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  • Wiley  (239,099)
  • American Institute of Physics  (163,092)
  • American Association for the Advancement of Science  (59,117)
  • Annual Reviews
  • Springer Science + Business Media
  • 2005-2009  (217,589)
  • 1995-1999  (158,097)
  • 1980-1984  (98,240)
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  • 1
    Publication Date: 2020-12-14
    Description: In this study we present an intercomparison of measurements of very low water vapor column content obtained with a Ground-Based Millimeter-wave Spectrometer (GBMS), Vaisala RS92k radiosondes, a Raman Lidar, and an IR Fourier Transform Spectrometer. These sets of measurements were carried out during the primary field campaign of the ECOWAR (Earth COoling by WAter vapor Radiation) project which took place on the Western Italian Alps from 3 to 16 March, 2007.
    Description: Published
    Description: 135-138
    Description: 1.8. Osservazioni di geofisica ambientale
    Description: N/A or not JCR
    Description: open
    Keywords: Precipitable Water Vapor ; ECOWAR ; IR and Millimeter-Wave Spectroscopy ; 01. Atmosphere::01.01. Atmosphere::01.01.01. Composition and Structure ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
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    Wiley
    In:  EPIC3The Ocean Floor : Bruce Heezen commemorative volume, (A Wiley-Interscience publication), Chichester, Wiley, pp. 147-163, ISBN: 0-471-10091-9
    Publication Date: 2014-05-12
    Description: The sedimentation regime off Northwest Africa is shaped by: (1) structur~al factors. which result in generallv low relief on land. shelf widths between 40 and more than 120 km. and av-erage sfope inclinations between 10 30' and 30; (2) land climates. which contral the delivery of terrigenous particles to the margin: (3) water movements including boundary currents and upwelling; and (4) the post- Pleistocene sea level rise. This chapter combines published and new results arising from research into the sedimentation processes off Northwest Africa. and emphasizes particularly the activities of the Kiel marine geological group during the past few years. Reviews of cruise activities and results were given in Closs et al. (1969) (Meteor cruise 8. 1967. off Morocco) . Seibold (1972) (Meteor cmise 25 . 1971. off Sahara to Central Senegal). Seibold and Hinz (1976) (Meteor cmise 39,1975 . and Valdivia cruise 10. 1975, from Morocco to South Senegal), and Waiden et al. (1974) (Meteor cmise 30, 1973, off Sierra Leone). Some of these cmises were used for pre- or post-site surveys for the Deep-Sea Drilling Project, or to add undisturbed Quaternary cores to the Glomar Challenger cores (leg 41, ] 975; Lancelot, et al .• 1978); leg 47 A, Arthur er al .• 1979; Lutze et al., 1979). We have concentrated our geological investigations on a number of standard profiles from the shelf to the upper continental rise as given in Figure 1. The manuscript was finished May 1979.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Inbook , peerRev
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  • 3
    Publication Date: 2018-12-07
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 4
    Publication Date: 2016-01-18
    Description: From a synthesis of recent oceanic observations and paleo-data it is evident that certain species of giant diatoms including Rhizosolenia spp. Thalassiothrix spp. and Ethmodiscus rex may become concentrated at oceanic frontal zones and subsequently form episodes of mass flux to the sediment. Within the nutrient bearing waters advecting towards frontal boundaries, these species are generally not dominant, but they appear selectively segregated at fronts, and thus may dominate the export flux. Ancient Thalassiothrix diatom mat deposits in the eastern equatorial Pacific and beneath the Polar Front in the Southern Ocean record the highest open ocean sedimentation rates ever documented and represent vast sinks of silica and carbon. Several of the species involved are adapted to a stratified water column and may thrive in Deep Chlorophyll Maxima. Thus in oceanic regions and/or at times prone to enhanced surface water stratification (e.g., during meltwater pulses) they provide a mechanism for generating substantial biomass at depth and its subsequent export with concomitant implications for Si export and C drawdown. This ecology has important implications for ocean biogeochemical models suggesting that more than one diatom “functional type” should be used. In spite of the importance of these giant diatoms for biogeochemical cycling, their large size coupled with the constraints of conventional oceanographic survey schemes and techniques means that they are undersampled. An improved insight into these key species will be an important prerequisite for enhancing our understanding of marine biogeochemical cycling and for assessing the impacts of climate change on ocean export production.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , peerRev
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  • 5
    Publication Date: 2017-04-04
    Description: The continuous volcanic and seismic activity at Mount Etna makes this volcano an important laboratory for seismological and geophysical studies. We used repeated three-dimensional tomography to detect variations in elastic parameters during different volcanic cycles, before and during the October 2002–January 2003 flank eruption. Well-defined anomalous low P- to S-wave velocity ratio volumes were revealed. Absent during the pre-eruptive period, the anomalies trace the intrusion of volatile-rich (Q4 weight percent) basaltic magma, most of which rose up only a few months before the onset of eruption. The observed time changes of velocity anomalies suggest that four-dimensional tomography provides a basis for more efficient volcano monitoring and shortand midterm eruption forecasting of explosive activity.
    Description: Published
    Description: 821-823
    Description: reserved
    Keywords: NONE ; 04. Solid Earth::04.01. Earth Interior::04.01.02. Geological and geophysical evidences of deep processes ; 04. Solid Earth::04.06. Seismology::04.06.07. Tomography and anisotropy ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 6
    Publication Date: 2017-04-04
    Description: COST (Co-operation in the field of Scientific and Technical Research) is an important instrument supporting co-operation among scientists and researchers across Europe now joining 35 member countries. Scientific projects in the COST framework are called COST Actions and have the objectives embodied in their respective Memorandum of Understanding (MoU). The main objectives of the COST Actions within the European ionospheric and radio propagation community have been: to study the influence of upper atmospheric conditions on terrestrial and Earthspace communications, to develop methods and techniques to improve existing and generate new ionospheric and propagation models over Europe for telecommunication and navigation applications and to transfer the results to the appropriate national and international organizations, institutions and industry dealing with the modern communication systems. This paper summarises in brief the background and historical context of four ionospheric COST Actions and outlines their main objectives and results. In addition, the paper discusses the dissemination of the results and the collaboration among the participating institutions and researchers.
    Description: DRS Codem Systems Ball Aerospace Corporation University of Massachusetts Lowell
    Description: Published
    Description: Lowell, Massachusetts, U.S.A., April 29, 2007
    Description: 3.9. Fisica della magnetosfera, ionosfera e meteorologia spaziale
    Description: open
    Keywords: Physics of the Ionosphere ; 01. Atmosphere::01.02. Ionosphere::01.02.99. General or miscellaneous ; 05. General::05.07. Space and Planetary sciences::05.07.02. Space weather
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Conference paper
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  • 7
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    American Association for the Advancement of Science
    Publication Date: 2017-04-04
    Description: BREVIA
    Description: Current emission inventories require an additional "unknown" source to balance the global atmospheric budgets of ethane (C2H6). Here, we provide evidence that a substantial part of the missing source can be attributed to natural gas seepage from petroliferous, geothermal, and volcanic areas. Such geologic sources also inject propane (C3H8) into the atmosphere. The analysis of a large data set of methane (CH4), ethane, and propane concentrations in surface gas emissions of 238 sites from different geographic and geologic areas, coupled with published estimates of geomethane emissions, suggests that Earth's degassing accounts for at least 17% and 10% of total ethane and propane emissions, respectively.
    Description: Published
    Description: 478
    Description: 3.8. Geofisica per l'ambiente
    Description: JCR Journal
    Description: reserved
    Keywords: Ethane ; Propane ; Geologic emissions ; Seepage ; 03. Hydrosphere::03.04. Chemical and biological::03.04.05. Gases
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 8
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    American Association for the Advancement of Science
    Publication Date: 2017-04-04
    Description: Episodes of nonvolcanic tremor and accompanying slow slip recently have been observed in the subduction zones of Japan and Cascadia. In Cascadia, such episodes typically last a few weeks, and differ from “normal” earthquakes in their source location and momentduration scaling. The three most recent episodes in the Puget Sound/Southern Vancouver Island portion of the Cascadia subduction zone have been exceptionally well recorded. In each episode, we see clear pulsing of tremor activity with periods of 12.4 and 24-25 hours, the same as the principal lunar and lunisolar tides. This indicates that the small stresses associated with the solid-earth and ocean tides influence the genesis of tremor much more effectively than they do “normal” earthquakes. Because the lithostatic stresses are 105 times larger than those associated with the tides, we argue that tremor occurs on very weak faults.
    Description: Published
    Description: 186 -189
    Description: 3.1. Fisica dei terremoti
    Description: JCR Journal
    Description: reserved
    Keywords: Nonvolcanic ; tremor ; 04. Solid Earth::04.06. Seismology::04.06.01. Earthquake faults: properties and evolution ; 04. Solid Earth::04.06. Seismology::04.06.02. Earthquake interactions and probability ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 9
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    American Institute of Physics
    Publication Date: 2020-02-24
    Description: A high-resolution Fabry–Perot interferometer was inserted in a feedback loop which, by monitoring elements of the fringe pattern, keeps the position of the transmitting window fixed with respect to a given line, taking into account the instability of the radiation source which would produce a wander of the line itself and the noise affecting the tuning of the receiving interferometer. The system, in this preliminary form, is able to lock itself and maintain its position indefinitely for slow and moderately fast varying disturbances.
    Description: Published
    Description: 2940-2944
    Description: 1.7. Osservazioni di alta e media atmosfera
    Description: JCR Journal
    Description: reserved
    Keywords: FABRY-PEROT ; INTERFEROMETER ; SERVOMECHANISMS ; FEEDBACK ; 01. Atmosphere::01.01. Atmosphere::01.01.08. Instruments and techniques
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 10
    Publication Date: 2019-07-17
    Description: A continuous high-resolution record of digital images has been obtained from the North Greenland Ice Core Project (NorthGRIP) ice core (75.1N, 42.3W) in the depth interval from 1330 m to the bedrock at 3085 m. The ice core stratigraphy is clearly visible throughout the glacial period with the most frequent and brightest visible layers appearing during the coldest events. Down to a depth of 2600 m the horizontal layeringis very regular; below this depth, small irregularities in the layering start to appear, and below 2800 m the visual stratigraphy becomes more uncertain, perhaps because of penetration into climatically warmer ice. Comparison of the visual stratigraphy with high-resolution continuous records of chemical impurities and dust reveals a high degree of correlation, which indicates that the visible layers are caused by these impurities. Anew approach is used to automatically determine annual layer thicknesses from the visual stratigraphy record by carrying out a frequency analysis of the most prominent visible layers in the profile. The result gives strong support for the NorthGRIP timescale model.
    Repository Name: EPIC Alfred Wegener Institut
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  • 11
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    Wiley
    In:  EPIC3The Ocean Floor, The Ocean Floor, Wiley, pp. 147-163
    Publication Date: 2016-03-17
    Repository Name: EPIC Alfred Wegener Institut
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  • 12
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    Wiley
    In:  EPIC3Journal of Geophysical Research: Atmospheres, Wiley, 102(D19), pp. 23505-23517, ISSN: 0148-0227
    Publication Date: 2019-07-17
    Repository Name: EPIC Alfred Wegener Institut
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  • 13
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    Wiley
    In:  EPIC3Journal of Geophysical Research: Atmospheres, Wiley, 102(D23), pp. 28195-28202, ISSN: 0148-0227
    Publication Date: 2019-07-17
    Description: Balloon-borne backscattersondes have been used to study the relationship between particle scattering and ambient temperature near the vertical edge of arctic polar stratospheric clouds (PSCs) as well as to delineate the cloud type occurrence probability as a function of temperature. The observed typical threshold temperatures as a function of altitude are about1°K warmer than the temperature TSTS expected for rapid growth of supercooled ternary solution aerosols. A more descriptive analysis shows that the threshold temperatures occur over a definable range of temperatures and tend to cluster near, but somewhat warmer than, TSTS. Considering the experimental and theoretical uncertainties, this difference may not be significant. The probability of type Ib PSC occurrence shows a dramatic increase at TSTS±1°K, while for type Ia PSCs the probability is roughly constant at 10% for temperatures below the formation point of nitric acid trihydrate (TNAT).
    Repository Name: EPIC Alfred Wegener Institut
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  • 14
    Publication Date: 2021-05-19
    Description: 1. Seahorses (Hippocampus spp.), many of which are listed as Vulnerable or Endangered on the IUCN Red List, are traded worldwide as souvenirs, aquarium fish and, primarily, for use in traditional medicines. Given concern over the sustainability of this trade, the genus was added to Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) in May 2004. 2. This paper reports findings of the first ever survey of seahorse trade in Africa, conducted in Kenya and Tanzania in May and June 2000. 3. Seahorse trade in Kenya was found to be negligible, with approximately 10 live seahorses exported as aquarium fish annually. Until 1998, however, Kenya may have imported somewhere from 1 to 2.3 t of dried seahorses annually from Tanzania for re-export to Asian medicine markets. Seahorse trade in Tanzania remained substantial, with at least 630–930 kg of dried seahorse exported directly to Asia each year. 4. Accounts of declines in seahorse availability and seahorse size, although few in number, could be early warning signs that wild populations are suffering, at least locally. Close monitoring of future developments in the trade will be essential to allow for timely conservation action as and when necessary, and would contribute to our understanding of the ecological and economical implications of small-scale, non-food fisheries. Copyright # 2004 John Wiley & Sons, Ltd.
    Description: Published
    Keywords: Hippocampus spp ; By catch ; Non-food fisheries ; Seahorse trade ; Endangered species ; Aquatic animals
    Repository Name: AquaDocs
    Type: Journal Contribution , Non-Refereed , Article
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  • 15
    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
    Type: Article
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  • 16
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    Annual Reviews
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2006. 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 Fluid Mechanics 38 (2006): 395-425, doi:10.1146/annurev.fluid.38.050304.092129.
    Description: Over the past four decades, the combination of in situ and remote sensing observations has demonstrated that long nonlinear internal solitary-like waves are ubiquitous features of coastal oceans. The following provides an overview of the properties of steady internal solitary waves and the transient processes of wave generation and evolution, primarily from the point of view of weakly nonlinear theory, of which the Korteweg-de Vries equation is the most frequently used example. However, the oceanographically important processes of wave instability and breaking, generally inaccessible with these models, are also discussed. Furthermore, observations often show strongly nonlinear waves whose properties can only be explained with fully nonlinear models.
    Description: KRH acknowledges support from NSF and ONR and an Independent Study Award from the Woods Hole Oceanographic Institution. WKM acknowledges support from NSF and ONR, which has made his work in this area possible, in close collaboration with former graduate students at Scripps Institution of Oceanography and MIT.
    Keywords: Solitary waves ; Nonlinear waves ; Stratified flow ; Physical Oceanography
    Repository Name: Woods Hole Open Access Server
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  • 17
    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
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 18
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    American Institute of Physics
    Publication Date: 2022-05-26
    Description: Author Posting. © American Institute of Physics, 2009. This article is posted here by permission of American Institute of Physics for personal use, not for redistribution. The definitive version was published in Physics Today 62 n.11 (2009): 39-44.
    Description: Most species of large whales are endangered because for centuries whaling fleets have decimated their populations. In the late 1960s, marine-mammal biologists discovered that fishermen setting nets for tuna in the Pacific Ocean were killing more than 100,000 dolphins a year. The cause of marine-mammal conservation became so popular at the dawn of the environmental movement that one of the first environmental accomplishments of the US Congress was to enact the Marine Mammal Protection Act of 1972, which prohibits the killing or injuring of marine mammals. Today, small remnant populations of whales, such as the North Atlantic right whale, are threatened by entanglement in fishing gear and collisions by ships. Indeed, marine biologists have estimated that hundreds of thousands of marine mammals are killed each year in fishing gear. Inadvertent effects of human activities can pose a serious risk to coastal populations, as evidenced by the recent extinction of the Chinese river dolphin due to fishing, pollution, and overdevelopment of the Yangtze River. A few decades ago, conservation efforts focused on reducing the intentional hunting of marine mammals. Nowadays, when hunts for marine mammals are better controlled, the slow degradation of habitat from a combination of sources may have a bigger impact. For example, biologists have documented cases in which the effects of coastal development—including noise, pollution, and dredging—have caused marine mammals to abandon critical breeding habitat. Noise in particular is at issue in legal actions that have been brought against the US Navy for sonar exercises that may have caused whales to strand and die.
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  • 19
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 209-237 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 20
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 239-267 
    ISSN: 1056-8700
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 269-292 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 293-318 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 319-350 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 351-377 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 379-404 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 405-434 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 435-462 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 463-493 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 495-522 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 85-116 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 59-83 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 117-140 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 141-165 
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    Annual Review of Biophysics and Biomolecular Structure 24 (1995), S. 523-549 
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  • 35
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 55-78 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 113-136 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 163-195 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 231-258 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 259-286 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 197-229 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 287-314 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 315-342 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 367-394 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 431-459 
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    Annual Review of Biophysics and Biomolecular Structure 25 (1996), S. 395-429 
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 1-25 
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 27-45 
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    Notes: Abstract The scope and utility of phage display is reviewed with emphasis on medical applications and structure-based ligand and drug design, from literature mostly after 1994. General principles by which phage-displayed peptides achieve affinity and selectivity for targets are described, along with selected structural or mechanistic studies of the binding of peptides or proteins discovered or engineered by phage display. Such engineered proteins whose wild-type or mutant crystal or 2D-NMR structures yield insight about the basis for enhanced affinity or altered specificity include antibodies, zinc fingers, human growth hormone, protein A, and atrial natriuretic peptide. Structures of complexes of de novo phage-discovered peptide ligands with targets such as the Src SH3 domain, streptavidin, and erythropoietin receptor reveal the structural basis for receptor-peptide recognition in these systems.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 83-112 
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    Notes: Abstract Chromatin structure is now believed to be dynamic and intimately related with cellular processes such as transcription. Over the past few years, high-resolution structures for the histones have become available. These structures and their implications for nucleosome organization are reviewed here.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 113-137 
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    Notes: Abstract The evidence showing that the self-assembly of complex RNAs occurs in discrete transitions, each relating to the folding of sub-systems of increasing size and complexity starting from a state with most of the secondary structure, is reviewed. The reciprocal influence of the concentration of magnesium ions and nucleotide mutations on tertiary structure is analyzed. Several observations demonstrate that detrimental mutations can be rescued by high magnesium concentrations, while stabilizing mutations lead to a lesser dependence on magnesium ion concentration. Recent data point to the central controlling and monitoring roles of RNA-binding proteins that can bind to the different folding stages, either before full establishment of the secondary structure or at the molten globule state before the cooperative transition to the final three-dimensional structure.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 139-156 
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    Notes: Abstract One of the fundamental properties of the RNA helix is its intrinsic resistance to bend- or twist-deformations. Results of a variety of physical measurements point to a persistence length of 700-800 A for double-stranded RNA in the presence of magnesium cations, approximately 1.5-2.0-fold larger than the corresponding value for DNA. Although helix flexibility represents an important, quantifiable measure of the forces of interaction within the helix, it must also be considered in describing conformational variation of nonhelix elements (e.g. internal loops, branches), since the latter always reflect the properties of the flanking helices; that is, such elements are never completely rigid. For one important element of tertiary structure, namely, the core of yeast tRNAPhe, the above consideration has led to the conclusion that the core is not substantially more flexible than an equivalent length of pure helix.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 157-179 
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    Notes: Abstract Phospholamban is a 52-amino-acid protein that assembles into a pentamer in sarcoplasmic reticulum membranes. The protein has a role in the regulation of the resident calcium ATPase through an inhibitory association that can be reversed by phosphorylation. The phosphorylation of phospholamban is initiated by beta-adrenergic stimulation, identifying phospholamban as an important component in the stimulation of cardiac activity by beta-agonists. It is this role of phospholamban that has motivated studies in recent decades. There is evidence that phospholamban may also function as a Ca2+-selective ion channel. The structural properties of phospholamban have been studied by mutagenesis, modeling, and spectroscopy, resulting in a new view of the organization of this key molecule in membranes.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 181-222 
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    Notes: Abstract Innovative algorithms have been developed during the past decade for simulating Newtonian physics for macromolecules. A major goal is alleviation of the severe requirement that the integration timestep be small enough to resolve the fastest components of the motion and thus guarantee numerical stability. This timestep problem is challenging if strictly faster methods with the same all-atom resolution at small timesteps are sought. Mathematical techniques that have worked well in other multiple-timescale contexts-where the fast motions are rapidly decaying or largely decoupled from others-have not been as successful for biomolecules, where vibrational coupling is strong. This review examines general issues that limit the timestep and describes available methods (constrained, reduced-variable, implicit, symplecttic, multiple-timestep, and normal-mode-based schemes). A section compares results of selected integrators for a model dipeptide, assessing physical and numerical performance. Included is our dual timestep method LN, which relies on an approximate linearization of the equations of motion every Deltat interval (5 fs or less), the solution of which is obtained by explicit integration at the inner timestep Deltatau (e.g., 0.5 fs). LN is computationally competitive, providing 4-5 speedup factors, and results are in good agreement, in comparison to 0.5 fs trajectories. These collective algorithmic efforts help fill the gap between the time range that can be simulated and the timespans of major biological interest (milliseconds and longer). Still, only a hierarchy of models and methods, along with experimentational improvements, will ultimately give theoretical modeling the status of partner with experiment.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 223-258 
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    Notes: Abstract Two sensory rhodopsins (SRI and SRII) mediate color-sensitive phototaxis responses in halobacteria. These seven-helix receptor proteins, structurally and functionally similar to animal visual pigments, couple retinal photoisomerization to receptor activation and are complexed with membrane-embedded transducer proteins (HtrI and HtrII) that modulate a cytoplasmic phosphorylation cascade controlling the flagellar motor. The Htr proteins resemble the chemotaxis transducers from Escherichia coli. The SR-Htr signaling complexes allow studies of the biophysical chemistry of signal generation and relay, from the photobiophysics of initial excitation of the receptors to the final output at the level of the flagellar motor switch, revealing fundamental principles of sensory transduction and more broadly the nature of dynamic interactions between membrane proteins. We review here recent advances that have led to new insights into the molecular mechanism of signaling by these membrane complexes.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 259-288 
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    Notes: Abstract A characteristic feature of cellular signal transduction pathways in eukaryotes is the separation of catalysis from target recognition. Several modular domains that recognize short peptide sequences and target signaling proteins to these sequences have been identified. The structural bases of the specificities of recognition by SH2, SH3, and PTB domains have been elucidated by X-ray crystallography and NMR, and these results are reviewed here. In addition, the mechanism of cooperative interactions between these domains is discussed.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 357-371 
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    Notes: Abstract Zinc-finger domains are small metal-binding modules that are found in a wide range of gene regulatory proteins. Peptides corresponding to these domains have provided valuable model systems for examining a number of biophysical parameters entirely unrelated to their nucleic acid binding properties. These include the chemical basis for metal-ion affinity and selectivity, thermodynamic properties related to hydrophobic packing and beta-sheet propensities, and constraints on the generation of ligand-binding and potential catalytic sites. These studies have laid the foundation for applications such as the generation of optically detected zinc probes and the design of metal-binding peptides and proteins with desired spectroscopic and chemical properties.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 327-355 
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    Notes: Abstract Over the past two decades, nanosecond absorption and vibrational spectroscopies have developed into powerful tools for monitoring the secondary, tertiary, and quaternary structural relaxations of biological macromolecules under near-physiological conditions of solvent and temperature. Observed through such methods, the dynamic response of a biomolecule to photoinitiated excursions from equilibrium can reveal valuable information about the structure-function relationship, information beyond that obtained from the static structures provided by X-ray crystallography, nuclear magnetic resonance spectroscopy, and other steady-state methods. Most recently, the development of ultra-sensitive polarization techniques for absorption spectroscopy has greatly enhanced the amount of time-resolved structural information that can be obtained from the broadened electronic spectra of biomolecules. This review examines nanosecond absorption, vibrational, and polarized absorption methods, and their applications to protein function and folding, emphasizing the complementary nature of information obtained from electronic and vibrational spectra measured on the nanosecond time scale.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 289-325 
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    Notes: Abstract Eukaryotes have three distinct RNA polymerases that catalyze transcription of nuclear genes. RNA polymerase II is responsible for transcribing nuclear genes encoding the messenger RNAs and several small nuclear RNAs. Like RNA polymerases I and III, polymerase II cannot recognize its target promoter directly and initiate transcription without accessory factors. Instead, this large multisubunit enzyme relies on general transcription factors and transcriptional activators and coactivators to regulate transcription from class II promoters. X-ray crystallography and nuclear magnetic resonance spectroscopy have been used to study complexes of general transcription factors and transcriptional activators with their specific DNA targets. This work has provided important structural insights into transcription initiation by polymerase II and the more general problem of DNA sequence recognition.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 47-82 
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    Notes: Abstract Researchers have made good progress in unraveling the molecular mechanisms of excitation-contraction (EC) coupling in striated muscle. Despite this progress, paradoxes abound. In skeletal muscle, the existence of a mechanical coupling between membrane charge movement and activation of sarcoplasmic reticulum (SR) release channels is essentially established, but the contribution of Ca2+-induced Ca2+ release (CICR) to the transient and steady-state components of Ca2+ release remains controversial. In cardiac muscle, the role of CICR as the primary mechanism of EC coupling is well established, but the stability and tight coupling between membrane Ca2+ current and release are paradoxical. Answers may lie in microdomain issues, and in the examination of discrete elementary release events, although quantitative treatments are needed. This review explores the theoretical and experimental methods used and the observations made in the study of microdomain Ca2+.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 373-399 
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    Notes: Abstract Measurements of trajectories of individual proteins or lipids in the plasma membrane of cells show a variety of types of motion. Brownian motion is observed, but many of the particles undergo non-Brownian motion, including directed motion, confined motion, and anomalous diffusion. The variety of motion leads to significant effects on the kinetics of reactions among membrane-bound species and requires a revision of existing views of membrane structure and dynamics.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 495-540 
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    Notes: Abstract This review focuses on the recent advances in EPR spectroscopy as they are applied both to photoinduced electron transfer in the photosynthetic apparatus and to biomimetic systems. The review deals with time-resolved direct-detection cw and pulsed EPR and ENDOR methods, both at conventional bands [X-(9.5 GHz), K-(24 GHz), and Q-(35 GHz)] and at high frequency bands (W-band, 95 GHz, and even highter frequency bands). EPR studies on photosynthetic and model systems in their doublet, triplet and radical pair states are surveyed, including their static and dynamic properties. Applications of time-resolved EPR in studying photoinduced electron and energy transfer in isotropic and anisotropic environments, and the concepts of electron spin polarization and magnetic field effects in photochemical reactions are also reviewed.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 541-566 
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    Notes: Abstract Surface plasmon resonance biosensors have become increasingly popular for the qualitative and quantitative characterization of the specific binding of a mobile reactant to a binding partner immobilized on the sensor surface. This article reviews the use of this new technique to measure the binding affinities and the kinetic constants of reversible interactions between biological macromolecules. Immobilization techniques, the most commonly employed experimental strategies, and various analytical approaches are summarized. In recent years, several sources of potential artifacts have been identified: immobilization of the binding partner, steric hindrance of binding to adjacent binding sites at the sensor surface, and finite rate of mass transport of the mobile reactant to the sensor surface. Described here is the influence of these artifacts on the measured binding kinetics and equilibria, together with suggested control experiments.
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    Annual Review of Biophysics and Biomolecular Structure 26 (1997), S. 597-627 
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    Notes: Abstract Analysis of the structures in the Protein Databank, released in June 1996, shows that the number of different protein folds, i.e. the number of different arrangements of major secondary structures and/or chain topologies, is 327. Of these folds, approximately 25% belong to the all-alpha class, 20% belong to the all-beta class, 30% belong to the alpha/beta class, and 25% belong to the alpha + beta class. We describe the types of folds now known for the all-beta and all-alpha classes, emphasizing those that have been discovered recently. Detailed theories for the physical determinants of the structures of most of these folds now exist, and these are reviewed.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 59-75 
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    Notes: Abstract This review surveys the kinds of protein complex that participate in cell communication and identifies, where possible, general principles by which they form and act. It also advances the notion that biophysical constraints imposed by macromolecular crowding and diffusion have had a controlling influence on the evolution of cell signaling pathways. Complexes associated with the bacterial aspartate receptor, with eucaryotic tyrosine kinase receptors, with T-cell receptors, and with focal contacts are examined together with proteins that serve as adaptors, anchors, and scaffolds for signaling complexes. The importance of diffusion in controlling the numbers and locations of signaling complexes is discussed, as is the special role played by membranes in signaling pathways.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 285-327 
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    Notes: Abstract The substrates for the essential biological processes of transcription, replication, recombination, DNA repair, and cell division are not naked DNA; rather, they are protein-DNA complexes known as chromatin, in one or another stage of a hierarchical series of compactions. These are exciting times for students of chromatin. New studies provide incontrovertible evidence linking chromatin structure to function. Exceptional progress has been made in studies of the structure of chromatin subunits. Surprising new dynamic properties have been discovered. And, much progress has been made in dissecting the functional roles of specific chromatin proteins and domains. This review focuses on in vitro studies of chromatin structure, dynamics, and function.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 249-284 
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    Notes: Abstract Retroviral protease (PR) from the human immunodeficiency virus type 1 (HIV-1) was identified over a decade ago as a potential target for structure-based drug design. This effort was very successful. Four drugs are already approved, and others are undergoing clinical trials. The techniques utilized in this remarkable example of structure-assisted drug design included crystallography, NMR, computational studies, and advanced chemical synthesis. The development of these drugs is discussed in detail. Other approaches to designing HIV-1 PR inhibitors, based on the concepts of symmetry and on the replacement of a water molecule that had been found tetrahedrally coordinated between the enzyme and the inhibitors, are also discussed. The emergence of drug-induced mutations of HIV-1 PR leads to rapid loss of potency of the existing drugs and to the need to continue the development process. The structural basis of drug resistance and the ways of overcoming this phenomenon are mentioned.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 199-224 
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    Notes: Abstract Biochemical and genetic approaches have identified the molecular mechanisms of many genetic reactions, particularly in bacteria. Now a comparably detailed understanding is needed of how groupings of genes and related protein reactions interact to orchestrate cellular functions over the cell cycle, to implement preprogrammed cellular development, or to dynamically change a cell's processes and structures in response to environmental signals. Simulations using realistic, molecular-level models of genetic mechanisms and of signal transduction networks are needed to analyze dynamic behavior of multigene systems, to predict behavior of mutant circuits, and to identify the design principles applicable to design of genetic regulatory circuits. When the underlying design rules for regulatory circuits are understood, it will be far easier to recognize common circuit motifs, to identify functions of individual proteins in regulation, and to redesign circuits for altered functions.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 329-356 
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    Notes: Abstract Cytochrome c oxidase, the terminal enzyme of the respiratory chains of mitochondria and aerobic bacteria, catalyzes electron transfer from cytochrome c to molecular oxygen, reducing the latter to water. Electron transfer is coupled to proton translocation across the membrane, resulting in a proton and charge gradient that is then employed by the F0F1-ATPase to synthesize ATP. Over the last years, substantial progress has been made in our understanding of the structure and function of this enzyme. Spectroscopic techniques such as EPR, absorbance and resonance Raman spectroscopy, in combination with site-directed mutagenesis work, have been successfully applied to elucidate the nature of the cofactors and their ligands, to identify key residues involved in proton transfer, and to gain insight into the catalytic cycle and the structures of its intermediates. Recently, the crystal structures of a bacterial and a mitochondrial cytochrome c oxidase have been determined. In this review, we provide an overview of the crystal structures, summarize recent spectroscopic work, and combine structural and spectroscopic data in discussing mechanistic aspects of the enzyme. For the latter, we focus on the structure of the oxygen intermediates, proton-transfer pathways, and the much-debated issue of how electron transfer in the enzyme might be coupled to proton translocation.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 357-406 
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    Notes: Abstract During the past thirty years, deuterium labeling has been used to improve the resolution and sensitivity of protein NMR spectra used in a wide variety of applications. Most recently, the combination of triple resonance experiments and 2H, 13C, 15N labeled samples has been critical to the solution structure determination of several proteins with molecular weights on the order of 30 kDa. Here we review the developments in isotopic labeling strategies, NMR pulse sequences, and structure-determination protocols that have facilitated this advance and hold promise for future NMR-based structural studies of even larger systems. As well, we detail recent progress in the use of solution 2H NMR methods to probe the dynamics of protein sidechains.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 475-502 
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    Notes: Abstract The hammerhead ribozyme is a small catalytic RNA that cleaves a target phosphodiester bond in a reaction dependent on divalent metal ions. Crystal structures of the hammerhead reveal the tertiary fold of an enzymatic "ground state" of the molecule; however, they do not clarify the catalytic mechanism of the ribozyme, presumably because a significant conformational rearrangement is required to reach an enzymatic transition state. The structural domains seen in the hammerhead can be related to sequence or structural motifs in transfer and ribosomal RNAs, suggesting that they represent tertiary building blocks that will be found in large, complex RNAs.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 1-27 
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    Notes: Abstract The Raman spectrum of a protein or nucleic acid consists of numerous discrete bands representing molecular normal modes of vibration and serves as a sensitive and selective fingerprint of three-dimensional structure, intermolecular interactions, and dynamics. Recent improvements in instrumentation, coupled with innovative approaches in experimental design, dramatically increase the power and scope of the method, particularly for investigations of large supramolecular assemblies. Applications are considered that involve the use of (a) time-resolved Raman spectroscopy to elucidate assembly pathways in icosahedral viruses, (b) polarized Raman microspectroscopy to determine detailed structural parameters in filamentous viruses, (c) ultraviolet-resonance Raman spectroscopy to probe selective DNA and protein residues in nucleoprotein complexes, and (d) difference Raman methods to understand mechanisms of protein/DNA recognition in gene regulatory and chromosomal complexes.
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    Annual Review of Biophysics and Biomolecular Structure 27 (1998), S. 503-528 
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    Notes: Abstract Pleckstrin homology (PH) motifs are approximately 100 amino-acid residues long and have been identified in nearly 100 different eukaryotic proteins, many of which participate in cell signaling and cytoskeletal regulation. Despite minimal sequence homology, the three-dimensional structures are remarkably conserved. This review gives an overview of the PH domain architecture and examines the best-studied examples in an attempt to understand their function.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 29-56 
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    Notes: Abstract Transcription in eukaryotes is frequently regulated by a mechanism termed combinatorial control, whereby several different proteins must bind DNA in concert to achieve appropriate regulation of the downstream gene. X-ray crystallographic studies of multiprotein complexes bound to DNA have been carried out to investigate the molecular determinants of complex assembly and DNA binding. This work has provided important insights into the specific protein-protein and protein-DNA interactions that govern the assembly of multiprotein regulatory complexes. The results of these studies are reviewed here, and the general insights into the mechanism of combinatorial gene regulation are discussed.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 75-100 
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    Notes: Abstract Analytical ultracentrifugation is a classical method of biochemistry and molecular biology. Because it is a primary technique, sedimentation can provide first-principle hydrodynamic and first-principle thermodynamic information for nearly any molecule, in a wide range of solvents and over a wide range of solute concentrations. For many questions, it is the technique of choice. This review stresses what information is available from analytical ultracentrifugation and how that information is being extracted and used in contemporary applications.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 129-153 
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    Notes: Abstract Measurement of the distance between two spin label probes in proteins permits the spatial orientation of elements of defined secondary structure. By using site-directed spin labeling, it is possible to determine multiple distance constraints and thereby build tertiary and quaternary structural models as well as measure the kinetics of structural changes. New analytical methods for determining interprobe distances and relative orientations for uniquely oriented spin labels have been developed using global analysis of multifrequency electron paramagnetic resonance data. New methods have also been developed for determining interprobe distances for randomly oriented spin labels. These methods are being applied to a wide range of structural problems, including peptides, soluble proteins, and membrane proteins, that are not readily characterized by other structural techniques.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 155-179 
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    Notes: Abstract Current computer simulations of biomolecules typically make use of classical molecular dynamics methods, as a very large number (tens to hundreds of thousands) of atoms are involved over timescales of many nanoseconds. The methodology for treating short-range bonded and van der Waals interactions has matured. However, long-range electrostatic interactions still represent a bottleneck in simulations. In this article, we introduce the basic issues for an accurate representation of the relevant electrostatic interactions. In spite of the huge computational time demanded by most biomolecular systems, it is no longer necessary to resort to uncontrolled approximations such as the use of cutoffs. In particular, we discuss the Ewald summation methods, the fast particle mesh methods, and the fast multipole methods. We also review recent efforts to understand the role of boundary conditions in systems with long-range interactions, and conclude with a short perspective on future trends.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 101-128 
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    Notes: Abstract Recent structural and biochemical studies have begun to illuminate how cells solve the problems of recognizing and removing damaged DNA bases. Bases damaged by environmental, chemical, or enzymatic mechanisms must be efficiently found within a large excess of undamaged DNA. Structural studies suggest that a rapid damage-scanning mechanism probes for both conformational deviations and local deformability of the DNA base stack. At susceptible lesions, enzyme-induced conformational changes lead to direct interactions with specific damaged bases. The diverse array of damaged DNA bases are processed through a two-stage pathway in which damage-specific enzymes recognize and remove the base lesion, creating a common abasic site intermediate that is processed by damage-general repair enzymes to restore the correct DNA sequence.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 181-204 
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    Notes: Abstract A significant number of exciting papain-like cysteine protease structures have been determined by crystallographic methods over the last several years. This trove of data allows for an analysis of the structural features that empower these molecules as they efficiently carry out their specialized tasks. Although the structure of the paradigm for the family, papain, has been known for twenty years, recent efforts have reaped several structures of specialized mammalian enzymes. This review first covers the commonalities of architecture and purpose of the papain-like cysteine proteases. From that broad platform, each of the lysosomal enzymes for which there is an X-ray structure (or structures) is then examined to gain an understanding of what structural features are used to customize specificity and activity. Structure-based design of inhibitors to control pathological cysteine protease activity will also be addressed.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 269-293 
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    Notes: Abstract For nuclear magnetic resonance determinations of the conformation of oligosaccharides in solution, simple molecular mechanics calculations and nuclear Overhauser enhancement measurements are adequate for small oligosaccharides that adopt single, relatively rigid conformations. Polysaccharides and larger or more flexible oligosaccharides generally require additional types of data, such as scalar and dipolar coupling constants, which are most conveniently measured in 13C-enriched samples. Nuclear magnetic resonance relaxation data provide information on the dynamics of oligosaccharides, which involves several different types of internal motion. Oligosaccharides complexed with lectins and antibodies have been successfully studied both by X-ray crystallography and by nuclear magnetic resonance spectroscopy. The complexes have been shown to be stabilized by a combination of polar hydrogen bonding interactions and van der Waals attractions. Although theoretical calculations of the conformation and stability of free oligosaccharides and of complexes with proteins can be carried out by molecular mechanics methods, the role of solvent water for these highly polar molecules continues to present computational problems.
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    Annual Review of Biophysics and Biomolecular Structure 28 (1999), S. 295-317 
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    Notes: Abstract Proteasomes are large multisubunit proteases that are found in the cytosol, both free and attached to the endoplasmic reticulum, and in the nucleus of eukaryotic cells. Their ubiquitous presence and high abundance in these compartments reflects their central role in cellular protein turnover. Proteasomes recognize, unfold, and digest protein substrates that have been marked for degradation by the attachment of a ubiquitin moiety. Individual subcomplexes of the complete 26S proteasome are involved in these different tasks: The ATP-dependent 19S caps are believed to unfold substrates and feed them to the actual protease, the 20S proteasome. This core particle appears to be more ancient than the ubiquitin system. Both prokaryotic and archaebacterial ancestors have been identified. Crystal structures are now available for the E. coli proteasome homologue and the T. acidophilum and S. cerevisiae 20S proteasomes. All three enzymes are cylindrical particles that have their active sites on the inner walls of a large central cavity. They share the fold and a novel catalytic mechanism with an N-terminal nucleophilic threonine, which places them in the family of Ntn (N terminal nucleophile) hydrolases. Evolution has added complexity to the comparatively simple prokaryotic prototype. This minimal proteasome is a homododecamer made from two hexameric rings stacked head to head. Its heptameric version is the catalytic core of archaebacterial proteasomes, where it is sandwiched between two inactive antichambers that are made up from a different subunit. In eukaryotes, both subunits have diverged into seven different subunits each, which are present in the particle in unique locations such that a complex dimer is formed that has six active sites with three major specificities that can be attributed to individual subunits. Genetic, biochemical, and high-resolution electron microscopy data, but no crystal structures, are available for the 19S caps. A first step toward a mechanistic understanding of proteasome activation and regulation has been made with the elucidation of the X-ray structure of the alternative, mammalian proteasome activator PA28.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 295-318 
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    Notes: Toroidal DNA condensates have attracted the attention of biophysicists, biochemists, and polymer physicists for more than thirty years. In the biological community, the quest to understand DNA toroid formation has been motivated by its relevance to gene packing in certain viruses and by the potential use of DNA toroids in artificial gene delivery (e.g., gene therapy). In the physical sciences, DNA toroids are appreciated as a superb model system for studying particle formation by the collapse of a semiflexible, polyelectrolyte polymer. This review focuses on experimental studies from the past few years that have significantly increased our understanding of DNA toroid structure and the mechanism of their formation. Highlights include structural studies that show the DNA strands within toroids to be packed in an ideal hexagonal lattice, and also in regions with a nonhexagonal lattice that are required by the topological constraints associated with winding DNA into a toroid. Recent studies of DNA toroid formation have also revealed that toroid size limits result from a complex interplay between kinetic and thermodynamic factors that govern both toroid nucleation and growth. The work discussed in this review indicates that it will ultimately be possible to obtain substantial control over DNA toroid dimensions.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 267-294 
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    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 
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    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 
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    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. 415-440 
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    Notes: A powerful approach to understanding protein enzyme catalysis is to examine the structural context of essential amino acid side chains whose deletion or modification negatively impacts catalysis. In principle, this approach can be even more powerful for RNA enzymes, given the wide variety and subtlety of functionally modified nucleotides now available. Numerous recent success stories confirm the utility of this approach to understanding ribozyme function. An anomaly, however, is the hammerhead ribozyme, for which the structural and functional data do not agree well, preventing a unifying view of its catalytic mechanism from emerging. To delineate the hammerhead structure-function comparison, we have evaluated and distilled the large body of biochemical data into a consensus set of functional groups unambiguously required for hammerhead catalysis. By examining the context of these functional groups within available structures, we have established a concise set of disagreements between the structural and functional data. The number and relative distribution of these inconsistencies throughout the hammerhead reaffirms that an extensive conformational rearrangement from the fold observed in the crystal structure must be necessary for cleavage to occur. The nature and energetic driving force of this conformational isomerization are discussed.
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    Annual Review of Cell and Developmental Biology 11 (1995), S. 35-71 
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    Annual Review of Cell and Developmental Biology 11 (1995), S. 241-265 
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 399-414 
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    Notes: The development of single-molecule detection and manipulation has allowed us to monitor the behavior of individual biological molecules and molecular complexes in real time. This approach significantly expands our capability to characterize complex dynamics of biological processes, allowing transient intermediate states and parallel kinetic pathways to be directly observed. Exploring this capability to elucidate complex dynamics, recent single-molecule experiments on RNA folding and catalysis have improved our understanding of the folding energy landscape of RNA and allowed us to better dissect complex RNA catalytic reactions, including translation by the ribosome.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 173-199 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    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 
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    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 Cell and Developmental Biology 11 (1995), S. 497-518 
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    Annual Review of Cell and Developmental Biology 11 (1995), S. 633-675 
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    Annual Review of Cell and Developmental Biology 12 (1996), S. 1-26 
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    Notes: Abstract Most chloroplast proteins are nuclear encoded, synthesized as larger precursor proteins in the cytosol, posttranslationally imported into the organelle, and routed to one of six different compartments. Import across the outer and inner envelope membranes into the stroma is the major means for entry of proteins destined for the stroma, the thylakoid membrane, and the thylakoid lumen. Recent investigations have identified several unique protein components of the envelope translocation machinery. These include two GTP-binding proteins that appear to participate in the early events of import and probably regulate precursor recognition and advancement into the translocon. Localization of imported precursor proteins to the thylakoid membrane and thylakoid lumen is accomplished by four distinct mechanisms; two are homologous to bacterial and endoplasmic reticulum protein transport systems, one appears unique, and the last may be a spontaneous mechanism. Thus chloroplast protein targeting is a unique and surprisingly complex process. The presence of GTP-binding proteins in the envelope translocation machinery indicates a different precursor recognition process than is present in mitochondria. Mechanisms for thylakoid protein localization are in part derived from the prokaryotic endosymbiont, but are more unusual and diverse than expected.
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    Annual Review of Cell and Developmental Biology 12 (1996), S. 181-220 
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    Notes: Abstract Receptors for the Fc domain of immunoglobulins play an important role in immune defense. There are two well-defined functional classes of mammalian receptors. One class of receptors transports immunoglobulins across epithelial tissues to their main sites of action. This class includes the neonatal Fc receptor (FcRn), which transports immunoglobulin G (IgG), and the polymeric immunoglobulin receptor (pIgR), which transports immunoglobulin A (IgA) and immunoglobulin M (IgM). Another class of receptors present on the surfaces of effector cells triggers various biological responses upon binding antibody-antigen complexes. Of these, the IgG receptors (FcgammaR) and immunoglobulin E (IgE) receptors (FcepsilonR) are the best characterized. The biological responses elicited include antibody-dependent, cell-mediated cytotoxicity, phagocytosis, release of inflammatory mediators, and regulation of lymphocyte proliferation and differentiation. We summarize the current knowledge of the structures and functions of FcRn, pIgR, and the FcgammaR and FcepsilonRI proteins, concentrating on the interactions of the extracellular portions of these receptors with immunoglobulins.
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    Annual Review of Cell and Developmental Biology 12 (1996), S. 335-363 
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    Notes: Abstract Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors that belong to the steroid/thyroid/retinoic acid receptor superfamily. All their characterized target genes encode proteins that participate in lipid homeostasis. The recent finding that antidiabetic thiazolidinediones and adipogenic prostanoids are ligands of one of the PPARs reveals a novel signaling pathway that directly links these compounds to processes involved in glucose homeostasis and lipid metabolism including adipocyte differentiation. A detailed understanding of this pathway could designate PPARs as targets for the development of novel efficient treatments for several metabolic disorders.
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    Annual Review of Cell and Developmental Biology 12 (1996), S. 441-461 
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    Notes: Abstract Proteins that function in transport vesicle docking are being identified at a rapid rate. So-called v- and t-SNAREs form the core of a vesicle docking complex. Additional accessory proteins are required to protect SNAREs from promiscuous binding and to deprotect SNAREs under conditions in which transport vesicle docking should occur. Because access to SNAREs must be regulated, other proteins must also contain specificity determinants to accomplish delivery of transport vesicles to their distinct and specific membrane targets.
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    Annual Review of Cell and Developmental Biology 12 (1996), S. 417-439 
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    Notes: Abstract Myosin is a highly conserved, ubiquitous protein found in all eukaryotic cells, where it provides the motor function for diverse movements such as cytokinesis, phagocytosis, and muscle contraction. All myosins contain an amino-terminal motor/head domain and a carboxy-terminal tail domain. Due to the extensive number of different molecules identified to date, myosins have been divided into seven distinct classes based on the properties of the head domain. One such class, class II myosins, consists of the conventional two-headed myosins that form filaments and are composed of two myosin heavy chain (MYH) subunits and four myosin light chain subunits. The MYH subunit contains the ATPase activity providing energy that is the driving force for contractile processes mentioned above, and numerous MYH isoforms exist in vertebrates to carry out this function. The MYHs involved in striated muscle contraction in mammals are the focus of the current review. The genetics, molecular biology, and biochemical properties of mammalian MYHs are discussed below. MYH gene expression patterns in developing and adult striated muscles are described in detail, as are studies of regulation of MYH genes in the heart. The discovery that mutant MYH isoforms have a causal role in the human disease familial hypertrophic cardiomyopathy (FHC) has implemented structure/function investigations of MYHs. The regulation of MYH genes expressed in skeletal muscle and the potential functional implications that distinct MYH isoforms may have on muscle physiology are addressed.
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    Annual Review of Cell and Developmental Biology 12 (1996), S. 697-715 
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    Notes: Abstract Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.
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    Annual Review of Cell and Developmental Biology 13 (1997), S. 1-23 
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    Notes: Abstract Transcriptional regulation is important in all eukaryotic organisms for cell growth, development, and responses to environmental change. Saccharomyces cerevisiae, or bakers' yeast, has provided a powerful system for genetic analysis of transcriptional regulation, and findings from the study of this model system have proven broadly applicable to higher organisms. Transcriptional regulation requires the interactions of regulatory proteins with various components of the transcription machinery. Recently, genetic analysis of a diverse set of transcriptional regulatory responses has converged with studies of the function of the RNA polymerase II carboxy-terminal domain (CTD) to reveal regulatory roles for proteins associated with the CTD. These proteins, designated Srb/mediator proteins, are broadly involved in both positive and negative regulatory responses in vivo. This review focuses on the connections between genetic analysis of transcriptional regulation and the functions of the Srb/mediator proteins associated with the RNA polymerase II CTD.
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    Annual Review of Cell and Developmental Biology 13 (1997), S. 53-82 
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    Notes: Abstract Most animal species exhibit left-right asymmetry in their body plans and show a strong bias for one handedness over the other. The mechanism of handedness choice, recognized as an intriguing problem over a century ago, is still a mystery. However, from recent advances in understanding when and how asymmetry arises in both invertebrates and vertebrates, developmental pathways for establishment and maintenance of left-right differences are beginning to take shape, and speculations can be made on the initial choice mechanism.
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    Annual Review of Cell and Developmental Biology 13 (1997), S. 83-117 
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    Notes: Abstract The polymerization dynamics of microtubules are central to their biological functions. Polymerization dynamics allow microtubules to adopt spatial arrangements that can change rapidly in response to cellular needs and, in some cases, to perform mechanical work. Microtubules utilize the energy of GTP hydrolysis to fuel a unique polymerization mechanism termed dynamic instability. In this review, we first describe progress toward understanding the mechanism of dynamic instability of pure tubulin and then discuss the function and regulation of microtubule dynamic instability in living cells.
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