cssi/SciSciGPT-SciSciNet huggingface dataset:
The Identification and Characterization of a Ligand for Bovine CD5

CD5, a type I glycoprotein expressed by T cells and a subset of B cells, is thought to play a significant role in modulating Ag receptor signaling. Previously, our laboratory has shown that bovine B cells are induced to express this key regulatory molecule upon Ag receptor cross-linking. To date, a ligand has not been described for bovine CD5. Given the importance ligand binding presumably plays in the functioning of CD5 on this B cell subset and on T cells, we sought to characterize the ligand for this protein using a bovine CD5-human IgG1 (CD5Ig) fusion protein produced by both mammalian and yeast cells. As determined by CD5Ig binding, expression of this ligand is negative to low on freshly isolated lymphocytes, with low-density expression being limited to activated B cells. Activation with LPS, PMA, and calcium ionophore, or ligation of CD40 alone or in combination with anti-IgM, resulted in B cell-specific expression of this ligand. Interestingly, activation through B cell Ag receptor cross-linking alone, although able to induce CD5 expression, did not result in expression of CD5 ligand (CD5L). In addition, we demonstrate a functional role for CD5L as a costimulatory molecule that augments CD40L-stimulated B cell proliferation. Finally, immunoprecipitation with CD5Ig suggests that the ligand characterized in this study has a molecular mass of approximately 200 kDa. The data reported herein, as well as future studies aimed at further characterizing this newly identified bovine CD5L, will undoubtedly aid in understanding the role that the CD5-CD5L interaction plays in immune responses.
Structural and mechanical parameters of trabecular bone estimated from in vivo high‐resolution magnetic resonance images at 3 tesla field strength

Purpose: To evaluate the performance of a new 3 Tesla (T) high-resolution trabecular bone (TB) imaging technique at two resolution regimens in terms of serial reproducibility and sensitivity. Materials and Methods: The left distal tibial metaphysis of seven healthy volunteers was imaged at three time-points using a FLASE (fast large-angle spin-echo) pulse sequence at 137 × 137 × 410 μm3 and (160 μm)3 voxel sizes. Image artifacts, motion degradation, and serial image volume misalignments were controlled to maximize reproducibility of image-derived measures of scale, topology, orientation in terms of structural anisotropy, and finite-element derived Young's and shear moduli. Coefficients of variation (CV) and intraclass correlation coefficients (ICC) for structural and mechanical parameters were evaluated as measures of reproducibility and reliability. The ability of structural and mechanical parameters to distinguish between subjects was tested by analysis of variance. Results: Reproducibility was generally higher in the anisotropic data (CVs 1–5% versus 1–9% for isotropic images). Anisotropic voxel size yielded greater measurement reliability (ICCs 0.75–0.99, mean = 0.92 versus 0.62–0.99, mean = 0.86) and better discrimination of the seven subjects (75% versus 50% of the possible comparisons were significantly different [P < 0.05]) except for measures of structural anisotropy and topology. Isotropic resolution improved detection of structural orientation and permitted visualization of small perforations in longitudinal trabecular plates not detected at anisotropic resolution. Conclusion: Improved image acquisition and processing techniques enhance reproducibility of structural and mechanical parameters derived from high-resolution MRI of metaphyseal bone in the distal tibia. J. Magn. Reson. Imaging 2010;31:1157–1168. © 2010 Wiley-Liss, Inc.
Component Specificity for the Thylakoidal Sec and Delta Ph–Dependent Protein Transport Pathways

Prokaryotes and prokaryote-derived thylakoid membranes of chloroplasts share multiple, evolutionarily conserved pathways for protein export. These include the Sec, signal recognition particle (SRP), and Delta pH/Tat systems. Little is known regarding the thylakoid membrane components involved in these pathways. We isolated a cDNA clone to a novel component of the Delta pH pathway, Tha4, and prepared antibodies against pea Tha4, against maize Hcf106, a protein implicated in Delta pH pathway transport by genetic studies, and against cpSecY, the thylakoid homologue of the bacterial SecY translocon protein. These components were localized to the nonappressed thylakoid membranes. Tha4 and Hcf106 were present in ∼10-fold excess over active translocation sites. Antibodies to either Tha4 or Hcf106 inhibited translocation of four known Delta pH pathway substrate proteins, but not of Sec pathway or SRP pathway substrates. This suggests that Tha4 and Hcf106 operate either in series or as subunits of a heteromultimeric complex. cpSecY antibodies inhibited translocation of Sec pathway substrates but not of Delta pH or SRP pathway substrates. These studies provide the first biochemical evidence that Tha4 and Hcf106 are specific components of the Delta pH pathway and provide one line of evidence that cpSecY is used specifically by the Sec pathway.
N-Formyl Peptide Receptor Phosphorylation Domains Differentially Regulate Arrestin and Agonist Affinity

Arrestins regulate the signaling and endocytosis of many G protein-coupled receptors (GPCRs). It has been suggested that the functions of arrestins are dependent upon both the number and pattern of phosphorylation sites present in an activated GPCR. However, little is currently known about the relationships between the sites of receptor phosphorylation, the resulting affinities of arrestin binding, and the ensuing mechanisms of receptor regulation for any given GPCR. To investigate these interactions, we used an active truncated mutant of arrestin (amino acids 1-382) and phosphorylation-deficient mutants of the N-formyl peptide receptor (FPR). In contrast to results with wild type arrestins, the truncated arrestin-2 protein bound to the unphosphorylated wild type FPR, although with lower affinity and a low affinity for the agonist as revealed by competition studies with heterotrimeric G proteins. Using FPR mutants, we further demonstrated that the phosphorylation status of serines and threonines between residues 328-332 is a key determinant that regulates the affinity of the FPR for arrestins. Furthermore, we found that the phosphorylation status of serine and threonine residues between amino acids 334 and 339 regulates the affinity of the receptor for agonist when arrestin is bound. These results suggest that the agonist affinity state of the receptor is principally regulated by phosphorylation at specific sites and is not simply a consequence of arrestin binding as has previously been proposed. Furthermore, this is the first demonstration that agonist affinity of a GPCR and the affinity of arrestin binding to the phosphorylated receptor are regulated by distinct receptor phosphodomains.
The kinetics of thin film polyesterification

The goal of this work was to investigate the increase in the rate of polyesterification that takes place as surface-to-volume ratio is increased. The polymer used in this reaction was derived from the esterification of adipic acid (hexanedioic acid) and propylene glycol (1,2-propanediol). The effect of three variables—film thickness, water concentration of the nitrogen atmosphere, and temperature—was studied to determine their effect on the reaction rate. The water content of the atmosphere was found to severely retard the progress of the esterification and this fact reaffirms that the reverse reaction, hydrolysis, is much more important than was realized by earlier investigators. The reaction in the film was found to have an activation energy of 22,600 cal/mole compared to 12,600 cal/mole in the batch reaction, indicating a possible change in controlling rate from the batch to the film system. New evidence was found which illustrates the possible role of reactant mobility at high conversions. It is suggested that a possible explanation for the change in controlling rate may be due to a complex surface phenomenon such as the alignment of reactive groups at the surface or the orientation of water molecules at the gas–liquid interface.
Changes in In Vitro Brain and Spinal Cord Protein Phosphorylation After a Single Oral Administration of Tri‐o‐Cresyl Phosphate to Hens

The effect of a single oral 750 mg/kg dose of tri-o-cresyl phosphate (TOCP) on the endogenous phosphorylation of brain and spinal cord proteins was assessed in hens during the development of and recovery from delayed neurotoxicity. Crude membrane and cytosolic fractions were prepared from the brains and spinal cords of control and TOCP-treated hens at 1, 7, 14, 21, 35, and 55 days after treatment. Brain and spinal cord protein phosphorylation with [gamma-32P]ATP was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), autoradiography, and microdensitometry. TOCP administration conferred calcium and calmodulin dependence on the phosphorylation of a few brain cytosolic proteins and caused an increase in the phosphorylation of a number of other cytosolic and membrane proteins. This effect of TOCP was large in magnitude, and its time course reflected the onset of and recovery from the signs of ataxia and paralysis associated with delayed neurotoxicity in the hen. The molecular weights (Mr) and maximal phosphorylation (percent of control) for the most prominently affected bands were as follows: brain cytosol--50K (183%), 55K (575%), 60K (529%), 65K (273%), and 70K (548%); brain membranes--50K (622%) and 60K (697%); and spinal cord cytosol--20K (182%). The role of endogenous phosphorylation reactions in and their potential usefulness as biochemical indicators of delayed neurotoxicity are being explored further.
NoShake: Content stabilization for shaking screens of mobile devices

Consumer electronics and mobile devices intended for pervasive applications are often subject to shaking that makes their screen difficult to read. To address this usability challenge, we present NoShake, a system for screen content stabilization. NoShake utilizes a single accelerometer, now present in numerous consumer electronics and mobile devices. The core of NoShake is a physics inspired model that dynamically compensates for the device shaking by shifting the screen content opposite the direction of the shake. The model is efficient, parametric, and can be fine tuned based on shaking pattern detection. We implement a prototype of NoShake on an Apple iPhone and conduct user studies in a number of scenarios, which highlight the strengths as well as limitations of NoShake in coping with shaking devices.
The Community Deficit

The European Union is suffering not just from a democratic deficit, but a community deficit. The level and scope of its integration activities far exceed the degree of community that it sustains. The article explains why community, particularly normative-affective community, is needed and how it can be built in the EU.
PDFMEF: A Multi-Entity Knowledge Extraction Framework for Scholarly Documents and Semantic Search

We introduce PDFMEF, a multi-entity knowledge extraction framework for scholarly documents in the PDF format. It is implemented with a framework that encapsulates open-source extraction tools. Currently, it leverages PDFBox and TET for full text extraction, the scholarly document filter described in [5] for document classification, GROBID for header extraction, ParsCit for citation extraction, PDFFigures for figure and table extraction, and algorithm extraction [27]. While it can be run as a whole, the extraction tool in each module is highly customizable. Users can substitute default extractors with other extraction tools they prefer by writing a thin wrapper to implement the abstracts. The framework is designed to be scalable and is capable of running in parallel using a multi-processing technique in Python. Experiments indicate that the system with default setups is CPU bounded, and leaves a small footprint in the memory, which makes it best to run on a multi-core machine. The best performance using a dedicated server of 16 cores takes 1.3 seconds on average to process one PDF document. It is used to index extracted information and help users to quickly locate relevant results in published scholarly documents and to efficiently construct a large knowledge base in order to build a semantic scholarly search engine. Part of it is running on CiteSeerX digital library search engine.
Characterization of Phospholipids from Glyphosate-Tolerant Soybeans

The phospholipids from three control and two glyphosate-tolerant soybean cultivars were isolated by extraction of soy flakes with hexane and characterized after separation by high-pressure liquid chromatography. In addition, several lots of commercial fluid lecithin were analyzed and the results were compared to values published in the literature. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid were identified as major components in these cultivars and in the commercial lecithin samples. The results showed that glyphosate-tolerant soybeans yield lecithin comparable and equivalent to conventional soybean cultivars.
The Future of Healthcare Infrastructure

Every country requires a national infrastructure for health care. This infrastructure must serve many needs and many individuals. In addition to providing a backbone for medical information and demographic information across populations, the infrastructure must index the nation’s health, using twenty-first century technologies to solve twenty-first century problems. The interactions with individuals will generate measurements of populations, as the input for massive data mining on large-scale supercomputers, to discover cohort-specific maximal quality at minimal cost. These information technologies will gather the data necessary to support healthcare infrastructure for viable healthcare, health and well-being.
Rejoinder to Comments by Cavert

W RORK in economics can proceed on a variety of levels. The writers of "The Scale of Operations in Agriculture" were attempting nothing more than to breathe a modicum of scientific rigor into the handling of a subject which has suffered badly in the hands of those who work hunches and prejudices to death and yet fail to advance economic analysis. Mr. Cavert takes his stand with this group. With respect to the questions at issue Mr. Cavert's stand seems hardly defensible-except insofar as he objects to abstraction. On this methodological aspect the writers merely state their case, and let it rest on its merits. They assert that economics is an abstracting science, despite the literature which testifies volubly to the contrary. They fully realize what must be sacrificed as a necessary consequence of abstraction. With the foregoing statement of what the writers were attempting, and the limitations involved in their method, the objections which Mr. Cavert raises can be dealt with briefly: 1. The fundamental objection is that the writers have overlooked the fact that the real difficulties in conducting a large scale agricultural undertaking are those of standardizing jobs and those of supervision of workers. The truth is not that these hoary, but not particularly venerable, notions were neglected in the paper being discussed, but rather that they are stated in economic terms. They were described as "management proper, composed in turn, of supervision and coordination or decision making." Further, they are certainly included in Keynes' delightful concept of the marginal efficiency of capital which occupies a central place in the paper being discussed.
Two New Species of Osbornellus from the Southwestern United States

Resembling scalaris in appearance and coloration but smaller and with distinct male genitalia. Length, 4.5-5 mm. Vertex rather sharply angled, basal width between eyes only about two-thirds as great as median length. Color: Pale brownish. Vertex with a marginal brown line just below apex of vertex and a narrow line almost transverse between anterior margins of ocelli. A median white spot encircled by brown just posterior to this line. Ocelli white, heavily margined with brown. Elytra subhyaline, dusky at apex, veins brown and with three brown spots along commissural line on clavus of each.
L-dopa in the treatment of Parkinson's disease.

Most patients with Parkinson's disease who are given L-dopa improve, and the response of some is dramatic. Sometimes, however, the amount of drug necessary to control tremor or rigidity or other features will also produce intolerable side effects. Minor and major untoward effects are numerous and frequent, and the ultimate safety and value of this treatment are undefined. Still its potential usefulness is confirmed in clinical trials.
Selective downregulation of ANP-clearance-receptor gene expression in lung of rats adapted to hypoxia

To test the hypothesis that expression of atrial natriuretic peptide (ANP)-receptor genes is modified to provide a compensatory mechanism against hypoxic pulmonary hypertension, steady state mRNA l...
Effect of epicardiectomy on myocardial blood flow

Summary Ventricular epicardiectomy was evaluated by measuring nutrient myocardial blood flow with a tracer of potassium. An acute increase in total myocardial blood flow was found immediately after epicardiectomy, but there was no acute increase in the myocardial flow from the ventricular chamber. There was also an increase in collateral myocardial blood flow 3 weeks after epicardiectomy.
Larva migrans then.

Paul Beaver, in the first major review paper he wrote on larva migrans in 1956, made reference to a quote by that eminent biologist-parasitologist Arthur Looss in 1911 which perhaps has summarized the basic philosophy of Dr. Beaver in his approach to parasite research in general over the past 6 decades: “What I wish here to emphasize is that a correct knowledge of the diseases of man caused by worms and all that is connected with them, is the more difficult to attain the more the parasites of animals are ignored.” Paul Beaver had great admiration for Looss, who was the first person to study in detail the tissue migration and development of the nematode Ancylostoma duodenale. In a biographical note about Looss, Baylis, in 1924, summarized him as follows: “Looss' enthusiasm and energy as a research worker have probably seldom been surpassed, and all his work was characterized by a painstaking attention to detail that is unfortunately rare.”
Cell-Cycle Dependent Variation in the Levels of Deoxyribonucleoside Triphosphate in Mouse T-Lymphoma Cells

De novo synthesis of deoxyribonucleotides occurs exclusively by the reduction of the corresponding ribonucleotides in a reaction catalyzed by the enzyme ribonucleotide reductase. The enzyme is subject to allosteric regulation in vitro and in vivo and its activity is closely correlated to the growth rate of cells. The changes in ribonucleotide reduction is correlated to changes in the measured deoxyribonucleoside triphosphate pools in a variety of cell lines but considerable variations in the relative levels of each of the four DNA precursors were found1.
Laryngeal cancer without spread to the neck: treatment options and outcome.

We examined treatment and outcome variables in patients who had laryngeal cancer without clinical evidence of spread to the neck. In our patient population, there was a 24% overall recurrence rate for N0 laryngeal cancer. Initial manifestations, including stage and location of tumor, did not influence recurrence (P greater than .1). Initial treatment of the primary T3 or T4 tumor with radiotherapy alone was positively correlated with recurrence (P less than .0 for T3, P less than .0 for T4), but initial treatment of the neck did not appear to affect chance of regional or distant recurrence (P greater than .1). Approximately half of the patients who had recurrent disease were salvaged. Neither chance of salvage nor final disease-free status was significantly associated with any of the variables (P greater than .1).
Enzyme-Based Cocaine Pharmacotherapies: Current Status and Projections for the Future

Cocaine abuse presents two issues on which pharmacotherapy should focus, viz., acute toxicity and chronic abuse. Treatment of acute toxicity requires an intervention with a very fast onset; duration of action is less critical. On the other hand, treatment of chronic abuse is feasible only with a very long-acting intervention. Research and development of two distinct types of anti-cocaine enzyme-based therapies, one bacterial and the other mammalian, are currently ongoing. A bacteria-based enzyme with pharmacokinetics appropriate for treatment of acute toxicity has been synthesized (cocaine esterase – CocE) and a derivative of it has reached clinical trial status. A mammalian-derived enzyme (cocaine hydrolase – CocH) with a half-life of two to three days is also in clinical trials for treatment of cocaine abuse; it remains to be seen whether this duration of action is sufficiently long to make this enzyme useful for most cocaine abusers. Pharmacological and behavioral procedures for evaluation of compounds of interest exist at both the preclinical and clinical levels. Discovery technology is making great strides toward the development of long-lasting enzyme therapeutics.
Structure and Dynamics of a Concentrated Microemulsion System

We have found for an AOT/H2O/decane Microemulsion System, microscopic water droplets formed a stable dispersed phase in the decane continuum. This was established both by a conventional and a double-constrast-variation method in small angle neutron scattering measurements. It was found that the droplet radius was given uniquely by the water-to-surfactant ratio, even in the concentrated microemulsion regime where the dispersed phase volume exceeded 60%.
Coupled Dynamic–Thermodynamic Forcings during Tropical Cyclogenesis. Part I: Diagnostic Framework

AbstractA diagnostic framework to investigate the role of processes around and during tropical cyclogenesis is presented. The key framework metric is the ratio of bulk differences of moist entropy over differences of angular momentum between an inner and outer region of a tropical disturbance or cyclone. This ratio is hypothesized to decrease and become negative as both the high-entropy core and low-level vortex in the inner region amplify during tropical cyclogenesis. The time tendency of this ratio can be split into two forcings: a moist entropy forcing and an angular momentum forcing. Each forcing can be further divided into components comprising differences in net advective fluxes and nonadvective boundary fluxes of moist entropy or angular momentum between each region. The framework provides a comprehensive way to compare the relative importance of processes leading to tropical cyclogenesis in a tractable, consistent manner. Suggestions on how to apply the framework to numerical model output are given.
Abstract IA25: Third-generation inhibitors of mTOR

Precision medicines exert selective pressure on tumor cells that leads to the preferential growth of resistant subpopulations, necessitating the development of next-generation therapies to treat the evolving cancer. The PIK3CA–AKT–mTOR pathway is one of the most commonly activated pathways in human cancers, which has led to the development of small-molecule inhibitors that target various nodes in the pathway. Among these agents, first-generation mTOR inhibitors (rapalogs) have caused responses in “N-of-1” cases, and second-generation mTOR kinase inhibitors (TORKi) are currently in clinical trials. Here we seek to delineate the likely resistance mechanisms to existing mTOR inhibitors in human cell lines, as a guide for next-generation therapies. The mechanism of resistance to the TORKi was unusual in that intrinsic kinase activity of mTOR was increased, rather than a direct active-site mutation interfering with drug binding. Indeed, identical drug-resistant mutations have been also identified in drug-naive patients, suggesting that tumors with activating MTOR mutations will be intrinsically resistant to second-generation mTOR inhibitors. We report the development of a new class of mTOR inhibitors that overcomes resistance to existing first- and second-generation inhibitors. The third-generation mTOR inhibitor exploits the unique juxtaposition of two drug-binding pockets to create a bivalent interaction that allows inhibition of these resistant mutants. Citation Format: Kevan M. Shokat. Third-generation inhibitors of mTOR. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr IA25.
Dynamic, distributed constraint solving and thermodynamic theory

There has been an increasing recognition that a number of key computational problems require distributed solution techniques. To facilitate the creation and advancement of these techniques, researchers have developed the distributed constraint satisfaction and optimization (DCSP/DCOP) formalisms with the understanding that many critical real-world problems can be represented using them. Subsequently, these formalisms have led to the creation of numerous protocols where most ignore a critical feature of the problems they are designed to solve: the problems change over time. Dynamic variations of the DCSP and DCOP formalisms were invented to address this deficiency, but these models have received inadequate attention from the research community. A key impediment to advancing this research area is the lack of a compelling theoretical underpinning to the analysis of these problems and the evaluation of the protocols used to solve them. This work creates a mapping of the DynDCSP and DynDCOP formalisms onto thermodynamic systems. Under this mapping, it shows that these problems obey the three laws of thermodynamics. Utilizing these laws, this work develops, for the first time, a method for characterizing the impact that dynamics has on a distributed problem as well as a technique for predicting the expected performance of distributed protocols under various levels of dynamics.
Chemical Warfare Agents (CWAs)

The extended usage of chemicals as weapons dates since classical times, when lighting of bonfires, irritant smokes, and several compositions of pitch, petroleum, and sulfur (Greek fire) delivered a serious advancement for a mass troop elimination.
Bridging the Gap: One Nursing School's Response to Clinical Evaluation Challenges

Abstract This article describes the experience of an associate degree nursing program as they developed a clinical evaluation tool based on entry-level registered nurse competencies, Quality and Safety Education for Nurses concepts, Massachusetts Department of Higher Education Nurse of the Future Competencies, and their end-of-program learning outcomes. The result is an effective tool, which facilitates the students' and faculty abilities to evaluate clinical performance objectively based on observed behaviors versus a checklist methodology.
Targeting CD38 to improve anti-PD-1/CTLA-4 combination therapy in lung cancer.

144Background: The combination of anti-PD-1 and anti-CTLA-4 is a promising strategy that is being clinically explored to treat a variety of cancer types. Some patients display primary resistance to this combination treatment, while others relapse after treatment. Although some cancer patients have long-term durable responses to the combination therapy of anti-PD-1 and anti-CTLA-4, physicians have been looking for biomarkers that predict response. Methods: Using multiple immunocompetent syngeneic and K-rasLA1/+p53R172H?g/+ spontaneous animal models of lung cancer, we have explored the mechanisms of resistance to anti-PD-1/CTLA-4 combination therapy by evaluating the molecular and cellular immune profiles of the tumor microenvironment. Antibody-mediated cell depletion assays were also conducted to validate the mechanisms. Lastly, to determine the applicability to patients, we analyzed 791 lung cancer patients’ specimens with immunohistochemistry staining and mined many immune markers in multiple large indep...
Optimized Formulation of Magnetic Chitosan Microspheres Containing the Anticancer Agent, Oxantrazole

A combined emulsion/polymer cross-linking/solvent evaporation technique was used to prepare magnetic chitosan microspheres (MCM) containing the anticancer drug, oxantrazole. A central composite experimental design was used to simultaneously evaluate a variety of formulation factors on a number of response variables, such as the percentage of oxantrazole entrapped in the MCM. In association with the study design, statistical optimization procedures indicated the factors that significantly influence MCM preparation and what levels of the factors are needed to produce optimum MCM. Entrapment of anticancer agents into biodegradable microspheres is difficult because of low aqueous drug solubility and porosity of the particles. The latter effect was circumvented by a chitosan cross-linking step that resulted in approximately 3% (w/w) oxantrazole entrapment in the MCM via the optimization procedures. The combined formulation and statistical optimization strategy provide a basis to develop other microparticulate systems and led to a dosage form that can be used for future in vivo investigations.
Failure Diagnosis of Complex Systems

Failure diagnosis is the process of identifying the causes of impairment in a system’s function based on observable symptoms, i.e., determining which fault led to an observed failure. Since multiple faults can often lead to very similar symptoms, failure diagnosis is often the first line of defense when things go wrong - a prerequisite before any corrective actions can be undertaken. The results of diagnosis also provide data about a system’s operational fault profile for use in offline resilience evaluation. While diagnosis has historically been a largely manual process requiring significant human input, techniques to automate as much of the process as possible have significantly grown in importance in many industries including telecommunications, Internet services, automotive systems, and aerospace. This chapter presents a survey of automated failure diagnosis techniques including both model-based and model-free approaches. Industrial applications of these techniques in the above domains are presented, and finally, future trends and open challenges in the field are discussed.
Application of EPR to Surface Chemistry: Coordination Chemistry of Paramagnetic Ions in Zeolites

The application of epr to transition metal complexes in zeolites is illustrated by examples which include ion migration during complex formation, the formation of fully coordinated complexes, the determination of spin state, spin-spin interactions, unusual oxidation states and redox reactions. Problems involved in the determination of coordination number and symmetry from epr data are discussed.
Transportation Routing Analysis Georgraphic Information System (WebTRAGIS) User's Manual

In the early 1980s, Oak Ridge National Laboratory (ORNL) developed two transportation routing models: HIGHWAY, which predicts truck transportation routes, and INTERLINE, which predicts rail transportation routes. Both of these models have been used by the U.S. Department of Energy (DOE) community for a variety of routing needs over the years. One of the primary uses of the models has been to determine population-density information, which is used as input for risk assessment with the RADTRAN model, which is available on the TRANSNET computer system. During the recent years, advances in the development of geographic information systems (GISs) have resulted in increased demands from the user community for a GIS version of the ORNL routing models. In April 1994, the DOE Transportation Management Division (EM-261) held a Baseline Requirements Assessment Session with transportation routing experts and users of the HIGHWAY and INTERLINE models. As a result of the session, the development of a new GIS routing model, Transportation Routing Analysis GIS (TRAGIS), was initiated. TRAGIS is a user-friendly, GIS-based transportation and analysis computer model. The older HIGHWAY and INTERLINE models are useful to calculate routes, but they cannot display a graphic of the calculated route. Consequently, many users have experienced difficulty determining the proper node for facilities and have been confused by or have misinterpreted the text-based listing from the older routing models. Some of the primary reasons for the development of TRAGIS are (a) to improve the ease of selecting locations for routing, (b) to graphically display the calculated route, and (c) to provide for additional geographic analysis of the route.
Preparing semisynthetic and fully synthetic histones h3 and h4 to modify the nucleosome core.

The purpose of this chapter is to provide practical chemical ligation procedures to prepare histone proteins suitable for the reconstitution of nucleosomes with specific posttranslational modifications in the nucleosome core. Detailed methods are described for the efficient preparation of semi synthetic histones H3 and H4 with modifications near the C-terminus of the proteins by expressed protein ligation and desulfurization. Additionally, we present optimized protocols for solid phase peptide synthesis combined with sequential native chemical ligation to generate fully synthetic modified histone H3, here in the context of H3 lysine 56 acetylation (H3K56ac).
Justice for all: trauma and the need for safety and fairness within juvenile justice facilities

Many adolescents in the juvenile justice system have been exposed to trauma, which has been linked with negative outcomes that may lead to ineffective adjustment while incarcerated. Trauma may decr...
Hydrogen Isotope Fractionation in the Epidote-Hydrogen and Epidote-Water Systems: Theoretical Study and Implications

Experimental data for hydrogen isotope and, in general, stable isotope fractionation between mineral and water often tend to be widely divergent primarily because of solution and reprecipitation of...
American sea power in the contemporary security environment

AbstractThis article assesses the relevance of US seapower in the contemporary security environment. This paper builds upon a rich literature on sea power, strategy, and maritime operations to asse...
On the proper formulation of conditionalization

Conditionalization is a norm that governs the rational reallocation of credence. I distinguish between factive and non-factive formulations of Conditionalization. Factive formulations assume that the conditioning proposition is true. Non-factive formulations allow that the conditioning proposition may be false. I argue that non-factive formulations provide a better foundation for philosophical and scientific applications of Bayesian decision theory. I furthermore argue that previous formulations of Conditionalization, factive and non-factive alike, have almost universally ignored, downplayed, or mishandled a crucial causal aspect of Conditionalization. To formulate Conditionalization adequately, one must explicitly address the causal structure of the transition from old credences to new credences. I offer a formulation of Conditionalization that takes these considerations into account, and I compare my preferred formulation with some prominent formulations found in the literature.
Quantifying the impact of U.S. electric vehicle sales on light-duty vehicle fleet CO2 emissions using a novel agent-based simulation

Abstract When understanding the effect of new technology on any sector, it is essential to have a quantitative understanding of the sector’s “turnover rate”: the sector-wide inertia based on buying and scrappage rates of existing products. To assess sector-wide inertia in the transportation sector, this paper develops an agent-based stochastic simulation for characterization of the U.S. light-duty (LD) vehicle fleet, applying the output to quantifying the effect of electric vehicles sales on the greenhouse gas (GHG) emissions of the fleet as a whole. Such a model framework allows us to study transportation policies that might affect scrappage rates, vehicle types, and car sharing adoption and comparing them to different exogenous electric vehicle adoption scenarios. Overall, we find that the impact of scrappage rate on emissions is small – but could have synergistic interactions with our exogenous electric vehicle adoption scenarios. Furthermore, the impact of restricting vehicle type is negligible. Grid decarbonization has a large effect, roughly the same as doubling EV saturation. Lastly, mandating shared fleet electrification could have the same effect as decarbonization.
Computer aided optimal design of elastic structures

This Section concentrates on two major objectives that are currently pursued at the research level, and that should soon be ready for implementation in practical Computer Aided Engineering systems. The first objective is to develop a general approach to shape optimal design of elastic structures discretized by the Finite Element Method (FEM). The key idea is to employ geometric modeling concepts typical of the Computer Aided Design (CAD) technology, in order to produce sensitivity analysis results. These sensitivity data can then be used by an optimizer to generate an improved design.
Rationale and roadmap for developing panels of hotspot cancer driver gene mutations as biomarkers of cancer risk

Cancer driver mutations (CDMs) are necessary and causal for carcinogenesis and have advantages as reporters of carcinogenic risk. However, little progress has been made toward developing measurements of CDMs as biomarkers for use in cancer risk assessment. Impediments for using a CDM-based metric to inform cancer risk include the complexity and stochastic nature of carcinogenesis, technical difficulty in quantifying low-frequency CDMs, and lack of established relationships between cancer driver mutant fractions and tumor incidence. Through literature review and database analyses, this review identifies the most promising targets to investigate as biomarkers of cancer risk. Mutational hotspots were discerned within the 20 most mutated genes across the 10 deadliest cancers. Forty genes were identified that encompass 108 mutational hotspot codons overrepresented in the COSMIC database; 424 different mutations within these hotspot codons account for approximately 63,000 tumors and their prevalence across tumor types is described. The review summarizes literature on the prevalence of CDMs in normal tissues and suggests such mutations are direct and indirect substrates for chemical carcinogenesis, which occurs in a spatially stochastic manner. Evidence that hotspot CDMs (hCDMs) frequently occur as tumor subpopulations is presented, indicating COSMIC data may underestimate mutation prevalence. Analyses of online databases show that genes containing hCDMs are enriched in functions related to intercellular communication. In its totality, the review provides a roadmap for the development of tissue-specific, CDM-based biomarkers of carcinogenic potential, comprised of batteries of hCDMs and can be measured by error-correct next-generation sequencing. Environ. Mol. Mutagen. 61:152-175, 2020. Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.
LA RELIGION ET LA POLITIQUE DANS LE MAGHREB ARABE: UNE RELATION AMBIGUË

Este artigo apresenta a relacao entre religiao e politica, ou melhor, a ambiguidade dessa relacao em uma regiao geografica especifica, a do Magrebe arabe ou do norte da Africa. Aqui e necessaria uma precisao geografica. Atualmente, Marrocos, Argelia e Tunisia constituem a base essencial do que chamamos Magrebe Arabe. E por esse motivo que nos contentaremos em esclarecer o estado dessa relacao entre religiao e politica apenas nesses tres paises basicos. A presenca da religiao no espaco publico tornou-se cada vez mais evidente desde os ultimos vinte anos do seculo passado. Essa presenca se tornou mais impressionante desde 2011, ou seja, desde os movimentos sociopoliticos de protesto no mundo arabe. Nesta regiao, o Isla aparece como a caracteristica comum mais importante. No entanto, em uma regiao tao diversa, tanto do ponto de vista da cultura popular como politico, o impacto do Isla e sua fisionomia sao diferentes de pais para pais. Nosso objetivo aqui e a superacao do secularismo francofano e a construcao de uma teologia da libertacao muculmana.
Comorbid PTSD and Depression Diagnoses Mediate the Association of Military Sexual Trauma and Suicide and Intentional Self-Inflicted Injury in VHA-Enrolled Iraq/Afghanistan Veterans, 2004-2014.

Abstract Background Exposure to military sexual trauma (MST) in veterans is associated with suicidal ideation. Previous research suggests there are mechanisms of this association, including posttraumatic stress disorder (PTSD) and depression. Research has yet to examine whether comorbid PTSD and depression mediate the association of MST and suicide and intentional self-inflicted injury, and whether this comorbidity confers a greater risk for suicide relative to PTSD-only and depression-only. The current study addressed this gap in our knowledge. Methods Screening results identifying MST exposure, PTSD and depression diagnoses, suicide and intentional self-inflicted injury, and demographic covariates in 435,690 Iraq/Afghanistan veterans were extracted from Veterans Health Administration (VHA) medical records. Veterans were included if they attended VHA from 2004-2014. Mediation was tested with path analyses. Results Suicide and intentional self-inflicted injury was observed in 16,149 (3.71%) veterans. The indirect effect of suicide and intentional self-inflicted injury, given a positive screen for MST, was highest among veterans with comorbid PTSD and depression diagnoses (indirect effect=3.18%, 95% confidence interval [CI] [3.01%, 3.32%]), with smaller probabilities observed for both PTSD-only (indirect effect=-0.18%, 95% CI [-0.20%, -0.14%]) and depression-only (indirect effect=0.56%, 95% CI [0.51%, 0.62%]; ps Limitations Data were limited to VHA-enrolled Iraq/Afghanistan veterans. Conclusions To reduce suicide risk among veterans with a history of MST, treatments may be most effective if they target comorbid PTSD and depression. Future research should examine the mechanisms through which comorbid PTSD and depression result in heightened risk for suicide and intentional self-inflicted injury.
Büttiker probes for dissipative phonon quantum transport in semiconductor nanostructures

Theoretical prediction of phonon transport in modern semiconductor nanodevices requires atomic resolution of device features and quantum transport models covering coherent and incoherent effects. The nonequilibrium Green's function method is known to serve this purpose well but is numerically expensive in simulating incoherent scattering processes. This work extends the efficient Buttiker probe approach widely used in electron transport to phonons and considers salient implications of the method. Different scattering mechanisms such as impurity, boundary, and Umklapp scattering are included, and the method is shown to reproduce the experimental thermal conductivity of bulk Si and Ge over a wide temperature range. Temperature jumps at the lead/device interface are captured in the quasi-ballistic transport regime consistent with results from the Boltzmann transport equation. Results of this method in Si/Ge heterojunctions illustrate the impact of atomic relaxation on the thermal interface conductance and th...
Starvation Responses Throughout the Caenorhabditis elegans Life Cycle

Caenorhabditis elegans survives on ephemeral food sources in the wild, and the species has a variety of adaptive responses to starvation. These features of its life history make the worm a powerful model for studying developmental, behavioral, and metabolic starvation responses. Starvation resistance is fundamental to life in the wild, and it is relevant to aging and common diseases such as cancer and diabetes. Worms respond to acute starvation at different times in the life cycle by arresting development and altering gene expression and metabolism. They also anticipate starvation during early larval development, engaging an alternative developmental program resulting in dauer diapause. By arresting development, these responses postpone growth and reproduction until feeding resumes. A common set of signaling pathways mediates systemic regulation of development in each context but with important distinctions. Several aspects of behavior, including feeding, foraging, taxis, egg laying, sleep, and associative learning, are also affected by starvation. A variety of conserved signaling, gene regulatory, and metabolic mechanisms support adaptation to starvation. Early life starvation can have persistent effects on adults and their descendants. With its short generation time, C. elegans is an ideal model for studying maternal provisioning, transgenerational epigenetic inheritance, and developmental origins of adult health and disease in humans. This review provides a comprehensive overview of starvation responses throughout the C. elegans life cycle.
Intranasal Allopregnanolone Confers Rapid Seizure Protection: Evidence for Direct Nose-to-Brain Delivery

Allopregnanolone, a positive modulator of GABAA receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED50, 5.6 mg/kg), picrotoxin (ED50, 5.9 mg/kg), and bicuculline seizure tests. The effect peaked at 15 min, decayed over 1 h, and was still evident in some experiments at 6 h. Intranasal allopregnanolone also delayed the onset of seizures in the maximal PTZ test. At an allopregnanolone dose (16 mg/kg) that conferred comparable effects on seizure threshold as the benzodiazepines midazolam and diazepam (both at doses of 1 mg/kg), allopregnanolone caused minimal sedation or motor toxicity in the horizontal screen test whereas both benzodiazepines produced marked behavioral impairment. In addition, intranasal allopregnanolone failed to cause loss-of-righting reflex in most animals, but when the same dose was administered intramuscularly, all animals became impaired. Intranasal allopregnanolone (10 mg/kg) caused a rapid increase in brain allopregnanolone with a Tmax of ~5 min after initiation of the intranasal delivery. High levels of allopregnanolone were recovered in the olfactory bulb (Cmax, 16,000 ng/mg) whereas much lower levels (Cmax, 670 ng/mg) were present in the remainder of the brain. We conclude that the unique ability of intranasal allopregnanolone to protect against seizures without inducing behavioral adverse effects is due in part to direct nose-to-brain delivery, with preferential transport to brain regions relevant to seizures. Benzodiazepines are commonly administered intranasally for acute seizure therapy, including for the treatment of acute repetitive seizures, but are not transported from nose-to-brain. Intranasal allopregnanolone acts with greater speed, has less propensity for adverse effects, and has the ability to overcome benzodiazepine refractoriness. This is the first study demonstrating rapid functional central nervous system activity of a nose-to-brain-delivered steroid. Intranasal delivery circumvents the poor oral bioavailability of allopregnanolone providing a route of administration permitting its evaluation as a treatment for diverse neuropsychiatric indications.