bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Structure and Composition of Nanoparticles by Extended X-Ray Absorption Fine-Structure Spectroscopy
Authors: Frenkel Anatoly I. , Yevick Aaron , Cooper Chana , Vasic Relja
Published: March 2011

Many metal clusters in the 1-nm size range are catalytically active, and their enhanced reactivity is often attributed to their size, structure, morphology, and details of alloying. Synchrotron sources provide a wide range of opportunities for studying catalysis. Among them, extended X-ray absorption fine-structure (EXAFS) spectroscopy is the premier method for investigating structure and composition of nanocatalysts. In this review, we summarize common methods of EXAFS analysis for geometric and compositional characterization of nanoparticles. We discuss several aspects of the experiments and analyses that are critical for reliably modeling EXAFS data. The most important are sample homogeneity, the width of the size and compositional distribution functions, and accounting for multiple-scattering contributions to EXAFS. We focus on the contribution of structural disorder and structural/compositional heterogeneity to the accuracy of three-dimensional modeling.
Heparin Characterization: Challenges and Solutions
Authors: Jones Christopher J. , Beni Szabolcs , Limtiaco John F.K. , Langeslay Derek J. , Larive Cynthia K.
Published: March 2011

Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size polydispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.
A Century of Progress in Molecular Mass Spectrometry
Authors: McLafferty Fred W.
Published: March 2011

The first mass spectrum of a molecule was measured by J.J. Thomson in 1910. Mass spectrometry (MS) soon became crucial to the study of isotopes and atomic weights and to the development of atomic weapons for World War II. Its notable applications to molecules began with the quantitative analysis of light hydrocarbons during World War II. When I joined the Dow Chemical Company in 1950, MS was not favored by organic chemists. This situation improved only with an increased understanding of gaseous ion chemistry, which was obtained through the use of extensive reference data. Gas chromatography–MS was developed in 1956, and tandem MS was first used a decade later. In neutralization-reionization MS, an unusual, unstable species is prepared by ion-beam neutralization and characterized by reionization. Electrospray ionization of a protein mixture produces its corresponding ionized molecules. In top-down proteomics, ions from an individual component can be mass separated and subjected to collision-activated and electron-capture dissociation to provide extensive sequence information.
Soft Landing of Complex Molecules on Surfaces
Authors: Johnson Grant E. , Hu Qichi , Laskin Julia
Published: March 2011

Soft and reactive landing of mass-selected ions onto surfaces has become a topic of substantial interest due to its promising potential for the highly controlled preparation of materials. For example, there are possible applications in the production of peptide and protein microarrays for use in high-throughput screening, protein separation and conformational enrichment of peptides, redox protein characterization, thin-film production, and the preparation of catalysts through deposition of clusters and organometallic complexes. Soft landing overcomes many of the limitations associated with conventional thin-film production techniques and offers unprecedented selectivity and specificity of preparation of deposited species. This review discusses the fundamental aspects of soft and reactive landing of mass-selected ions on surfaces that pertain to applications of these techniques in biomaterials, molecular electronics, catalysis, and interfacial chemistry.
Vibrational Spectroscopy of Biomembranes
Authors: Schultz Zachary D. , Levin Ira W.
Published: March 2011

Vibrational spectroscopy, commonly associated with IR absorption and Raman scattering, has provided a powerful approach for investigating interactions between biomolecules that make up cellular membranes. Because the IR and Raman signals arise from the intrinsic properties of these molecules, vibrational spectroscopy probes the delicate interactions that regulate biomembranes with minimal perturbation. Numerous innovative measurements, including nonlinear optical processes and confined bilayer assemblies, have provided new insights into membrane behavior. In this review, we highlight the use of vibrational spectroscopy to study lipid-lipid interactions. We also examine recent work in which vibrational measurements have been used to investigate the incorporation of peptides and proteins into lipid bilayers, and we discuss the interactions of small molecules and drugs with membrane structures. Emerging techniques and measurements on intact cellular membranes provide a prospective on the future of vibrational spectroscopic studies of biomembranes.
Cosmological Parameters from Observations of Galaxy Clusters
Authors: Allen Steven W. , Evrard August E. , Mantz Adam B.
Published: March 2011

Studies of galaxy clusters have proved crucial in helping to establish the standard model of cosmology, with a Universe dominated by dark matter and dark energy. A theoretical basis that describes clusters as massive, multicomponent, quasi-equilibrium systems is growing in its capability to interpret multiwavelength observations of expanding scope and sensitivity. We review current cosmological results, including contributions to fundamental physics, obtained from observations of galaxy clusters. These results are consistent with and complementary to those from other methods. We highlight several areas of opportunity for the next few years, and emphasize the need for accurate modeling of survey selection and sources of systematic error. Capitalizing on these opportunities will require a multiwavelength approach and the application of rigorous statistical frameworks, utilizing the combined strengths of observers, simulators, and theorists.
Dark Matter Searches with Astroparticle Data
Authors: Porter Troy A. , Johnson Robert P. , Graham Peter W.
Published: March 2011

The existence of dark matter (DM) was first noticed by Zwicky in the 1930s, but its nature remains one of the great unsolved problems of physics. A variety of observations indicate that it is nonbaryonic and nonrelativistic. One of the preferred candidates for nonbaryonic DM is a weakly interacting massive particle (WIMP) that in most models is stable. WIMP self-annihilation can produce cosmic rays, gamma rays, and other particles with signatures that may be detectable. Hints of anomalous cosmic-ray spectra found by recent experiments, such as PAMELA, have motivated interesting interpretations in terms of DM annihilation and/or decay. However, these signatures also have standard astrophysical interpretations, so additional evidence is needed in order to make a case for detection of DM annihilation or decay. Searches by the Fermi-LAT for gamma-ray signals from clumps, nearby dwarf spheroidal galaxies, and galaxy clusters have also been performed, along with measurements of the diffuse Galactic and extragalactic gamma-ray emission. In addition, Imaging Air Cherenkov Telescopes like HESS, MAGIC, and VERITAS have reported on searches for gamma-ray emission from dwarf galaxies. In this review, we examine the status of searches for particle DM by these instruments and discuss the interpretations and resulting DM limits.
Physical Properties of Galaxies fromz= 2–4
Authors: Shapley Alice E.
Published: March 2011

The epoch of galaxy assembly from 2⩽z⩽4 marks a critical stage during the evolution of today's galaxy population. During this period, the star-formation activity in the Universe was at its peak level, and the structural patterns observed among galaxies in the local Universe were not yet in place. A variety of novel techniques have been employed over the past decade to assemble multiwavelength observations of galaxies during this important epoch. In this primarily observational review, I present a census of the methods used to find distant galaxies and the empirical constraints on their multiwavelength luminosities and colors. I then discuss what is known about the stellar content and past histories of star formation in high-redshift galaxies; their interstellar contents including dust, gas, and heavy elements; and their structural and dynamical properties. I conclude by considering some of the most pressing and open questions regarding the physics of high-redshift galaxies, which are to be addressed with future facilities.
Protoplanetary Disks and Their Evolution
Authors: Williams Jonathan P. , Cieza Lucas A.
Published: March 2011

Flattened, rotating disks of cool dust and gas extending for tens to hundreds of astronomical units are found around almost all low-mass stars shortly after their birth. These disks generally persist for several million years, during which time some material accretes onto the star, some is lost through outflows and photoevaporation, and some condenses into centimeter- and larger-sized bodies or planetesimals. Through observations mainly at IR through millimeter wavelengths, we can determine how common disks are at different ages; measure basic properties including mass, size, structure, and composition; and follow their varied evolutionary pathways. In this way, we see the first steps toward exoplanet formation and learn about the origins of the Solar System. This review addresses observations of the outer parts, beyond 1 AU, of protoplanetary disks with a focus on recent IR and (sub)millimeter results and an eye to the promise of new facilities in the immediate future.
The Interstellar Medium Surrounding the Sun
Authors: Frisch Priscilla C. , Redfield Seth , Slavin Jonathan D.
Published: March 2011

The Solar System is embedded in a flow of low-density, warm, and partially ionized interstellar material that has been sampled directly by in situ measurements of interstellar neutral gas and dust in the heliosphere. Absorption line data reveal that this interstellar gas is part of a larger cluster of local interstellar clouds, which is spatially and kinematically divided into additional small-scale structures indicating ongoing interactions. An origin for the clouds that is related to star formation in the Scorpius-Centaurus OB association is suggested by the dynamic characteristics of the flow. Variable depletions observed within the local interstellar medium (ISM) suggest an inhomogeneous Galactic environment, with shocks that destroy grains in some regions. Although photoionization models of the circumheliospheric ISM do an excellent job of reproducing the observed properties of the surrounding ISM, the unknown characteristics of the very low-density hot plasma filling the Local Bubble introduces uncertainty about the source of ionization and nature of cloud boundaries. Recent observations of small cold clouds provide new insight into the processes affecting the local ISM. A fuller understanding of the local ISM can provide insights into the past and future Galactic environment of the Sun, and deeper knowledge of the astrospheres of nearby stars.
Galaxy Disks
Authors: van der Kruit P.C. , Freeman K.C.
Published: March 2011

The disks of disk galaxies contain a substantial fraction of their baryonic matter and angular momentum, and much of the evolutionary activity in these galaxies, such as the formation of stars, spiral arms, bars and rings, and the various forms of secular evolution, takes place in their disks. The formation and evolution of galactic disks are therefore particularly important for understanding how galaxies form and evolve and the cause of the variety in which they appear to us. Ongoing large surveys, made possible by new instrumentation at wavelengths from the UV (Galaxy Evolution Explorer), via optical (Hubble Space Telescope and large groundbased telescopes) and IR (Spitzer Space Telescope), to the radio are providing much new information about disk galaxies over a wide range of redshift. Although progress has been made, the dynamics and structure of stellar disks, including their truncations, are still not well understood. We do now have plausible estimates of disk mass-to-light ratios, and estimates of Toomre's Q parameter show that they are just locally stable. Disks are mostly very flat and sometimes very thin, and they have a range in surface brightness from canonical disks with a central surface brightness of about 21.5 B-mag arcsec−2down to very low surface brightnesses. It appears that galaxy disks are not maximal, except possibly in the largest systems. Their Hi layers display warps whenever Hi can be detected beyond the stellar disk, with low-level star formation going on out to large radii. Stellar disks display abundance gradients that flatten at larger radii and sometimes even reverse. The existence of a well-defined baryonic (stellar + Hi) Tully-Fisher relation hints at an approximately uniform baryonic to dark matter ratio. Thick disks are common in disk galaxies, and their existence appears unrelated to the presence of a bulge component; they are old, but their formation is not yet understood. Disk formation was already advanced at redshifts of ∼2, but at that epoch disks were not yet quiescent and in full rotational equilibrium. Downsizing (the gradual reduction with time in the mass of the most actively star-forming galaxies) is now well-established. The formation and history of star formation in S0s are still not fully understood.
Corneal Biomechanics and Biomaterials
Authors: Ruberti Jeffrey W. , Sinha Roy Abhijit , Roberts Cynthia J.
Published: March 2011

The ability to clearly observe one's environment in the visible spectrum provides a tremendous evolutionary advantage in most of the world's habitats. The complex optical processing system that has evolved in higher vertebrate animals gathers, focuses, detects, transduces, and interprets incoming visible light. The cornea resides at the front end of this imaging system, where it provides a clear optical aperture, substantial refractive power, and the structural stability required to protect the fragile intraocular components. Nature has resolved these simultaneous design requirements through an exceedingly clever manipulation of common extracellular-matrix structural materials (e.g., collagen and proteoglycans). In this review, we (a) examine the biophysical and optical roles of the cornea, (b) discuss increasingly popular approaches to altering its natural refractive properties with an emphasis on biomechanics, and (c) investigate the fast-rising science of corneal replacement via synthetic biomaterials. We close by considering relevant open problems that would benefit from the increased attention of bioengineers.
Microfluidic Reactors for Diagnostics Applications
Authors: McCalla Stephanie E. , Tripathi Anubhav
Published: March 2011

Diagnostic assays are an important part of health care, both in the clinic and in research laboratories. In addition to improving treatments and clinical outcomes, rapid and reliable diagnostics help track disease epidemiology, curb infectious outbreaks, and further the understanding of chronic illness. Disease markers such as antigens, RNA, and DNA are present at low concentrations in biological samples, such that the majority of diagnostic assays rely on an amplification reaction before detection is possible. Ideally, these amplification reactions would be sensitive, specific, inexpensive, rapid, integrated, and automated. Microfluidic technology currently in development offers many advantages over conventional benchtop reactions that help achieve these goals. The small reaction volumes and energy consumption make reactions cheaper and more efficient in a microfluidic reactor. Additionally, the channel architecture could be designed to perform multiple tests or experimental steps on one integrated, automated platform. This review explores the current research on microfluidic reactors designed to aid diagnostic applications, covering a broad spectrum of amplification techniques and designs.
The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies
Authors: Esch M.B. , King T.L. , Shuler M.L.
Published: March 2011

High-quality, in vitro screening tools are essential in identifying promising compounds during drug development. Tests with currently used cell-based assays provide an indication of a compound's potential therapeutic benefits to the target tissue, but not to the whole body. Data obtained with animal models often cannot be extrapolated to humans. Multicompartment microfluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models, may contribute to improving the drug development process. These scaled-down devices, termed micro cell culture analogs (μCCAs) or body-on-a-chip devices, can simulate multitissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response. The devices also provide a means for relatively high-throughput screening of drug combinations and, when utilized with a patient's tissue sample, an opportunity for individualized medicine. Here we review efforts made toward the development of microfabricated cell culture systems and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multiorgan metabolic interactions. In addition to their use in drug development, the devices also can be used to estimate the toxicity of chemicals as occupational hazards and environmental contaminants.
Artificial Noses
Authors: Stitzel Shannon E. , Aernecke Matthew J. , Walt David R.
Published: March 2011

The mammalian olfactory system is able to detect many more odorants than the number of receptors it has by utilizing cross-reactive odorant receptors that generate unique response patterns for each odorant. Mimicking the mammalian system, artificial noses combine cross-reactive sensor arrays with pattern recognition algorithms to create robust odor-discrimination systems. The first artificial nose reported in 1982 utilized a tin-oxide sensor array. Since then, however, a wide range of sensor technologies have been developed and commercialized. This review highlights the most commonly employed sensor types in artificial noses: electrical, gravimetric, and optical sensors. The applications of nose systems are also reviewed, covering areas such as food and beverage quality control, chemical warfare agent detection, and medical diagnostics. A brief discussion of future trends for the technology is also provided.
Mapping Fetal Brain Development In Utero Using Magnetic Resonance Imaging: The Big Bang of Brain Mapping
Authors: Studholme Colin
Published: March 2011

The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.
MRI-Guided Nanorobotic Systems for Therapeutic and Diagnostic Applications
Authors: Vartholomeos Panagiotis , Fruchard Matthieu , Ferreira Antoine , Mavroidis Constantinos
Published: March 2011

This review presents the state of the art of magnetic resonance imaging (MRI)-guided nanorobotic systems that can perform diagnostic, curative, and reconstructive treatments in the human body at the cellular and subcellular levels in a controllable manner. The concept of an MRI-guided nanorobotic system is based on the use of an MRI scanner to induce the required external driving forces to propel magnetic nanocapsules to a specific target. It is an active targeting mechanism that provides simultaneous propulsion and imaging capabilities, which allow the implementation of real-time feedback control of the targeting process. The architecture of the system comprises four main modules: (a) the nanocapsules, (b) the MRI propulsion module, (c) the MRI tracking module (for image processing), and (d) the controller module. A key concept is the nanocapsule technology, which is based on carriers such as liposomes, polymer micelles, gold nanoparticles, quantum dots, metallic nanoshells, and carbon nanotubes. Descriptions of the significant challenges faced by the MRI-guided nanorobotic system are presented, and promising solutions proposed by the involved research community are discussed. Emphasis is placed on reviewing the limitations imposed by the scaling effects that dominate within the blood vessels and also on reviewing the control algorithms and computational tools that have been developed for real-time propulsion and tracking of the nanocapsules.
Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds
Authors: Badylak Stephen F. , Taylor Doris , Uygun Korkut
Published: March 2011

The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. Critical challenges and future directions are also discussed.
Vision-Based Navigation in Image-Guided Interventions
Authors: Mirota Daniel J. , Ishii Masaru , Hager Gregory D.
Published: March 2011

The trend toward minimally invasive surgical interventions has created new challenges for visualization during surgical procedures. However, at the same time, the introduction of high-definition digital endoscopy offers the opportunity to apply methods from computer vision to provide visualization enhancements such as anatomic reconstruction, surface registration, motion tracking, and augmented reality. This review provides a perspective on this rapidly evolving field. It first introduces the clinical and technical background necessary for developing vision-based algorithms for interventional applications. It then discusses several examples of clinical interventions where computer vision can be applied, including bronchoscopy, rhinoscopy, transnasal skull-base neurosurgery, upper airway interventions, laparoscopy, robotic-assisted surgery, and Natural Orifice Transluminal Endoscopic Surgery (NOTES). It concludes that the currently reported work is only the beginning. As the demand for minimally invasive procedures rises, computer vision in surgery will continue to advance through close interdisciplinary work between interventionists and engineers.
Biophysical Dynamics in Disorderly Environments
Authors: Nelson David R.
Published: March 2011

Three areas where time-independent disorder plays a key role in biological dynamics far from equilibrium are reviewed. We first discuss the anomalous localization dynamics that arises when a single species spreads in space and time via diffusion and fluid advection in the presence of frozen heterogeneities in the growth rate. Next we treat the unzipping of double-stranded DNA as a function of force and temperature, a challenge that must be surmounted every time a cell divides. Heterogeneity in the DNA sequence dominates the physics of single-molecule force-extension curves for a broad range of forces upon approaching a sharp unzipping transition. The dynamics of the unzipping fork exhibits anomalous drift and diffusion in a similar range above this transition, with energy barriers that scale as the square root of the genome size. Finally, we describe how activated peptidoglycan strand extension sites, called dislocations in materials science, can mediate the growth of bacterial cell walls. Enzymatically driven circumferential motions of a few dozen of these defects are sufficient to describe the exponential elongation rates observed in experiments on Escherichia coli in a nutrient-rich environment. However, long-range elastic forces transmitted by the peptidoglycan meshwork cause the moving dislocations to interact not only with each other, but also with a disorderly array of frozen, inactivated strand ends.
High-Pressure Protein Crystallography and NMR to Explore Protein Conformations
Authors: Collins Marcus D. , Kim Chae Un , Gruner Sol M.
Published: March 2011

High-pressure methods for solving protein structures by X-ray crystallography and NMR are maturing. These techniques are beginning to impact our understanding of thermodynamic and structural features that define not only the protein's native conformation, but also the higher free energy conformations. The ability of high-pressure methods to visualize these mostly unexplored conformations provides new insight into protein function and dynamics. In this review, we begin with a historical discussion of high-pressure structural studies, with an eye toward early results that paved the way to mapping the multiple conformations of proteins. This is followed by an examination of several recent studies that emphasize different strengths and uses of high-pressure structural studies, ranging from basic thermodynamics to the suggestion of high-pressure structural methods as a tool for protein engineering.
The Cyanobacterial Circadian System: From Biophysics to Bioevolution
Authors: Johnson Carl Hirschie , Stewart Phoebe L. , Egli Martin
Published: March 2011

Recent studies have unveiled the molecular machinery responsible for the biological clock in cyanobacteria and found that it exerts pervasive control over cellular processes including global gene expression. Indeed, the entire chromosome undergoes daily cycles of topology/compaction! The circadian system comprises both a posttranslational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO can be reconstituted in vitro with three purified proteins (KaiA, KaiB, and KaiC) and ATP. These are the only circadian proteins for which high-resolution structures are available. Phase in this nanoclockwork has been associated with key phosphorylations of KaiC. Structural considerations illuminate the mechanism by which the KaiABC oscillator ratchets unidirectionally. Models of the complete in vivo system have important implications for our understanding of circadian clocks in higher organisms, including mammals. The conjunction of structural, biophysical, and biochemical approaches to this system has brought our understanding of the molecular mechanisms of biological timekeeping to an unprecedented level.
Protein Folding at the Exit Tunnel
Authors: Fedyukina Daria V. , Cavagnero Silvia
Published: March 2011

Over five decades of research have yielded a large body of information on how purified proteins attain their native state when refolded in the test tube, starting from a chemically or thermally denatured state. Nevertheless, we still know little about how proteins fold and unfold in their natural biological habitat: the living cell. Indeed, a variety of cellular components, including molecular chaperones, the ribosome, and crowding of the intracellular medium, modulate folding mechanisms in physiologically relevant environments. This review focuses on the current state of knowledge in protein folding in the cell with emphasis on the early stage of a protein's life, as the nascent polypeptide traverses and emerges from the ribosomal tunnel. Given the vectorial nature of ribosome-assisted translation, the transient degree of chain elongation becomes a relevant variable expected to affect nascent protein foldability, aggregation propensity and extent of interaction with chaperones and the ribosome.
Molecular Origin of the Hierarchical Elasticity of Titin: Simulation, Experiment, and Theory
Authors: Hsin Jen , Strümpfer Johan , Lee Eric H. , Schulten Klaus
Published: March 2011

This review uses the giant muscle protein titin as an example to showcase the capability of molecular dynamics simulations. Titin is responsible for the passive elasticity in muscle and is a chain composed of immunoglobulin (Ig)-like and fibronectin III (FN-III)-like domains, as well as PEVK segments rich in proline (P), glutamate (E), valine (V), and lysine (K). The elasticity of titin is derived in stages of extension under increasing external force: Ig domain straightening occurs first (termed tertiary structure elasticity), followed by the extension of the disordered PEVK segments. At larger extension and force, Ig domains unfold one by one (termed secondary structure elasticity). With the availability of crystal structures of single and connected Ig domains, the tertiary and secondary structure elasticity of titin was investigated through molecular dynamics simulations, unveiling the molecular origin of titin's elasticity.
Quantum Mechanical Modeling of Catalytic Processes
Authors: Bell Alexis T. , Head-Gordon Martin
Published: March 2011

Advances in quantum chemical methods in combination with exponential growth in the computational speed of computers have enabled researchers in the field of catalysis to apply electronic structure calculations to a wide variety of increasingly complex problems. Such calculations provide insights into why and how changes in the composition and structure of catalytically active sites affect their activity and selectivity for targeted reactions. The aim of this review is to survey the recent advances in the methods used to make quantum chemical calculations and to define transition states as well as to illustrate the application of these methods to a selected series of examples taken from the authors' recent work.
Microsystem Technologies for Medical Applications
Authors: Cima Michael J.
Published: March 2011

Medical technologies are evolving at a very rapid pace. Portable communication devices and other handheld electronics are influencing our expectations of future medical tools. The advanced medical technologies of our future will not necessarily be large expensive systems. They are just as likely to be small and disposable. This paper reviews how microsystems are already impacting health care as commercial products or in clinical development. Example systems for point-of-care testing (POCT), patient monitoring tools, systemic drug delivery, local drug delivery, and surgical tools are described. These technologies are moving care from hospitals to outpatient settings, physicians' offices, community health centers, nursing homes, and the patients' homes. Microsystems that are rapidly adopted fulfill significant medical needs and are compatible with existing clinical practice.
Coal and Biomass to Fuels and Power
Authors: Williams Robert H. , Liu Guangjian , Kreutz Thomas G. , Larson Eric D.
Published: March 2011

Systems with CO2 capture and storage (CCS) that coproduce transportation fuels and electricity from coal plus biomass can address simultaneously challenges of climate change from fossil energy and dependence on imported oil. Under a strong carbon policy, such systems can provide competitively clean low-carbon energy from secure domestic feedstocks by exploiting the negative emissions benefit of underground storage of biomass-derived CO2, the low cost of coal, the scale economies of coal energy conversion, the inherently low cost of CO2 capture, the thermodynamic advantages of coproduction, and expected high oil prices. Such systems require much less biomass to make low-carbon fuels than do biofuels processes. The economics are especially attractive when these coproduction systems are deployed as alternatives to CCS for stand-alone fossil fuel power plants. If CCS proves to be viable as a major carbon mitigation option, the main obstacles to deployment of coproduction systems as power generators would be institutional.
Engineering Antibodies for Cancer Therapy
Authors: Boder Eric T. , Jiang Wei
Published: March 2011

The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.
Microfluidic Chemical Analysis Systems
Authors: Livak-Dahl Eric , Sinn Irene , Burns Mark
Published: March 2011

The field of microfluidics has exploded in the past decade, particularly in the area of chemical and biochemical analysis systems. Borrowing technology from the solid-state electronics industry and the production of microprocessor chips, researchers working with glass, silicon, and polymer substrates have fabricated macroscale laboratory components in miniaturized formats. These devices pump nanoliter volumes of liquid through micrometer-scale channels and perform complex chemical reactions and separations. The detection of reaction products is typically done fluorescently with off-chip optical components, and the analysis time from start to finish can be significantly shorter than that of conventional techniques. In this review we describe these microfluidic analysis systems, from the original continuous flow systems relying on electroosmotic pumping for liquid motion to the large diversity of microarray chips currently in use to the newer droplet-based devices and segmented flow systems. Although not currently widespread, microfluidic systems have the potential to become ubiquitous.
Crystal Polymorphism in Chemical Process Development
Authors: Lee Alfred Y. , Erdemir Deniz , Myerson Allan S.
Published: March 2011

Polymorphism in molecular crystals is a prevalent phenomenon and is of great interest to the pharmaceutical community. The solid-state form is a key quality attribute of a crystalline product. Inconsistencies in the solid phase produced during the manufacturing and storage of drug substances and drug products may have severe consequences. It is essential to understand the solid-state behavior of the drug and to judiciously select the optimal solid form for development. This review highlights the pervasiveness and relevance of polymorphism and describes solid form screening and selection processes. Moreover, case studies on controlling polymorphs from a chemical development perspective are provided.
My Contribution to Broadening the Base of Chemical Engineering
Authors: Sargent Roger W.H.
Published: March 2011

This paper is a short account, from a personal viewpoint, of the various contributions I have made to expand the academic basis of chemical engineering from its origin in the unifying concept of unit operations, focussed on process design, to encompassing all the professional activities of industrial chemical engineers. This includes all aspects of planning and scheduling the operations as well as designing and controlling the process plant. The span of my career also happens to include the birth of the age of computing, with all the consequential implications.
Risk Taking and Effective R&D Management
Authors: Banholzer William F. , Vosejpka Laura J.
Published: March 2011

Several key strategies can be used to manage the risk associated with innovation to create maximum value. These include balancing the timing of investments versus cash flows, management of fads, prioritization across the company, savvy portfolio management, and a system of metrics that measure real success. Successful R&D managers will do whatever is necessary to manage the risks associated with an R&D program and stick to their long-term strategy.
Surface Reactions in Microelectronics Process Technology
Authors: Levitin Galit , Hess Dennis W.
Published: March 2011

Current integrated circuit (IC) manufacturing consists of more than 800 process steps, nearly all of which involve reactions at surfaces that significantly impact device yield and performance. From initial surface preparation through film deposition, patterning, etching, residue removal, and metallization, an understanding of surface reactions and interactions is critical to the successful continuous scaling, yield, and reliability of electronic devices. In this review, some of the most important surface reactions that drive the development of microelectronic device fabrication are described. The reactions discussed do not constitute comprehensive coverage of this topic in IC manufacture but have been selected to demonstrate the importance of surface/interface reactions and interactions in the development of new materials, processing sequences, and process integration challenges. Specifically, the review focuses on surface reactions related to surface cleaning/preparation, semiconductor film growth, dielectric film growth, metallization, and etching (dry and wet).
CO2 Capture from Dilute Gases as a Component of Modern Global Carbon Management
Authors: Jones Christopher W.
Published: March 2011

The growing atmospheric CO2 concentration and its impact on climate have motivated widespread research and development aimed at slowing or stemming anthropogenic carbon emissions. Technologies for carbon capture and sequestration (CCS) employing mass separating agents that extract and purify CO2 from flue gas emanating from large point sources such as fossil fuel–fired electricity-generating power plants are under development. Recent advances in solvents, adsorbents, and membranes for postcombust- ion CO2 capture are described here. Specifically, room-temperature ionic liquids, supported amine materials, mixed matrix and facilitated transport membranes, and metal-organic framework materials are highlighted. In addition, the concept of extracting CO2 directly from ambient air (air capture) as a means of reducing the global atmospheric CO2 concentration is reviewed. For both conventional CCS from large point sources and air capture, critical research needs are identified and discussed.
Delivery of Molecular and Nanoscale Medicine to Tumors: Transport Barriers and Strategies
Authors: Chauhan Vikash P. , Stylianopoulos Triantafyllos , Boucher Yves , Jain Rakesh K.
Published: March 2011

Tumors are similar to organs, with unique physiology giving rise to an unusual set of transport barriers to drug delivery. Cancer therapy is limited by nonuniform drug delivery via blood vessels, inhomogeneous drug transport into tumor interstitium from the vascular compartment, and hindered transport through tumor interstitium to the target cells. Four major abnormal physical and physiological properties contribute to these transport barriers. Accumulated solid stress compresses blood vessels to diminish the drug supply to many tumor regions. Immature vasculature with high viscous and geometric resistances and reduced pressure gradients leads to sluggish and heterogeneous blood flow in tumors to further limit drug supply. Nonfunctional lymphatics coupled with highly permeable blood vessels result in elevated hydrostatic pressure in tumors to abrogate convective drug transport from blood vessels into and throughout most of the tumor tissue. Finally, a dense structure of interstitial matrix and cells serves as a tortuous, viscous, and steric barrier to diffusion of therapeutic agents. In this review, we discuss the origins and implications of these barriers. We then highlight strategies for overcoming these barriers by modulating either drug properties or the tumor microenvironment itself to enhance the delivery and effectiveness of drugs in tumors.
Outcome Measures for Practice
Authors: Whipple Jason L. , Lambert Michael J.
Published: March 2011

The current review targets efforts to use outcome measures in routine care for the purpose of enhancing psychotherapy outcome, particularly for patients who are predicted to have a negative treatment outcome. The place of outcome measures in solving the negative effects problem is emphasized, with a narrow focus on one set of measures that is relatively well advanced in its clinical utility. This clinical innovation relies on research-based clinical decision tools that provide psychotherapists with timely warnings and problem-solving strategies when a patient deviates from an expected treatment response. Summary of a meta-analytic review using this patient feedback methodology suggests that measuring, monitoring, predicting treatment failure, and providing clinical support tools to clinicians enhance treatment outcome for patients who have an early negative treatment response. Other measures are then briefly reviewed before we turn to future directions. Clinicians are encouraged to employ these methods in routine practice.
Studying Two-Dimensional Systems with the Density Matrix Renormalization Group
Authors: Stoudenmire E.M. , White Steven R.
Published: March 2011

The density matrix renormalization group (DMRG) is one of the most powerful numerical methods for studying two-dimensional quantum lattice systems, despite a perception that it is only suitable for one dimension. Reviewing past applications of DMRG in 2D demonstrates its success in treating a wide variety of problems, although it remains underutilized in this context. We present techniques for performing cutting-edge 2D DMRG studies including methods for ensuring convergence, extrapolating finite-size data, and extracting gaps and excited states. Finally, we consider a selection of recently developed 2D tensor network methods and compare the performance of one of these to 2D DMRG.
Quantum Computation by Local Measurement
Authors: Raussendorf Robert , Wei Tzu-Chieh
Published: March 2011

Quantum computation is a novel way of information processing that allows, for certain classes of problems, exponential speedups over classical computation. Various models of quantum computation exist, such as the adiabatic, circuit, and measurement-based models. They have been proven equivalent in their computational power, but operate very differently. As such, they may be suitable for realization in different physical systems, and also offer different perspectives on open questions such as the precise origin of the quantum speedup. Here, we give an introduction to the one-way quantum computer, a scheme of measurement-based quantum computation (MBQC). In this model, the computation is driven by local measurements on a carefully chosen, highly entangled state. We discuss various aspects of this computational scheme, such as the role of entanglement and quantum correlations. We also give examples for ground states of simple Hamiltonians that enable universal quantum computation by local measurements.
Pairing Mechanism in Fe-Based Superconductors
Authors: Chubukov Andrey
Published: March 2011

I review recent works on the symmetry and the structure of the superconducting gap in Fe-based superconductors (FeSCs) and on the underlying pairing mechanism in these systems. The experimental data on superconductivity show very rich behavior, with potentially different symmetry of a superconducting state for different compositions of the same material. The variety of different pairing states raises the issue of whether the physics of FeSCs is model dependent or is universal, governed by a single underlying pairing mechanism. I argue that the physics is universal and that all pairing states obtained so far can be understood within the same universal pairing scenario and are well described by the effective low-energy model with small numbers of input parameters.
Phase Change Materials: Challenges on the Path to a Universal Storage Device
Authors: Siegrist T. , Merkelbach P. , Wuttig M.
Published: March 2011

Phase change materials, in which a material is reversibly switched between an amorphous and crystalline state with corresponding contrast in optical and electronic transport properties, are excellent nonvolatile storage media. Rewritable digital versatile disks (DVDs) and Blu-ray discs are based on such materials in which the optical contrast between the amorphous and crystalline phases enables data storage. Additionally, the large change in electronic transport properties with resistivity contrast of up to six orders of magnitude on crystallization and fast switching speed is at the heart of a new class of nonvolatile data storage devices with electronic read/write operation and potential for future miniaturization. The amorphous state is characterized by saturated covalent bonds, whereas the crystalline phase forms resonant bonds. This bonding mechanism can account for the high electronic polarizabilities that characterize crystalline phase change materials. Interestingly, the relevant electronic states also govern the charge transport in the crystalline phase, leading to unique transport properties including a high degree of electronic localization, in those phase change materials, which are characterized by a high degree of disorder.
Planetary Atmospheres as Nonequilibrium Condensed Matter
Authors: Marston J.B.
Published: March 2011

Planetary atmospheres, and models of them, are discussed from the viewpoint of condensed matter physics. Atmospheres are a form of condensed matter, and many of the most interesting concepts of condensed matter systems are realized by them. The essential physics of the general circulation is illustrated with idealized two-layer and one-layer models of the atmosphere. Equilibrium and nonequilibrium statistical mechanics are used to directly ascertain the statistics of these models.