26 ). These reviews provide a good summary of much of the relevant literatureĐ??including the older literature. We have, therefore, chosen to focus the present review on the insights gained from recent studies on genetically modified mice, particularly with respect to the function of adenosine receptors and their potential as therapeutic targets. The information gained from studies of drug effects is discussed in this context, and discrepancies between genetic and pharmacological results are highlighted.
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    Annual Review of Pharmacology 45 (2005), S. 657-687 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Cardiac fibroblasts play a central role in the maintenance of extracellular matrix in the normal heart and as mediators of inflammatory and fibrotic myocardial remodeling in the injured and failing heart. In this review, we evaluate the cardiac fibroblast as a therapeutic target in heart disease. Unique features of cardiac fibroblast cell biology are discussed in relation to normal and pathophysiological cardiac function. The contribution of cardiac fibrosis as an independent risk factor in the outcome of heart failure is considered. Candidate drug therapies that derive benefit from actions on cardiac fibroblasts are summarized, including inhibitors of angiotensin-aldosterone systems, endothelin receptor antagonists, statins, anticytokine therapies, matrix metalloproteinase inhibitors, and novel antifibrotic/anti-inflammatory agents. These findings point the way to future challenges in cardiac fibroblast biology and pharmacotherapy.
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    Annual Review of Immunology 23 (2005), S. 367-386 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In vertebrates, serum antibodies are an essential component of innate and adaptive immunity and immunological memory. They also can contribute significantly to immunopathology. Their composition is the result of tightly regulated differentiation of B lymphocytes into antibody-secreting plasma blasts and plasma cells. The survival of antibody-secreting cells determines their contribution to the immune response in which they were generated and to long-lasting immunity, as provided by stable serum antibody levels. Short-lived plasma blasts and/or plasma cells secrete antibodies for a reactive immune response. Short-lived plasma blasts can become long-lived plasma cells, probably by competition with preexisting plasma cells for occupation of a limited number of survival niches in the body, in a process not yet fully understood. Limitation of the number of long-lived plasma cells allows the immune system to maintain a stable humoral immunological memory over long periods, to react to new pathogenic challenges, and to adapt the humoral memory in response to these antigens.
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    Annual Review of Immunology 23 (2005), S. 337-366 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: C reactive protein, the first innate immunity receptor identified, and serum amyloid P component are classic short pentraxins produced in the liver. Long pentraxins, including the prototype PTX3, are expressed in a variety of tissues. Some long pentraxins are expressed in the brain and some are involved in neuronal plasticity and degeneration. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. PTX3 acts as a functional ancestor of antibodies, recognizing microbes, activating complement, and facilitating pathogen recognition by phagocytes, hence playing a nonredundant role in resistance against selected pathogens. In addition, PTX3 is essential in female fertility because it acts as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility.
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    Annual Review of Immunology 23 (2005), S. 225-274 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The integrated processing of signals transduced by activating and inhibitory cell surface receptors regulates NK cell effector functions. Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition.
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    Annual Review of Immunology 23 (2005), S. 787-819 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Lymphotoxins (LT) provide essential communication links between lymphocytes and the surrounding stromal and parenchymal cells and together with the two related cytokines, tumor necrosis factor (TNF) and LIGHT (LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), form an integrated signaling network necessary for efficient innate and adaptive immune responses. Recent studies have identified signaling pathways that regulate several genes, including chemokines and interferons, which participate in the development and function of microenvironments in lymphoid tissue and host defense. Disruption of the LT/TNF/LIGHT network alleviates inflammation in certain autoimmune disease models, but decreases resistance to selected pathogens. Pharmacological disruption of this network in human autoimmune diseases such as rheumatoid arthritis alleviates inflammation in a significant number of patients, but not in other diseases, a finding that challenges our molecular paradigms of autoimmunity and perhaps will reveal novel roles for this network in pathogenesis.
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    Annual Review of Immunology 23 (2005), S. 387-414 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The newly discovered CATERPILLER (CLR) gene family encodes proteins with a variable but limited number of N-terminal domains, followed by a nucleotide-binding domain (NBD) and leucine-rich repeats (LRR). The N-terminal domain consists of transactivation, CARD, Pyrin, or BIR domains, with a minority containing undefined domains. These proteins are remarkably similar in structure to the TIR-NBD-LRR and CC-NBD-LRR disease resistance (R) proteins that mediate immune responses in plants. The NBD-LRR architecture is conserved in plants and vertebrates, but only remnants are found in worms and flies. The CLRs regulate inflammatory and apoptotic responses, and some act as sensors that detect pathogen products. Several CLR genes have been genetically linked to susceptibility to immunologic disorders. We describe prominent family members, including CIITA, CARD4/NOD1, NOD2/CARD15, CIAS1, CARD7/NALP1, and NAIP, in more detail. We also discuss implied roles of these proteins in diversifying immune detection and in providing a check-and-balance during inflammation.
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    Annual Review of Immunology 23 (2005), S. 901-944 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Macrophages express a broad range of plasma membrane receptors that mediate their interactions with natural and altered-self components of the host as well as a range of microorganisms. Recognition is followed by surface changes, uptake, signaling, and altered gene expression, contributing to homeostasis, host defense, innate effector mechanisms, and the induction of acquired immunity. This review covers recent studies of selected families of structurally defined molecules, studies that have improved understanding of ligand discrimination in the absence of opsonins and differential responses by macrophages and related myeloid cells.
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    Annual Review of Immunology 23 (2005), S. 601-649 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment.
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    Annual Review of Immunology 23 (2005), S. 307-335 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The significance of type I interferons (IFN-ʼ̛/?‚) in biology and medicine renders research on their activities continuously relevant to our understanding of normal and abnormal (auto) immune responses. This relevance is bolstered by discoveries that unambiguously establish IFN-ʼ̛/?‚, among the multitude of cytokines, as dominant in defining qualitative and quantitative characteristics of innate and adaptive immune processes. Recent advances elucidating the biology of these key cytokines include better definition of their complex signaling pathways, determination of their importance in modifying the effects of other cytokines, the role of Toll-like receptors in their induction, their major cellular producers, and their broad and diverse impact on both cellular and humoral immune responses. Consequently, the role of IFN-ʼ̛/?‚ in the pathogenesis of autoimmunity remains at the forefront of scientific inquiry and has begun to illuminate the mechanisms by which these molecules promote or inhibit systemic and organ-specific autoimmune diseases.
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    Annual Review of Immunology 23 (2005), S. 127-159 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Secondary lymphoid organs serve as hubs for the adaptive immune system, bringing together antigen, antigen-presenting cells, and lymphocytes. Two families of G proteinĐ??coupled receptors play essential roles in lymphocyte migration through these organs: chemokine receptors and sphingosine-1-phosphate (S1P) receptors. Chemokines expressed by lymphoid stromal cells guide lymphocyte and dendritic cell movements during antigen surveillance and the initiation of adaptive immune responses. S1P receptor-1 is required for lymphocyte egress from thymus and secondary lymphoid organs and is downregulated by the immunosuppressive drug FTY720. Here, we review the steps associated with the initiation of adaptive immune responses in secondary lymphoid organs, highlighting the roles of chemokines and S1P.
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    Annual Review of Immunology 23 (2005), S. 749-786 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review focuses on recent progress in our understanding of how mast cells can contribute to the initiation, development, expression, and regulation of acquired immune responses, both those associated with IgE and those that are apparently expressed independently of this class of Ig. We emphasize findings derived from in vivo studies in mice, particularly those employing genetic approaches to influence mast cell numbers and/or to alter or delete components of pathways that can regulate mast cell development, signaling, or function. We advance the hypothesis that mast cells not only can function as proinflammatory effector cells and drivers of tissue remodeling in established acquired immune responses, but also may contribute to the initiation and regulation of such responses. That is, we propose that mast cells can also function as immunoregulatory cells. Finally, we show that the notion that mast cells have primarily two functional configurations, off (or resting) or on (or activated for extensive mediator release), markedly oversimplifies reality. Instead, we propose that mast cells are "tunable," by both genetic and environmental factors, such that, depending on the circumstances, the cell can be positioned phenotypically to express a wide spectrum of variation in the types, kinetics, and/or magnitude of its secretory functions.
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    Annual Review of Immunology 23 (2005), S. 1-21 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This essay summarizes my 40 years of research in immunology. As a young physician, I encountered a patient with Waldenstro?m's macroglobulinemia, and this inspired me to study the structure of IgM. I began to ask how antibody responses are regulated. In the late 1960s, the essential role of T cells in antibody production had been reported. In search of molecules mediating T cell helper function, I discovered activities in the culture supernatant of T cells that induced proliferation and differentiation of B cells. This led to my life's work: studying one of those factors, interleukin-6 (IL-6). To my surprise, IL-6 turned out to play additional roles, including myeloma growth factor and hepatocyte-stimulating factor activities. More importantly, it was involved in a number of diseases, such as rheumatoid arthritis and Castleman's disease. I feel exceptionally fortunate that my work not only revealed the framework of cytokine signaling, including identification of the IL-6 receptor, gp130, NF-IL6, STAT3, and SOCS-1, but also led to the development of a new therapy for chronic inflammatory diseases.
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    Annual Review of Immunology 23 (2005), S. 853-875 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Most mammalian cells have nuclei that contain DNA, which replicates during cell proliferation. DNA is destroyed by various developmental processes in mammals. It is degraded during programmed cell death that accompanies mammalian development. The nuclei of erythrocytes and eye lens fiber cells are also removed during their differentiation into mature cells. If DNA is not properly degraded in these processes, it can cause various diseases, including tissue atrophy, anemia, cataract, and autoimmune diseases, which indicates that DNA can be a pathogenic molecule. Here, I present how DNA is degraded during programmed cell death, erythroid cell differentiation, and lens cell differentiation. I discuss what might be or will be learned from understanding the molecular mechanisms of DNA degradation that occurs during mammalian development.
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    Annual Review of Pharmacology 45 (2005), S. 465-476 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Normal cellular functioning requires processing of proteins regulating cell cycle, growth, and apoptosis. The ubiquitin-proteasome pathway (UBP) modulates intracellular protein degradation. Specifically, the 26S proteasome is a multienzyme protease that degrades misfolded or redundant proteins; conversely, blockade of the proteasomal degradation pathways results in accumulation of unwanted proteins and cell death. Because cancer cells are more highly proliferative than normal cells, their rate of protein translation and degradation is also higher. This notion led to the development of proteasome inhibitors as therapeutics in cancer. The FDA recently approved the first proteasome inhibitor bortezomib (VelcadeĐ?„), formerly known as PS-341, for the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Ongoing studies are examining other novel proteasome inhibitors, in addition to bortezomib, for the treatment of MM and other cancers.
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    Annual Review of Pharmacology 45 (2005), S. 565-585 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The enormous public health problem posed by malaria has been substantially worsened in recent years by the emergence and worldwide spread of drug-resistant parasites. The utility of two major therapies, chloroquine and the synergistic combination of pyrimethamine/sulfadoxine, is now seriously compromised. Although several genetic mechanisms have been described, the major source of drug resistance appears to be point mutations in protein target genes. Clinically significant resistance to these agents requires the accumulation of multiple mutations, which genetic studies of parasite populations suggest arise focally and sweep through the population. Efforts to circumvent resistance range from the use of combination therapy with existing agents to laboratory studies directed toward discovering novel targets and therapies. The prevention and management of drug resistance are among the most important practical problems of tropical medicine and public health. Leonard J. Bruce-Chwatt, 1972
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    Annual Review of Immunology 23 (2005), S. 197-223 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi. Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myeloperoxidase. We now know this is incorrect. The oxidase pumps electrons into the phagocytic vacuole, thereby inducing a charge across the membrane that must be compensated. The movement of compensating ions produces conditions in the vacuole conducive to microbial killing and digestion by enzymes released into the vacuole from the cytoplasmic granules.
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    Annual Review of Immunology 23 (2005), S. 821-852 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The complement system not only represents an effective innate immune mechanism of host defense to eradicate microbial pathogens, but it is also widely involved in many forms of acute and chronic inflammatory diseases including sepsis, acute lung injury, ischemia-reperfusion injury, and asthma, to give just a few examples. The complement-activated product, C5a, displays powerful biological activities that lead to inflammatory sequelae. C5a is a strong chemoattractant and is involved in the recruitment of inflammatory cells such as neutrophils, eosinophils, monocytes, and T lymphocytes, in activation of phagocytic cells and release of granule-based enzymes and generation of oxidants, all of which may contribute to innate immune functions or tissue damage. Accumulating data suggest that C5a provides a vital bridge between innate and adaptive immune functions, extending the roles of C5a in inflammation. Herein, we review human and animal data describing the cellular and molecular mechanisms of C5a in the development of inflammatory disorders, sepsis, acute lung injury, ischemia-reperfusion injury, and asthma.
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    Annual Review of Immunology 23 (2005), S. 275-306 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Type 1 interferon-(ʼ̛, ?‚, ?)-producing cells (IPCs), also known as plasmacytoid dendritic cell precursors (pDCs), represent 0.2%Đ??0.8% of peripheral blood mononuclear cells in both humans and mice. IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and are specialized in rapidly secreting massive amounts of type 1 interferon following viral stimulation. IPCs can promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons during an antiviral immune response. At a later stage of viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity. Understanding IPC biology holds future promise for developing cures for infectious diseases, cancer, and autoimmune diseases.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 267-294 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: With genome sequencing nearing completion for the model organisms used in biomedical research, there is a rapidly growing appreciation that proteomics, the study of covalent modification to proteins, and transcriptional regulation will likely dominate the research headlines in the next decade. Protein methylation plays a central role in both of these fields, as several different residues (Arg, Lys, Gln) are methylated in cells and methylation plays a central role in the "histone code" that regulates chromatin structure and impacts transcription. In some cases, a single lysine can be mono-, di-, or trimethylated, with different functional consequences for each of the three forms. This review describes structural aspects of methylation of histone lysine residues by two enzyme families with entirely different structural scaffolding (the SET proteins and Dot1p) and methylation of protein arginine residues by PRMTs.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 153-171 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Potassium (K+) channels are tetrameric membrane-spanning proteins that provide a selective pore for the conductance of K+ across the cell membranes. These channels are most remarkable in their ability to discriminate K+ from Na+ by more than a thousandfold and conduct at a throughput rate near diffusion limit. The recent progress in the structural characterization of K+ channel provides us with a unique opportunity to understand their function at the atomic level. With their ability to go beyond static structures, molecular dynamics simulations based on atomic models can play an important role in shaping our view of how ion channels carry out their function. The purpose of this review is to summarize the most important findings from experiments and computations and to highlight a number of fundamental mechanistic questions about ion conduction and selectivity that will require further work.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 91-118 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Proteins have become accessible targets for chemical synthesis. The basic strategy is to use native chemical ligation, Staudinger ligation, or other orthogonal chemical reactions to couple synthetic peptides. The ligation reactions are compatible with a variety of solvents and proceed in solution or on a solid support. Chemical synthesis enables a level of control on protein composition that greatly exceeds that attainable with ribosome-mediated biosynthesis. Accordingly, the chemical synthesis of proteins is providing previously unattainable insight into the structure and function of proteins.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 71-90 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Despite the central importance of peripheral membrane proteins to cellular signaling and metabolic pathways, the structures of protein-membrane interfaces remain largely inaccessible to high-resolution structural methods. In recent years a number of laboratories have contributed to the development of an electron paramagnetic resonance (EPR) power saturation approach that utilizes site-directed spin labeling to determine the key geometric parameters of membrane-docked proteins, including their penetration depths and angular orientations relative to the membrane surface. Representative applications to Ca2+-activated, membrane-docking C2 domains are described.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 119-151 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Research in the past decade has revealed that many cytosolic proteins are recruited to different cellular membranes to form protein-protein and lipid-protein interactions during cell signaling and membrane trafficking. Membrane recruitment of these peripheral proteins is mediated by a growing number of modular membrane-targeting domains, including C1, C2, PH, FYVE, PX, ENTH, ANTH, BAR, FERM, and tubby domains, that recognize specific lipid molecules in the membranes. Structural studies of these membrane-targeting domains demonstrate how they specifically recognize their cognate lipid ligands. However, the mechanisms by which these domains and their host proteins are recruited to and interact with various cell membranes are only beginning to unravel with recent computational studies, in vitro membrane binding studies using model membranes, and cellular translocation studies using fluorescent protein-tagged proteins. This review summarizes the recent progress in our understanding of how the kinetics and energetics of membrane-protein interactions are regulated during the cellular membrane targeting and activation of peripheral proteins.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 173-199 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Water plays a central role in the structures and properties of biomoleculesĐ??proteins, nucleic acids, and membranesĐ??and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global propertiesĐ??water's thermodynamics, phase diagram, and solvation properties, for exampleĐ??and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of waterĐ??as a pure liquid and as a solventĐ??derive from the geometric and hydrogen bonding properties of water.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 379-398 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Structural data on protein-DNA complexes provide clues for understanding the mechanism of protein-DNA recognition. Although the structures of a large number of protein-DNA complexes are known, the mechanisms underlying their specific binding are still only poorly understood. Analysis of these structures has shown that there is no simple one-to-one correspondence between bases and amino acids within protein-DNA complexes; nevertheless, the observed patterns of interaction carry important information on the mechanisms of protein-DNA recognition. In this review, we show how the patterns of interaction, either observed in known structures or derived from computer simulations, confer recognition specificity, and how they can be used to examine the relationship between structure and specificity and to predict target DNA sequences used by regulatory proteins.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 319-349 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Progress in experimental and theoretical biology is likely to provide us with the opportunity to assemble detailed predictive models of mammalian cells. Using a functional format to describe the organization of mammalian cells, we describe current approaches for developing qualitative and quantitative models using data from a variety of experimental sources. Recent developments and applications of graph theory to biological networks are reviewed. The use of these qualitative models to identify the topology of regulatory motifs and functional modules is discussed. Cellular homeostasis and plasticity are interpreted within the framework of balance between regulatory motifs and interactions between modules. From this analysis we identify the need for detailed quantitative models on the basis of the representation of the chemistry underlying the cellular process. The use of deterministic, stochastic, and hybrid models to represent cellular processes is reviewed, and an initial integrated approach for the development of large-scale predictive models of a mammalian cell is presented.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 319-346 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Bacteria communicate with one another using chemical signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing the activities of large groups of cells. In bacteria, chemical communication involves producing, releasing, detecting, and responding to small hormone-like molecules termed autoinducers . This process, termed quorum sensing, allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number and/or species present in a community. Most quorum-sensing-controlled processes are unproductive when undertaken by an individual bacterium acting alone but become beneficial when carried out simultaneously by a large number of cells. Thus, quorum sensing confuses the distinction between prokaryotes and eukaryotes because it enables bacteria to act as multicellular organisms. This review focuses on the architectures of bacterial chemical communication networks; how chemical information is integrated, processed, and transduced to control gene expression; how intra- and interspecies cell-cell communication is accomplished; and the intriguing possibility of prokaryote-eukaryote cross-communication.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 177-201 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Brassinosteroids (BRs), the polyhydroxylated steroid hormones of plants, regulate the growth and differentiation of plants throughout their life cycle. Over the past several years, genetic and biochemical approaches have yielded great progress in understanding BR signaling. Unlike their animal counterparts, BRs are perceived at the plasma membrane by direct binding to the extracellular domain of the BRI1 receptor S/T kinase. BR perception initiates a signaling cascade, acting through a GSK3 kinase, BIN2, and the BSU1 phosphatase, which in turn modulates the phosphorylation state and stability of the nuclear transcription factors BES1 and BZR1. Microarray technology has been used extensively to provide a global view of BR genomic effects, as well as a specific set of target genes for BES1 and BZR1. These gene products thus provide a framework for how BRs regulate the growth of plants.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 381-410 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: ʼ̛?‚ heterodimeric integrins mediate dynamic adhesive cell-cell and cell-extracellular matrix (ECM) interactions in metazoa that are critical in growth and development, hemostasis, and host defense. A central feature of these receptors is their capacity to change rapidly and reversibly their adhesive functions by modulating their ligand-binding affinity. This is normally achieved through interactions of the short cytoplasmic integrin tails with intracellular proteins, which trigger restructuring of the ligand-binding site through long-range conformational changes in the ectodomain. Ligand binding in turn elicits conformational changes that are transmitted back to the cell to regulate diverse responses. The publication of the integrin ʼ̛V?‚3 crystal structure has provided the context for interpreting decades-old biochemical studies. Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 105-131 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review surveys what is known about the structure and function of the subnuclear domains called Cajal bodies (CBs). The major focus is on CBs in mammalian cells but we provide an overview of homologous CB structures in other organisms. We discuss the protein and RNA components of CBs, including factors recently found to associate in a cell cycle-dependent fashion or under specific metabolic or stress conditions. We also consider the dynamic properties of both CBs and their molecular components, based largely on recent data obtained thanks to the advent of improved in vivo detection and imaging methods. We discuss how these data contribute to an understanding of CB functions and highlight major questions that remain to be answered. Finally, we consider the interesting links that have emerged between CBs and alterations in nuclear structure apparent in a range of human pathologies, including cancer and inherited neurodegenerative diseases. We speculate on the relationship between CB function and molecular disease.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 581-603 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Over the past decades, intravital microscopy (IVM), the imaging of cells in living organisms, has become a valuable tool for studying the molecular determinants of lymphocyte trafficking. Recent advances in microscopy now make it possible to image cell migration and cell-cell interactions in vivo deep within intact tissues. Here, we summarize the principal techniques that are currently used in IVM, discuss options and tools for fluorescence-based visualization of lymphocytes in microvessels and tissues, and describe IVM models used to explore lymphoid and non-lymphoid organs. The latter will be introduced according to the physiologic itinerary of developing and differentiating T and B lymphocytes as they traffic through the body, beginning with their development in bone marrow and thymus and continuing with their migration to secondary lymphoid organs and peripheral tissues.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 223-245 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In eukaryotes, the entwined pathways of RNA transport and local translational regulation are key determinants in the spatio-temporal articulation of gene expression. One of the main advantages of this mechanism over transcriptional control in the nucleus lies in the fact that it endows local sites with independent decision-making authority, a consideration that is of particular relevance in cells with complex cellular architecture such as neurons. Localized RNAs typically contain codes, expressed within cis-acting elements, that specify subcellular targeting. Such codes are recognized by trans-acting factors, adaptors that mediate translocation along cytoskeletal elements by molecular motors. Most transported mRNAs are assumed translationally dormant while en route. In some cell types, especially in neurons, it is considered crucial that translation remains repressed after arrival at the destination site (e.g., a postsynaptic microdomain) until an appropriate activation signal is received. Several candidate mechanisms have been suggested to participate in the local implementation of translational repression and activation, and such mechanisms may target translation at the level of initiation and/or elongation. Recent data indicate that untranslated RNAs may play important roles in the local control of translation.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 297-318 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: RNA silencing refers to a broad range of phenomena sharing the common feature that large, double-stranded RNAs or stem-loop precursors are processed to ca. 21Đ??26 nucleotide small RNAs, which then guide the cleavage of cognate RNAs, block productive translation of these RNAs, or induce methylation of specific target DNAs. Although the core mechanisms are evolutionarily conserved, epigenetic maintenance of silencing by amplification of small RNAs and the elaboration of mobile, RNA-based silencing signals occur predominantly in plants. Plant RNA silencing systems are organized into a network with shared components and overlapping functions. MicroRNAs, and probably trans-acting small RNAs, help regulate development at the posttranscriptional level. Small interfering RNAs associated with transgene- and virus-induced silencing function primarily in defending against foreign nucleic acids. Another system, which is concerned with RNA-directed methylation of DNA repeats, seems to have roles in epigenetic silencing of certain transposable elements and genes under their control.
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    Annual Review of Materials Research 35 (2005), S. 315-350 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: There is a pressing need for cleaner fuels (free or aromatics and of minimal sulfur content) or ones that convert chemical energy directly to electricity, silently and without production of noxious oxides and particulates; chemical, petrochemical and pharmaceutical processes that may be conducted in a one-step, solvent-free manner and that use air as the preferred oxidant; and industrial processes that minimize consumption of energy, production of waste, or the use of corrosive, explosive, volatile, and nonbiodegradable materials. All these needs and other desiderata, such as the in situ production and containment of aggressive and hazardous reagents, and the avoidance of use of ecologically harmful elements, may be achieved by designing the appropriate heterogeneous inorganic catalyst, which ideally should be cheap, readily preparable and fully characterizable, preferably under in situ reaction conditions. A range of nanoporous and nanoparticle catalysts that meet most of the stringent demands of sustainable development and responsible (clean) technology is described. Specific examples that are highlighted include the production of adipic acid (precursor of polyamides and urethanes) without the use of concentrated nitric acid nor the production of greenhouse gases such as nitrous oxide; the production of caprolactam (precursor of nylon) without the use of oleum and hydroxylamine sulfate; and the terminal oxyfunctionalization of linear alkanes in air. The topic of biocatalysis and sustainable development is also briefly discussed for the epoxidation of terpenes and fatty acid methyl esters; for the generation of polymers, polylactides, and polyesters; and for the production of 1,3-propanediol from corn.
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    Annual Review of Materials Research 35 (2005), S. 571-615 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: The review highlights the state-of-the-art research regarding the application of modern in situ spectroscopic, microscopic, and electrochemical techniques to improve the understanding of the interaction of organic molecules with metal surfaces. We also consider the chemical and electrochemical processes that lead to a de-adhesion of polymers from metal surfaces. Spectroscopic techniques such as surface-enhanced infrared or Raman spectroscopy provide molecular understanding of organic molecules and water at buried metal surfaces. This information is complementary to adhesion studies by means of atomic force microscopy and de-adhesion studies of polymer layers from metals by means of a scanning Kelvin probe. Adhesion and de-adhesion mechanisms are discussed, especially those involving humid and corrosive environments, which are the predominant and most important for metal/polymer composites in engineering applications.
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    Annual Review of Materials Research 35 (2005), S. 239-314 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Chemical analysis at high spatial resolution is the domain of analytical transmission electron microscopy. Owing to rapid instrumental developments during the past decade, electron energy-loss spectroscopy offers now a spatial resolution close to 0.1 nm and an energy resolution close to 0.1 eV. This development has been accompanied by the introduction of numerous new techniques and methods for data acquisition and analysis, which are outlined in the present article. Recent results for a wide range of material systems are addressed. These comprise first-principles calculations, which have contributed to enormous progress in the calculation of near-edge fine structures, and fingerprinting methods, which are still important for the interpretation of experimental data.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 169-189 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Plant secondary metabolites (PSMs) significantly impact the nutritional ecology of terrestrial vertebrate herbivores. Herbivores have a wide range of mechanisms (herbivore offenses) to mitigate the negative effects of PSMs. We discuss several behavioral and physiological offenses used by terrestrial vertebrates. Several newly recognized herbivore offenses such as regulated absorption and regulation of toxin intake are presented. We give a detailed description of the biotransformation system with respect to PSMs. We also summarize recent findings of plantĐ??animal interactions for lizards, birds, and mammals. Finally, we discuss some new tools that can be applied to long-standing questions of plantĐ??vertebrate interactions.
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    Annual Review of Fluid Mechanics 37 (2005), S. 357-392 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The objective of this review is to critically assess the different approaches developed in recent years to understand the dynamics of open flows such as mixing layers, jets, wakes, separation bubbles, boundary layers, and so on. These complex flows develop in extended domains in which fluid particles are continuously advected downstream. They behave either as noise amplifiers or as oscillators, both of which exhibit strong nonlinearities ( Huerre & Monkewitz 1990 ). The local approach is inherently weakly nonparallel and it assumes that the basic flow varies on a long length scale compared to the wavelength of the instability waves. The dynamics of the flow is then considered as a superposition of linear or nonlinear instability waves that, at leading order, behave at each streamwise station as if the flow were homogeneous in the streamwise direction. In the fully global context, the basic flow and the instabilities do not have to be characterized by widely separated length scales, and the dynamics is then viewed as the result of the interactions between Global modes living in the entire physical domain with the streamwise direction as an eigendirection. This second approach is more and more resorted to as a result of increased computational capability. The earlier review of Huerre & Monkewitz (1990) emphasized how local linear theory can account for the noise amplifier behavior as well as for the onset of a Global mode. The present survey first adopts the opposite point of view by demonstrating how fully global theory accounts for the noise amplifier behavior of open flows. From such a perspective, there is strong emphasis on the very peculiar nonorthogonality of linear Global modes, which in turn allows a novel interpretation of recent numerical simulations and experimental observations. The nonorthogonality of linear Global modes also imposes severe constraints on the extension of linear global theory to the fully nonlinear re??gime. When the flow is weakly nonparallel, this limitation is so severe that the linear Global mode theory is of little help. It is then much more appropriate to develop a fully nonlinear formulation involving the presence of a front separating the base state region from the bifurcated state region.
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    Annual Review of Fluid Mechanics 37 (2005), S. 71-98 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The flow in turbomachines is unsteady due to the relative motion of the rows of blades. In the low-pressure turbine, the wakes from the upstream bladerows provide the dominant source of unsteadiness. Because much of the blade-surface boundary-layer flow is laminar, one of the most important consequences of this unsteadiness is the interaction of the wakes with the suction-side boundary layer of a downstream blade. This is important because the blade suctionĐ??side boundary layers are responsible for most of the loss of efficiency and because the combined effects of random (wake turbulence) and periodic disturbances (wake velocity defect and pressure fields) cause the otherwise laminar boundary layer to undergo transition and eventually become turbulent. This article summarizes the process of wake-induced boundary-layer transition in low-pressure turbines and the loss generation processes that result. Particular emphasis is placed on how the effects of wakes may be exploited to control loss generation and how this has enabled successful development of ultra-high-lift low-pressure turbines.
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    Annual Review of Fluid Mechanics 37 (2005), S. 295-328 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Chaotic advection and, more generally, ideas from dynamical systems, have been fruitfully applied to a diverse, and varied, collection of mixing and transport problems arising in engineering applications over the past 20 years. Indeed, the "dynamical systems approach" was developed, and tested, to the point where it can now be considered a standard tool for understanding mixing and transport issues in many disciplines. This success for engineering-type flows motivated an effort to apply this approach to transport and mixing problems in geophysical flows. However, there are fundamental difficulties arising in this endeavor that must be properly understood and overcome. Central to this approach is that the starting point for analysis is a velocity field (i.e., the "dynamical system"). In many engineering applications this can be obtained sufficiently accurately, either analytically or computationally, so that it describes particle trajectories for the actual flow. However, in geophysical flows (and we concentrate here almost exclusively on oceanographic flows), the wide range of dynamically significant time and length scales makes the justification of any velocity field, in the sense of reproducing particle trajectories for the actual flow, a much more difficult matter. Nevertheless, the case for this approach is compelling due to the advances in observational capabilities in oceanography (e.g., drifter deployments, remote sensing capabilities, satellite imagery, etc.), which reveal space-time structures that are highly suggestive of the structures one visualizes in the global, geometrical study of dynamical systems theory. This has been pursued in recent years through a combination of laboratory studies, kinematic models, and dynamically consistent models that have all been compared with observational data. During the course of these studies it has become apparent that a new type of dynamical system is necessary to consider in these studies (i.e., a finite time, aperiodically time-dependent velocity field defined as a data set), which requires the development of new analytical and computational tools, as well as the necessity to discard some of the standard ideas and results from dynamical systems theory. In this article we review a number of the key developments to date in this young, but rapidly developing, area at the interface between geophysical fluid dynamics and applied and computational mathematics. We also describe the wealth of new directions for research that this approach unlocks.
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    Annual Review of Genetics 39 (2005), S. 263-291 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Species of the genus Drosophila exhibit enormous variation in all of their reproductive behaviors: resource use and specialization, courtship signaling, sperm utilization, and female remating. The genetic bases of this variability and its evolution are poorly understood. At the same time, Drosophila comparative genomics now has developed to a point at which approaches previously only possible with D. melanogaster can be exploited to address these questions. We have taken advantage of the known phylogenetic relationships of this group of flies not only to place these behaviors in an evolutionary framework, but to provide a roadmap for future genetic studies.
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    Annual Review of Genetics 39 (2005), S. 359-407 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.
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    Annual Review of Genetics 39 (2005), S. 69-94 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Cell-cycle control of transcription seems to be a universal feature of proliferating cells, although relatively little is known about its biological significance and conservation between organisms. The two distantly related yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have provided valuable complementary insight into the regulation of periodic transcription as a function of the cell cycle. More recently, genome-wide studies of proliferating cells have identified hundreds of periodically expressed genes and underlying mechanisms of transcriptional control. This review discusses the regulation of three major transcriptional waves, which roughly coincide with three main cell-cycle transitions (initiation of DNA replication, entry into mitosis, and exit from mitosis). I also compare and contrast the transcriptional regulatory networks between the two yeasts and discuss the evolutionary conservation and possible roles for cell cycle-regulated transcription.
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    Annual Review of Genetics 39 (2005), S. 409-429 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The lysis-lysogeny decision of bacteriophage lambda (??) is a paradigm for developmental genetic networks. There are three key features, which characterize the network. First, after infection of the host bacterium, a decision between lytic or lysogenic development is made that is dependent upon environmental signals and the number of infecting phages per cell. Second, the lysogenic prophage state is very stable. Third, the prophage enters lytic development in response to DNA-damaging agents. The CI and Cro regulators define the lysogenic and lytic states, respectively, as a bistable genetic switch. Whereas CI maintains a stable lysogenic state, recent studies indicate that Cro sets the lytic course not by directly blocking CI expression but indirectly by lowering levels of CII which activates cI transcription. We discuss how a relatively simple phage like ?? employs a complex genetic network in decision-making processes, providing a challenge for theoretical modeling.
    Type of Medium: Electronic Resource
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