ALBERT

Notes: Abstract Fungal pathogens of plants or animals invade their hosts either by secretion of lytic enzymes, exerting force, or by a combination of both. Although many fungi are thought to rely mostly on lysis of the host tissue, some plant pathogenic fungi differentiate complex infection cells that develop enormous turgor pressure, which in turn is translated into force used for invasion. In order to understand mechanisms of fungal infection in detail, methods have been developed that indirectly or directly measure turgor pressure and force. In this article, these methods are described and critically discussed, and their importance in analysis of fungal infection are outlined.

Notes: Abstract The field of computational cell biology has emerged within the past 5 years because of the need to apply disciplined computational approaches to build and test complex hypotheses on the interacting structural, physical, and chemical features that underlie intracellular processes. To meet this need, newly developed software tools allow cell biologists and biophysicists to build models and generate simulations from them. The construction of general-purpose computational approaches is especially challenging if the spatial complexity of cellular systems is to be explicitly treated. This review surveys some of the existing efforts in this field with special emphasis on a system being developed in the authors' laboratory, Virtual Cell. The theories behind both stochastic and deterministic simulations are discussed. Examples of respective applications to cell biological problems in RNA trafficking and neuronal calcium dynamics are provided to illustrate these ideas.

Notes: Abstract Cyclooxygenases-1 and -2 (COX-1 and COX-2, also known as prostaglandin H2 synthases-1 and -2) catalyze the committed step in prostaglandin synthesis. COX-1 and -2 are of particular interest because they are the major targets of nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2-selective inhibitors. Inhibition of the COXs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces the incidence of fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of COXs relate mechanistically to cyclooxygenase and peroxidase catalysis and how alternative fatty acid substrates bind within the COX active site. We further examine how NSAIDs interact with COXs and how differences in the structure of COX-2 result in enhanced selectivity toward COX-2 inhibitors.

Notes: Abstract Understanding the action of enzymes on an atomistic level is one of the important aims of modern biophysics. This review describes the state of the art in addressing this challenge by simulating enzymatic reactions. It considers different modeling methods including the empirical valence bond (EVB) and more standard molecular orbital quantum mechanics/molecular mechanics (QM/MM) methods. The importance of proper configurational averaging of QM/MM energies is emphasized, pointing out that at present such averages are performed most effectively by the EVB method. It is clarified that all properly conducted simulation studies have identified electrostatic preorganization effects as the source of enzyme catalysis. It is argued that the ability to simulate enzymatic reactions also provides the chance to examine the importance of nonelectrostatic contributions and the validity of the corresponding proposals. In fact, simulation studies have indicated that prominent proposals such as desolvation, steric strain, near attack conformation, entropy traps, and coherent dynamics do not account for a major part of the catalytic power of enzymes. Finally, it is pointed out that although some of the issues are likely to remain controversial for some time, computer modeling approaches can provide a powerful tool for understanding enzyme catalysis.

Notes: The effect of force on the thermodynamics and kinetics of reactions is described. The key parameters are the difference in end-to-end distance between reactant and product for thermodynamics, and the distance to the transition state for kinetics. I focus the review on experimental results on force unfolding of RNA. Methods to measure Gibbs free energies and kinetics for reversible and irreversible reactions are described. The use of the worm-like-chain model to calculate the effects of force on thermodynamics and kinetics is illustrated with simple models. The main purpose of the review is to describe the simple experiments that have been done so far, and to encourage more people to enter a field that is new and full of opportunities.

Notes: The structural elucidation of clear but distant homologs of actin and tubulin in bacteria and GFP labeling of these proteins promises to reinvigorate the field of prokaryotic cell biology. FtsZ (the tubulin homolog) and MreB/ParM (the actin homologs) are indispensable for cellular tasks that require the cell to accurately position molecules, similar to the function of the eukaryotic cytoskeleton. FtsZ is the organizing molecule of bacterial cell division and forms a filamentous ring around the middle of the cell. Many molecules, including MinCDE, SulA, ZipA, and FtsA, assist with this process directly. Recently, genes much more similar to tubulin than to FtsZ have been identified in Verrucomicrobia. MreB forms helices underneath the inner membrane and probably defines the shape of the cell by positioning transmembrane and periplasmic cell wall-synthesizing enzymes. Currently, no interacting proteins are known for MreB and its relatives that help these proteins polymerize or depolymerize at certain times and places inside the cell. It is anticipated that MreB-interacting proteins exist in analogy to the large number of actin binding proteins in eukaryotes. ParM (a plasmid-borne actin homolog) is directly involved in pushing certain single-copy plasmids to the opposite poles by ParR/parC-assisted polymerization into double-helical filaments, much like the filaments formed by actin, F-actin. Mollicutes seem to have developed special systems for cell shape determination and motility, such as the fibril protein in Spiroplasma.

Notes: Molecular motions are widely regarded as contributing factors in many aspects of protein function. The enzyme dihydrofolate reductase (DHFR), and particularly that from Escherichia coli, has become an important system for investigating the linkage between protein dynamics and catalytic function, both because of the location and timescales of the motions observed and because of the availability of a large amount of structural and mechanistic data that provides a detailed context within which the motions can be interpreted. Changes in protein dynamics in response to ligand binding, conformational change, and mutagenesis have been probed using numerous experimental and theoretical approaches, including X-ray crystallography, fluorescence, nuclear magnetic resonance (NMR), molecular dynamics simulations, and hybrid quantum/classical dynamics methods. These studies provide a detailed map of changes in conformation and dynamics throughout the catalytic cycle of DHFR and give new insights into the role of protein motions in the catalytic activity of this enzyme.

Notes: The genomics revolution has provided a deluge of new targets for drug discovery. To facilitate the drug discovery process, many researchers are turning to fragment-based approaches to find lead molecules more efficiently. One such method, Tethering1, allows for the identification of small-molecule fragments that bind to specific regions of a protein target. These fragments can then be elaborated, combined with other molecules, or combined with one another to provide high-affinity drug leads. In this review we describe the background and theory behind Tethering and discuss its use in identifying novel inhibitors for protein targets including interleukin-2 (IL-2), thymidylate synthase (TS), protein tyrosine phosphatase 1B (PTP-1B), and caspases.

Notes: Recent work is extending the methodology of X-ray crystallography to the structure determination of noncrystalline specimens. The phase problem is solved using the oversampling method, which takes advantage of "continuous" diffraction patterns from noncrystalline specimens. Here we review the principle of this newly developed technique and discuss the ongoing experiments of imaging nonperiodic objects, such as cells and cellular structures, using coherent and bright X rays produced by third-generation synchrotron sources. In the longer run, the technique may be applicable to image single biomolecules using anticipated X-ray free electron lasers. Here, computer simulations have so far demonstrated two important steps: (a) by using an extremely intense femtosecond X-ray pulse, a diffraction pattern can be recorded from a macromolecule before radiation damage manifests itself; and (b) the phase information can be retrieved in an ab initio fashion from a set of calculated noisy diffraction patterns of single protein molecules.

Notes: Topoisomerases are enzymes that use DNA strand scission, manipulation, and rejoining activities to directly modulate DNA topology. These actions provide a powerful means to effect changes in DNA supercoiling levels, and allow some topoisomerases to both unknot and decatenate chromosomes. Since their initial discovery over three decades ago, researchers have amassed a rich store of information on the cellular roles and regulation of topoisomerases, and have delineated general models for their chemical and physical mechanisms. Topoisomerases are now known to be necessary for the survival of cellular organisms and many viruses and are rich clinical targets for anticancer and antimicrobial treatments. In recent years, crystal structures have been obtained for each of the four types of topoisomerases in a number of distinct conformational and substrate-bound states. In addition, sophisticated biophysical methods have been utilized to study details of topoisomerase reaction dynamics and enzymology. A synthesis of these approaches has provided researchers with new physical insights into how topoisomerases employ chemistry and allostery to direct the large-scale molecular motions needed to pass DNA strands through each other.

Notes: Emerging methods in cryo-electron microscopy allow determination of the three-dimensional architectures of objects ranging in size from small proteins to large eukaryotic cells, spanning a size range of more than 12 orders of magnitude. Advances in determining structures by "single particle" microscopy and by "electron tomography" provide exciting opportunities to describe the structures of subcellular assemblies that are either too large or too heterogeneous to be investigated by conventional crystallographic methods. Here, we review selected aspects of progress in structure determination by cryo-electron microscopy at molecular resolution, with a particular emphasis on topics at the interface of single particle and tomographic approaches. The rapid pace of development in this field suggests that comprehensive descriptions of the structures of whole cells and organelles in terms of the spatial arrangements of their molecular components may soon become routine.

Notes: F1-ATPase is a rotary motor made of a single protein molecule. Its rotation is driven by free energy obtained by ATP hydrolysis. In vivo, another motor, Fo, presumably rotates the F1 motor in the reverse direction, reversing also the chemical reaction in F1 to let it synthesize ATP. Here we attempt to answer two related questions, How is free energy obtained by ATP hydrolysis converted to the mechanical work of rotation, and how is mechanical work done on F1 converted to free energy to produce ATP? After summarizing single-molecule observations of F1 rotation, we introduce a toy model and discuss its free-energy diagrams to possibly answer the above questions. We also discuss the efficiency of molecular motors in general.

Notes: Mass spectrometry provides key tools for the analysis of proteins. New types of mass spectrometers that provide enhanced capability to discover protein identities and perform improved proteomic experiments are discussed. Handling the complex mixtures of peptides and proteins generated from protein complexes and whole cells requires multidimensional separations; several forms of separation are discussed. Applications of mass spectrometry-based approaches for contemporary proteomic analyses are described.

Notes: Nucleic acids are characterized by a vast structural variability. Secondary structural conformations include the main polymorphs A, B, and Z, cruciforms, intrinsic curvature, and multistranded motifs. DNA secondary motifs are stabilized and regulated by the primary base sequence, contextual effects, environmental factors, as well as by high-order DNA packaging modes. The high-order modes are, in turn, affected by secondary structures and by the environment. This review is concerned with the flow of structural information among the hierarchical structural levels of DNA molecules, the intricate interplay between the various factors that affect these levels, and the regulation and physiological significance of DNA high-order structures.

Notes: Abstract The common envelope phase of binary star evolution plays an essential role in the formation of short period systems containing a compact object. In this process, significant mass and angular momentum are lost, transforming a wide progenitor system into a close remnant binary. The pathways leading to this phase and the outcomes are described. Emphasis is placed on the conditions that are required for survival of the binary according to the results of three-dimensional hydrodynamics calculations. The evolution of high-mass systems containing neutron stars is discussed, including double neutron stars, binary pulsars, Thorne-Zytkow objects, and high- and low-mass X-ray binaries.

Notes: Abstract In this article we first review the main physical effects to be considered in the building of evolutionary models of rotating stars on the Upper Main-Sequence (MS). The internal rotation law evolves as a result of contraction and expansion, meridional circulation, diffusion processes, and mass loss. In turn, differential rotation and mixing exert a feedback on circulation and diffusion, so that a consistent treatment is necessary. We review recent results on the evolution of internal rotation and the surface rotational velocities for stars on the Upper MS, for red giants, supergiants, and W-R stars. A fast rotation enhances the mass loss by stellar winds and, conversely, high mass loss removes a lot of angular momentum. The problem of the breakup or Omega-limit is critically examined in connection with the origin of Be and LBV stars. The effects of rotation on the tracks in the HR diagram, the lifetimes, the isochrones, the blue-to-red supergiant ratios, the formation of Wolf-Rayet stars, and the chemical abundances in massive stars as well as in red giants and AGB stars are reviewed in relation to recent observations for stars in the Galaxy and Magellanic Clouds. The effects of rotation on the final stages and on the chemical yields are examined, along with the constraints placed by the periods of pulsars. On the whole, this review points out that stellar evolution is not only a function of mass M and metallicity Z, but of angular velocity Omega as well.

Notes: Abstract Our understanding of the evolution of organic molecules, and their voyage from molecular clouds to the early solar system and Earth, has changed dramatically. Incorporating recent observational results from the ground and space, as well as laboratory simulation experiments and new methods for theoretical modeling, this review recapitulates the inventory and distribution of organic molecules in different environments. The evolution, survival, transport, and transformation of organics is monitored, from molecular clouds and the diffuse interstellar medium to their incorporation into solar system material such as comets and meteorites. We constrain gas phase and grain surface formation pathways to organic molecules in dense interstellar clouds, using recent observations with the Infrared Space Observatory (ISO) and ground-based radiotelescopes. The main spectroscopic evidence for carbonaceous compounds in the diffuse interstellar medium is discussed (UV bump at 2200 A, diffuse interstellar bands, extended red emission, and infrared absorption and emission bands). We critically review the signatures and unsolved problemsrelated to the main organic components suggested to be present in the diffuse gas, such as polycyclic aromatic hydrocarbons (PAHs), fullerenes, diamonds, and carbonaceous solids. We also briefly discuss the circumstellar formation of organics around late-typestars. In the solar system, space missions to comet Halley and observations of the bright comets Hyakutake and Hale-Bopp have recently allowed a reexamination of the organic chemistry of dust and volatiles in long-period comets. We review the advances in this area and also discuss progress being made in elucidating the complex organic inventory of carbonaceous meteorites. The knowledge of organic chemistry in molecular clouds, comets, and meteorites and their common link provides constraints for the processes that lead to the origin, evolution, and distribution of life in the Galaxy.

Notes: Abstract More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 mum band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory1, the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy, and spectrophotometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far-IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.

Notes: Abstract The Orion Nebula (M 42) is one of the best studied objects in the sky. The advent of multi-wavelength investigations and quantitative high resolution imaging has produced a rapid improvement in our knowledge of what is widely considered the prototype H II region and young galactic cluster. Perhaps uniquely among this class of object, we have a good three dimensional picture of the nebula, which is a thin blister of ionized gas on the front of a giant molecular cloud, and the extremely dense associated cluster. The same processes that produce the nebula also render visible the circumstellar material surrounding many of the pre-main sequence low mass stars, while other circumstellar clouds are seen in silhouette against the nebula. The process of photoevaporation of ionized gas not only determines the structure of the nebula that we see, but is also destroying the circumstellar clouds, presenting a fundamental conundrum about why these clouds still exist.

Notes: Abstract Distant type Ia supernovae (SNe Ia) appear fainter than their local counterparts. Independent of what explanation will eventually be found to be correct, this implies a significant change in how we see the distant universe and what we understand of these stellar explosions. The observational characteristics of nearby SNe Ia show some differences from event to event. Despite their considerable range in observed peak luminosity, they can be normalized by their light-curve shape. Through this normalization, SNe Ia can be used as exquisite distance indicators. The Hubble diagram of nearby SNe Ia, demonstrating the linear cosmic expansion at small scales, is the simplest observational proof for the standard character of these objects. Compared with Friedmann models of the universe, the distant SNe are too faint even for a freely coasting, "empty" universe, barring other influences that could dim the events. This result is independent of the absolute calibration of the peak luminosity, which is needed to derive the Hubble constant. Possible noncosmological explanations could be gray dust, with properties that do not change the color of the objects significantly, evolution of the explosions, or deamplification by gravitational lensing. Current indications are that none of these alternatives alone can explain the dimness of the distant SNe. The intrinsic colors of the distant SNe Ia are typically bluer when compared with the local sample. This in itself makes the dust hypothesis less likely. On the other hand, it could be a signature of evolutionary trends that could influence the peak luminosity. This trend is contrary to the observations in the local sample, where bluer objects typically are more luminous. However, current lack of understanding of the explosion physics and the radiation transport of SNe Ia encumbers any investigation of evolutionary changes. Any change in the peak luminosity of SNe Ia must be inferred from indirect observations, such as light-curve shape, colors, and spectral evolution. At the moment, many of the distant SNe do not have the required data set for a detailed investigation of these parameters. The near-uniform light-curve and spectral evolution of SNe Ia can be used as accurate cosmic clocks to demonstrate the time dilation as predicted from expanding world models. The test has been performed through both photometry and spectroscopy, and is fully consistent with the predictions. The supernova (SN) results can be reconciled only with cosmological models that provide some form of acceleration. The simplest such models either include the cosmological constant or refer to a decaying particle field ("quintessence"). Combined with recent measurements of the cosmic microwave background that indicate a flat geometry of the universe, and low-matter density, as derived from bulk flows and the evolution of galaxy clusters, the SNe define a fairly narrow likelihood region for OmegaM and OmegaLambda. With these new values for the cosmological parameters, the long-standing problem of the dynamical age of the universe appears to be solved. On the other hand, the size of the acceleration, if interpreted as a cosmological constant, is in clear contradiction to predictions from particle theories. In addition, we live in a very privileged period when matter density and the cosmological constant are equal contributors to the cosmic expansion.

Notes: Abstract The search for evidence of extraterrestrial intelligence is placed in the broader astronomical context of the search for extrasolar planets and biomarkers of primitive life elsewhere in the universe. A decision tree of possible search strategies is presented as well as a brief history of the search for extraterrestrial intelligence (SETI) projects since 1960. The characteristics of 14 SETI projects currently operating on telescopes are discussed and compared using one of many possible figures of merit. Plans for SETI searches in the immediate and more distant future are outlined. Plans for success, the significance of null results, and some opinions on deliberate transmission of signals (as well as listening) are also included. SETI results to date are negative, but in reality, not much searching has yet been done.

Notes: Abstract Dusty circumstellar disks in orbit around main-sequence stars were discovered in 1983 by the infrared astronomical satellite. It was the first time material that was not another star had been seen in orbit around a main-sequence star other than our Sun. Since that time, analyses of data from the infrared astronomical satellite, the infrared space observatory, and ground-based telescopes have enabled astronomers to paint a picture of dusty disks around numerous main-sequence and post-main-sequence stars. This review describes, primarily in an evolutionary framework, the properties of some dusty disks orbiting, first, pre-main-sequence stars, then main-sequence and post-main-sequence stars, and ending with white dwarfs.

Notes: Abstract The cosmic infrared background records much of the radiant energy released by processes of structure formation that have occurred since the decoupling of matter and radiation following the Big Bang. In the past few years, data from the Cosmic Background Explorer (COBE) mission provided the first measurements of this background, with additional constraints coming from studies of the attenuation of TeV gamma-rays. At the same time, there has been rapid progress in resolving a significant fraction of this background with the deep galaxy counts at infrared wavelengths from the Infrared Space Observatory (ISO) instruments and at submillimeter wavelengths from the Submillimeter Common User Bolometer Array (SCUBA) instrument. This article reviews the measurements of the infrared background and sources contributing to it and discusses the implications for past and present cosmic processes.

Notes: Abstract The inner few parsecs at the Galactic Center have come under intense scrutiny in recent years, in part due to the exciting broad-band observations of this region, but also because of the growing interest from theorists motivated to study the physics of black hole accretion, magnetized gas dynamics, and unusual star formation. The Galactic Center is now known to contain arguably the most compelling supermassive black hole candidate, weighing in at a little over 2.6 million suns. Its interaction with the nearby environment, comprised of clusters of evolved and young stars, a molecular dusty ring, ionized gas streamers, diffuse hot gas, and a hypernova remnant, is providing a wealth of accretion phenomenology and high-energy processes for detailed modeling. In this review, we summarize the latest observational results and focus on the physical interpretation of the most intriguing object in this region-the compact radio source Sgr A*, thought to be the radiative manifestation of the supermassive black hole.

Notes: Abstract The field of optical and infrared (IR) interferometry has seen rapid technical and scientific progress over the past few years. A number of instruments capable of precise visibility measurements have been built, and closure-phase imaging with multitelescope arrays has been demonstrated. Astronomical results from these instruments include measurements of stellar diameters and their wavelength dependence, limb darkening, stellar surface structure, and distances of Cepheids and of Nova Cygni 1992. Precise stellar masses have been obtained from interferometric observations of spectroscopic binaries, and circumstellar disks and shells have been resolved. Searches for substellar companions and extrasolar planets with interferometric astrometry will begin soon. Nulling interferometry will enable studies of exozodiacal disks from the ground and the detection and characterization of terrestrial extrasolar planets from space. These developments are reviewed, as well as progress in some key technological areas.

Notes: Abstract Since the first radio astronomy observations in the 1930s, the angular resolution of radio telescopes has improved from tens of degrees to better than one thousandth of a second of arc. This advancement has been the result of technological innovations such as stable, sensitive, short-wavelength radio receivers, digital correlators, atomic clocks, and high-speed tape recorders, as well as the development of sophisticated image processing algorithms implemented on inexpensive, fast, digital computers.

Notes: Abstract Outflow activity is associated with all stages of early stellar evolution, from deeply embedded protostellar objects to visible young stars. Herbig-Haro (HH) objects are the optical manifestations of this powerful mass loss. Analysis of HH flows, and in particular of the subset of highly collimated HH jets, provides indirect but important insights into the nature of the accretion and mass-loss processes that govern the formation of stars. The recent recognition that HH flows may attain parsec-scale dimensions opens up the possibility of partially reconstructing the mass-ejection history of the newly born driving sources and, therefore, their mass-accretion history. Furthermore, HH flows are astrophysical laboratories for the analysis of shock structures, of hydrodynamics in collimated flows, and of their interaction with the surrounding environment. HH flows may be an important source of turbulence in molecular clouds. Recent technological developments have enabled detailed observations of outflows from young stars at near-infrared, mid-infrared, submillimeter, millimeter, and centimeter wavelengths, providing a comprehensive picture of the outflow phenomenon of young stars.

Notes: The galaxies of the Local Group serve as important laboratories for understanding the physics of massive stars. Here I discuss what is involved in identifying various kinds of massive stars in nearby galaxies: the hydrogen-burning O-type stars and their evolved He-burning evolutionary descendants, the luminous blue variables, red supergiants, and Wolf-Rayet stars. Primarily I review what our knowledge of the massive star population in nearby galaxies has taught us about stellar evolution and star formation. I show that the current generation of stellar evolutionary models do well at matching some of the observed features and provide a look at the sort of new observational data that will provide a benchmark against which new models can be evaluated.

Notes: Abstract I fled with my parents from Hitler's Austria to Australia and studied physics at Sydney University. I obtained my Ph.D. in quantum electrodynamics with Rudolf Peierls at Birmingham University and came to Cornell to work with Hans Bethe. I have stayed at Cornell ever since, and I have essentially had only a single job in my whole life, but have switched fields quite often. I worked in nuclear astrophysics and in late-stellar evolution, estimated the Initial Mass Function for star formation and the metal enrichment of the interstellar medium. I suggested black hole accretion as the energy source for quasars, worked on molecule formation on dust grain surfaces, and was involved in 21-cm studies of gas clouds and disk galaxies. I collaborated with my wife on the neurobiology of the neuromuscular junction and with one of my daughters on the epidemiology of tuberculosis.

Notes: Abstract Although we have a general understanding of the manner in which individual stars form, our understanding of how binary stars form is far from complete. This is in large part due to the fact that the star formation process happens very quickly and in regions of the Galaxy that are difficult to study observationally. We review the theoretical models that have been developed in an effort to explain how binaries form. Several proposed mechanisms appear to be quite promising, but none is completely satisfactory.

Notes: Abstract Radio astronomy has provided evidence for the presence of ionized atmospheres around almost all classes of nondegenerate stars. Magnetically confined coronae dominate in the cool half of the Hertzsprung-Russell diagram. Their radio emission is predominantly of nonthermal origin and has been identified as gyrosynchrotron radiation from mildly relativistic electrons, apart from some coherent emission mechanisms. Ionized winds are found in hot stars and in red giants. They are detected through their thermal, optically thick radiation, but synchrotron emission has been found in many systems as well. The latter is emitted presumably by shock-accelerated electrons in weak magnetic fields in the outer wind regions. Radio emission is also frequently detected in pre-main sequence stars and protostars and has recently been discovered in brown dwarfs. This review summarizes the radio view of the atmospheres of nondegenerate stars, focusing on energy release physics in cool coronal stars, wind phenomenology in hot stars and cool giants, and emission observed from young and forming stars. Eines habe ich in einem langen Leben gelernt, namlich, dass unsere ganze Wissenschaft, an den Dingen gemessen, von kindlicher Primitivitat ist-und doch ist es das Kostlichste, was wir haben. One thing I have learned in a long life: that all our science, measured against reality, is primitive and childlike-and yet it is the most precious thing we have. A. Einstein 1951, in a letter to H. Muhsam, Einstein Archive 36-610

Notes: Abstract Study of radio supernovae over the past 20 years includes two dozen detected objects and more than 100 upper limits. From this work it is possible to identify classes of radio properties, demonstrate conformance to and deviations from existing models, estimate the density and structure of the circumstellar material and, by inference, the evolution of the presupernova stellar wind, and reveal the last stages of stellar evolution before explosion. It is also possible to detect ionized hydrogen along the line of sight, to demonstrate binary properties of the stellar system, and to show clumpiness of the circumstellar material. More speculatively, it may be possible to provide distance estimates to radio supernovae. Over the past four years the afterglow of gamma-ray bursters has occasionally been detected in the radio, as well in other wavelengths bands. In particular, the interesting and unusual gamma-ray burst GRB980425, thought to be related to SN1998bw, is a possible link between supernovae and gamma-ray bursters. Analyzing the extensive radio emission data avaliable for SN1998bw, one can describe its time evolution within the well-established framework available for the analysis of radio emission from supernovae. This allows relatively detailed description of a number of physical properties of the object. The radio emission can best be explained as the interaction of a mildly relativistic (Gamma~ 1.6) shock with a dense preexplosion stellar wind-established circumstellar medium that is highly structured both azimuthally, in clumps or filaments, and radially, with observed density enhancements. Because of its unusual characteristics for a Type Ib/c supernova, the relation of SN1998bw to GRB980425 is strengthened and suggests that at least some classes of GRBs originate in massive star explosions. Thus, employing the formalism for describing the radio emission from supernovae and following the link through SN1998bw/GRB980425, it is possible to model the gross properties of the radio and optical/infrared emission from the half-dozen GRBs with extensive radio observations. From this we conclude that at least some members of the "slow-soft" class of GRBs can be attributed to the explosion of a massive star in a dense, highly structured circumstellar medium that was presumably established by the preexplosion stellar system.

Notes: Abstract The Sunyaev-Zel'dovich effect (SZE) provides a unique way to map the large-scale structure of the universe as traced by massive clusters of galaxies. As a spectral distortion of the cosmic microwave background, the SZE is insensitive to the redshift of the galaxy cluster, making it well-suited for studies of clusters at all redshifts, and especially at reasonably high redshifts (z〉 1) where the abundance of clusters is critically dependent on the underlying cosmology. Recent high signal-to-noise detections of the SZE have enabled interesting constraints on the Hubble constant and on the matter density of the universe using small samples of galaxy clusters. Upcoming SZE surveys are expected to find hundreds to thousands of new galaxy clusters, with a mass selection function that is remarkably uniform with redshift. In this review we provide an overview of the SZE and its use for cosmological studies, with emphasis on the cosmology that can, in principle, be extracted from SZE survey yields. We discuss the observational and theoretical challenges that must be met before precise cosmological constraints can be extracted from the survey yields.

Notes: The first law of theoretical physics, the Newtonian law of gravitation, relies on the concept of action at a distance. The success of this law led to the concept being applied to electricity and magnetism, which were next to be explored in depth. Here the action at a distance had a limited success and ultimately had to be abandoned in favor of the increasingly more popular field theory. Nevertheless, in the 1940s, an attempt was made to revive the concept of action at a distance in a relativistically invariant way by Wheeler & Feynman (1945, 1949). It inspired a series of investigations in both electrodynamics and gravity in which the field concept was not used but the interaction was described as taking place directly between particles. As it impinged very intimately on cosmology, Hoyle was keenly interested in it. This review discusses the work by Hoyle, the author, and others on the development of electrodynamics and gravitation as direct particle theories. In this review, the author discusses how the work was started and went through stages of increasing sophistication, e.g., extending the Wheeler-Feynman electrodynamics to curved spacetime, its consequences in different cosmologies, and the issues arising from its quantization. The resolution of ultraviolet divergences in quantum electrodynamics is also briefly discussed. The parallel development of a Machian theory of gravitation followed the lead from electrodynamics. In both theories one sees a strong link between the large-scale structure of the universe and local physics, as might be expected from an action-at-a-distance framework.

Notes: Targeted laboratory astrophysics measurements are being conducted to address the needs of X-ray astronomy. The measurements are producing large sets of reliable atomic data, which include ionization and recombination cross sections for charge balance calculations, as well as line lists, excitation cross sections, and dielectronic recombination rates for interpreting X-ray line formation. Additional experiments focus on resolving specific puzzles posed by astrophysical observations, as well as on calibrating existing and developing new X-ray line diagnostics. We discuss the types of data produced and illustrate how the laboratory measurements support such missions as ASCA, EUVE, Chandra, XMM, and ASTRO-E2.

Notes: Photoionized clouds are ubiquitous. They define the endpoints of stellar evolution (H II regions and planetary nebulae), constitute the interstellar and intergalactic media, and are found in high redshift quasars and star-forming galaxies. The spectra of these objects are dominated by emission lines that are sensitive to details of the emitting gas. These details include the microscopic atomic processes that cause the gas to glow; the density, composition, and temperature of the gas; and the radiation field of the central continuum source. Large-scale numerical codes that incorporate all the needed physics and predict the observed spectrum have become essential tools in understanding these objects. This article reviews the current status of the numerical simulations of emitting gas, with particular emphasis on photoionized clouds and the underlying simplicity that governs these nebulae; the types of questions that can be addressed by today's codes; and the big questions that remain unanswered.

Notes: Meteorites and interplanetary dust particles contain presolar stardust grains: solid samples of stars that can be studied in the laboratory. The stellar origin of the grains is indicated by enormous isotopic ratio variations compared with Solar System materials, explainable only by nuclear reactions occurring in stars. Known presolar phases include diamond, SiC, graphite, Si3N4, Al2O3, MgAl2O4, CaAl12O19, TiO2, Mg(Cr,Al)2O4, and most recently, silicates. Subgrains of refractory carbides (e.g., TiC), and Fe-Ni metal have also been observed within individual presolar graphite grains. We review the astrophysical implications of these grains for the sciences of nucleosynthesis, stellar evolution, grain condensation, and the chemical and dynamic evolution of the Galaxy. Unique scientific information derives primarily from the high precision (in some cases 〈1%) of the measured isotopic ratios of large numbers of elements in single stardust grains. Stardust science is just now reaching maturity and will play an increasingly important role in nucleosynthesis applications.

Notes: This chapter reviews the properties of faint IR-selected field galaxies and the extremely red color-selected populations in particular. These populations are a mix of passively evolving stellar systems and heavily obscured star-forming galaxies. The star-forming component appears to constitute 20-50% of the population depending on the magnitude and color cuts employed. The remaining objects are a mix of passively evolving ellipticals and early-type disk galaxies. The passively evolving red galaxies are strongly clustered in space and are likely the high-mass high-luminosity end of the elliptical galaxy progenitor population at redshifts between one and two. These galaxies have masses and space densities that appear to be in conflict with late-forming hierarchical galaxy-formation models. The red galaxies appear to be a population that is distinct from the moderately star-forming Lyman-Break galaxies but may be related to the starburst population at z 〉 2 seen in deep submillimeter surveys.

Notes: Abstract The relationship between flow in the arteries, particularly the wall shear stresses, and the sites where atherosclerosis develops has motivated much of the research on arterial flow in recent decades. It is now well accepted that it is sites where shear stresses are low, or change rapidly in time or space, that are most vulnerable. These conditions are likely to prevail at places where the vessel is curved; bifurcates; has a junction, a side branch, or other sudden change in flow geometry; and when the flow is unsteady. These flows, often but not always involving flow separation or secondary motions, are also the most difficult ones in fluid mechanics to analyze or compute. In this article we review the modeling studies and experiments on steady and unsteady, two-and three-dimensional flows in arteries, and in arterial geometries most relevant in the context of atherosclerosis. These include studies of normal vessels-to identify, on the basis of the fluid mechanics, lesion foci-and stenotic vessels, to model and measure flow in vessels after the lesions have evolved into plaques sufficiently large to significantly modify the flow. We also discuss recent work that elucidates many of the pathways by which mechanical forces, primarily the wall shear stresses, are transduced to effect changes in the arterial wall at the cellular, subcellular, and genetic level.

Notes: Abstract New developments have occurred in recent years in the field of dynamo theory. The increase in computer capacity has permitted simulations of convection-driven dynamos in rotating spherical fluid shells in parameter ranges much closer to those of the Earth's core than has been possible before. The progress in handling flows of liquid sodium in large containers, on the other hand, has opened opportunities for realizations of homogeneous dynamos in the laboratory. These developments will lead to a deeper understanding of the origin of magnetic fields in planets and in stars.

Notes: Abstract The single-point statistics of turbulence in the 'roughness sub-layer' occupied by the plant canopy and the air layer just above it differ significantly from those in the surface layer. The mean velocity profile is inflected, second moments are strongly inhomogeneous with height, skewnesses are large, and second-moment budgets are far from local equilibrium. Velocity moments scale with single length and time scales throughout the layer rather than depending on height. Large coherent structures control turbulence dynamics. Sweeps rather than ejections dominate eddy fluxes and a typical large eddy consists of a pair of counter-rotating streamwise vortices, the downdraft between the vortex pair generating the sweep. Comparison with the statistics and instability modes of the plane mixing layer shows that the latter rather than the boundary layer is the appropriate model for canopy flow and that the dominant large eddies are the result of an inviscid instability of the inflected mean velocity profile. Aerodynamic drag on the foliage is the cause both of the unstable inflected velocity profile and of a 'spectral short cut' mechanism that removes energy from large eddies and diverts it to fine scales, where it is rapidly dissipated, bypassing the inertial eddy-cascade. Total dissipation rates are very large in the canopy as a result of the fine-scale shear layers that develop around the foliage.

Notes: Abstract Lava flows are gravity currents of partially molten rock that cool as they flow, in some cases melting the surface over which they flow but in all cases gradually solidifying until they come to rest. They present a wide range of flow regimes from turbulent channel flows at moderate Reynolds numbers to extremely viscous or plastic, creeping flows, and even brittle rheology may play a role once some solid has formed. The cooling is governed by the coupling of heat transport in the flowing lava with transfer from the lava surface into the surrounding atmosphere or water or into the underlying solid, and it leads to large changes in rheology. Instabilities, mostly resulting from cooling, lead to flow branching, surface folding, rifting, and fracturing, and they contribute to the distinctive styles and surface appearances of different classes of flows. Theoretical and laboratory models have complemented field studies in developing the current understanding of lava flows, motivated by the extensive roles they play in the development of planetary crusts and ore deposits and by the immediate hazards posed to people and property. However, much remains to be learned about the mechanics governing creeping, turbulent, and transitional flows in the presence of large rheology change on cooling and particularly about the advance of flow fronts, flow instabilities, and the development of flow morphology. I introduce the dynamical problems involved in the study of lava flows and review modeling approaches.

Notes: Abstract Predicting the motion of bubbles in dispersed flows is a key problem in fluid mechanics that has a bearing on a wide range of applications from oceanography to chemical engineering. In this review we synthesize the recent progress made in describing bubble motion in inhomogeneous flow. A trident approach consisting of experimental, analytical, and numerical work has given a clearer description of the hydrodynamic forces experienced by isolated bubbles moving either in inviscid flows or in slightly viscous laminar flows. A significant part of the paper is devoted to a discussion of drag, added-mass force, and shear-induced lift experienced by spheroidal bubbles moving in inertially dominated, time-dependent, rotational, nonuniform flows. The important influence of surfactants and shape distortion on bubble motion in a quiescent liquid is highlighted. Examples of bubble motion in inhomogeneous flows combining several of the effects mentioned above are discussed.

Notes: Abstract This review summarizes results for Rayleigh-Benard convection that have been obtained over the past decade or so. It concentrates on convection in compressed gases and gas mixtures with Prandtl numbers near one and smaller. In addition to the classical problem of a horizontal stationary fluid layer heated from below, it also briefly covers convection in such a layer with rotation about a vertical axis, with inclination, and with modulation of the vertical acceleration.

Notes: Abstract An optical technique is described that is often used nowadays to measure surface pressures on wind tunnel models and flight vehicles. The technique uses luminescent coatings, which are painted on the model surface, excited by light of appropriate wavelength, and imaged with digital cameras. The intensity of the emitted light is inversely proportional to the surface pressure. Hence, the surface pressures can be measured efficiently and affordably with a high spatial resolution. The theory and chemistry of how such coatings work and the parameters that affect them are presented. The required hardware and software are described, with emphasis on the different measurement systems and procedures. The various error sources are discussed, and correction schemes that can be used to minimize them are presented. Sample results, covering a wide range of conditions and applications, are presented and discussed.

Notes: Abstract Early work of Ricardo is described, in which squish is used in flat-head engines to generate turbulence levels comparable to those in overhead-valve engines, leading to rapid flame propagation, and suppressing knock. Work by NACA before World War II is described, in which turbulence levels were measured in overhead-valve engines, indicating indirectly that surprisingly high levels were achieved just before ignition, possibly due to a tumble instability. Finally, work of Obukhov of 30 years ago is described, in which instabilities of tumbling flow are investigated in ellipsoids crudely modeling the engine cylinder as the piston rises; this suggests that there is an instability leading to intense small-scale motion just before ignition. Suggestions for further work are given.

Notes: Abstract Polymer melts exhibit extrusion instabilities at sufficiently high levels of stress, and they appear to exhibit wall slip. I explore the evidence for slip, the possible mechanisms of slip, and the relation between slip and extrusion instabilities.

Notes: Abstract Junction flows occur when a boundary layer encounters an obstacle attached to the same surface. Physical phenomena that have been observed for blunt and streamlined obstacles are discussed for both laminar and turbulent approaching boundary layers. The pressure gradients around an obstacle produce a three-dimensional separation with horseshoe vortices that wrap around the obstacle. Except for very low Reynolds number laminar flows, these vortices are highly unsteady and are responsible for high turbulence intensities, high surface pressure fluctuations and heat transfer rates, and erosion scour in the nose region of the obstacle. Calculation methods are also reviewed; methods that capture the large-scale chaotic vortical motions should be used for computations. Some work on the control, modification, or elimination of such vortices is also reviewed.

Notes: Abstract This article describes some of the fundamental ideas underlying methods for induced-drag prediction and reduction. A review of current analysis and design methods, including their development and common approximations, is followed by a survey of several approaches to lift-dependent drag reduction. Recent concepts for wing planform optimization, highly nonplanar surfaces, and various tip devices may lead to incremental but important gains in aircraft performance. Focusing on relatively high-aspect-ratio subsonic wings, the review suggests that opportunities for new concepts remain, but the greatest challenge lies in their integration with other aspects of the system.

Notes: Abstract Spilling breakers receive much less attention from casual observers of the ocean surface than their more dramatic and powerful plunging counterparts. However, spilling breakers probably occur more frequently than plunging breakers and are important contributors to turbulence, spray, and bubble generation at the water surface. Recent research has concentrated primarily on relatively weak and/or short-wavelength spillers whose crests are strongly affected by surface tension forces both during wave steepening and the resulting turbulent free-surface flow. When surface tension forces are dominant, the free surface does not overturn or splash during the breaking process but undergoes some unique and interesting motions. In this review, recent research contributions are discussed and placed in the context of spilling behavior over a wide range of wavelengths and breaking intensities.

Notes: Abstract The compression system instabilities known as surge and rotating stall are natural limits to the performance of all compressors and are especially troubling in gas turbine engines. In the last 15 years, rapid progress has been made in understanding this complex problem through the application of control technology; in particular, system identification techniques have proven to be useful. New findings include the roles of compressibility and nonlinearity in the stall-inception process. These findings have been used to implement feedback control schemes that have achieved increased stability in a variety of compressors and engines. Approaches fall into one of two categories: (a) operating range extension through active damping of linear disturbances, or (b) manipulation of the nonlinear system dynamics to maintain the operating point close to the instability boundary in the presence of disturbances seen in operation.

Notes: Abstract This essay is based on the G.K. Batchelor Memorial Lecture that I delivered in May 2000 at the Institute for Theoretical Physics (ITP), Santa Barbara, where two parallel programs on Turbulence and Astrophysical Turbulence were in progress. It focuses on George Batchelor's major contributions to the theory of turbulence, particularly during the postwar years when the emphasis was on the statistical theory of homogeneous turbulence. In all, his contributions span the period 1946-1992 and are for the most part concerned with the Kolmogorov theory of the small scales of motion, the decay of homogeneous turbulence, turbulent diffusion of a passive scalar field, magnetohydrodynamic turbulence, rapid distortion theory, two-dimensional turbulence, and buoyancy-driven turbulence.

Notes: Abstract Turbulent flows driven by thermal buoyancy are featured by phenomena that pose a special challenge to conventional one-point closure models. Inherent unsteadiness, energy nonequilibrium, counter-gradient diffusion, strong pressure fluctuations, and lack of universal scaling, all believed to be associated with distinct large-scale coherent eddy structures, are hardly tractable by Reynolds-type averaging. Second-moment closures, though inadequate for providing information on eddy structure, offer better prospects than eddy-viscosity models for capturing at least some of the phenomena. For some configurations (e.g., with heating from below), unsteady computational solutions of ensemble-averaged equations, using a one-point closure as the subscale model, may be unavoidable for accurate prediction of flow details and wall heat transfer. This article reviews the rationale and some specific modeling issues related to buoyant flows within the realm of one-point closures. The inadequacy of isotropic eddy-diffusivity models is discussed first, followed by the rationale of the second-moment modeling and its term-by-term scrutiny based on direct numerical simulations (DNS). Algebraic models based on a rational truncation of the differential second-moment closure are proposed as the minimum closure level for complex flows. These closures are also recommended as subscale models for transient statistical modeling (T-RANS) and very large eddy simulations (VLES). Examples of applications illustrate some recent achievements.

Notes: Abstract Remote observations of a surface ship wake using synthetic aperture radar (SAR) show distinct features such as a dark trailing centerline region, bright V-images aligned at some angle to the ship's path, and, sometimes, either the transverse or the diverging waves of the Kelvin-wave pattern. The dark region of relatively low radar backscatter is usually associated with a region that is relatively lacking in short wave components, whereas the bright line feature suggests a region of enhanced radar return within the apparent angular confines of the ship's usual Kelvin-wave pattern. This review provides a survey of remotely sensed wake images, the systems that have collected these images, and an overview of the theory of Kelvin wakes-a primary source of the phenomena that cause the dark centerline and bright V-images-with example predictions. The review concludes with a survey of the phenomena that cause the dark centerline returns and some example predictions of the radar reflectivity across these dark centerline returns.

Notes: Abstract We review the mechanisms of steepening and breaking for internal gravity waves in a continuous density stratification. After discussing the instability of a plane wave of arbitrary amplitude in an infinite medium at rest, we consider the steepening effects of wave reflection on a sloping boundary and propagation in a shear flow. The final process of breaking into small-scale turbulence is then presented. The influence of those processes upon the fluid medium by mean flow changes is discussed. The specific properties of wave turbulence, induced by wave-wave interactions and breaking, are illustrated by comparative studies of oceanic and atmospheric observations, as well as laboratory and numerical experiments. We then review the different attempts at a statistical description of internal gravity wave fields, whether weakly or strongly interacting.

Notes: Abstract The modern study of a crowd as a flowing continuum is a recent development. Distinct from a classical fluid because of the property that a crowd has the capacity to think, interesting new physical ideas are involved in its study. An appealing property of a crowd in motion is that the nonlinear, time-dependent, simultaneous equations representing a crowd are conformably mappable. This property makes many interesting applications analytically tractable. In this review examples are given in which the theory has been used to provide possible assistance in the annual Muslim Hajj, to understand the Battle of Agincourt, and, surprisingly, to locate barriers that actually increase the flow of pedestrians above that when there are no barriers present. Modern developments may help prevent some of the approximately two thousand deaths that annually occur in accidents owing to crowding.The field of crowd motion, that is, the field of "thinking fluids," is an intriguing area of research with great promise.

Notes: Abstract The recent avalanche of research activity in the field of granular matter has yielded much progress. The use of state-of-the-art (and other) computational and experimental methods has led to the discovery of new states and patterns and enabled detailed tests of theories and models. The application of statistical mechanical methods and phenomenology has contributed to the understanding of the microscopic a nd macroscopic properties of granular systems. Some previously open problems seem to be solved. Fluidized granular systems (rapid granular flows), recently referred to as granular gases, are often modeled by hydrodynamic equations of motion, some of which are based on systematic expansions applied to the pertinent Boltzmann equation. The undeniable success of granular hydrodynamics is somewhat surprising in view of the lack of scale separation in these systems and the neglect of certain correlations in most derivations of the hydrodynamic equations. Microstructures have been recognized as key features of granular gases; explanations for their existence have been proposed, and many of their properties elucidated. Granular-gas multistability can often be traced back to microstructure dynamics. In spite of these and other impressive advances, this field still poses serious challenges.

Notes: Abstract Recent advances in achieving textbook multigrid efficiency for fluid simulations are presented. Textbook multigrid efficiency is defined as attaining the solution to the governing system of equations in a computational work that is a small multiple of the operation counts associated with discretizing the system. Strategies are reviewed to attain this efficiency by exploiting the factorizability properties inherent to a range of fluid simulations, including the compressible Navier-Stokes equations. Factorizability is used to separate the elliptic and hyperbolic factors contributing to the target system; each of the factors can then be treated individually and optimally. Boundary regions and discontinuities are addressed with separate (local) treatments. New formulations and recent calculations demonstrating the attainment of textbook efficiency for aerodynamic simulations are shown.

Notes: This paper reviews the current state of the art in accidental explosion modeling using methods based on computational fluid dynamics (CFD) in the petrochemical process industries. We discuss the problem in terms of its industrial importance and its technical difficulty, which stems mainly from the large range of length and timescales that must be represented. Explicit representation of all scales is not feasible due to limitations of computational cost, and modeling of unresolved physical features is required. We also discuss geometry modeling using the porosity/distributed resistance (PDR) method and review relevant combustion modeling. We describe an advanced CFD approach using unstructured adaptive gridding and discuss its usefulness in the context of results obtained for both two dimensional and three dimensional simulations of gas explosion phenomena in complex geometries.

Notes: Early concepts in shock wave drag reduction enabled modern aeronautical systems, and continuing research progress in this arena is crucial for significant improvements in long haul transports and various military platforms and weapons. The research area is rich in concepts/approaches, but many of these have not progressed into the realm of application. This is due in part to a lack of knowledge on the part of the fluids research community concerning the multidisciplinary "real-world" design space/metrics and a consequent lack of the requisite breadth and depth of research information required to evaluate/apply the concept. The article reviews the extant wave drag reduction approaches that are (a) well understood/applied, (b) under active study/indicate considerable promise, and (c) those in the nascent stage only.

Notes: Almost all vessels carrying fluids within the body are flexible, and interactions between an internal flow and wall deformation often underlie a vessel's biological function or dysfunction. Such interactions can involve a rich range of fluid-mechanical phenomena, including nonlinear pressure-drop/flow-rate relations, self-excited oscillations of single-phase flow at high Reynolds number and capillary-elastic instabilities of two-phase flow at low Reynolds number. We review recent advances in understanding the fundamental mechanics of flexible-tube flows, and discuss physiological applications spanning the cardiovascular system (involving wave propagation and flow-induced instabilities of blood vessels), the respiratory system (involving phonation, the closure and reopening of liquid-lined airways, and Marangoni flows on flexible surfaces), and elsewhere in the body (involving active peristaltic transport driven by fluid-structure/muscle interactions).

Notes: We review the use of ray models for internal waves, particularly formulations for calculating wave amplitudes along the ray. These are expressed in spatial, wave number, and phase-space coordinates. The choice of formulation affects not only the difficulty of the calculations for rays and caustics but also the degree to which the waves satisfy slowly varying assumptions. We describe several examples taken from atmospheric and oceanic applications that illustrate the variety of options for ray models.

Notes: The characterization of blood flow is important for understanding the function of the cardiovascular system under normal and diseased conditions, designing cardiovascular devices, and diagnosing and treating congenital and acquired cardiovascular disease. Experimental methods, especially magnetic resonance imaging techniques can be used to noninvasively quantify blood flow for diagnosing cardiovascular disease, researching disease mechanisms, and validating assumptions and predictions of mathematical models. Computational methods can be used to simulate blood flow and vessel dynamics, test hypotheses of disease formation under controlled conditions, and evaluate devices that have not yet been built and treatments that have not yet been implemented. In this article we review experimental and computational methods for quantifying blood flow velocity and pressure fields in human arteries. We place particular emphasis on providing an introduction to the physics and applications of magnetic resonance imaging, and surveying lumped parameter, one-dimensional, and three-dimensional numerical methods used to model blood flow.

Notes: We review the experimental evidence on turbulent flows over rough walls. Two parameters are important: the roughness Reynolds number ks+ , which measures the effect of the roughness on the buffer layer, and the ratio of the boundary layer thickness to the roughness height, which determines whether a logarithmic layer survives. The behavior of transitionally rough surfaces with low ks+ depends a lot on their geometry. Riblets and other drag-reducing cases belong to this regime. In flows with delta/k 〈 50, the effect of the roughness extends across the boundary layer, and is also variable. There is little left of the original wall-flow dynamics in these flows, which can perhaps be better described as flows over obstacles. We also review the evidence for the phenomenon of d-roughness. The theoretical arguments are sound, but the experimental evidence is inconclusive. Finally, we discuss some ideas on how rough walls can be modeled without the detailed computation of the flow around the roughness elements themselves.

Notes: We review artificial boundary conditions (BCs) for simulation of inflow, outflow, and far-field (radiation) problems, with an emphasis on techniques suitable for compressible turbulent shear flows. BCs based on linearization near the boundary are usually appropriate for inflow and radiation problems. A variety of accurate techniques have been developed for this case, but some robustness and implementation issues remain. At an outflow boundary, the linearized BCs are usually not accurate enough. Various ad hoc models have been proposed for the nonlinear case, including absorbing layers and fringe methods. We discuss these techniques and suggest directions for future modeling efforts.

Notes: Abstract Genome sequencing and structural genomics projects are providing new insights into the evolutionary history ofprote in domains. As methods for sequence and structure comparison improve, more distantly related domains are shown to be homologous. Thus there is a need for domain families to be classified within a hierarchy similar to Linnaeus' Systema Naturae, the classification of species. With such a hierarchy in mind, we discuss the evolution of domains, their combination into proteins, and evidence as to the likely origin of protein domains. We also discuss when and how analysis of domains can be used to understand details of protein function. Unconventional features of domain evolution such as intragenomic competition, domain insertion, horizontal gene transfer, and convergent evolution are seen as analogs of organismal evolutionary events. These parallels illustrate how the concept of domains can be applied to provide insights into evolutionary biology.

Notes: Abstract Nearly twenty years after the first high-resolution crystal structures of specific protein-DNA complexes were determined, the stereo-chemical basis for protein-DNA recognition remains an active area of investigation. One outstanding question is, how are proteins able to detect noncontacted sequences in their binding sites? The papillomavirus E2 proteins represent a particularly suitable group of proteins in which to examine the mechanisms of "indirect readout." Coordinated structural and thermodynamic studies of the E2-DNA interaction conducted over the past five years are summarized in this review. The data support a model in which the electrostatic properties of the individual E2 proteins correlate with their affinities for intrinsically flexible or rigidly prebent DNA targets.

Notes: Abstract Mass spectrometry has provided a powerful method for monitoring hydrogen exchange of protein backbone amides with deuterium from solvent. In comparison to popular NMR approaches, mass spectrometry has the advantages of higher sensitivity, wider coverage of sequence, and the ability to analyze larger proteins. Proteolytic fragmentation of proteins following the exchange reaction provides moderate structural resolution, in some cases enabling measurements from single amides. The technique has provided new insight into protein-protein and protein-ligand interfaces, as well as conformational changes during protein folding or denaturation. In addition, recent studies illustrate the utility of hydrogen exchange mass spectrometry toward detecting protein motions relevant to allostery, covalent modifications, and enzyme function.

Notes: Abstract Cations are bound to nucleic acids in a solvated state. High-resolution X-ray diffraction studies of oligonucleotides provide a detailed view of Mg2+, and occasionally other ions bound to DNA. In a survey of several such structures, certain general observations emerge. First, cations bind preferentially to the guanine base in the major groove or to phosphate group oxygen atoms. Second, cations interact with DNA most frequently via water molecules in their primary solvation shell, direct ion-DNA contacts being only rarely observed. Thus, the solvated ions should be viewed as hydrogen bond donors in addition to point charges. Finally, ion interaction sites are readily exchangeable: The same site may be occupied by any ion, including spermine, as well as by a water molecule.

Notes: Abstract Although protein function is thought to depend on flexibility, precisely how the dynamics of the molecule and its environment contribute to catalytic mechanisms is unclear. We review experimental and computational work relating to enzyme dynamics and function, including the role of solvent. The evidence suggests that fast motions on the 100 ps timescale, and any motions coupled to these, are not required for enzyme function. Proteins where the function is electron transfer, proton tunneling, or ligand binding may have different dynamical dependencies from those for enzymes, and enzymes with large turnover numbers may have different dynamical dependencies from those that turn over more slowly. The timescale differences between the fastest anharmonic fluctuations and the barrier-crossing rate point to the need to develop methods to resolve the range of motions present in enzymes on different time- and lengthscales.

Notes: Abstract The OB-fold domain is a compact structural motif frequently used for nucleic acid recognition. Structural comparison of all OB-fold/nucleic acid complexes solved to date confirms the low degree of sequence similarity among members of this family while highlighting several structural sequence determinants common to most of these OB-folds. Loops connecting the secondary structural elements in the OB-fold core are extremely variable in length and in functional detail. However, certain features of ligand binding are conserved among OB-fold complexes, including the location of the binding surface, the polarity of the nucleic acid with respect to the OB-fold, and particular nucleic acid-protein interactions commonly used for recognition of single-stranded and unusually structured nucleic acids. Intriguingly, the observation of shared nucleic acid polarity may shed light on the longstanding question concerning OB-fold origins, indicating that it is unlikely that members of this family arose via convergent evolution.

Notes: Abstract The observation of liquid-liquid immiscibility in cholesterol-phospholipid mixtures in monolayers and bilayers has opened a broad field of research into their physical chemistry. Some mixtures exhibit multiple immiscibilities. This unusual property has led to a thermodynamic model of "condensed complexes." These complexes are the consequence of an exothermic, reversible reaction between cholesterol and phospholipids. In this quantitative model the complexes are sometimes concentrated in a separate liquid phase. The phase separation into a complex-rich phase depends on membrane composition and intensive variables such as temperature. The properties of defined cholesterol-phospholipid mixtures provide a conceptual foundation for the exploration of a number of aspects of the biophysics and biochemistry of animal cell membranes.

Notes: DNA secondary structure plays an important role in biology, genotyping diagnostics, a variety of molecular biology techniques, in vitro-selected DNA catalysts, nanotechnology, and DNA-based computing. Accurate prediction of DNA secondary structure and hybridization using dynamic programming algorithms requires a database of thermodynamic parameters for several motifs including Watson-Crick base pairs, internal mismatches, terminal mismatches, terminal dangling ends, hairpins, bulges, internal loops, and multibranched loops. To make the database useful for predictions under a variety of salt conditions, empirical equations for monovalent and magnesium dependence of thermodynamics have been developed. Bimolecular hybridization is often inhibited by competing unimolecular folding of a target or probe DNA. Powerful numerical methods have been developed to solve multistate-coupled equilibria in bimolecular and higher-order complexes. This review presents the current parameter set available for making accurate DNA structure predictions and also points to future directions for improvement.

Notes: Phosphoserine/threonine-binding domains integrate intracellular signal transduction events by forming multiprotein complexes with substrates of protein serine/threonine kinases. These phosphorylation-dependent molecular recognition events are responsible for coordinating the precise temporal and spatial response of cells to a wide range of stimuli, particularly those involved in cell cycle control and the response to DNA damage. The known families of phosphoserine/threonine-binding modules include 14-3-3 proteins, WW domains, FHA domains, WD40 repeats, and the Polo-box domains of Polo-like kinases. Peptide-library experiments reveal the optimal sequence motifs recognized by these domains, and facilitate high-resolution structural studies elucidating the mechanisms of phospho-dependent binding and the molecular basis for domain function within intricate signaling networks. Information emerging from these studies is critical for the design of novel experimental and therapeutic tools aimed at altering signal transduction cascades in normal and diseased cells.

Notes: Abstract During the last decade, the understanding of fine features of the structure and evolution of stars has become possible as a result of enormous progress made in the acquisition of high-quality observational and experimental data, and of new developments and refinements in the theoretical description of stellar plasmas. The confrontation of high-quality observations with sophisticated stellar models has allowed many aspects of the theory to be validated, and several characteristics of stars relevant to Galactic evolution and cosmology to be inferred. This paper is a review of the results of recent studies undertaken in the context of the Hipparcos mission, taking benefit of the high-quality astrometric data it has provided. Successes are discussed, as well as the problems that have arisen and suggestions proposed to solve them. Future observational and theoretical developments expected and required in the field are also presented.

Notes: Abstract Because calibrated light curves of type Ia supernovae have become a major tool to determine the local expansion rate of the universe and also its geometrical structure, considerable attention has been given to models of these events over the past couple of years. There are good reasons to believe that perhaps most type Ia supernovae are the explosions of white dwarfs that have approached the Chandrasekhar mass, , and are disrupted by thermonuclear fusion of carbon and oxygen. However, the mechanism whereby such accreting carbon-oxygen white dwarfs explode continues to be uncertain. Recent progress in modeling type Ia supernovae as well as several of the still open questions are addressed in this review. Although the main emphasis is on studies of the explosion mechanism itself and on the related physical processes, including the physics of turbulent nuclear combustion in degenerate stars, we also discuss observational constraints.

Notes: Abstract Since the discovery of the first bona-fide brown dwarfs and extra-solar planets in 1995, the field of low-mass stars and substellar objects has progressed considerably, both from theoretical and observational viewpoints. Recent developments in the physics entering the modeling of these objects have led to significant improvements in the theory and to a better understanding of these objects' mechanical and thermal properties. This theory can now be confronted with observations directly in various observational diagrams (color-color, color-magnitude, mass-magnitude, mass-spectral type), a stringent and unavoidable constraint that became possible only recently with the generation of synthetic spectra. In this paper we present the current state-of-the-art general theory of low-mass stars and sub stellar objects, from one solar mass to one Jupiter mass, regarding primarily their interior structure and evolution. This review is a natural complement to the previous review by Allard et al (1997) on the atmosphere of low-mass stars and brown dwarfs. Special attention is devoted to the comparison of the theory with various available observations. The contribution of low-mass stellar and sub stellar objects to the Galactic mass budget is also analyzed.

Notes: Abstract The discovery of counterparts in X-ray and optical to radio wavelengths has revolutionized the study of gamma-ray bursts, until recently the most enigmatic of astrophysical phenomena. We now know that gamma-ray bursts are the biggest explosions in nature, caused by the ejection of ultrarelativistic matter from a powerful energy source and its subsequent collision with its environment. We have just begun to uncover a connection between supernovae and gamma-ray bursts, and are finally constraining the properties of the ultimate source of gamma-ray burst energy. We review here the observations that have led to this breakthrough in the field; we describe the basic theory of the fireball model and discuss the theoretical understanding that has been gained from interpreting the new wealth of data on gamma-ray bursts.

Notes: Astrophysics has been an important part of my personal and scientific life three times. The first was in 1938 when I did work on stellar energy production. The second was a joyful period nearly 30 years later when that work was rewarded with the Nobel Prize in physics. And the third has lasted over the time since my retirement in 1975 during which Gerry Brown and I have had a very satisfactory collaboration exploring various aspects of supernovae and, more recently, binary pairs.

Notes: Blueshifted absorption lines in the UV and X-ray spectra of active galaxies reveal the presence of massive outflows of ionized gas from their nuclei. The "intrinsic" UV and X-ray absorbers show large global covering factors of the central continuum source, and the inferred mass loss rates are comparable to the mass accretion rates. Many absorbers show variable ionic column densities, which are attributed to a combination of variable ionizing flux and motion of gas into and out of the line of sight. Detailed studies of the intrinsic absorbers, with the assistance of monitoring observations and photoionization models, provide constraints on their kinematics, physical conditions, and locations relative to the central continuum source, which range from the inner nucleus (~0.01 pc) to the galactic disk or halo (~10 kpc). Dynamical models that make use of thermal winds, radiation pressure, and/or hydromagnetic flows have reached a level of sophistication that permits comparisons with the observational constraints.

Notes: Old, cool white dwarfs convey valuable information about the early history of our Galaxy. They have been used to determine the age of the galactic disk, several open clusters, and a globular cluster. We review the current understanding of the physics of cool white dwarfs, including their mass distribution, chemical evolution, magnetism, and cooling. We also examine the role of white dwarfs as tracers of various stellar populations, both in terms of observational searches and theoretical models.