cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular basis for substrate-dependent transmembrane signaling in an outer-membrane transporter.

The uptake of rare nutrients by Gram negative bacteria is facilitated by a series of high-affinity outer-membrane transporters that derive energy for transport by coupling to the inner-membrane protein TonB.1 The N-terminal end of these TonB-dependent transporters contains a highly conserved energy-coupling segment termed the Ton box, which is localized at the periplasmic side of the transporter. In BtuB, substrate binding on the extracellular surface of the protein unfolds the Ton box,2 producing a disordered protein segment that includes the first 15 residues on the N-terminus.3 This order-disorder transition results in the extension of the Ton box 20 to 30 Angstroms into the periplasmic space (Fig. 1a) where it may function as a recognition signal to promote binding of the transporter to TonB.4 Figure 1 Molecular models of BtuB. (a) Upon the binding of substrate (vitamin B12) the energy coupling segment, or Ton box, of BtuB undergoes an unfolding so that it projects into the periplasm. The model shown for BtuB is based upon x-ray crystallography, except ... At the present time, the molecular interactions leading to this transmembrane signaling event are not understood; however, inspection of the high-resolution models of BtuB,5; 6 suggests that an ion pair within the protein interior might be involved in this structural change. The positively charged side chain of Arg 14 on the C-terminal side of the Ton box is in close proximity to the side chain of Asp 316 on the inner surface of the BtuB barrel (see Fig. 1b). This suggests that these side-chains interact electrostatically, and that a favorable interaction between these residues might prevent the Ton box from unfolding. Addition of substrate increases the distance between this charge pair from 4.3 to 7.5 Angstroms, which may weaken and subsequently break the interaction. A loss of this interaction might then lead to the unfolding event seen in Fig. 1a. This conformational transition is seen by EPR spectroscopy and by chemical derivatization, but is not revealed by crystallography due to the solute conditions used to produce protein crystals.7
Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery

The design, synthesis, and application of novel biodegradable and biocompatible pentablock (PB) copolymers, i.e., polyglycolic acid-polycaprolactone-polyethylene glycol-polycaprolactone-polyglycolic acid (PGA-PCL-PEG-PCL-PGA) and polylactic acid-polycaprolactone-polyethylene glycol-polycaprolactone-polylactic acid (PLA-PCL-PEG-PCL-PLA) for sustained protein delivery, are reported. The PB copolymers can be engineered to generate sustained delivery of protein therapeutics to the posterior segment of the eye. PB copolymers with different block arrangements and molecular weights were synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography (GPC), and X-ray diffraction (XRD) spectroscopy. Immunoglobulin G (IgG) was selected as a model protein due to its structural similarity to bevacizumab. The influence of polymer molecular weight, composition, and isomerism on formulation parameters such as entrapment efficiency, drug loading, and in vitro release profile was delineated. Crystallinity and molecular weight of copolymers exhibited a substantial effect on formulation parameters. A secondary structure of released IgG was confirmed by circular dichroism (CD) spectroscopy. In vitro cytotoxicity, cell viability, and biocompatibility studies performed on human retinal pigment epithelial cells (ARPE-19) and/or macrophage cell line (RAW 264.7) demonstrated PB copolymers to be excellent biomaterials. Novel PB polymers may be the answer to the unmet need of a sustained release protein formulation.
Nitric Oxide Donors Increase Blood Flow and Reduce Brain Damage in Focal Ischemia: Evidence That Nitric Oxide is Beneficial in the Early Stages of Cerebral Ischemia

We studied whether administration of nitric oxide (NO) donors reduces the ischemic damage resulting from middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats (SHRs). In halothane-anesthetized and ventilated SHRs, the MCA was occluded. CBF was monitored using a laser-Doppler flowmeter. Three to five minutes after MCA occlusion, the NO donors sodium nitroprusside (SNP; 3 mg/kg/h) or 3-morpholino-sydnonimine (SIN 1; 1.5–6 mg/kg/h) were administered into the carotid artery for 60 min. As a control, the effect of papaverine (3.6 mg/kg/h), a vasodilator that acts independently of NO, was also studied. The hypotension evoked by these agents was counteracted by intravenous infusion of phenylephrine. At the end of the infusion, rats were allowed to recover. Stroke size was determined 24 h later in thionin-stained sections. In sham occluded rats, SNP (n = 5), SIN 1 (n = 5), and papaverine (n = 5) produced comparable increases in CBF (p > 0.05 from vehicle). After MCA occlusion, SNP (n = 5) and ...
Proton collisions with the water dimer at keV energies

Proton collisions with the water dimer are studied using a nonadiabatic, direct, time-dependent approach called electron nuclear dynamics (END). Fragmentation of the water dimer in collisions with protons at energies of 5.0, 1.0 keV and 200 eV is the primary aim of this initial study of water clusters using END. We report on the initial fragmentation dynamic, that is, for times less than 200 fs. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
Polyelectrolyte theory and chromatin-DNA quaternary structure: Role of ionic strength and Hl histone☆

Abstract Under the assumptions outlined in this paper and those of Manning's theory of polyelectrolyte screening the electrostatic interaction of histone 1 and DNA is examined and shown to lead to spontaneous bending of DNA. Critical variables for this bending are the ionic strength, the length of DNA interacting with each histone 1 molecule, and the fraction of DNA phosphate charges neutralized by the histone 1 molecule. This interaction is postulated as accounting for the observed folding of polynucleosomes into the “solenoid” regular structure. Wherever possible comparison is made between theoretical predictions and available experimental results. Finally, biological implications are briefly discussed.
A study on a boundary-layer equation arising in an incompressible fluid

In this paper, a differential equation of mixing layer that arises in viscous incompressible fluid will be investigated. The series solution method will be effectively implemented to a related integro-differential equation. The condition at infinity will be applied to a related Pade approximants of the obtained series solution.
Cubic to Tetragonal Martensitic Transformation in Lead Titanate (PbTiO3) Single Crystals

The cubic to tetragonal (C/T) phase transformation in PbTiO 3 single crystals has been studied in both the forward and reverse modes and found to show martensitic characteristics. Microstructural features were investigated by heating stage optical microscopy, and room temperature transmission electron microscopy. During transformation, a small hysteresis is involved. The phase front passes swiftly through the crystal and surface relief accompanying the transformation is seen
Modeling of neutral particle distributions at the L to H transition in DIII-D

Abstract In order to study possible effects of neutrals on the power threshold for transition from L-mode to H-mode confinement in DIII-D, the problem of reconstructing neutral particle distributions inside the separatrix from available edge, scrape-off layer, and divertor plasma diagnostic data is addressed. Neutral particle profiles in the shear layer are reconstructed primarily with the DEGAS code using plasma parameters obtained by fitting discharge data with the B2.5 code. A series of discharges in which the ion grad B drift direction is toward the X-point is analyzed. For reversed Bt, the L to H transition power threshold is 2–4 times higher than normal Bt discharges at the same density: one discharge of this type is analyzed. The variation of the L–H transition power threshold divided by the density is seen to be correlated with the neutral density scale length in the shear layer for both directions of the magnetic field. Radial and poloidal neutral particle profile results for three low density discharges in which the L–H transition power threshold varies from 1.3 to 5.3 MW are presented.
Anatomy of an anachronistic carbonate platform: Lower Triassic carbonates of the southwestern United States

Examination of Lower Triassic carbonate rocks from around the world has revealed the resurgence of atypical carbonates that were last common during the Proterozoic (‘anachronistic facies’). Anachronistic facies are attributed to a combination of post-extinction paleoecologic factors and widespread, harsh environmental conditions, particularly the presence of anoxic, alkaline waters in the global ocean. The marine rocks of the Moenkopi Formation (Virgin Limestone) of southern Nevada and laterally equivalent deep-water limestones of the Union Wash Formation of east-central California provide a means to reconstruct depositional environments across a Lower Triassic carbonate ramp and place the atypical facies and fabrics that occur within those rocks into a larger ‘Anachronistic Platform Model.’ Examination of shallow subtidal and intertidal facies reveal widespread ooid shoals in both the Union Wash Formation and Virgin Limestone, as well as the presence of small, fringing stromatolite bioherms in shallow su...
Orchestrating sulfur incorporation into RNA

The modified tRNA base 2-thiouridine is required for many steps in translation. Surprisingly, the biosynthesis of this simple derivative requires a minimum of four sulfur transfer reactions involving seven proteins.
The Lipoprotein Composition of Dog Lymph

Deposition of lipids during development of atherosclerosis may come from extracellular fluid rather than directly from plasma. The lipoprotein composition of lymph thus assumes importance in the genesis of atherosclerosis. The predominant component found in thoracic duct lymph was the -S1.21 4 and 7, with lesser amounts of the 23. It was similar qualitatively but not quantitatively to dog's serum. The bulk of lymph lipoproteins derive from blood plasma. After fat feeding the absorbed lipid is delivered by the lymph to the blood in large aggregates containing large quantities of -S > 70 component. The > 70 component seemed to reflect changes in lipid transport in dogs more actively than the relatively more stable -S, 4, 7 and 23 components.
Childhood and adolescent anorexia nervosa.

Anorexia nervosa (AN) is a serious condition that usually begins in adolescence or childhood and is associated with the highest mortality rate of any psychiatric disorder [50]; untreated, 18% to 20% of patients with AN die within 20 years. The long-term morbidity for patients with AN is significant and includes growth retardation, pubertal delay or interruption, early-onset osteoporosis, and abnormalities in brain structure. The estimated lifetime prevalence of AN ranges from approximately 0.5% to 3.7% [15]. The current diagnostic criteria are difficult to apply to children, and many adolescents have atypical presentations; thus, the actual prevalence of AN, including atypical forms, may be higher. Much of the research related to epidemiology, treatment, outcome, and prevention has been conducted with adolescents with AN. Much less is known about children with AN or related disorders. Current work regarding the cause of AN is exciting. Genetic studies suggest that more than half the risk is related to genetic factors. There is also a possibility that some cases of AN may have an infectious origin related to Group A betahemolytic streptococci. Evidence-based treatments also are available for adolescent anorexic patients. For example, a specific family therapy has been found to be useful for many adolescents, and certain types of inpatient treatments that result in ideal body weight are associated with a favorable outcome.
Developmental testing of abstract data types

Abstract data types (ADTs) represent the fundamental building blocks of object-oriented software development. Consequently, a number of different testing techniques for ADT modules have been proposed in the literature. Most of these techniques at least tacitly assume that the ADT module under test has been completely implemented. In this paper, we present a class of testing techniques that are easily applicable to partially completed ADT modules, thus supporting an incremental approach to ADT module development. We then present a testing tool that automatically generates test cases for partially completed ADTs with very little overhead. As such, our testing techniques may be repeatedly applied, with relatively little expense, to generate new test cases as the ADT module increases in size. >
Strong converse rates for classical communication over thermal and additive noise bosonic channels

We prove that several known upper bounds on the classical capacity of thermal and additive noise bosonic channels are actually strong converse rates. Our results strengthen the interpretation of these upper bounds, in the sense that we now know that the probability of correctly decoding a classical message rapidly converges to 0 in the limit of many channel uses if the communication rate exceeds these upper bounds. In order for these theorems to hold, we need to impose a maximum photon number constraint on the states input to the channel (the strong converse property need not hold if there is only a mean photon number constraint). Our first theorem demonstrates that Koenig and Smith's upper bound on the classical capacity of the thermal bosonic channel is a strong converse rate, and we prove this result by utilizing the structural decomposition of a thermal channel into a pure-loss channel followed by an amplifier channel. Our second theorem demonstrates that Giovannetti et al.'s upper bound on the classical capacity of a thermal bosonic channel corresponds to a strong converse rate, and we prove this result by relating the success probability to the rate, the effective dimension of the output space, and the purity of the channel as measured by the R\'enyi collision entropy. Finally, we use similar techniques to prove that similar previously known upper bounds on the classical capacity of an additive noise bosonic channel correspond to strong converse rates.
Putting together the psoriasis puzzle: an update on developing targeted therapies

Psoriasis vulgaris is a chronic, debilitating skin disease that affects millions of people worldwide. There is no mouse model that accurately reproduces all facets of the disease, but the accessibility of skin tissue from patients has facilitated the elucidation of many pathways involved in the pathogenesis of psoriasis and highlighted the importance of the immune system in the disease. The pathophysiological relevance of these findings has been supported by genetic studies that identified polymorphisms in genes associated with NFκB activation, IL-23 signaling and T helper 17 (Th17)-cell adaptive immune responses, and in genes associated with the epidermal barrier. Recently developed biologic agents that selectively target specific components of the immune system are highly effective for treating psoriasis. In particular, emerging therapeutics are focused on targeting the IL-23–Th17-cell axis, and several agents that block IL-17 signaling have shown promising results in early-phase clinical trials. This review discusses lessons learned about the pathogenesis of psoriasis from mouse-and patient-based studies, emphasizing how the outcomes of clinical trials with T-cell-targeted and cytokine-blocking therapies have clarified our understanding of the disease.
Middleware design issues for application management in heterogeneous networks

With the increase of the heterogeneity of the Internet and the complexity of distributed computing, application management is facing more and more sophisticated requirements. In a dynamic, synergistic, and geographically broad environment, cross-domain resource management is becoming an important factor for application quality of service. We present a middleware architecture and initial implementation of that middleware that satisfies applications according to expected requirements, application service level agreement and distributed networked resources in and beyond the local environment. The networked resources are grouped in a hierarchical manner and their usage is optimized through the resource management system. This framework presents the same interface for any given resource type, with only the parameters changing to reflect that resources' specific requirements. This system enables interoperability, dynamic service discovery, and management functions such as monitoring, controlling and reporting, and dynamic reconfiguration and management.
Technical efficiency in developing country agriculture: a meta‐analysis

Abstract A meta-analysis is performed to review empirical estimates of technical efficiency (TE) in developing country agriculture. The objective of the study is to contribute to a better understanding of the factors that influence estimates of mean TE. A data set of 51 observations of TE from 32 studies is used in order to test if specific characteristics of the data and econometric specifications account for systematic differences in the efficiency estimates. Results using the two-limit Tobit procedure indicate that factors such as primal versus dual, number of fixed inputs and number of variable inputs increase average TE estimates. On the other hand, using the Cobb–Douglas functional form and cross-sectional data yields a lower level of TE. Other factors, including the number of variables in the model, crop type, stochastic versus deterministic frontiers and sample size, do not seem to significantly affect estimates of TE across studies.
Transmitting Range Assignments Using Steiner Tree in Ad Hoc Wireless Networks

In this paper, we discuss the problem of assigning transmitting ranges and establishing connectivity in ad hoc wireless networks from the practical perspective. That is, setup a communication links by introducing extraneous nodes to the network in the emergencies. Furthermore, transmitting ranges of nodes must be assigned in such a way that the energy cost is minimum. The main contribution of this work is the O(N log N) algorithm to add relay nodes to the network and 2-approximation to assign transmitting ranges of nodes (original and relay). The output of the algorithm is the minimal Steiner tree on the graph consists of terminal (original) nodes and relay (additional) nodes. The output of approximation is the range assignments to the nodes. The paper also analyzed the complexity and established the correctness of the proposed algorithm.
Bounding supply noise induced path delay variation by a relaxation approach

This paper presents a general ILP model for analyzing the supply noise induced worst path delay variation. The proposed model can address various modes of supply noise analysis: function based, two-vector pattern based, or multiple cycle analysis, additionally capable of including user-specified constraints. The formulated ILP problem is solved via a relaxation approach, which produces a conservative upper-bound estimation to the worst path delay variation at any iteration. The paper applies sub-gradient optimization to improve those upper bounds. Experimentations have demonstrated the efficiency of the proposed approach, by comparisons with a commercial ILP solver and traditional supply noise modeling approaches.
Treating Tobacco Use and Dependence: An Evidence-Based Clinical Practice Guideline for Tobacco Cessation

The prevention of tobacco-related morbidity and mortality through smoking cessation intervention is among the most vital missions of the chest clinician. This article summarizes the major findings and clinical recommendations of the US Department of Health and Human Services/Public Health Service Guideline, Treating Tobacco Use and Dependence, which is a comprehensive, evidence-based blueprint for smoking cessation. By becoming fluent in the clinical interventions and by implementing the simple institutional changes described in this article and in the guideline, chest clinicians can more effectively intervene with their patients who smoke.
Decreased Cough Sensitivity and Aspiration in Parkinson Disease

BACKGROUND Aspiration pneumonia is a leading cause of death in people with Parkinson disease (PD). The pathogenesis of these infections is largely attributed to the presence of dysphagia with silent aspiration or aspiration without an appropriate cough response. The goal of this study was to test reflex cough thresholds and associated urge-to-cough (UTC) ratings in participants with PD with and without dysphagia. METHODS Twenty participants with PD were recruited for this study. They completed a capsaicin challenge with three randomized blocks of 0, 50, 100, and 200 μM capsaicin and rated their UTC by modified Borg scale. The concentration of capsaicin that elicited a two-cough response, total number of coughs, and sensitivity of the participant to the cough stimulus (UTC) were measured. The dysphagia severity of participants with PD was identified with the penetration-aspiration scale. RESULTS Most participants with PD did not have a consistent two-cough response to 200 μM capsaicin. UTC ratings and total number of coughs produced at 200 μM capsaicin were significantly influenced by dysphagia severity but not by general PD severity, age, or disease duration. Increasing levels of dysphagia severity resulted in significantly blunted cough sensitivity (UTC). CONCLUSIONS UTC ratings may be important in understanding the mechanism underlying morbidity related to aspiration pneumonia in people with PD and dysphagia. Further understanding of decreased UTC in people with PD and dysphagia will be essential for the development of strategies and treatments to address airway protection deficits in this population.
Efficient wideband channelizer for software radio systems using modulated PR filterbanks

An efficient method is proposed for channelizing frequency division multiplexed (FDM) channels in wideband software radio (SWR) received signals that do not satisfy the conditions required for polyphase decomposition of the discrete filterbank (DFB) channelizer. The proposed method, which uses modulated perfect reconstruction (PR) filterbanks, requires fewer computations than DFBs for channelizing wideband signals that are composed of FDM channels of nonequal bandwidths, especially when a large number of channels are extracted. The proposed channelizer, if applied in the reverse direction, can be used to synthesize a set of channels with nonequal bandwidths into a single wideband signal in SWR transmitters. A method is also proposed for efficiently designing the modulated PR filterbanks, which have a large number of subchannels and prototype filters with high stopband attenuations that are used in the proposed channelizer. The computational complexity of the proposed channelizer is compared with the complexity of the DFB channelizer for channelizing the wideband and high-dynamic-range signals that are typical of SWR systems, and simulation results of the proposed channelization method are discussed.
Wealth, Health, and Democracy in East Asia and Latin America

Why do some societies fare well, and others poorly, at reducing the risk of early death? Wealth, Health, and Democracy in East Asia and Latin America finds that the public provision of basic health care and other inexpensive social services has reduced mortality rapidly even in tough economic circumstances, and that political democracy has contributed to the provision and utilization of such social services, in a wider range of ways than is sometimes recognized. These conclusions are based on case studies of Argentina, Brazil, Chile, Costa Rica, Indonesia, South Korea, Taiwan, and Thailand, as well as on cross-national comparisons involving these cases and others.
Through the membrane & along the channel flooding in PEMFCs

Neutron imaging of a polymer electrolyte membrane fuel cell (PEMFC) revealed distinct patterns of water fronts moving through the gas diffusion layers (GDL) and channels [1]. The PEMFC was operating with dead-ended, straight and almost vertically-oriented anode channels; hence the gravity driven accumulation of liquid water at the end of the channel caused flooding in an upward direction. In order to predict the spatiotemporal evolution of water patterns inside severely-flooded fuel cells, various distributed parameter models of the water transport through the membrane and GDLs to the cathode and anode channels have been developed by the authors and others. In this paper, a zero-dimensional moving front model is presented which captures the location of the water phase transition inside the GDL, instead of using the standard partial differential equation (PDE) approach for modeling liquid water in porous media which is numerically difficult to solve. This model uses three nonlinear states (the anode and cathode GDL front location and the membrane water content) and three inputs (the anode and cathode vapor concentration and the current density) to predict the slowly evolving front locations in both anode and cathode side GDLs during flooding and drying as well as the dynamic changes in membrane water content. The unit cell model is finally formulated with three hybrid modes and their transition laws. The hybrid-state model will be parameterized in the future using experimentally observed front evolutions. This parameterized unit cell model will be used to model the water accumulation along the channel in order to predict and avoid severe flooding conditions.
Youth access to tobacco: Policies and politics

The late 1980s marked the beginning of a sea change in research and intervention on tobacco use by young people, when the first studies were published demonstrating the ease with which adolescents could purchase cigarettes. Since then concern with the commercial availability of tobacco products to youth has grown, becoming deeply entrenched in both research and policy efforts. This paper reviews the history of restrictions on youth access to tobacco, the evidence that commercial sources of tobacco are available and important to adolescents, and the rationale for various components of policies to restrict access. We also review the recent expansion of policies addressing youth access to tobacco at all levels of government, the tobacco industry response to this expansion, and issues that have arisen as this expansion has developed.
Tick saliva regulates migration, phagocytosis, and gene expression in the macrophage-like cell line, IC-21

We studied the effects of tick saliva on cell migration, cell signaling, phagocytosis, and gene expression in the murine macrophage cell line, IC-21. Saliva increased both basal- and platelet-derived growth factor (PDGF)-stimulated migration in IC-21 cells. However, saliva did not affect PDGF-stimulated extracellular signal-regulated kinase (ERK) activity. Zymosan-mediated interleukin-1 receptor associated kinase (IRAK) activity increased when cells were pretreated with saliva. Saliva suppressed phagocytosis of zymosan particles by IC-21 cells. An RT(2) Profiler™ PCR Array revealed that saliva regulates gene expression in a manner consistent with an immune response skewed toward a Th2 reaction, which is characterized by production of anti-inflammatory cytokines IL-4 and IL-10. Our results using IC-21 cells suggest that Dermacentor variabilis has evolved a mechanism for regulating macrophage function, which may contribute to the tick's ability to modulate immune function.
High precision range extenders for an AC calibrator up to 600 V and 100 A

Summary form only given. The development of high-precision range extenders for high voltage (600 V) and large current (100 A) as separate units to be used with a previously developed AC calibrator is discussed. To obtain high accuracy and stable operation, an error feedforward technique was implemented. A current-comparator-based capacitance bridge was used for the gain, and phase calibration of the range extender. A precision two-stage current transformer and a very stable time-division-based watt-converter were used to verify its performances. >
Enhancing public health law communication linkages

Although interest in the field of public health law has dramatically increased over the past two decades, there remain significant challenges in communicating and sharing public health law-related knowledge. Access to quality information, which may assist in a public health department's efforts to protect the public's health, welfare, and safety, varies widely from jurisdiction to jurisdiction, and interjurisdictional communication remains at best a patchwork quilt with many holes. What follows is an analysis of several approaches the Public Health Law Association or other public health law-related organizations might undertake to serve as a conduit for the identification, gathering, and dissemination of extant public health law information, as well as the development of new public health law-related content, with a particular focus on the use of electronic means for such efforts.
Storage compliance in coupled CO2-EOR and storage

CO2 storage compliance refers to the safe and consistent storage of a captured anthropogenic CO2 slug in an underground geological structure. This paper investigates the storage compliance in coupled CO2 enhanced oil recovery (EOR) and storage projects. Storage compliance requires an oilfield operator to maintain sufficient CO2 injection and storage capacities throughout an industrial-scale CO2 capture and EOR-storage operation. We investigate the uncertainty in two operational parameters that may raise a compliance consideration: annual captured CO2 from the power plant and CO2 injection loss in the oilfield. The objective is to maintain sufficient CO2 injection and storage capacities and maximize the economic benefits from the EOR-storage operation. We formulate and optimize the storage compliance problem using the method of optimization with Monte Carlo simulation. The results show that appropriate adjustment of the water-alternating-gas (WAG) ratio increases both the compliance and the economic benefits. Also, a CO2 storage back-up in a saline aquifer allows the oilfield operator to implement more profitable EOR-storage designs. A risk-seeking operator may practice the saline aquifer back-up option to simultaneously maximize the benefits and mitigate the risk of storage capacity shortage. Finally, EOR-storage operation is less efficient than aquifer storage in terms of storage efficiency, and considerably more profitable in terms of tangible economic benefits.
Multiple Folding Pathways of the SH3 Domain

Experimental observations suggest that proteins follow different folding pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the c-Crk SH3 domain over a broad range of temperatures, and identify distinct pathways in the folding transition. We determine the kinetic partition temperature—the temperature for which the c-Crk SH3 domain undergoes a rapid folding transition with minimal kinetic barriers—and observe that below this temperature the model protein may undergo a folding transition by multiple folding pathways via only one or two intermediates. Our findings suggest the hypothesis that the SH3 domain, a protein fold for which only two-state folding kinetics was observed in previous experiments, may exhibit intermediate states under conditions that strongly stabilize the native state.
Setting Up User Action Probabilities in User Simulations for Dialog System Development

User simulations are shown to be useful in spoken dialog system development. Since most current user simulations deploy probability models to mimic human user behaviors, how to set up user action probabilities in these models is a key problem to solve. One generally used approach is to estimate these probabilities from human user data. However, when building a new dialog system, usually no data or only a small amount of data is available. In this study, we compare estimating user probabilities from a small user data set versus handcrafting the probabilities. We discuss the pros and cons of both solutions for different dialog system development tasks.
The Domestic Politics of International Hierarchy: Indirect Rule in the American System

The United States has maintained extensive international hierarchies over the Western Hemisphere for more than a century and over Western Europe and Northeast Asia for nearly seven decades. More recently, it has extended similar hierarchies over states in the Middle East, and especially the Persian Gulf. This paper examines how the United States exercises more or less authority over other countries and, in turn, the domestic politics of subordination within client states. Most important, in a world of juridically sovereign states that are, in principle, formal equals, it asks how is U.S. rule accepted as legitimate? The core argument is that hierarchy benefits subordinate countries but has interstate and intrastate distributional consequences for domestic ruling coalitions and regime types. When the gains from hierarchy are large or subordinate societies share policy preferences similar to those of the United States, international hierarchy is compatible with democracy. Thus, American indirect rule has coexisted with democracy in West European since World War II. When the gains from hierarchy are small and the median citizen has policy preferences distant from those of the United States, international hierarchy requires autocracy and the benefits of foreign rule will be concentrated within the governing elite. This has characterized U.S. rule over Central America for much of the last century. In the contemporary Middle East, the gains from hierarchy also appear small and policy preferences are distant from those of the United States. Despite rhetorical support for democracy, even in the Arab Spring, the United States has consistently backed sympathetic authoritarian rulers. The paper concludes with an analysis of the tradeoffs between subordination to the United States and democracy within the newest states of the American empire.
Angiostatin inhibits tumor growth via the regulation of fibrinolytic system through binding its receptor annexin II

4783 Angiostatin, an internal fragment of plasminogen, was discovered based on its potent and selective endothelial cytostatic activity in vitro. Angiostatin was shown to posses’ potent anti-angiogenic and anti-tumor activity without any visible toxicity in animal studies. Promising preclinical studies showed that AS inhibits the growth of solid tumors and prevents their metastasis, this anti-angiogenic compound was one of the earliest to enter anti-tumor clinical trials. Despite many pharmacological studies, the current knowledge of AS’s molecular mode of action is limited. Various mechanism(s) of AS’s mode of action have been suggested including from our laboratory. We reported that AS binds to fibrinolytic receptor annexin II on EC surface and may be blocking plasmin generation, strong serine protease, which facilitate angiogenic process via degradation of extra cellular matrix (ECM) ( Microvascular Research 64, 448-462, 2002 ). Our results further provide evidence that fibrinolytic and clotting system directly involved in the angiogenic process.In the present report we demonstrate that annexin II is up regulated by potent angiogenic cytokine bFGF. Interestingly, annexin II expression was found specifically in endothelial cells but not in fibroblast cells (NIH3T3) suggesting its possible role in angiogenesis. We further showed that AS competes for plasminogen (PLG) binding on EC surface annexin II and interfering with plasmin generation, which is crucial for angiogenesis. We further tested whether blocking annexin II in EC will inhibit proliferation, angiogenesis in vitro and tumor growth in vivo. Surprisingly, anti-annexin II antibody treatment induces EC death and inhibits proliferation in a dose dependent manner. Antibody treatment also disrupted microvessels formation on collagen gel. We further explored the feasibility of treating solid Lewis lung carcinoma in mice model using monoclonal anti-annexin II antibody. Intravenous injection of single dose of antibody (200mg/kg of body weight) inhibited tumor growth almost 75%. Serum analysis of these animals showed complete inhibition of plasmin generation after antibody treatment but in contrast very high levels of plasmin was detected in IgG treated animals. These data suggest that annexin II facilitate angiogenic process by fostering cell surface proteolytic activity of plasmin and promote new vessel remodeling. To the best of my knowledge this is the first report showing that targeted blocking of angiostatin’s receptor annexin II may be used as a therapy for cancer. These observations provide great deal of hope that functional blocking of AS’s receptor annexin II may be used to inhibit pathological angiogenesis and tumor growth.
Deduction of the differential equation for the bootstrap degeneracy

The differential equation for the mass degeneracy at fixed particle number is deduced by starting from the recursive relation of the Yellin coefficients.
TOWARD THE MINIMUM INNER EDGE DISTANCE OF THE HABITABLE ZONE

We explore the minimum distance from a host star where an exoplanet could potentially be habitable in order not to discard close-in rocky exoplanets for follow-up observations. We find that the inner edge of the Habitable Zone for hot desert worlds can be as close as 0.38 AU around a solar-like star, if the greenhouse effect is reduced (~1% relative humidity) and the surface albedo is increased. We consider a wide range of atmospheric and planetary parameters such as the mixing ratios of greenhouse gases (water vapor and CO2), surface albedo, pressure, and gravity. Intermediate surface pressure (~1-10 bars) is necessary to limit water loss and to simultaneously sustain an active water cycle. We additionally find that the water loss timescale is influenced by the atmospheric CO2 level, because it indirectly influences the stratospheric water mixing ratio. If the CO2 mixing ratio of dry planets at the inner edge is smaller than 10–4, the water loss timescale is ~1 billion years, which is considered here too short for life to evolve. We also show that the expected transmission spectra of hot desert worlds are similar to an Earth-like planet. Therefore, an instrument designed to identify biosignature gases in an Earth-like atmosphere can also identify similarly abundant gases in the atmospheres of dry planets. Our inner edge limit is closer to the host star than previous estimates. As a consequence, the occurrence rate of potentially habitable planets is larger than previously thought.
PCI bus content-addressable-memory (CAM) implementation on FPGA for pattern recognition/image retrieval in a distributed environment

Recently surveillance and Automatic Target Recognition (ATR) applications are increasing as the cost of computing power needed to process the massive amount of information continues to fall. This computing power has been made possible partly by the latest advances in FPGAs and SOPCs. In particular, to design and implement state-of-the-Art electro-optical imaging systems to provide advanced surveillance capabilities, there is a need to integrate several technologies (e.g. telescope, precise optics, cameras, image/compute vision algorithms, which can be geographically distributed or sharing distributed resources) into a programmable system and DSP systems. Additionally, pattern recognition techniques and fast information retrieval, are often important components of intelligent systems. The aim of this work is using embedded FPGA as a fast, configurable and synthesizable search engine in fast image pattern recognition/retrieval in a distributed hardware/software co-design environment. In particular, we propose and show a low cost Content Addressable Memory (CAM)-based distributed embedded FPGA hardware architecture solution with real time recognition capabilities and computing for pattern look-up, pattern recognition, and image retrieval. We show how the distributed CAM-based architecture offers a performance advantage of an order-of-magnitude over RAM-based architecture (Random Access Memory) search for implementing high speed pattern recognition for image retrieval. The methods of designing, implementing, and analyzing the proposed CAM based embedded architecture are described here. Other SOPC solutions/design issues are covered. Finally, experimental results, hardware verification, and performance evaluations using both the Xilinx Virtex-II and the Altera Apex20k are provided to show the potential and power of the proposed method for low cost reconfigurable fast image pattern recognition/retrieval at the hardware/software co-design level.
Gene Therapy for the Critically Ill Mouse

An expanding component of murine basic science research is the use of gene therapy. Not unexpectedly, much of the development of gene therapy ultimately for human use has been initiated, developed and refined in murine species. Gene therapy was initially introduced as a method of treating inherited diseases, such as cystic fibrosis and adenosine deaminase deficiency-severe combined immunodeficiency4’8, or as a means to treat acquired diseases with a genetic component, such as viral infections and cancer. In 1995, however, Crystal proposed using gene therapy as a drug delivery system to express protein-based therapies in individual tissues rather than to only restore normal gene function11. The potential application of gene therapy as a drug delivery system became readily apparent to almost all aspects of clinical medicine. As with other fields of research, much of the basic research in gene therapy was performed in the mouse, including our knowledge of the mouse genome, the availability of “knock-out” or transgenic mice lacking or overexpressing specific genes, and the availability of these animals in relatively large numbers. These advantages are also true for murine research involving critical illness, or more specifically sepsis, a field in which there has been very slow progress in determining pathophysiology and treatments for this disease.
Optimizing invokedynamic

In order to support the needs of non-Java languages, the JSR 292 Expert Group has designed a new bytecode "invokedynamic" which allows JVM bytecodes to contain call sites with pluggable, user-defined behavior. The bytecode is accompanied by a new data type called a "method handle" that reifies the pluggable behavior, in the form of a functional value. The authors have been building the JSR 292 Reference Implementation on top of Oracle's HotSpot JVM. This paper describes their implementation tactics. Interesting subtopics include connecting the novel features of JSR 292 to classic HotSpot optimizations, creating new code optimization techniques for HotSpot in support of JSR 292, using Java (along with HotSpot's customary C++) as an implementation language for method handles, using internally-generated bytecodes as an intermediate language for "freezing" dynamic call sites before optimization, and designing specialized "adapter" calling sequences which match callers and callees of differing type descriptors.
Structural, Mechanical and Corrosion Properties of Mg/SiO2 and MgO/SiO2 Multilayer Coatings for Magnesium Implant Devices

In this study, Mg/SiO2 and MgO/SiO2 multilayer coatings with bilayer thicknesses (Λ) 10, 20, 40, 100, 200 and 1000 nm were deposited on glass substrates using DC and reactive pulsed DC magnetron sputtering processes. The aim of these coatings is to control the initial degradation and provide mechanical strength to magnesium implant during handling and installation. The initial thickness calibrations and deposition rates optimization were conducted using stylus profilometer. After deposition of the multilayer coatings, the values of their bilayer thicknesses (Λ) were obtained from X-ray reflectometery. The mechanical properties, surface morphology and roughness of multilayer coatings were studied using nanoindentation, SEM and AFM respectively. The nanoindentation results showed higher hardness of MgO/SiO2 multilayer coatings compared to single layer Mg. The roughness analyses showed improved roughness for bilayer thicknesses (Λ) less than 20 nm. It was observed from the SEM images that SiO2 coatings has pores. By adding Mg and/or MgO in the form of multilayers improves the pores significantly. The Mg/SiO2 multilayer coatings showed controlled degradation rate when immersed in saline solution compared to the monolithic SiO2 coating. In conclusion, conditions for depositing Mg/SiO2 and MgO/SiO2 multilayer coatings has been optimized. Alternating brittle SiO2 ceramic layers with soft and ductile Mg layers significantly improved the hardness of the Mg coating. Hardness of multilayer coatings can be fine-tuned by modifying bilayer thicknesses. Significant improvement in the corrosion and mechanical properties of the multilayer coatings can be used to protect surface of magnesium implant material during handling, storage and installation.Copyright © 2015 by ASME
Effects of Three Insect Growth Regulators, Feeding Substrates, and Colony Origin on Survival and Presoldier Production of the Formosan Subterranean Termite (Isoptera: Rhinotermitidae)

Effects of three insect growth regulators (IGR’s)-methoprene, fenoxycarb (Ro13-5223), and 2-[p-m-(Flurophenoxy) phenoxy] ethyl ethylcarbamate (Ro16-1295)-at ca. 500, 1,000, and 1,500 ppm on three feeding substrates-filter paper, absorbent pure cellulose filter pads, and ponderosa pine ( Pinus ponderosa Dougl. ex Laws) blocks-were evaluated on laboratory experimental groups of 150 Coptotermes formosanus Shiraki (130 workers and 20 soldiers) collected from three field colonies in Oahu, Hawaii. Ro16-1295 killed ca. 16% workers while only ca. 2% of workers died after 2-weeks exposure to methoprene and fenoxycarb. A considerably larger proportion of soldiers was killed as a result of exposure to these IGR’s; ca. 25% were killed by methoprene and ca. 40% were killed by the other IGR’s. All three IGR’s induced presoldier formation. Approximately 12-22 presoldiers were found in treated groups after 2 weeks, while no presoldiers were observed in untreated controls. Feeding substrates did not affect worker mortality. However, IGR-impregnated pine blocks caused significantly lower soldier mortality and produced more presoldiers than the other two substrates. All three colonies were significantly different from each other in worker and soldier mortality and presoldier production in response to IGR’s and feeding substrates.
Cryogenic automobile propulsion - Heat exchanger design and performance issues

The University of Washington is studying a concept in the field of zero-emission vehicles (ZEV): the cryogenic automobile. The cryogenic automobile uses nitrogen, stored in liquid stale, as its working fluid. The liquid nitrogen is pumped up to the system pressure, then vaporized in a heat exchanger in contact with ambient air. The resulting high pressure gas is injected into a quasi-isothermal expander which produces the system's motive work. The spent, low pressure gas is exhausted to the atmosphere. One of the greatest technical challenges of this concept is designing a heat exchanger that is structurally robust, works well in a variety of driving conditions and is not hampered by the buildup of frost. This paper explores issues pertaining to the design, fabrication and testing of such a heat exchanger.
Energy and Sustainability

In selecting energy options, there are obvious factors such as the cost of the energy feedstock. There are also factors that are not as obvious such as the impact of tax infrastructures and the time it takes to realize the return on an investment. This chapter covers the underlying factors that impact investments and evaluates how artificial barriers may be overcome in the future.