bluuebunny/crossref_metadata_2025 huggingface dataset:
High-speed x-ray reflectometory in multiwavelength-dispersive mode
Authors: Matsushita Tadashi , Niwa Yasuhiro , Inada Yasuhiro , Nomura Masaharu , Ishii Masashi , Sakurai Kenji , Arakawa Etsuo
Published: January 2008

The potential of a high speed x-ray reflectometer for time-resolved studies on the subsecond to millisecond timescales is demonstrated by recording x-ray reflection curves from a small area (1mm×10mm) of a 14.3nm thick gold film on a silicon substrate with data collection times of 0.05–1s. A horizontally convergent x-ray beam having a one-to-one correlation between ray direction and energy is produced by a curved crystal polychromator, and the beam is incident on and vertically reflected by a specimen placed at the focus. The x-ray reflectivity is measured as a function of the x-ray energy downstream of the focus using a one dimensional detector with no need for angle scan of the specimen and detector.
Two photon absorption in quantum dot-in-a-well infrared photodetectors
Authors: Aivaliotis P. , Zibik E. A. , Wilson L. R. , Cockburn J. W. , Hopkinson M. , Vinh N. Q.
Published: January 2008

Two photon absorption processes in InAs∕In01.5Ga0.85As∕GaAs quantum dot-in-a-well photodetectors are studied using free electron laser excitation. Two photon induced, normal incidence photocurrent, observed in the range of 20–30μm, arises from sequential near-resonant two-step transitions involving electron ground to first excited states in the dot, to quantum well final states. We find a two photon absorption coefficient of β∼1×107cm∕GW at 26.5μm (47meV) and 0.8V applied bias. Second-order autocorrelation measurements exhibit two characteristic time constants of ∼3 and ∼40ps. The latter is associated with the intermediate state electron lifetime, whereas the short decay is explained by the involvement of acoustic phonon assisted transitions.
Self-organized twinning of actuated particles for microfluidic pumping
Authors: Derks Roy J. S. , Frijns Arjan J. H. , Prins Menno W. J. , Dietzel Andreas H.
Published: January 2008

The motion of monodisperse particle ensembles in fluidic channels actuated by axial magnetic or gravitation forces is studied. Interactions between particles, fluid, and nearby walls induce unforeseen self-organization phenomena. Superparamagnetic microparticles aligned on a channel axis successively organize toward a stable polytwin system under constant force conditions. In the absence of repelling particle interactions, full contact twinning is observed for particles driven by gravity. The mechanisms of successive twinning and spacing regulation are explained by a one-dimensional model based on the axis flow profile. Related performance enhancements for particle based microfluidic pumping are discussed.
Near- to far-field imaging of free-space and surface-bound waves emanating from a metal nanoslit
Authors: Jung Yun Suk , Wuenschell Jeff , Schmidt Tyler , Kim Hong Koo
Published: January 2008

The authors report the radiation pattern (radial and angular distribution of light intensity) of a silver nanoslit measured in the near- to far-field regimes. In most far fields, the 1∕r dependence of intensity distribution, expected from a cylindrical wave emanating from a line source, is clearly observed. The glancing angle regime is found to be governed by the presence of surface plasmons, showing higher intensity closer to the metal surface. From the radiation patterns measured with a tilted-probe, radial-scan method, a branching ratio is quantitatively determined for the free-space radiation and surface plasmon components, emerging from the nanoslit.
The Origins and Future of Nuclear Magnetic Resonance Imaging
Authors: Wehrli Felix W.
Published: January 2008

During the past two decades nuclear magnetic resonance has revolutionized chemistry, biochemistry, biology and, more recently, diagnostic medicine. Nuclear magnetic resonance imaging, or mri as it is commonly called, is fundamentally different from x-ray-based techniques in terms of the principles of spatial encoding and mechanisms of signal and contrast generation involved. Mri has a far richer ultimate potential than any other imaging technique known today, and its technology and applications are still far from maturation, which may not occur until early in the 21st century.
Physics with Radioactive Nuclear Beams
Authors: Boyd Richard N. , Tanihata Isao
Published: January 2008

The purpose of nuclear physics is to measure properties of specific nuclides and infer from them global properties common to all nuclides. One goal, for example, is to understand nuclear sizes and matter distributions in terms of basic nuclear forces. Another is to understand the variation throughout the periodic table of the dominant quantum states, which are known as the “nuclear shell model” states and are characterized, much as are atomic states, by a principal quantum number and by orbital and total angular momentum quantum numbers. In turn other nuclear phenomena, such as the collective excitations known as giant resonances, can be understood in terms of the shell-model configurations and basic nuclear parameters.
Iraq's Secret Nuclear Weapons Program
Authors: Davis Jay C. , Kay David A.
Published: January 2008

The inspections of Iraq mandated by the United Nations as a cease-fire condition at the end of the Gulf War in February 1991 have revealed a clandestine nuclear materials production and weapons design program of unexpected size and sophistication. The total value of that program, in terms of equipment and personnel deployed between 1981 and 1991, may be on the order of $5-10 billion. The program employed an estimated 7000 scientists and 20 000 workers.
The Eventful Life of Fritz Houtermans
Authors: Khriplovich Iosif B.
Published: January 2008

“Why are you interested in this man?” they usually ask me. I don't know the answer. It just happened. Maybe my interest in the life of Fritz Houtermans started when I began coming across repeated references in various books to a gifted German physicist who emigrated to the USSR after Hitler came to power, was arrested by the Soviets in 1937 as a German spy and then was extradited back to Germany in 1940, only to return to occupied Kharkov two years later with the conquering Nazis.
New Opportunities at Soft-X-Ray Wavelengths
Authors: Attwood David
Published: January 2008

A once dark region of the electromagnetic spectrum is now becoming very bright. The soft-x-ray spectral region, nominally extending from wavelengths of several angstroms to several hundred angstroms and including photon energies from tens of electron volts to several thousand electron volts, is providing many new research and development opportunities in the physical and life sciences and in industry. The move toward shorter wavelengths is driven in part by the desire to see and write smaller features. But the numerous and distinct atomic resonances in this region of the spectrum also provide for elemental identification and, in some cases, chemical sensitivity. (See the article by Bernd Crasemann and Francois Wuilleumier in PHYSICS TODAY, June 1984, page 34.) Developments in x-ray optics and new sources of highbrightness, partially coherent radiation make it possible to study materials and biological samples with feature sizes of several hundred angstroms.
Women in Physics: Reversing the Exclusion
Authors: Fehrs Mary , Czujko Roman
Published: January 2008

Two decades ago US women earned about 4% of the nation's physics PhDs. Today, they earn about 5%. Although discussed in various forums in recent years, the low representation of women in physics persists. The problem is especially perplexing given the dramatic increases in the percentages of women in other sciences and in engineering.
The Heard Island Feasibility Test
Authors: Baggeroer Arthur , Munk Walter
Published: January 2008

The release of carbon dioxide and other greenhouse gases into the atmosphere is associated with temperature changes in both the atmosphere and the oceans. The oceans play a vital role in global temperature changes, storing both heat and greenhouse gases. Without the oceans the atmosphere would warm at two to three times greater a rate, other factors remaining equal. To understand and predict global warming, then, it is important to measure, rather than just speculate on, changes in the heat content of the ocean.
Energy from Inertial Fusion
Authors: Hogan William J. , Bangerter Roger , Kulcinski Gerald L.
Published: January 2008

Fusion is potentially a safe clean source not limited by political boundaries. Magnetic and inertial fusion share this promise, but there are differences between them. An inertial fusion power plant is based on different physics and technology from a magnetic fusion power plant and therefore presents somewhat different benefits and challenges. The facilities required to demonstrate inertial fusion power are potentially much smaller. In this article we describe concepts for such a power plant, its beneficial features and a low-cost reactor test facility for developing practical fusion power.
Special Issue: Optics of Nanostructures
Authors: Chemla Daniel S.
Published: January 2008

During the last decade semiconductor technology has continued to make impressive advances in miniaturization. It is now possible to fabricate artificial structures whose chemical compositions and shapes are controlled with a nanometer accuracy—comparable to interatomic distances. These man-made systems are too small to behave like the bulk parent compounds and too big to behave like atoms or molecules. We know from the basic principles of quantum mechanics that when the size of a system becomes comparable to the characteristic length scale that determines the coherence of the wavefunctions, quantum size effects occur. The properties then become size and shape dependent. The ability of modern technologies to actually make solid-state systems in which these conditions are realized opens new opportunities for investigation of condensed matter that has two, one or zero dimensions. Furthermore, because we can tailor some of the properties of these systems for specific purposes, nanostructures have the potential for revolutionary applications in electronics and optoelectronics. Feasibility demonstrations of some of these applications have already been performed, and implementations in actual devices have been achieved.
The Spectroscopy of Quantum Dot Arrays
Authors: Heitmann Detlef , Kotthaus Jörg P.
Published: January 2008

For three decades individual transistors in integrated semiconductor circuits have been getting smaller and smaller. Soon they will be approaching the 100-nanometer regime, where the classical description of diffusive electron motion breaks down and quantum concepts become important, bringing about fundamental changes in electronic and optical properties. Already in the widely used silicon MOSFET transistors, the interface between the semiconductor and the oxide layer serves as a potential well less than 10 nm wide. While electrons remain free to wander in the plane of the interface, their motion in the perpendicular direction is quantized by this very narrow well. Such two-dimensional electron systems, best realized in high-mobility modulation-doped semiconductor heterostructures, have been found over the years to exhibit new and quite unexpected quantum phenomena, like the integral and fractional quantum Hall effects.
Optical Processes in Microcavities
Authors: Yamamoto Yoshihiso , Slusher Richart E.
Published: January 2008

Studies of optical microresonators with dimensions between 0.1 and 10 microns are now under way in a wide variety of condensed matter systems. Ideally, one can isolate a single mode of the optical field in a cube a halfwavelength on a side with perfectly reflecting walls. Liquid droplets, polymer spheres and semiconductor Fabry-Perot microcavities with dielectric mirrors are examples of microresonators with which one can approach this ideal limit and nearly isolate a few modes of the electromagnetic field from the continuum of surrounding free-space modes.
Exploring Mesoscopia: The Bold New World of Nanostructures
Authors: Siegel Richard W.
Published: January 2008

Interest in the physics of condensed matter at size scales larger than that of atoms but smaller than that of bulk solids—so-called mesoscopic physics—has grown rapidly over the past two decades, but it stems from much earlier beginnings in diverse disciplines. Indeed, nanostructured matter apparently had its genesis with the Big Bang. The structures of the earliest meteorites suggest that matter formed by the condensation of atoms into nanoscale clusters that then aggregated into larger masses under the action of gravity. Many examples of natural nanostructures can be found as well in biological systems from seashells to the human body.
Medical Cyclotrons
Authors: Blosser Henry G.
Published: January 2008

Each day in Detroit and Seattle and a score of other cities around the world, dozens of cancer patients report for neutron treatments of tumors resistant to conventional photon-based radiation therapy. Few, if any, of these patients know that the healing radiations are being produced by a cyclotron operating in accord with basic principles first promulgated some 60 years ago in a journal, the Physical Review, which they also know nothing of. And Ernest Lawrence and Stanley Livingston, as they wrote their pioneering 1932 paper, spoke of the relevance and need for such a device in the study of the atomic nucleus, but at least in their earliest papers, no thought of a future benefit in the treatment of cancer is considered.
Atom Motion on Surfaces
Authors: Lagally Max G.
Published: January 2008

Atoms wandering on surfaces lead complex lives. For example, they face many restrictions on their freedom to move. High walls sometimes leave only one road open, and that road may have checkpoints. Such walls and checkpoints are a consequence of the crystal structure of the surface and the interaction between the surface atoms and the wandering atom. The crystal structure in turn is controlled by the nature of the bonding—metallic, covalent, ionic—between atoms in the crystal.
Physics, Community and the Crisis in Physical Theory
Authors: Schweber Silvan S.
Published: January 2008

A deep sense of unease permeates the physical sciences. We are in a time of great change: The end of the cold war has ushered in an era of shrinking budgets, painful restructuring and changing objectives. At the same time, the underlying assumptions of physics research have shifted. Traditionally, physics has been highly reductionist, analyzing nature in terms of smaller and smaller building blocks and revealing underlying, unifying fundamental laws. In the past this grand vision has bound the subdisciplines together. Now, however, the reductionist approach that has been the hallmark of theoretical physics in the 20th century is being superseded by the investigation of emergent phenomena, the study of the properties of complexes whose “elementary” constituents and their interactions are known. Physics, it could be said, is becoming like chemistry.
Initial Employment of Physics Doctorate Recipients: Class of 1992
Authors: Ellis Susanne D.
Published: January 2008

The current folklore regarding today's job market for recent physics PhD recipients describes a dichotomy between discouragement and the challenge to be imaginative. Hard statistics are needed to help put into perspective the much publicized but meager anecdotal information about the initial employment of physics doctorate recipients in the 1990s. Such data are available from a battery of annual surveys conducted by the American Institute of Physics.
The Protein Folding Problem
Authors: Chan Hue Sun , Dill Ken A.
Published: January 2008

Thousands of different types of proteins occur in biological organisms. They are responsible for catalyzing and regulating biochemical reactions, transporting molecules, the chemistry of vision and of the photosynthetic conversion of light to growth, and they form the basis of structures such as skin, hair and tendon. Protein molecules have remarkable structures. A protein is a linear chain of a particular sequence of monomer units. A major class of proteins, globular proteins, ball up into compact configurations that can have much internal symmetry. (See figure 1.) Each globular protein has a unique folded state, determined by its sequence of monomers.
Special Issue: High-Performance Computing and Physics
Authors: Orszag Steven A. , Zabusky Norman J.
Published: January 2008

Computers commonly process data and do simulations these days at rates of gigaflops (109 floating-point operations per second). In the next few years teraflop (1012 flops) computers will open an age in which we can study physics in new parameter domains, providing insights that may lead to new discoveries. These teraflop computers will be massively parallel, involving hundreds if not thousands of coupled processors tackling problems involving trillions of data points. To make effective use of these new resources will require new ideas about which problems should be solved, what numerical algorithms should be used to solve them, and what visualization and quantification methods should be used to enable scientists to comprehend and analyze the vast amounts of data that will be generated.
Nodes, Modes and Flow Codes
Authors: Karniadakis George Em , Orszag Steven A.
Published: January 2008

Understanding turbulent flows is a “grand challenge” comparable to other prominent scientific problems such as the large-scale structure of the universe and the nature of subatomic particles. In contrast to many of the other grand challenges, progress on the basic theory of turbulence translates nearly immediately into a wide range of engineering applications and technological advances that affect many aspects of everyday life.
Modeling Oceanic and Atmospheric Vortices
Authors: Dritschel David G. , Legras Bernard
Published: January 2008

Many of the physical systems in the universe are fluids. Our understanding of the Earth, the planets, stars and even galaxies depends crucially on fluid dynamics. This mathematical discipline has been instrumental in the development of meteorology, oceanography and, to a lesser extent, astrophysics. From the beginning, observations and calculations have made apparent the rich dynamical structure of astronomical fluids: Satellite observations told us that the Great Red Spot of Jupiter was simply the most prominent object within the turbulent Jovian atmosphere, which exhibits hundreds of observable vortices embedded in a complex structure of bands or jets extending from one pole to the other. Similar structures have been observed, though in less detail, on the other Jovian planets. Complex dynamical structures are also believed to characterize condensing nebulae, evolving galaxies, stellar convective layers and the accretion disks of neutron stars and black holes.
Computer Models of Colliding Galaxies
Authors: Barnes Joshua E. , Hernquist Lars E.
Published: January 2008

Galaxies come in a wide variety of sizes and shapes. Most have an ordered structure and can be classified as spirals or ellipticals. Spiral galaxies are flattened disks in which nearly all the stars orbit in the same direction about a common center; ellipticals are oval swarms of stars distributed in complicated three-dimensional orbits. These are highly symmetric forms, suggesting a good degree of stability. Some galaxies, however, possess markedly irregular features. The nature of such “peculiar” galaxies and their relationship to more ordinary galaxies has long been a matter of controversy. Computer models, combined with increasingly powerful observations, offer a resolution: Many peculiar systems are ordinary galaxies in collision, and these collisions are transforming galaxies from one type to another.
Early Magnetic Resonance Experiments: Roots and Offshoots
Authors: Ramsey Norman F.
Published: January 2008

In 1937 I. I. Rabi described the fundamental theory for magnetic resonance experiments in his great paper “Space Quantization in a Gyrating Magnetic Field.” This theory stimulated many subsequent developments, including molecular-beam magnetic resonance, radiofrequency spectroscopy, nuclear magnetic resonance, masers and atomic clocks. Its imprint now stamps a tremendous range of experimental techniques and technological applications.
A Semicentury of Semiconductors
Authors: Fowler Alan B.
Published: January 2008

For more than 50 years the symbiotic relationship among semiconductor physics, technology and device engineering has exemplified cooperative activity that spans the continuum of the scientific enterprise, from the purest physics to the marketplace. In physics this activity has led to the observation of unexpectedly rich and intricate phenomena; in technology it has resulted in expanded techniques and invention with broad applications and key contributions to the electronics, communications and computer revolutions. Semiconductors have changed our world profoundly and probably beneficially, touching the lives of almost everyone in it—and not just by fueling advances in data handling and communications but also by making possible such consumer staples as the transistor radio and the compact disk player. Some might choose to designate the last half-century as the nuclear age or the jet age; others might think of it as the age of semiconductor electronics.
The Search for Forming Planetary Systems
Authors: Sargent Anneila I. , Beckwith Steven V. W.
Published: January 2008

For the first few million years of its life, the Sun was a large red star surrounded by a disk of gas and dust—the primitive solar nebula—that reached out beyond the boundaries of our present planetary system. Like all stars, the Sun was created by the collapse of a cold, dense core within a rotating cloud of interstellar material, debris from supernovae and other evolved stars of a previous generation. Angular momentum in the cloud allowed collapse along only one axis, thus leaving the material in a thin orbital plane around the new Sun. During the next hundred thousand years, the dust began to coagulate into larger particles, which eventually became planetesimals, the seeds for the nine planets. Over a further 10 million years, these planetesimals grew larger, clearing the residual gas and dust by dynamical sweeping and gravitational capture. Collisions led to further growth and the creation of a system of planets, comets and asteroids orbiting the young Sun. Within a billion years, the first life came into existence on one of those planets. Now, 5 billion years later, that life has developed to a degree of sophistication that seemingly defies the second law of thermodynamics.
Atom-Probe Field Ion Microscopy
Authors: Tsong Tien T.
Published: January 2008

Scientists are always pushing to new frontiers, which often involve questions about phenomena that occur on very large or very small scales. Astronomers search for new stars millions of light-years away in a quest to learn how these stars and the universe were born, and particle physicists look at elementary particles of size less than 10−17 cm in an effort to understand fundamental interactions. Meanwhile, however, many biologists, chemists and condensed matter physicists are trying to understand natural phenomena that we encounter every day and that occur on some intermediate scale. Questions at this scale are posed in terms of interactions between electrons or atoms and chemical bonds or in terms of atomic theories. The motivation is not only scientific curiosity but also a desire to discover new effects, create new molecules and materials, and develop new technologies that may benefit society. Although a single interaction, electromagnetism, determines the chemical and physical properties of molecules and materials, nature manifests electromagnetic forces in so many forms and in so many phenomena that many of them are by no means understood. One of the powerful tools at our disposal for studies on the microscopic scale or atomic scale is the atomic-resolution microscope.
Probing Dense Nuclear Matter in the Laboratory
Authors: Gupta Subal Das , Westfall Gary D.
Published: January 2008

A 150-meter-long outdoor beam line wanders through eucalyptus trees down the 45-meter slope connecting the SuperHILAC and the Bevatron at the Lawrence Berkeley Laboratory. The SuperHILAC is a linear accelerator designed to accelerate heavy nuclei at high intensities to energies of up to 8 MeV/nucleon for the purpose of studying heavy and superheavy elements. The Bevatron is a weak focusing synchrotron born in 1954 with the mission of discovering the antiproton and exploring the riddle of the hadrons using beams of 6.2-GeV protons. In 1974 these two machines were coupled to create the Bevalac, and with it a new field of research: relativistic heavy-ion reactions.
Functional consequences of realistic biodiversity changes in a marine ecosystem
Authors: Bracken Matthew E. S. , Friberg Sara E. , Gonzalez-Dorantes Cirse A. , Williams Susan L.
Published: January 2008

Declines in biodiversity have prompted concern over the consequences of species loss for the goods and services provided by natural ecosystems. However, relatively few studies have evaluated the functional consequences of realistic, nonrandom changes in biodiversity. Instead, most designs have used randomly selected assemblages from a local species pool to construct diversity gradients. It is therefore difficult, based on current evidence, to predict the functional consequences of realistic declines in biodiversity. In this study, we used tide pool microcosms to demonstrate that the effects of real-world changes in biodiversity may be very different from those of random diversity changes. Specifically, we measured the relationship between the diversity of a seaweed assemblage and its ability to use nitrogen, a key limiting nutrient in nearshore marine systems. We quantified nitrogen uptake using both experimental and model seaweed assemblages and found that natural increases in diversity resulted in enhanced rates of nitrogen use, whereas random diversity changes had no effect on nitrogen uptake. Our results suggest that understanding the real-world consequences of declining biodiversity will require addressing changes in species performance along natural diversity gradients and understanding the relationships between species' susceptibility to loss and their contributions to ecosystem functioning.
Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location
Authors: Yauk Carole , Polyzos Aris , Rowan-Carroll Andrea , Somers Christopher M. , Godschalk Roger W. , Van Schooten Frederik J. , Berndt M. Lynn , Pogribny Igor P. , Koturbash Igor , Williams Andrew , Douglas George R. , Kovalchuk Olga
Published: January 2008

Particulate air pollution is widespread, yet we have little understanding of the long-term health implications associated with exposure. We investigated DNA damage, mutation, and methylation in gametes of male mice exposed to particulate air pollution in an industrial/urban environment. C57BL/CBA mice were exposed
in situ
to ambient air near two integrated steel mills and a major highway, alongside control mice breathing high-efficiency air particulate (HEPA) filtered ambient air. PCR analysis of an expanded simple tandem repeat (ESTR) locus revealed a 1.6-fold increase in sperm mutation frequency in mice exposed to ambient air for 10 wks, followed by a 6-wk break, compared with HEPA-filtered air, indicating that mutations were induced in spermatogonial stem cells. DNA collected after 3 or 10 wks of exposure did not exhibit increased mutation frequency. Bulky DNA adducts were below the detection threshold in testes samples, suggesting that DNA reactive chemicals do not reach the germ line and cause ESTR mutation. In contrast, DNA strand breaks were elevated at 3 and 10 wks, possibly resulting from oxidative stress arising from exposure to particles and associated airborne pollutants. Sperm DNA was hypermethylated in mice breathing ambient relative to HEPA-filtered air and this change persisted following removal from the environmental exposure. Increased germ-line DNA mutation frequencies may cause population-level changes in genetic composition and disease. Changes in methylation can have widespread repercussions for chromatin structure, gene expression and genome stability. Potential health effects warrant extensive further investigation.
An essential role for orexins in emergence from general anesthesia
Authors: Kelz Max B. , Sun Yi , Chen Jingqiu , Cheng Meng Qing , Moore Jason T. , Veasey Sigrid C. , Dixon Shelley , Thornton Marcus , Funato Hiromasa , Yanagisawa Masashi
Published: January 2008

The neural mechanisms through which the state of anesthesia arises and dissipates remain unknown. One common belief is that emergence from anesthesia is the inverse process of induction, brought about by elimination of anesthetic drugs from their CNS site(s) of action. Anesthetic-induced unconsciousness may result from specific interactions of anesthetics with the neural circuits regulating sleep and wakefulness. Orexinergic agonists and antagonists have the potential to alter the stability of the anesthetized state. In this report, we refine the role of the endogenous orexin system in impacting emergence from, but not entry into the anesthetized state, and in doing so, we distinguish mechanisms of induction from those of emergence. We demonstrate that isoflurane and sevoflurane, two commonly used general anesthetics, inhibit c-Fos expression in orexinergic but not adjacent melanin-concentrating hormone (MCH) neurons; suggesting that wake-active orexinergic neurons are inhibited by these anesthetics. Genetic ablation of orexinergic neurons, which causes acquired murine narcolepsy, delays emergence from anesthesia, without changing anesthetic induction. Pharmacologic studies with a selective orexin-1 receptor antagonist confirm a specific orexin effect on anesthetic emergence without an associated change in induction. We conclude that there are important differences in the neural substrates mediating induction and emergence. These findings support the concept that emergence depends, in part, on recruitment and stabilization of wake-active regions of brain.
Universality and diversity of folding mechanics for three-helix bundle proteins
Authors: Yang Jae Shick , Wallin Stefan , Shakhnovich Eugene I.
Published: January 2008

In this study we evaluate, at full atomic detail, the folding processes of two small helical proteins, the B domain of protein A and the Villin headpiece. Folding kinetics are studied by performing a large number of
ab initio
Monte Carlo folding simulations using a single transferable all-atom potential. Using these trajectories, we examine the relaxation behavior, secondary structure formation, and transition-state ensembles (TSEs) of the two proteins and compare our results with experimental data and previous computational studies. To obtain a detailed structural information on the folding dynamics viewed as an ensemble process, we perform a clustering analysis procedure based on graph theory. Moreover, rigorous
p
fold
analysis is used to obtain representative samples of the TSEs and a good quantitative agreement between experimental and simulated Φ values is obtained for protein A. Φ values for Villin also are obtained and left as predictions to be tested by future experiments. Our analysis shows that the two-helix hairpin is a common partially stable structural motif that gets formed before entering the TSE in the studied proteins. These results together with our earlier study of Engrailed Homeodomain and recent experimental studies provide a comprehensive, atomic-level picture of folding mechanics of three-helix bundle proteins.
Defective signal transduction in B lymphocytes lacking presenilin proteins
Authors: Yagi Tomohito , Giallourakis Cosmas , Mohanty Subhasis , Scheidig Christina , Shen Jie , Zheng Hui , Xavier Ramnik J. , Shaw Albert C.
Published: January 2008

The mammalian presenilin (PS) proteins mediate the posttranslational cleavage of several protein substrates, including amyloid precursor protein, Notch family members, and CD44, but they have also been suggested to function in diverse cellular processes, including calcium-dependent signaling and apoptosis. We carried out an integrative computational study of multiple genomic datasets, including RNA expression, protein interaction, and pathway analyses, which implicated PS proteins in Toll-like receptor signaling. To test these computational predictions, we analyzed mice carrying a conditional allele of
PS1
and a germ line-inactivating allele of
PS2
, together with Cre site-specific recombinase expression under the influence of CD19 control sequences. Notably, B cells deficient in both PS1 and PS2 function have an unexpected and substantial deficit in both lipopolysaccharide and B cell antigen receptor-induced proliferation and signal transduction events, including a defect in anti-IgM-mediated calcium flux. Taken together, these results demonstrate a fundamental and unanticipated role for PS proteins in B cell function and emphasize the potency of (systems level) integrative analysis of whole-genome datasets in identifying novel biologic signal transduction relationships. Our findings also suggest that pharmacologic inhibition of PS for the treatment of conditions such as Alzheimer's disease may have potential consequences for immune system function.
Key role of tissue plasminogen activator in neurovascular coupling
Authors: Park Laibaik , Gallo Eduardo F. , Anrather Josef , Wang Gang , Norris Erin H. , Paul Justin , Strickland Sidney , Iadecola Costantino
Published: January 2008

The increase in blood flow evoked by synaptic activity is essential for normal brain function and underlies functional brain imaging signals. Nitric oxide, a vasodilator released by NMDA receptor activation, is critical for the flow increase, but the factors linking NMDA receptor activity to nitric oxide-dependent hyperemia are poorly understood. Here, we show that tissue plasminogen activator (tPA), a serine protease implicated in NMDA receptor signaling, is required for the flow increase evoked by somatosensory stimulation. tPA acts by facilitating neuronal nitric oxide release, but this effect does not involve enhancement of NMDA currents or the associated intracellular Ca
2+
rise. Rather, the evidence suggests that tPA controls NMDA-dependent nitric oxide synthesis by influencing the phosphorylation state of neuronal nitric oxide synthase. These findings unveil a previously unrecognized role of tPA in vital homeostatic mechanisms coupling NMDA receptor signaling with nitric oxide synthesis and local cerebral perfusion.
Food limitation leads to behavioral diversification and dietary specialization in sea otters
Authors: Tinker M. Tim , Bentall Gena , Estes James A.
Published: January 2008

Dietary diversity often varies inversely with prey resource abundance. This pattern, although typically measured at the population level, is usually assumed to also characterize the behavior of individual animals within the population. However, the pattern might also be produced by changes in the degree of variation among individuals. Here we report on dietary and associated behavioral changes that occurred with the experimental translocation of sea otters from a food-poor to a food-rich environment. Although the diets of all individuals were broadly similar in the food-rich environment, a behaviorally based dietary polymorphism existed in the food-poor environment. Higher dietary diversity under low resource abundance was largely driven by greater variation among individuals. We further show that the dietary polymorphism in the food-poor environment included a broad suite of correlated behavioral variables and that the individuals that comprised specific behavioral clusters benefited from improved foraging efficiency on their individually preferred prey. Our findings add to the growing list of examples of extreme individuality in behavior and prey choice within populations and suggest that this phenomenon can emerge as a behavioral manifestation of increased population density. Individuality in foraging behavior adds complexity to both the fitness consequences of prey selection and food web dynamics, and it may figure prominently as a diversifying process over evolutionary timescales.
HSP90 regulates cell survival via inositol hexakisphosphate kinase-2
Authors: Chakraborty Anutosh , Koldobskiy Michael A. , Sixt Katherine M. , Juluri Krishna R. , Mustafa Asif K. , Snowman Adele M. , van Rossum Damian B. , Patterson Randen L. , Snyder Solomon H.
Published: January 2008

Heat-shock proteins (HSPs) are abundant, inducible proteins best known for their ability to maintain the conformation of proteins and to refold damaged proteins. Some HSPs, especially HSP90, can be antiapoptotic and the targets of anticancer drugs. Inositol hexakisphosphate kinase-2 (IP6K2), one of a family of enzymes generating the inositol pyrophosphate IP7 [diphosphoinositol pentakisphosphate (5-PP-IP5)], mediates apoptosis. Increased IP6K2 activity sensitizes cancer cells to stressors, whereas its depletion blocks cell death. We now show that HSP90 physiologically binds IP6K2 and inhibits its catalytic activity. Drugs and selective mutations that abolish HSP90–IP6K2 binding elicit activation of IP6K2, leading to cell death. Thus, the prosurvival actions of HSP90 reflect the inhibition of IP6K2, suggesting that selectively blocking this interaction could provide effective and safer modes of chemotherapy.
Copepod growth in detail: pattern similarity to decapod larvae
Authors: Miller Charles B.
Published: January 2008

Miller, C. B. 2008. Copepod growth in detail: pattern similarity to decapod larvae. – ICES Journal of Marine Science, 65: 332–338. It is proposed that copepods grow between one moult and the next in much the same fashion as established by Klaus Anger and others for decapod crustacean larvae. The analogy is justified by commonality of (i) approximately isochronal development patterns, (ii) potential for continuously exponential growth at stage-to-stage resolution, and (iii) demonstrated points of reserve saturation. Thus, as for crab zoeae, the copepod pattern should be very fast initial growth, then slowing as activity shifts to preparation of the new exoskeleton prior to moult. As much as 80% of growth may occur in the first half of the moult cycle, with no growth at all in the last third. Establishing the exact patterns for copepods faces difficulties not presented by decapod larvae, and some solutions to these problems are suggested. Obtaining precise data will help to predict and interpret (model correctly) the effects of food limitation in the field.
Meniscus and viscous forces during separation of hydrophilic and hydrophobic smooth/rough surfaces with symmetric and asymmetric contact angles
Authors: Cai Shaobiao , Bhushan Bharat
Published: January 2008

Adhesive or repulsive forces contributed by both meniscus and viscous forces can be significant and become one of the main reliability issues when the contacting surfaces are ultra smooth, and the normal load is small, as is common for micro/nano devices. In this study, both meniscus and viscous forces during separation for smooth and rough hydrophilic and hydrophobic surfaces are studied. The effects of separation distance, initial meniscus height, separation time, contact angle and roughness are presented. Meniscus force decreases with an increase of separation distance, whereas the viscous force has an opposite trend. Both forces decrease with an increase of initial meniscus height. An increase of separation time, initial meniscus height or a decrease of contact angle leads to an increase of critical meniscus area at which both forces are equivalent. An increase in contact angle leads to a decrease of attractive meniscus force but an increase of repulsive meniscus force (attractive or repulsive dependent on hydrophilic or hydrophobic surface, respectively). Contact angle has a limited effect on the viscous force. For asymmetric contact angles, the magnitude of the meniscus force and the critical meniscus area are in between the values for the two angles. An increase in the number of surface asperities (roughness) leads to an increase of meniscus force; however, its effect on viscous force is trivial. A slightly attractive force is observed for the hydrophobic surface during the end stage of separation though the magnitude is small. The study provides a fundamental understanding of the physics of the separation process and it can be useful for control of the forces in nanotechnology applications.
Beyond linear sequence comparisons: the use of genome-level characters for phylogenetic reconstruction
Authors: Boore Jeffrey L , Fuerstenberg Susan I
Published: January 2008

The first whole genomes to be compared for phylogenetic inference were those of mitochondria, which provided the first sets of genome-level characters for phylogenetic reconstruction. Most powerful among these characters has been the comparisons of the relative arrangements of genes, which has convincingly resolved numerous branch points, including those that had remained recalcitrant even to very large molecular sequence comparisons. Now the world faces a tsunami of complete nuclear genome sequences. In addition to the tremendous amount of DNA sequence that is becoming available for comparison, there is also a potential for many more genome-level characters to be developed, including the relative positions of introns, the domain structures of proteins, gene family membership, the presence of particular biochemical pathways, aspects of DNA replication or transcription, and many others. These characters can be especially convincing owing to their low likelihood of reverting to a primitive condition or occurring independently in separate lineages, thereby reducing the occurrence of homoplasy. The comparisons of organelle genomes pioneered the way for using such features for phylogenetic reconstructions, and it is almost certainly true, as ever more genomic sequence becomes available, that further use of genome-level characters will play a big role in outlining the relationships among major animal groups.
The animal in the genome: comparative genomics and evolution
Authors: Copley Richard R
Published: January 2008

Comparisons between completely sequenced metazoan genomes have generally emphasized how similar their encoded protein content is, even when the comparison is between phyla. Given the manifest differences between phyla and, in particular, intuitive notions that some animals are more complex than others, this creates something of a paradox. Simplistic explanations have included arguments such as increased numbers of genes; greater numbers of protein products produced through alternative splicing; increased numbers of regulatory non-coding RNAs and increased complexity of the
cis
-regulatory code. An obvious value of complete genome sequences lies in their ability to provide us with inventories of such components. I examine progress being made in linking genome content to the pattern of animal evolution, and argue that the gap between genomic and phenotypic complexity can only be understood through the totality of interacting components.
Improvement of molecular phylogenetic inference and the phylogeny of Bilateria
Authors: Lartillot Nicolas , Philippe Hervé
Published: January 2008

Inferring the relationships among Bilateria has been an active and controversial research area since Haeckel. The lack of a sufficient number of phylogenetically reliable characters was the main limitation of traditional phylogenies based on morphology. With the advent of molecular data, this problem has been replaced by another one, statistical inconsistency, which stems from an erroneous interpretation of convergences induced by multiple changes. The analysis of alignments rich in both genes and species, combined with a probabilistic method (maximum likelihood or Bayesian) using sophisticated models of sequence evolution, should alleviate these two major limitations. We applied this approach to a dataset of 94 genes and 79 species using CAT, a previously developed model accounting for site-specific amino acid replacement patterns. The resulting tree is in good agreement with current knowledge: the monophyly of most major groups (e.g. Chordata, Arthropoda, Lophotrochozoa, Ecdysozoa, Protostomia) was recovered with high support. Two results are surprising and are discussed in an evo–devo framework: the sister-group relationship of Platyhelminthes and Annelida to the exclusion of Mollusca, contradicting the Neotrochozoa hypothesis, and, with a lower statistical support, the paraphyly of Deuterostomia. These results, in particular the status of deuterostomes, need further confirmation, both through increased taxonomic sampling, and future improvements of probabilistic models.
Conserved developmental processes and the formation of evolutionary novelties: examples from butterfly wings
Authors: Saenko Suzanne V , French Vernon , Brakefield Paul M , Beldade Patrícia
Published: January 2008

The origin and diversification of evolutionary novelties—lineage-specific traits of new adaptive value—is one of the key issues in evolutionary developmental biology. However, comparative analysis of the genetic and developmental bases of such traits can be difficult when they have no obvious homologue in model organisms. The finding that the evolution of morphological novelties often involves the recruitment of pre-existing genes and/or gene networks offers the potential to overcome this challenge. Knowledge about shared developmental processes obtained from extensive studies in model organisms can then be used to understand the origin and diversification of lineage-specific structures. Here, we illustrate this approach in relation to eyespots on the wings of
Bicyclus anynana
butterflies. A number of spontaneous mutations isolated in the laboratory affect eyespots, lepidopteran-specific features, and also processes that are shared by most insects. We discuss how eyespot mutants with disturbed embryonic development may help elucidate the genetic pathways involved in eyespot formation, and how venation mutants with altered eyespot patterns might shed light on mechanisms of eyespot development.
Molecular genetic insights into deuterostome evolution from the direct-developing hemichordateSaccoglossus kowalevskii
Authors: Lowe Christopher J
Published: January 2008

Progress in developmental biology, phylogenomics and palaeontology over the past five years are all making major contributions to a long-enduring problem in comparative biology: the early origins of the deuterostome phyla. Recent advances in the developmental biology of hemichordates have given a unique insight into developmental similarities between this phylum and chordates. Transcriptional and signalling gene expression patterns between the two groups during the early development of the anteroposterior and dorsoventral axes reveal close similarities, despite large morphological disparity between the body plans. These genetic networks have been proposed to play conserved roles in patterning centralized nervous systems in metazoans, yet seem to play a conserved role in patterning the diffusely organized basiepithelial nerve net of the hemichordates. Developmental genetic data are providing a unique insight into early deuterostome evolution, revealing a complexity of genetic regulation previously attributed only to vertebrates. While these data allow for key insights into the development of early deuterostomes, their utility for reconstructing ancestral morphologies is less certain, and morphological, palaeontological and molecular datasets should all be considered carefully when speculating about ancestral deuterostome features.