ALBERT

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.

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.

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.

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.

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.

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.

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.

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.

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.

Notes: Abstract Ubiquitous among eukaryotes, the ADF/cofilins are essential proteins responsible for the high turnover rates of actin filaments in vivo. In vertebrates, ADF and cofilin are products of different genes. Both bind to F-actin cooperatively and induce a twist in the actin filament that results in the loss of the phalloidin-binding site. This conformational change may be responsible for the enhancement of the off rate of subunits at the minus end of ADF/cofilin-decorated filaments and for the weak filament-severing activity. Binding of ADF/cofilin is competitive with tropomyosin. Other regulatory mechanisms in animal cells include binding of phosphoinositides, phosphorylation by LIM kinases on a single serine, and changes in pH. Although vertebrate ADF/cofilins contain a nuclear localization sequence, they are usually concentrated in regions containing dynamic actin pools, such as the leading edge of migrating cells and neuronal growth cones. ADF/cofilins are essential for cytokinesis, phagocytosis, fluid phase endocytosis, and other cellular processes dependent upon actin dynamics.

Notes: Abstract Endoderm, one of the three principal germ layers, contributes to all organs of the alimentary tract. For simplicity, this review divides formation of endodermal organs into four fundamental steps: (a) formation of endoderm during gastrulation, (b) morphogenesis of a gut tube from a sheet of cells, (c) budding of organ domains from the tube, and (d) differentiation of organ-specific cell types within the growing buds. We discuss possible mechanisms that regulate how undifferentiated endoderm becomes specified into a myriad of cell types that populate the respiratory and gastrointestinal tracts.

Notes: Abstract Information can be transferred between the nucleus and the cytoplasm by translocating macromolecules across the nuclear envelope. Communication of extracellular or intracellular changes to the nucleus frequently leads to a transcriptional response that allows cells to survive in a continuously changing environment. Eukaryotic cells have evolved ways to regulate this movement of macromolecules between the cytoplasm and the nucleus such that the transfer of information occurs only under conditions in which a transcriptional response is required. This review focuses on the ways in which cells regulate movement of proteins across the nuclear envelope and the significance of this regulation for controlling diverse biological processes.

Notes: Abstract In Dictyostelium amoebae, cell-type differentiation, spatial patterning, and morphogenesis are controlled by a combination of cell-autonomous mechanisms and intercellular signaling. A chemotactic aggregation of ~105 cells leads to the formation of a multicellular organism. Cell-type differentiation and cell sorting result in a small number of defined cell types organized along an anteroposterior axis. Finally, a mature fruiting body is created by the terminal differentiation of stalk and spore cells. Analysis of the regulatory program demonstrates a role for several molecules, including GSK-3, signal transducers and activators of transcription (STAT) factors, and cAMP-dependent protein kinase (PKA), that control spatial patterning in metazoans. Unexpectedly, two component systems containing histidine kinases and response regulators also play essential roles in controlling Dictyostelium development. This review focuses on the role of cAMP, which functions intracellularly to mediate the activity of PKA, an essential component in aggregation, cell-type specification, and terminal differentiation. Cytoplasmic cAMP levels are controlled through both the regulated activation of adenylyl cyclases and the degradation by a phosphodiesterase containing a two-component system response regulator. Extracellular cAMP regulates G-protein-dependent and -independent pathways to control aggregation as well as the activity of GSK-3 and the transcription factors GBF and STATa during multicellular development. The integration of these pathways with others regulated by the morphogen DIF-1 to control cell fate decisions are discussed.

Notes: Abstract Cotranslational protein translocation across and integration into the membrane of the endoplasmic reticulum (ER) occur at sites termed translocons. Translocons are composed of several ER membrane proteins that associate to form an aqueous pore through which secretory proteins and lumenal domains of membrane proteins pass from the cytoplasm to the ER lumen. These sites are not passive holes in the bilayer, but instead are quite dynamic both structurally and functionally. Translocons cycle between ribosome-bound and ribosome-free states, and convert between translocation and integration modes of operation. These changes in functional state are accompanied by structural rearrangements that alter translocon conformation, composition, and interactions with ligands such as the ribosome and BiP. Recent studies have revealed that the translocon is a complex and sophisticated molecular machine that regulates the movement of polypeptides through the bilayer, apparently in both directions as well as laterally into the bilayer, all while maintaining the membrane permeability barrier.

Notes: Abstract Synaptic vesicles, which have been a paradigm for the fusion of a vesicle with its target membrane, also serve as a model for understanding the formation of a vesicle from its donor membrane. Synaptic vesicles, which are formed and recycled at the periphery of the neuron, contain a highly restricted set of neuronal proteins. Insight into the trafficking of synaptic vesicle proteins has come from studying not only neurons but also neuroendocrine cells, which form synaptic-like microvesicles (SLMVs). Formation and recycling of synaptic vesicles/SLMVs takes place from the early endosome and the plasma membrane. The cytoplasmic machinery of synaptic vesicle/SLMV formation and recycling has been studied by a variety of experimental approaches, in particular using cell-free systems. This has revealed distinct machineries for membrane budding and fission. Budding is mediated by clathrin and clathrin adaptors, whereas fission is mediated by dynamin and its interacting protein SH3p4, a lysophosphatidic acid acyl transferase.

Notes: Abstract I present the general picture of how galactic magnetic fields grow in disks according to the alpha-Omega dynamo theory. Emphasis is placed on following the lines of force during the dynamo process. The dynamo equation is presented together with a simple growing solution for the galactic disk. Then I take up the various critical questions that have been raised concerning the galactic dynamo theory. These are (1) the importance of the escape of flux from the disk in order for the magnetic field to grow; (2) the physics of turbulent diffusion and its mixing of field lines together so that the rms field is possibly greater than the mean field; (3) whether magnetic reconnection plays a role in the galactic dynamo; (4) whether small-scale fields can grow large enough to swamp the dynamo. Then I discuss the possible seed fields from which the dynamo starts and their relation to the primordial hypothesis. Finally I take up the question of the final evolution of the galactic field after the alpha effect saturates. My conclusion is that all these problems warrant attention but none of them seem to be serious enough to cast any real doubt on the dynamo as the most likely generator of galactic fields.

Notes: Abstract Advances in wide-angle astrometric measurements of three to four orders of magnitude in the last thirty years have resulted in a redefinition of the fundamental astronomical reference frame. This new frame, the International Celestial Reference Frame (ICRF), is based on the radio positions of 212 compact extragalactic radio sources. The ICRF defines the direction of the axes of the International Celestial Reference System (ICRS) with a precision of approximately 20 muas. At optical wavelengths, the Hipparcos catalog is the realization of this frame. The precision with which the ICRF is now determined requires that the ICRS models for precession, nutation, and others, be revised. Increases in the precision of measurements from astrometric space missions will further improve the celestial reference frame and may require its redefinition within the next ten years. These improvements will again challenge the models for the celestial reference system.

Notes: Abstract Black holes of stellar mass and neutron stars in binary systems are first detected as hard X-ray sources using high-energy space telescopes. Relativistic jets in some of these compact sources are found by means of multiwavelength observations with ground-based telescopes. The X-ray emission probes the inner accretion disk and immediate surroundings of the compact object, whereas the synchrotron emission from the jets is observed in the radio and infrared bands, and in the future could be detected at even shorter wavelengths. Black-hole X-ray binaries with relativistic jets mimic, on a much smaller scale, many of the phenomena seen in quasars and are thus called microquasars. Because of their proximity, their study opens the way for a better understanding of the relativistic jets seen elsewhere in the Universe. From the observation of two-sided moving jets it is inferred that the ejecta in microquasars move with relativistic speeds similar to those believed to be present in quasars. The simultaneous multiwavelength approach to microquasars reveals in short timescales the close connection between instabilities in the accretion disk seen in the X-rays, and the ejection of relativistic clouds of plasma observed as synchrotron emission at longer wavelengths. Besides contributing to a deeper understanding of accretion disks and jets, microquasars may serve in the future to determine the distances of jet sources using constraints from special relativity, and the spin of black holes using general relativity.

Notes: Abstract Far-ultraviolet radiation is a ubiquitous, if unanticipated, phenomenon in elliptical galaxies and early-type spiral bulges. It is the most variable photometric feature associated with old stellar populations. Recent observational and theoretical evidence shows that it is produced mainly by low-mass, small-envelope, helium-burning stars in extreme horizontal branch and subsequent phases of evolution. These are probably descendants of the dominant, metal rich population of the galaxies. Their lifetime UV outputs are remarkably sensitive to their physical properties and hence to the age and the helium and metal abundances of their parents. UV spectra are therefore exceptionally promising diagnostics of old stellar populations, although their calibration requires a much improved understanding of giant branch mass loss, helium enrichment, and atmospheric diffusion.

Notes: Abstract Nuclear magnetic resonance (NMR) measurements of flowing materials are reviewed with emphasis on applications to multiphase flows. After a brief presentation of NMR physics, experimental considerations related to flow measurements are discussed. Both imaging and non-imaging NMR as well as topics such as Earth's field NMR and rapid imaging are covered. Specific topics that follow are tagging and time-of-flight, phase measurement of velocity, diffusion, turbulence, and calibration and validations. Finally, recent applications are reviewed in the areas of sedimentation, suspension flows in Couette and pipe geometries, rheometers and viscometers, liquid-liquid multiphase flows, porous media flow, granular flows, and turbulence.

Notes: Abstract In this review, we describe the dynamics and thermodynamics of liquid and vapor flow through hot fractured rock. Such flows occur in geothermal reservoirs and have important implications for geothermal power generation; we describe both forced flows associated with liquid injection into such systems, and natural convective flows associated with the vertical heat transfer through such systems. First we focus on permeable media and describe the heat transfer of single-phase liquid or vapor flow through a medium of different temperature. Then we consider the dynamics and thermodynamics of a liquid front as it advances into a superheated region and boils. The morphological stability of such an interface is discussed, and we describe conditions under which the interface breaks down to form a two-phase zone between the liquid and vapor. We next examine the heat transfer and boiling in gravity-driven flows advancing through a superheated permeable rock, identifying that at large times such currents asymptote to a family of similarity solutions. In the second part of the review, we describe the analogous heat transfer and boiling processes associated with liquid flow along a fracture embedded in an impermeable rock. We describe some simple asymptotic solutions for the temperature distribution in the bounding rock, which reveal that in the fracture, a two-phase boiling region develops between the purely liquid and purely vapor zones. Model predictions are successfully tested with laboratory experiments. In the final section of the review, we briefly discuss natural convective flows, illustrating how single-phase and two-phase convective regions interact and in some cases produce instability.

Notes: Abstract We discuss the thickness of the liquid layer entrained by a solid drawn out of a bath, focusing on the case where the solid is a fiber or a wire. Slow withdrawals out of a pure or a complex fluid are described as well as quick coatings. We specify the general laws of entrainment and stress the cases where the fiber curvature plays a role. We finally give an overview on the further evolution of the coated film.

Notes: Abstract Noncircular jets have been the topic of extensive research in the last fifteen years. These jets were identified as an efficient technique of passive flow control that allows significant improvements of performance in various practical systems at a relatively low cost because noncircular jets rely solely on changes in the geometry of the nozzle. The applications of noncircular jets discussed in this review include improved large- and small-scale mixing in low- and high-speed flows, and enhanced combustor performance, by improving combustion efficiency, reducing combustion instabilities and undesired emissions. Additional applications include noise suppression, heat transfer, and thrust vector control (TVC). The flow patterns associated with noncircular jets involve mechanisms of vortex evolution and interaction, flow instabilities, and fine-scale turbulence augmentation. Stability theory identified the effects of initial momentum thickness distribution, aspect ratio, and radius of curvature on the initial flow evolution. Experiments revealed complex vortex evolution and interaction related to self-induction and interaction between azimuthal and axial vortices, which lead to axis switching in the mean flow field. Numerical simulations described the details and clarified mechanisms of vorticity dynamics and effects of heat release and reaction on noncircular jet behavior. The research on noncircular jets has also led to technology transfer. A topic that started as an academic curiosity-an interesting flow phenomenon-subsequently has had various industrial applications. The investigations reviewed include experimental, theoretical, numerical, and technological aspects of the subject.

Notes: Abstract An overview of preconditioning for the steady-state compressible inviscid fluid dynamic equations is presented. Extensions to the Navier-Stokes equations are also considered. These preconditioners are necessary for many algorithms in order to have the correct behavior at low speeds and to converge to the solution of the incompressible equations as the Mach number goes to zero. In addition, the preconditioning accelerates the convergence to a steady state for problems in which a significant portion of the flow is low speed. This low speed preconditioner can be combined with Jacobi and line preconditioners to damp high frequencies at all speeds. This is necessary for use with multigrid methods. Such combined methods are also better at accelerating problems with high aspect ratios. Details of the implementation are presented including several different variants for the preconditioning matrix.

Notes: Abstract The paper reviews striking features of swirling flows-collapse, swirl generation, vortex breakdown, hysteresis, and axisymmetry breaking-and the mechanisms involved with the help of conical similarity solutions of the Navier-Stokes equations. The strong accumulation of axial and angular momenta, observed in tornadoes and flows over delta wings, corresponds to collapse, i.e. the singularity development in these solutions. Bifurcation of swirl explains the threshold character of swirl development in capillary and electrovortex flows. Analytical solutions for fold catastrophes and hysteresis reveal why there are so few stable states and why the jump transitions between the states occur-features typical of tornadoes, of flows over delta wings, and in vortex devices. Finally, the divergent instability explains such effects as the splitting of a tornado and the development of spiral branches in tree and near-wall swirling flows.

Notes: Abstract A decade of research on adaptive mutation has revealed a plethora of mutagenic mechanisms that may be important in evolution. The DNA synthesis associated with recombination could be an important source of spontaneous mutation in cells that are not proliferating. The movement of insertion elements can be responsive to environmental conditions. Insertion elements not only activate and inactivate genes, they also provide sequence homology that allows large-scale genomic rearrangements. Some conjugative plasmids can recombine with their host's chromosome, and may acquire chromosomal genes that could then spread through the population and even to other species. Finally, a subpopulation of transient hypermutators could be a source of multiple variant alleles, providing a mechanism for rapid evolution under adverse conditions.

Notes: Abstract Lentiviruses are associated with chronic diseases of the hematological and neurological systems in animals and man. In particular, human immunodeficiency virus type 1 (HIV-1) is the etiological agent of the global AIDS epidemic. The genomes of lentiviruses are complex, encoding a number of regulatory and accessory proteins not found in other retroviruses. This complexity is reflected in their replication cycle, which reveals intricate regulatory pathways and unique mechanisms for viral persistence. In this review, we highlight some of these unique features for HIV-1, with particular focus on the transcriptional and posttranscriptional control of gene expression. Although our understanding of the biology of HIV-1 is far from complete, the knowledge gained thus far has already led to novel strategies for both virus intervention and exploiting the lentiviruses for therapeutic applications.

Notes: Abstract The stability of mRNA in prokaryotes depends on multiple factors and it has not yet been possible to describe the process of mRNA degradation in terms of a unique pathway. However, important advances have been made in the past 10 years with the characterization of the cis-acting RNA elements and the trans-acting cellular proteins that control mRNA decay. The trans-acting proteins are mainly four nucleases, two endo- (RNase E and RNase III) and two exonucleases (PNPase and RNase II), and poly(A) polymerase. RNase E and PNPase are found in a multienzyme complex called the degradosome. In addition to the host nucleases, phage T4 encodes a specific endonuclease called RegB. The cis-acting elements that protect mRNA from degradation are stable stem-loops at the 5' end of the transcript and terminators or REP sequences at their 3' end. The rate-limiting step in mRNA decay is usually an initial endonucleolytic cleavage that often occurs at the 5' extremity. This initial step is followed by directional 3' to 5' degradation by the two exonucleases. Several examples, reviewed here, indicate that mRNA degradation is an important step at which gene expression can be controlled. This regulation can be either global, as in the case of growth rate-dependent control, or specific, in response to changes in the environmental conditions.

Notes: Abstract Due to the increase of human migrations, the appearance of emerging and reemerging endemies, growing antibiotic resistance, and climatic changes, infectious diseases most probably constitute the major challenge for medicine in the next century. The advent of molecular methods of pathogen characterization has considerably improved our knowledge of the epidemiology of these diseases. However, the use of concepts of evolutionary genetics for interpreting "molecular epidemiology" data remains limited, although the application of such methods would broaden considerably the scope of this field of research, and allow epidemiologic and taxonomic approaches to be ascertained on a much firmer basis. In turn, pathogens, hosts, and vectors provide fascinating models for basic research. The artificial character of the border between "basic" and "applied" research is especially apparent with regard to the "integrated genetic epidemiology of infectious diseases" concept. The goal of this chapter is to evaluate the respective impact, on the transmission and pathogenicity of infectious diseases, of the host's, the pathogen's, and the vector's (for vector-borne diseases) genetic diversity, and the interactions between these three parameters (coevolution phenomena).

Notes: Abstract An RNA fold is the result of packing together two or more coaxial helical stacks. To date, four RNA folds have been determined at near-atomic resolution by X-ray crystallography: transfer RNA, the hammerhead ribozyme, the P4-P6 domain of the Tetrahymena group I intron, and the hepatitis delta virus ribozyme. All four folds result in RNAs that are considerably more compact than isolated A-form duplexes. These structures illustrate, to varying degrees, three modes of fold stabilization: association of complementary molecular surfaces, stabilization of close RNA packing by binding of cations, and stabilization through pseudoknotting.

Notes: Abstract The F0F1 ATP synthase is a large multisubunit complex that couples translocation of protons down an electrochemical gradient to the synthesis of ATP. Recent advances in structural analyses have led to the demonstration that the enzyme utilizes a rotational catalytic mechanism. Kinetic and biochemical evidence is consistent with the expected equal participation of the three catalytic sites in the alpha3beta3 hexamer, which operate in sequential, cooperative reaction pathways. The rotation of the core gamma subunit plays critical roles in establishing the conformation of the sites and the cooperative interactions. Mutational analyses have shown that the rotor subunits are responsible for coupling and in doing so transmit specific conformational information between transport and catalysis.

Notes: Abstract Solid-state nuclear magnetic resonance (NMR) is rapidly emerging as a successful and important technique for protein and peptide structural elucidation from samples in anisotropic environments. Because of the diversity of nuclei and nuclear spin interactions that can be observed, and because of the broad range of sample conditions that can be studied by solid-state NMR, the potential for gaining structural constraints is great. Structural constraints in the form of orientational, distance, and torsional constraints can be obtained on proteins in crystalline, liquid-crystalline, or amorphous preparations. Great progress in the past few years has been made in developing techniques for obtaining these constraints, and now it has also been clearly demonstrated that these constraints can be assembled into uniquely defined three-dimensional structures at high resolution. Although much progress toward the development of solid-state NMR as a routine structural tool has been documented, the future is even brighter with the continued development of the experiments, of NMR hardware, and of the molecular biological methods for the preparation of labeled samples.

Notes: Abstract Stably folded membrane proteins reside in a free energy minimum determined by the interactions of the peptide chains with each other, the lipid bilayer hydrocarbon core, the bilayer interface, and with water. The prediction of three-dimensional structure from sequence requires a detailed understanding of these interactions. Progress toward this objective is summarized in this review by means of a thermodynamic framework for describing membrane protein folding and stability. The framework includes a coherent thermodynamic formalism for determining and describing the energetics of peptide-bilayer interactions and a review of the properties of the environment of membrane proteins-the bilayer milieu. Using a four-step thermodynamic cycle as a guide, advances in three main aspects of membrane protein folding energetics are discussed: protein binding and folding in bilayer interfaces, transmembrane helix insertion, and helix-helix interactions. The concepts of membrane protein stability that emerge provide insights to fundamental issues of protein folding.

Notes: Abstract Bacteriorhodopsin is the best understood ion transport protein and has become a paradigm for membrane proteins in general and transporters in particular. Models up to 2.5 A resolution of bacteriorhodopsin's structure have been published during the last three years and are basic for understanding its function. Thus one focus of this review is to summarize and to compare these models in detail. Another focus is to follow the protein through its catalytic cycle in summarizing more recent developments. We focus on literature published since 1995; a comprehensive series of reviews was published in 1995 (112).

Notes: Abstract The [PSI+] factor of the yeast Saccharomyces cerevisiae is an epigenetic regulator of translation termination. More than three decades ago, genetic analysis of the transmission of [PSI+] revealed a complex and often contradictory series of observations. However, many of these discrepancies may now be reconciled by a revolutionary hypothesis: protein conformation-based inheritance (the prion hypothesis). This model predicts that a single protein can stably exist in at least two distinct physical states, each associated with a different phenotype. Propagation of one of these traits is achieved by a self-perpetuating change in the protein from one form to the other. Mounting genetic and biochemical evidence suggests that the determinant of [PSI+] is the nuclear encoded Sup35p, a component of the translation termination complex. Here we review the series of experiments supporting the yeast prion hypothesis and provide another look at the 30 years of work preceding this theory in light of our current state of knowledge.

Notes: Abstract Gravitational lenses can provide crucial information on the geometry of the Universe, on the cosmological scenario of formation of its structures as well as on the history of its components with look-back time. In this review, I focus on the most recent results obtained during the last five years from the analysis of the weak lensing regime. The potential of weak lensing as a probe of dark matter and the study of the coupling between light and mass on scales of clusters of galaxies, large-scale structures and galaxies is discussed first. Then I present the impact of weak lensing for the study of distant galaxies and of the population of lensed sources as a function of redshift. Finally, I discuss the potential of weak lensing to constrain the cosmological parameters, either from pure geometrical effects observed in peculiar lenses, or from the coupling of weak lensing with the CMB.

Notes: Abstract Because of mean distortion, most turbulent flows are anisotropic. Two-point descriptions, forming the heart of this review of anisotropic models, capture the continuum of anisotropically structured turbulent scales and, moreover, allow exact treatment of the linear terms representing mean distortion, only needing closure assumptions for the nonlinear part of the model. The rapid-distortion limit, in which nonlinear terms are neglected, is the main subject of Section 2, while Section 3 introduces nonlinearity. It is shown that, even with significant nonlinearity, many features of turbulence can, at least qualitatively, be understood using linear theory alone, e.g. the directionality of velocity fluctuations and correlation lengths induced by strong mean shear near a wall or straining by duct flow, whereas some, e.g. wave resonances in rotating turbulence, involve a subtle combination of linear and nonlinear terms. The importance of linear effects is reflected in the triadic models of Section 3, which contain no approximations of the linear terms and whose anisotropic nonlinear closures are heavily dependent on linear theory. Despite being fundamentally less satisfactory (because they involve additional ad hoc hypotheses to compensate for the lack of two-point information), one-point models dominate industrial calculations because they are robust, well-established, and computationally relatively cheap. Although there are too many spectral degrees of freedom for a one-point model to reproduce two-point results in all circumstances, two-point theories-in particular RDT-have been exploited to develop new one-point models, as discussed in Section 4. Given the significant limitation of classical two-point models to homogeneous turbulence, some inhomogeneous extensions are described in Section 5.

Notes: Abstract Natural ventilation of buildings is the flow generated by temperature differences and by the wind. The governing feature of this flow is the exchange between an interior space and the external ambient. Although the wind may often appear to be the dominant driving mechanism, in many circumstances temperature variations play a controlling feature on the ventilation since the directional buoyancy force has a large influence on the flow patterns within the space and on the nature of the exchange with the outside. Two forms of ventilation are discussed: mixing ventilation, in which the interior is at an approximately uniform temperature, and displacement ventilation, where there is strong internal stratification. The dynamics of these buoyancy-driven flows are considered, and the effects of wind on them are examined. The aim behind this work is to give designers rules and intuition on how air moves within a building; the research reveals a fascinating branch of fluid mechanics.

Notes: Abstract This review deals primarily with the bifurcation, stability, and evolution of gravity and capillary-gravity waves. Recent results on the bifurcation of various types of capillary-gravity waves, including two-dimensional solitary waves at the minimum of the dispersion curve, are reviewed. A survey of various mechanisms (including the most recent ones) to explain the frequency downshift phenomenon is provided. Recent significant results are given on "horseshoe" patterns, which are three-dimensional structures observable on the sea surface under the action of wind or in wave tank experiments. The so-called short-crested waves are then discussed. Finally, the importance of surface tension effects on steep waves is studied.

Notes: Abstract A review of planetary-entry gas dynamics is presented. Evolution of a blunt-body flowfield from a free molecular flow environment to a continuum environment is described. Simulations of near-wake flow phenomena, important for defining aerobrake payload environments, are also discussed. Some topics to be highlighted include aerodynamic coefficient predictions with emphasis on high-temperature gas effects; surface heating and temperature predictions for thermal protection system (TPS) design in a high-temperature, thermochemical nonequilibrium environment; and thermochemical models required for numerical flow simulation. Recent applications involving atmospheric entry into Jupiter (Galileo), Mars (Pathfinder and Global Surveyor), and a planned mission in which dust from the tail of a comet will be returned to Earth (Stardust) will provide context for this discussion.

Notes: Abstract This review of plant population genetics focuses on the genetic foundations of the processes that have led to documentable improvements in cultivated plants since the earliest domestications took place perhaps 13,000 years ago. Nearly all human civilizations have depended heavily on inbreeding plants (particularly wheat, barley, soybeans and other inbreeding legumes), as well as outbreeding vegetatively propagated species (white potatoes, yams) as their dietary standbys. The principal exception is maize (corn), an annual seed-produced outbreeder in nature. It is noteworthy that maize joined wheat, rice, and barley as a truly major crop worldwide only after its conversion to self-pollination combined with hybridization between favorably interacting inbred lines increased yield of maize several-fold in the twentieth century.

Notes: Abstract The immune response is regulated not only by cell proliferation and differentiation, but also by programmed cell death, or apoptosis. In response to various stimuli, death factors bind to their respective receptors and activate the apoptotic death program in target cells. A cascade of specific proteases termed caspases mediates the apoptotic process. The activated caspases cleave various cellular components, a process that leads to morphological changes of the cells and nuclei, as well as to degradation of the chromosomal DNA. Loss-of-function mutations in the signaling molecules involved in apoptosis cause hyper-proliferation of cells in mouse and human. In contrast, exaggeration of this death cascade causes the destruction of various tissues.

Notes: Abstract The past decade has witnessed extraordinary progress in retinal disease gene identification, the analysis of animal and tissue culture models of disease processes, and the integration of this information with clinical observations and with retinal biochemistry and physiology. During this period over twenty retinal disease genes were identified and for many of these genes there are now significant insights into their role in disease. This review presents an overview of the basic and clinical biology of the retina, summarizes recent progress in understanding the molecular mechanisms of inherited retinal diseases, and offers an assessment of the role that genetics will play in the next phase of research in this area.

Notes: Abstract Conservative site-specific recombination functions to create biological diversity in prokaryotes. Simple site-specific recombination systems consist of two recombination sites and a recombinase gene. The plasmid R64 shufflon contains seven recombination sites, which flank and separate four DNA segments. Site-specific recombinations mediated by the product of the rci gene between any two inverted recombination sites result in the inversion of four DNA segments independently or in groups. The shufflon functions as a biological switch to select one of seven C-terminal segments of the PilV proteins, which is a minor component of R64 thin pilus. The shufflon determines the recipient specificity in liquid matings of plasmid R64. Other multiple inversion systems as well as integrons, which are multiple insertion systems, are also described in this review.

Notes: Abstract The synthesis of ribosomes is one of the major metabolic pathways in all cells. In addition to around 75 individual ribosomal proteins and 4 ribosomal RNAs, synthesis of a functional eukaryotic ribosome requires a remarkable number of trans-acting factors. Here, we will discuss the recent, and often surprising, advances in our understanding of ribosome synthesis in the yeast Saccharomyces cerevisiae. These will underscore the unexpected complexity of eukaryotic ribosome synthesis.

Notes: Abstract Molecular genetic analysis of chemotaxis and thermotaxis in Caenorhabditis elegans has revealed the molecular bases of olfaction, taste, and thermosensation, which, in turn, has demonstrated that sensory signaling in C. elegans is very similar to that in vertebrates. A cyclic nucleotide-gated channel (TAX-2/TAX-4) that is highly homologous to the olfactory and photoreceptor channels in vertebrates is required for taste and thermosensation, in addition to olfaction. A cation channel (OSM-9) that is closely related to a capsaicin receptor channel is required for olfactory adaptation in one olfactory neuron and olfactory sensation in the other olfactory neuron. A novel Galpha protein (ODR-3) is essential for olfactory responses in all olfactory neurons and aversive responses in a polymodal sensory neuron. A G protein-coupled seven-transmembrane receptor (ODR-10) is the first olfactory receptor whose ligand was elucidated. Using chemotaxis and thermotaxis as behavioral paradigms, neural plasticity including learning and memory can be studied genetically in C. elegans.

Notes: Abstract HK022 is a temperate coliphage related to phage lamba. Its chromosome has been completely sequenced, and several aspects of its life cycle have been intensively studied. In the overall arrangement, expression, and function of most of its genes, HK022 broadly resembles lamba and other members of the lamba family. Upon closer view, significant differences emerge. The differences reveal alternative strategies used by related phages to cope with similar problems and illuminate previously unknown regulatory and structural motifs. HK022 prophages protect lysogens from superinfection by producing a sequence-specific RNA binding protein that prematurely terminates nascent transcripts of infecting phage. It uses a novel RNA-based mechanism to antiterminate its own early transcription. The HK022 protein shell is strengthened by a complex pattern of covalent subunit interlinking to form a unitary structure that resembles chainmail armor. Its integrase and repressor proteins are similar to those of lamba, but the differences provide insights into the evolution of biological specificity and the elements needed for construction of a stable genetic switch.

Notes: Abstract Recent results from ancestral (minimally derived) protists testify to the tremendous diversity of the mitochondrial genome in various eukaryotic lineages, but also reinforce the view that mitochondria, descendants of an endosymbiotic alpha-Proteobacterium, arose only once in evolution. The serial endosymbiosis theory, currently the most popular hypothesis to explain the origin of mitochondria, postulates the capture of an alpha-proteobacterial endosymbiont by a nucleus-containing eukaryotic host resembling extant amitochondriate protists. New sequence data have challenged this scenario, instead raising the possibility that the origin of the mitochondrion was coincident with, and contributed substantially to, the origin of the nuclear genome of the eukaryotic cell. Defining more precisely the alpha-proteobacterial ancestry of the mitochondrial genome, and the contribution of the endosymbiotic event to the nuclear genome, will be essential for a full understanding of the origin and evolution of the eukaryotic cell as a whole.

Notes: Abstract Formation of the bacterial division septum is catalyzed by a number of essential proteins that assemble into a ring structure at the future division site. Assembly of proteins into the cytokinetic ring appears to occur in a hierarchial order that is initiated by the FtsZ protein, a structural and functional analog of eukaryotic tubulins. Placement of the division site at its correct location in Escherichia coli requires a division inhibitor (MinC), that is responsible for preventing septation at unwanted sites near the cell poles, and a topological specificity protein (MinE), that forms a ring at midcell and protects the midcell site from the division inhibitor. However, the mechanism responsible for identifying the position of the midcell site or the polar sites used for spore septum formation is still unclear. Regulation of the division process and its coordination with other cell cycle events, such as chromosome replication, are poorly understood. However, a protein has been identified in Caulobacter (CtrA) that regulates both the initiation of chromosome regulation and the transcription of ftsZ, and that may play an important role in the coordination process.

Notes: Abstract DNA mismatch repair (MMR) is one of multiple replication, repair, and recombination processes that are required to maintain genomic stability in prokaryotes and eukaryotes. In the wake of the discoveries that hereditary nonpolyposis colorectal cancer (HNPCC) and other human cancers are associated with mutations in MMR genes, intensive efforts are under way to elucidate the biochemical functions of mammalian MutS and MutL homologs, and the consequences of defects in these genes. Genetic studies in cultured mammalian cells and mice are proving to be instrumental in defining the relationship between the functions of MMR in mutation and tumor avoidance. Furthermore, these approaches have raised awareness that MMR homologs contribute to DNA damage surveillance, transcription-coupled repair, and recombinogenic and meiotic processes.

Notes: Abstract Meiotic chromosomes have been studied for many years, in part because of the fundamental life processes they represent, but also because meiosis involves the formation of homolog pairs, a feature which greatly facilitates the study of chromosome behavior. The complex events involved in homolog juxtaposition necessitate prolongation of prophase, thus permitting resolution of events that are temporally compressed in the mitotic cycle. Furthermore, once homologs are paired, the chromosomes are connected by a specific structure: the synaptonemal complex. Finally, interaction of homologs includes recombination at the DNA level, which is intimately linked to structural features of the chromosomes. In consequence, recombination-related events report on diverse aspects of chromosome morphogenesis, notably relationships between sisters, development of axial structure, and variations in chromatin status. The current article reviews recent information on these topics in an historical context. This juxtaposition has suggested new relationships between structure and function. Additional issues were addressed in a previous chapter (551).

Notes: Abstract In the past few years great progress has been made in identifying and characterizing plant photoreceptors active in the blue/UV-A regions of the spectrum. These photoreceptors include cryptochrome 1 and cryptochrome 2, which are similar in structure and chromophore composition to the prokaryotic DNA photolyases. However, they have a C-terminal extension that is not present in photolyases and lack photolyase activity. They are involved in regulation of cell elongation and in many other processes, including interfacing with circadian rhythms and activating gene transcription. Animal cryptochromes that play a photoreceptor role in circadian rhythms have also been characterized. Phototropin, the protein product of the NPH1 gene in Arabidopsis, likely serves as the photoreceptor for phototropism and appears to have no other role. A plasma membrane protein, it serves as photoreceptor, kinase, and substrate for light-activated phosphorylation. The carotenoid zeaxanthin may serve as the chromophore for a photoreceptor involved in blue-light-activated stomatal opening. The properties of these photoreceptors and some of the downstream events they are known to activate are discussed.

Notes: Abstract The neural crest is a transient population of multipotent precursor cells named for its site of origin at the crest of the closing neural folds in vertebrate embryos. Following neural tube closure, these cells become migratory and populate diverse regions throughout the embryo where they give rise to most of the neurons and support cells of the peripheral nervous system (PNS), pigment cells, smooth muscle, craniofacial cartilage, and bone. Because of its remarkable ability to generate such diverse derivatives, the neural crest has fascinated developmental biologists for over one hundred years. A great deal has been learned about the migratory pathways neural crest cells follow and the signals that may trigger their differentiation, but until recently comparatively little was known about earlier steps in neural crest development. In the past few years progress has been made in understanding these earlier events, including how the precursors of these multipotent cells are specified in the early embryo and the mechanisms by which they become migratory. In this review, we first examine the mechanisms underlying neural crest induction, paying particular attention to a number of growth factor and transcription factor families that have been implicated in this process. We also discuss when and how the fate of neural crest precursors may diverge from those of nearby neural and epidermal populations. Finally, we review recent advances in our understanding of how neural crest cells become migratory and address the process of neural crest diversification.

Notes: Abstract Proteins of the kinesin superfamily utilize a conserved catalytic motor domain to generate movements in a wide variety of cellular processes. In this review, we discuss the rapid expansion in our understanding of how eukaryotic cells take advantage of these proteins to generate force and movement in diverse functional contexts. We summarize several recent examples revealing that the simplest view of a kinesin motor protein binding to and translocating a cargo along a microtubule track is inadequate. In fact, this paradigm captures only a small subset of the many ways in which cells harness force production to the generation of intracellular movements and functions. We also highlight several situations where the catalytic kinesin motor domain may not be used to generate movement, but instead may be used in other biochemical and functional contexts. Finally, we review some recent ideas about kinesin motor regulation, redundancy, and cargo attachment strategies.

Notes: Abstract The Drosophila phototransduction cascade has emerged as an attractive paradigm for understanding the molecular mechanisms underlying visual transduction, as well as other G protein-coupled signaling cascades that are activated and terminated with great rapidity. A large collection of mutants affecting the fly visual cascade have been isolated, and the nature and function of many of the affected gene products have been identified. Virtually all of the proteins, including those that were initially classified as novel, are highly related to vertebrate homologs. Recently, it has become apparent that most of the proteins central to Drosophila phototransduction are coupled into a supramolecular signaling complex, signalplex, through association with a PDZ-containing scaffold protein. The characterization of this complex has led to a re-evaluation of the mechanisms underlying the activation and deactivation of the phototransduction cascade.

Notes: Abstract Subcellular asymmetry, cell polarity, is fundamental to the diverse specialized functions of eukaryotic cells. In yeast, cell polarization is essential to division and mating. As a result, this highly accessible experimental system serves as a paradigm for deciphering the molecular mechanisms underlying the generation of polarity. Beyond yeast, cell polarity is essential to the partitioning of cell fate in embryonic development, the generation of axons and their guidance during neuronal development, and the intimate communication between lymphocytes within the immune system. The polarization of yeast cells shares many features with that of these more complex examples, including regulation by both intrinsic and extrinsic cues, conserved regulatory molecules such as Cdc42 GTPase, and asymmetry of the cytoskeleton as its centerpiece. This review summarizes the molecular pathways governing the generation of cell polarity in yeast.

Notes: Abstract At a certain stage in their life cycle, plants switch from vegetative to reproductive development. This transition is regulated by multiple developmental and environmental cues. These ensure that the plant switches to flowering at a time when sufficient internal resources have been accumulated and the environmental conditions are favorable. The use of a molecular genetic approach in Arabidopsis has resulted in the identification and cloning of many of the genes involved in regulating floral transition. The current view on the molecular function of these genes, their division into different genetic pathways, and how the pathways interact in a complex regulatory network are summarized.

Notes: Abstract Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic-helix-loop-helix-PAS transcription factor consisting of HIF-1alpha and HIF-1beta subunits. HIF-1alpha expression and HIF-1 transcriptional activity increase exponentially as cellular O2 concentration is decreased. Several dozen target genes that are transactivated by HIF-1 have been identified, including those encoding erythropoietin, glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. The products of these genes either increase O2 delivery or allow metabolic adaptation to reduced O2 availability. HIF-1 is required for cardiac and vascular development and embryonic survival. In fetal and postnatal life, HIF-1 is required for a variety of physiological responses to chronic hypoxia. HIF-1 expression is increased in tumor cells by multiple mechanisms and may mediate adaptation to hypoxia that is critical for tumor progression. HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology.

Notes: Abstract Viruses are ubiquitous and dangerous obligate intracellular parasites. To facilitate recognition of virus-infected cells by the immune system, vertebrates evolved a system that displays oligopeptides derived from viral proteins on the surface of cells in association with class I molecules of the major histocompatibility complex. Here we review the mechanisms counter-evolved by viruses to interfere with the generation of viral peptides, their intracellular trafficking, or the cell surface expression of class I molecules bearing viral peptides. This topic is important in its own right because the viruses that encode these proteins represent medically important pathogens, are potential vectors for vaccines or gene therapy, and provide strategies and tools for blocking immune recognition in transplantation, autoimmunity, and gene therapy. In addition, studies on viral interference provide unique insights into unfettered antigen processing and normal cellular functions that are exploited and exaggerated by viruses.

Notes: Abstract The compartmentation of eukaryotic cells requires all nuclear proteins to be imported from the cytoplasm, whereas, for example, transfer RNAs, messenger RNAs, and ribosomes are made in the nucleus and need to be exported to the cytoplasm. Nuclear import and export proceed through nuclear pore complexes and can occur along a great number of distinct pathways, many of which are mediated by importin beta-related nuclear transport receptors. These receptors shuttle between nucleus and cytoplasm, and they bind transport substrates either directly or via adapter molecules. They all cooperate with the RanGTPase system to regulate the interactions with their cargoes. Another focus of our review is nuclear export of messenger RNA, which apparently largely relies on export mediators distinct from importin beta-related factors. We discuss mechanistic aspects and the energetics of transport receptor function and describe a number of pathways in detail.

Notes: Abstract I was born and educated in Canada, obtaining my PhD in experimental nuclear physics. When I learned that technetium had been found in stellar spectra, I taught myself some astrophysics and began to study stellar nucleosynthesis. This is an account of those studies and of the pathway through much of theoretical astrophysics and planetary physics that was a natural outgrowth of the pursuit of nucleosynthesis problems. I also discuss my experiences in government service and in academia, in organization of conferences, in governmental advising, and in academic administration. In particular, I emphasize the logical connections among the various scientific themes that I have pursued.

Notes: Abstract In 1960 ICSU set up an Inter-Union Commission (IUCAF) on the Allocation of Frequencies for Space Research and Radio Astronomy, to keep key parts of the radio spectrum clear for passive, scientific use. IUCAF represents URSI, IAU and COSPAR at World Radio Conferences (WRCs) convened by the International Telecommunications Union (ITU) in Geneva; the WRCs establish the international law which governs users of the radio spectrum. This review recounts many serious threats posed to passive scientific research by commercial and military operations, particularly those involving radio emissions from aircraft and spacecraft. The continual conflict between commercial greed and scientific curiosity has often put the future of radio astronomy, space research, and earth exploration in jeopardy. The conflict increases as we move into the Information Age.

Notes: Abstract We present a review of nucleosynthesis in AGB stars outlining the development of theoretical models and their relationship to observations. We focus on the new high resolution codes with improved opacities, which recently succeeded in accounting for the third dredge-up. This opens the possibility of understanding low luminosity C stars (enriched in s-elements) as the normal outcome of AGB evolution, characterized by production of 12C and neutron-rich nuclei in the He intershell and by mass loss from strong stellar winds. Neutron captures in AGB stars are driven by two reactions: 13C(alpha,n)16O, which provides the bulk of the neutron flux at low neutron densities (Nn〈= 107 n/cm3), and 22Ne(alpha,n)25Mg, which is mildly activated at higher temperatures and mainly affects the production of s-nuclei depending on reaction branchings. The first reaction is now known to occur in the radiative interpulse phase, immediately below the region previously homogenized by third dredge-up. The second reaction occurs during the convective thermal pulses. The resulting nucleosynthesis phenomena are rather complex and rule out any analytical approximation (exponential distribution of neutron fluences). Nucleosynthesis in AGB stars, modeled at different metallicities, account for several observational constraints, coming from a wide spectrum of sources: evolved red giants rich in s-elements, unevolved stars at different metallicities, presolar grains recovered from meteorites, and the abundances of s-process isotopes in the solar system. In particular, a good reproduction of the solar system main component is obtained as a result of Galactic chemical evolution that mixes the outputs of AGB stars of different stellar generations, born with different metallicities and producing different patterns of s-process nuclei. The main solar s-process pattern is thus not considered to be the result of a standard archetypal s-process occurring in all stars. Concerning the 13C neutron source, its synthesis requires penetration of small amounts of protons below the convective envelope, where they are captured by the abundant 12C forming a 13C-rich pocket. This penetration cannot be modeled in current evolutionary codes, but is treated as a free parameter. Future hydrodynamical studies of time dependent mixing will be required to attack this problem. Evidence of other insufficiencies in the current mixing algorithms is common throughout the evolution of low and intermediate mass stars, as is shown by the inadequacy of stellar models in reproducing the observations of CNO isotopes in red giants and in circumstellar dust grains. These observations require some circulation of matter between the bottom of convective envelopes and regions close to the H-burning shell (cool bottom processing). AGB stars are also discussed in the light of their possible contribution to the inventory of short-lived radioactivities that were found to be alive in the early solar system. We show that the pollution of the protosolar nebula by a close-by AGB star may account for concordant abundances of 26Al, 41Ca, 60Fe, and 107Pd. The AGB star must have undergone a very small neutron exposure, and be of small initial mass ( ). There is a shortage of 26Al in such models, that however remains within the large uncertainties of crucial reaction rates. The net 26Al production problem requires further investigation.

Notes: Abstract Quasar (QSO) elemental abundances provide unique probes of high-redshift star formation and galaxy evolution. There is growing evidence from both the emission and intrinsic absorption lines that QSO environments have roughly solar or higher metallicities out to redshifts 〉4. The range is not well known, but solar to a few times solar metallicity appears to be typical. There is also evidence for higher metallicities in more luminous objects and for generally enhanced N/C and Fe/alpha abundances compared with solar ratios. These results identify QSOs with vigorous, high-redshift star formation-consistent with the early evolution of massive galactic nuclei or dense protogalactic clumps. However, the QSOs offer new constraints. For example, (a) most of the enrichment and star formation must occur before the QSOs "turn on" or become observable, on time scales of 1 Gyr at least at the highest redshifts. (b) The tentative result for enhanced Fe/alpha suggests that the first local star formation began at least ~1 Gyr before the QSO epoch. (c) The star formation must ultimately be extensive to reach high metallicities; that is, a substantial fraction of the local gas must be converted into stars and stellar remnants. The exact fraction depends on the shape of the initial mass function (IMF). (d) The highest derived metallicities require IMFs that are weighted slightly more toward massive stars than in the solar neighborhood. (e) High metallicities also require deep gravitational potentials. By analogy with the well-known mass-metallicity relation among low-redshift galaxies, metal-rich QSOs should reside in galaxies (or protogalaxies) that are minimally as massive (or as tightly bound) as our own Milky Way.