cssi/SciSciGPT-SciSciNet huggingface dataset:
Value at Risk (VaR) Backtesting Techniques and P-Value Risk Decomposition Analysis

This paper presents a methodology to analyze the Value at Risk (VaR) backtesting probability values to detect the soundness of the VaR model, the integrity of the VaR input and output as well as providing information about the type of the risk that a subportfolio is exposed to in every trading day. The paper presets statistical methods to back test the number of VaR breaches when there is no or some autocorrelation in the P&L daily values. It illustrates a method to evaluate the model by backtesting all quintiles. It also presents a methodology to test the integrity of the P&L and consequently the p-values using the run test. Finally a model is presented to decompose the subportfolios’ P&L risk into systematic and idiosyncratic risk using a Gaussian Copula model. The risk decomposition can be used to detect any unusual subportfolio exposures to specific risk or detect the unusual rise in the systematic risk across different subportfolios.
Sandstone-matrix mélanges, architectural subdivision, and geologic history of accretionary complexes: A sedimentological and structural perspective from the Franciscan Complex of Sonoma and Marin counties, California, USA

Understanding details of accretionary complex architecture is essential to understanding construction of oceanic “outer” sides of orogens. The architecture of the Franciscan Complex (California), considered by many to be the “type” accretionary complex, is widely viewed in the context of terranes or belts delimited by reconnaissance mapping that reveals neither regional variations within terranes nor critical details of stratigraphy and structure. The architectural importance of Franciscan melanges is recognized, but the importance of sandstone-matrix melanges and olistostromal sandstones is not. Large-scale mapping in Sonoma and Marin counties, California, shows that Franciscan rocks are deformed, submarine-fan units of Facies A–E, plus Facies F olistolith-bearing submarine channel sandstones and olistostromal sandstone- and shale-matrix melanges. Some melanges are polygenetic with a sedimentary origin and a tectonic overprint. Glaucophane schists were recycled into conglomerates and olistostromes. Mappable units constitute members, broken and dismembered formations, and melanges. Considering the stratigraphy and structure evident at the 1:24,000 scale, accretion via a subduction channel mechanism is impossible. The Sonoma-Marin Central belt or Central terrane (melange) is not a monolithic shale-matrix melange and lacks this characteristic of rocks assigned the same name to the north. Franciscan rocks here structurally underlie thrust-faulted fragments of a regional ultramafic sheet and, locally, an underlying exotic block-bearing serpentinite-matrix melange. The detailed mapping shows that regional relations among and within Franciscan terranes and belts are poorly understood and suggests that such mapping is needed to clarify accretionary complex architecture and history. The implication for accretionary complex studies, in general, is that, while terrane or belt designations provide a general picture of the collage nature of accretionary complexes and clarification of regional relationships, only large-scale structural and stratigraphic studies can elucidate the architectural details of these orogenic complexes.
Nucleotide sequence of the splice junction of feline leukemia virus envelope mRNA.

Abstract The splice donor and acceptor sequences for the subgenomic envelope messenger RNA of feline leukemia virus (FeLV) were determined. The splice junction was characterized for viral mRNA from a prototype subgroup A FeLV and an immunodeficiency-inducing FeLV variant. Thirty-seven of 38 partial envelope cDNAs, cloned after PCR amplification from T cells infected with either virus, utilized the same splice donor and acceptor sites to generate a mRNA that would be predicted to encode envelope protein. One novel cDNA, which could also code for envelope protein, was generated from a cryptic splice acceptor 109 nucleotides downstream of the normal junction. No additional subgenomic FeLV gene products were detected using reverse transcription and polymerase chain reaction amplification of FeLV sequences from chronically infected cells.
Multivariable Control of Vapor Compression Cycle With Transient Heat Flux

This paper investigates feedback control of refrigeration cycles for high heat-flux cooling applications, where large transient heat loads may be present. We apply H∞ controller synthesis for disturbance rejection, with the evaporator heat-flux treated as the disturbance input. The controller synthesis is based on model linearization about a chosen operating point. We analyze model uncertainty due to the linearization error to ensure robustness of the closed-loop systems. We use a low-order, lumped-element nonlinear model for the vapor compression cycle. We obtain linearized systems at different operating points, and quantify system nonlinearity using the H∞ norm. Controllers synthesized for the chosen nominal systems are tested for both nominal (near the operating point) and the worst-case performance in nonlinear simulations. For systems close to critical heat-flux (CHF), it is shown that a trade-off exists between the nominal performance and robust stability. For systems far away from CHF, it is shown that the open-loop system has the optimal cooling capacity. The performance of H∞ controller for systems near CHF is validated by experiment.© 2013 ASME
Transient axially asymmetric response of an elastic plate

Abstract The problem of finding the response of a thick infinite plate to the application of body forces is considered. Transform techniques are employed to reduce the problem to that of an initial boundary value problem for a one-dimensional hyperbolic system. The latter is solved by the method of eigenfunction expansion. A representation of the displacement field is obtained which may be used to compute the transient response of the plate. As ab example we apply this method to obtain the plate response to the application of a point force. We discuss the computer implementation of this approach. Numerical simulations are presented for the case of an oblique force with a short burst time function.
Recognition of simulated telephone speech by cochlear implant users.

Purpose To evaluate cochlear implant users’ understanding of telephone speech. Method Telephone speech was simulated by band-limiting broadband speech stimuli. Multitalker vowel, consonant, and sen...
Direct minimization of Hartree—Fock energy for alternant hydrocarbons in the PPP model

Abstract The bond-order matrix in the PPP model of alternant hydrocarbons is expressed in terms of independent parameters and, hence, the SCF energy itself is explicitly obtained in terms of these parameters. Direct minimization of the energy expression gives, besides those normally obtained, some new minima which cannot be reached by the customary iterative SCF procedure.
Comparison of passive enforcement techniques for DRAM package models

Passivity enforcement techniques are widely used in DRAM package model development. The Hamiltonian method is one of the common methods used for checking/enforcing passivity of these multiport networks. Enforcing the passivity for non-passive models is not trivial because it is built on several approximation steps starting from building the macromodel, which captures the frequency domain response, and ending with a suitable spice model for the DRAM circuits. Several approximation steps take place to achieve that result, and multiple constraints are used to preserve the original design characteristics. In this paper, we compared residue perturbation with and without error control in order to calculate how passivity enforcement affects the original model accuracy.
Fidelity of T Cell Activation Through Multistep T Cell Receptor ζ Phosphorylation

The T cell receptor (TCR) αβ heterodimer interacts with its ligands with high specificity, but surprisingly low affinity. The role of the ζ component of the murine TCR in contributing to the fidelity of antigen recognition was examined. With sequence-specific phosphotyrosine antibodies, it was found that ζ undergoes a series of ordered phosphorylation events upon TCR engagement. Completion of phosphorylation steps is dependent on the nature of the TCR ligand. Thus, the phosphorylation steps establish thresholds for T cell activation. This study documents the sophisticated molecular events that follow the engagement of a low-affinity receptor.
Three‐dimensional spectral‐spatial excitation

A method of three-dimensional spectral-spatial excitation is presented which is selective simultaneously in two spatial dimensions and in the spectral or chemical shift dimension. This method can be used to create spectral passbands whose center frequency varies as a function of spatial location within an imaging plane. This variation of passband center frequency may be specified by an acquired main field (B0) map; the resulting excitations compensate for inhomogeneity of the B0 field. In vivo images are presented in which three-dimensional spectral-spatial excitation allows selective water-only imaging in the presence of large B0 inhomogeneity where conventional spectrally selective imaging falls. Phantom studies give a detailed profile of the performance of three-dimensional spectral-spatial pulses suitable for water-only or fat-saturation imaging. These pulses may also be useful for fat and water suppression in spectroscopic imaging. Performance constraints imposed by limited gradient slew rates are analyzed and quantified.
Palmitoylation and Intracellular Domain Interactions Both Contribute to Raft Targeting of Linker for Activation of T Cells

Some transmembrane proteins must associate with lipid rafts to function. However, even if acylated, transmembrane proteins should not pack well with ordered raft lipids, and raft targeting is puzzling. Acylation is necessary for raft targeting of linker for activation of T cells (LAT). To determine whether an acylated transmembrane domain is sufficient, we examined raft association of palmitoylated and nonpalmitoylated LAT transmembrane peptides in lipid vesicles by a fluorescence quenching assay, by microscopic examination, and by association with detergent-resistant membranes (DRMs). All three assays detected very low raft association of the nonacylated LAT peptide. DRM association was the same as a control random transmembrane peptide. Acylation did not measurably enhance raft association by the first two assays but slightly enhanced DRM association. The palmitoylated LAT peptide and a FLAG-tagged LAT transmembrane domain construct expressed in cells showed similar DRM association when both were reconstituted into mixed vesicles (containing cell-derived proteins and lipids and excess artificial raft-forming lipids) before detergent extraction. We conclude that the acylated LAT transmembrane domain has low inherent raft affinity. Full-length LAT in mixed vesicles associated better with DRMs than the peptide. However, cells appeared to contain two pools of LAT, with very different raft affinities. Since some LAT (but not the transmembrane domain construct) was isolated in a protein complex, and the Myc- and FLAG-tagged forms of LAT could be mutually co-immunoprecipitated, oligomerization or interactions with other proteins may enhance raft affinity of one pool of LAT. We conclude that both acylation and other factors, possibly protein-protein interactions, target LAT to rafts.
Yielding Elastic Tethers Stabilize Robust Cell Adhesion

Many bacteria and eukaryotic cells express adhesive proteins at the end of tethers that elongate reversibly at constant or near constant force, which we refer to as yielding elasticity. Here we address the function of yielding elastic adhesive tethers with Escherichia coli bacteria as a model for cell adhesion, using a combination of experiments and simulations. The adhesive bond kinetics and tether elasticity was modeled in the simulations with realistic biophysical models that were fit to new and previously published single molecule force spectroscopy data. The simulations were validated by comparison to experiments measuring the adhesive behavior of E. coli in flowing fluid. Analysis of the simulations demonstrated that yielding elasticity is required for the bacteria to remain bound in high and variable flow conditions, because it allows the force to be distributed evenly between multiple bonds. In contrast, strain-hardening and linear elastic tethers concentrate force on the most vulnerable bonds, which leads to failure of the entire adhesive contact. Load distribution is especially important to noncovalent receptor-ligand bonds, because they become exponentially shorter lived at higher force above a critical force, even if they form catch bonds. The advantage of yielding is likely to extend to any blood cells or pathogens adhering in flow, or to any situation where bonds are stretched unequally due to surface roughness, unequal native bond lengths, or conditions that act to unzip the bonds.
A novel method for monitoring protoplast fusion

Two fluorescent compounds, scopoletin and carboxyfluorescein, have been used to label both tissue culture and leaf mesophyll cells and protoplasts. The compounds localized within the vacuoles of cells in approximately 15 hours. They remained in the vacuole during cell wall digestion, and fluorescence was observable for several hours after protoplast release. A one day pulse of these fluorescent labels had no deleterious effect on the growth of cells or protoplasts. When morphologically indistinguishable protoplasts were labeled and treated with polyethylene glycol, multicolored fluorescent fusion products were observable. These fluorescent labels provide a convenient method for selection of heterokaryon fusion products of whole plant and tissue culture cell protoplasts.
Evaluation of Supplemental Protein Sources for Broiler Chicks

Abstract Two chick growth assays were completed to evaluate cottonseed meal, single-cell protein (torula yeast) and dehulled soybean meal in various combinations. In all cases, ground yellow corn supplied 4% of the total dietary crude protein (23%) with the balance coming from supplemental protein sources under study. To simulate conditions in those parts of the world where crystalline methionine and lysine are not readily available or economical, no amino acid fortification was carried out. As the sole source of supplemental protein, soybean meal was far superior to the rest, but equal protein contributions from soybean meal and cottonseed meal or from soybean meal, cottonseed meal and single-cell protein resulted in weight gains similar to those obtained with soybean meal alone. Equal protein contributions from cottonseed meal and single-cell protein resulted in gains and gain/feed ratios considerably greater than those occurring when either of these ingredients was fed alone. With soybean meal-cottonseed meal combinations, chicks gained similarly when fed soy-cottonseed protein ratios of 1:0, 5:1, 2:1, 1:1 or 1:2, but gain/feed declined linearly as cottonseed protein replaced soy protein in the diet.
Nonlinear excitation of acoustic modes by large-amplitude Alfvén waves in a laboratory plasma.

The nonlinear three-wave interaction process at the heart of the parametric decay process is studied by launching counterpropagating Alfven waves from antennas placed at either end of the Large Plasma Device. A resonance in the beat wave response produced by the two launched Alfven waves is observed and is identified as a damped ion acoustic mode based on the measured dispersion relation. Other properties of the interaction including the spatial profile of the beat mode and response amplitude are also consistent with theoretical predictions for a three-wave interaction driven by a nonlinear ponderomotive force.
Visual feedback in the control of pheromone-mediated flight ofHeliothis virescens males (Lepidoptera: Noctuidae)

MaleHeliothis virescens (F.) (Lepidoptera: Noctuidae) were made to fly into a uniformly white and translucent tube within a large wind tunnel while responding to sex pheromone. Different visual patterns placed within the tube greatly affected the ability of the male moths to maintain upwind progress or remain oriented to the wind while in contact with the plume. Over 89% of males attempting to fly through a blank tube, lacking visual patterns, became disoriented, the males gaining or losing altitude and repeatedly hitting the sides of the tube. Patterns of 20–40 dots placed on the sides of the tube at or slightly above plume level resulted in high levels of sustained upwind flight (47–74%) relative to patterns placed directly below (30–40%), directly above (35%), or slightly below the level of the flight path (26–44%). Optimal upwind progression in pheromone-responding males occurred when image motion could be resolved both transversely (T), orthogonally to the longitudinal axis of the body relative to the horizontal plane of the environment, and longitudinally (L), along the body axis. Even very sparse patterns (single rows of dots) could elicit high levels of sustained upwind flight (53–63%) when positioned within the tube such that the males' movements would create both L and T image motion. However, successful negotiation of the tube was also unexpectedly facilitated by patterns apparently providing no horizontal transverse component for flying males but providing longitudinal flow while centering the moth in the plume through a symmetrical left-right input (4–40%).
Lithium stops hereditary shuddering in Drosophila melanogaster

Shudderer is an X-linked dominant mutation of Drosophila melanogaster. The mutant is characterized by sporadically occurring leg jerks which cause the fly to lurch and shudder. This behavior was suppressed by adding lithium chloride, lithium acetate, or ammonium chloride to the fly's diet. These same salts also restored the fly's reactive climbing abilities toward normal levels.
Equality as the Virtue of Sovereigns: A Reply to Ronald Dworkin

My article was not a review of Sovereign Virtue nor was it primarily a critique of Dworkin's theory. The article's primary topic was the position that Anderson has labeled "luck egalitarianism." I said at the outset of the article that there are many different versions of luck egalitarianism, but that they share a common core idea. The core idea is that inequalities deriving from people's voluntary choices are acceptable, whereas inequalities deriving from unchosen features of people's circumstances are unjust. Parts of my discussion were devoted to identifying what I take to be some general difficulties with this core idea, when it is taken at face value. In his reply, Dworkin responds to a number of these generic criticisms as if they had been aimed specifically at him, but I am well aware that his theory departs from the generic luck-egalitarian position in certain respects. Indeed, I emphasized that the reason I was devoting special attention to his theory was precisely because of the ways in which it departs from the generic luck-egalitarian position, and thus avoids some of the difficulties of that position.
Chromatin modification by SUMO-1 stimulates the promoters of translation machinery genes

SUMOylation of transcription factors and chromatin proteins is in many cases a negative mark that recruits factors that repress gene expression. In this study, we determined the occupancy of Small Ubiquitin-like MOdifier (SUMO)-1 on chromatin in HeLa cells by use of chromatin affinity purification coupled with next-generation sequencing. We found SUMO-1 localization on chromatin was dynamic throughout the cell cycle. Surprisingly, we observed that from G1 through late S phase, but not during mitosis, SUMO-1 marks the chromatin just upstream of the transcription start site on many of the most active housekeeping genes, including genes encoding translation factors and ribosomal subunit proteins. Moreover, we found that SUMO-1 distribution on promoters was correlated with H3K4me3, another general chromatin activation mark. Depletion of SUMO-1 resulted in downregulation of the genes that were marked by SUMO-1 at their promoters during interphase, supporting the concept that the marking of promoters by SUMO-1 is associated with transcriptional activation of genes involved in ribosome biosynthesis and in the protein translation process.
Nursing Perceptions of Clinical Research in the Neonatal Intensive Care Unit

Abstract The purpose of the study is to determine perceptions of clinical research in the NICU. This is a survey study. Nurses (n = 68) employed in a level III NICU in the Midwestern United States were included. The main outcome variable is the cross-sectional analysis of responses to a survey exploring perceptions of clinical research. Ninety-seven percent of nurses (n = 66) agree that clinical research is important for improving care, while 57% (n = 39) report that it affects their day positively. Thirty-seven percent reported excellent communication between clinical and research teams. In addition, 27% (n = 18) of nurses reported research presents complications for families, and 79% (n = 54) reported that it is acceptable to cease a research protocol for infant benefit. Years of practice and whether nurses read research affected various responses. Clinical research is imperative to inform best practice, and nurses are an integral part of care. Therefore, it is essential to better define strategies to bridge the gap between clinical and research teams.
Publishing Patterns Evidenced in the Core Higher Education Journals.

Using a framework for analyzing manuscripts that appear in the higher education journal literature, this paper examines eight core journals' publishing patterns for the period 1975 to 1981. In addition to examining publishing patterns by year and journal, the paper also presents the institutional affiliations and roles of papers' senior authors. The data, which comprise the operational editorial policies of higher education journals, can be used by authors, editors, and other field members to better understand the epistemological directions of journals in higher education.
Radiation exposure prior to traumatic brain injury induces responses that differ as a function of animal age

AbstractPurpose: Uncontrolled radiation exposure due to radiological terrorism, industrial accidents or military circumstances is a continuing threat for the civilian population. Age plays a major role in the susceptibility to radiation; younger children are at higher risk of developing cognitive deterioration when compared to adults. Our objective was to determine if an exposure to radiation affected the vulnerability of the juvenile hippocampus to a subsequent moderate traumatic injury.Materials and methods: Three-week-old (juvenile) and eight-week-old young adult C57BL/J6 male mice received whole body cesium-137 (137Cs) irradiation with 4 gray (Gy). One month later, unilateral traumatic brain injury was induced using a controlled cortical impact system. Two months post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water-maze. After cognitive testing, animals were euthanized and their brains frozen for immunohistochemical assessment of activated microglia...
Primeiro pré-molar superior com três canais: diagnóstico e tratamento - quatro casos clínicos

Resumo Apesar da presenca de dois canais radiculares ser a anatomia mais comum nos primeiros pre-molares superiores, derivacoes anatomicas para um e tres canais estao tambem descritas. Um correcto conhecimento das diversas morfologias, uma correcta analise radiografica e auxiliares de ampliacao potenciam o sucesso nestes casos. O objectivo deste texto e, apresentando uma serie de casos clinicos, contribuir para o melhor conhecimento e abordagem deste tipo de situacoes clinicas.
Modulation of Y356 photooxidation in E. coli class Ia ribonucleotide reductase by Y731 across the α2: β2 interface

Substrate turnover in class Ia ribonucleotide reductase (RNR) requires reversible radical transport across two subunits over 35 A, which occurs by a multistep proton-coupled electron-transfer mechanism. Using a photooxidant-labeled β2 subunit of Escherichia coli class Ia RNR, we demonstrate photoinitiated oxidation of a tyrosine in an α2:β2 complex, which results in substrate turnover. Using site-directed mutations of the redox-active tyrosines at the subunit interface, Y356F(β) and Y731F(α), this oxidation is identified to be localized on Y356. The rate of Y356 oxidation depends on the presence of Y731 across the interface. This observation supports the proposal that unidirectional PCET across the Y356(β)–Y731(α)–Y730(α) triad is crucial to radical transport in RNR.
Magnetic circular dichroism at the K and L edges of Co and Cu in Co/Cu(001)

The fcc Co/Cu(001) system is investigated using the full potential linearized augmented plane wave method. Through the atomic force approach, large multilayer relaxations (6.5%, 5.3%, and 2.8%) are found between the adjacent Cu layers, which reduces the total energy by 128 meV. The spin and orbital magnetic moments for Co atoms are 1.79 and 0.12 μB, respectively. At the interfacial Cu site, we found a sizable induced magnetic moment, 0.05 μB, which can be split into d (0.074 μB) and s,p(0.024 μB) contributions. Interestingly, the spin polarization of d and s,p states can be detected separately through the magnetic circular dichroism at the L and K edges, for which the calculated results agree very well with experiments.
Expanded HOXA13 polyalanine tracts in a monotreme.

SUMMARY The N-terminal region of human HOXA13 has seven discrete polyalanine tracts. Our previous analysis of these tracts in multiple major vertebrate clades suggested that three are mammal-specific. We now report the N-terminal HOXA13 repetitive tract structures in the monotreme Tachyglossus aculeatus (echidna). Contrary to our expectations, echidna HOXA13 possesses a unique set of polyalanine tracts and an unprecedented polyglycine tract. The data support the conclusion that the emergence of expanded polyalanine tracts in proteins occurred very early in the stem lineage that gave rise to mammals, between 162 and 315Ma.
Defining Dystonic Tremor

A strong association between dystonia and tremor has been known for more than a century. Two forms of tremor in dystonia are currently recognized: 1) dystonic tremor, which is tremor produced by dystonic muscle contraction and 2) tremor associated with dystonia, which is tremor in a body part that is not dystonic, but there is dystonia elsewhere. Both forms of tremor in dystonia frequently resemble essential tremor or another pure tremor syndrome (e.g., isolated head and voice tremors and task-specific writing tremor), and relationships among these tremor disorders have long been debated. Misdiagnosis is common because mild dystonia is frequently overlooked in patients with tremor. It is now clear that essential tremor is a syndrome, not a specific disease, and the use of essential tremor as a specific clinical diagnosis is arguably an impediment to elucidating this and other pure tremor syndromes and their relationship to dystonia. A new classification, primary tremor, is proposed and would be used for any disorder in which tremor is the sole or principal abnormality with no identifiable etiology other than possible genetic inheritance. This classification scheme would facilitate tremor research by moving the focus from the narrow question “Is it essential tremor?” to a broader consideration of what genetic and environmental factors cause primary tremor disorders, and how do they relate to dystonia and other neurological disorders.
Separation of P And S-Waves On Multicomponent Cross-Borehole And VSP Data

In order to process multi-component seismic data recorded on crossborehole and VSP configurations, it is often convenient to separate events into P and S modes. In this paper, a new wave-mode separation technique is described. Our technique performs decomposition of Pand S-waves on multi-component data in time-space domain, Ranzinger (1990). The technique was tested on both cross-borehole and VSP elastic physical model data sets. The results are compared with those obtained using Dankbaar's (1985,1987) mode separation technique which decomposes tne multicomponent data in frequency-wavenumber (f-k) domain. Both methods give comparable results. However, our method does better when variable velocity media are involved.
Spectra of 208Po and the Hyperfine Structure of 209Po

Data are presented on the wavelengths of 97 lines of 208Po and on the hyperfine structure of 31 lines of 209Po. From these data, relative values of 26 energy levels of 208Po I have been deduced. The hyperfine-structure splittings of 14 of these levels in 209Po have been determined. Some tentative identifications of the levels have been made, based on a determination of the absolute value of the fundamental level 6p4 3P2′ by application of a Ritz formula to three levels taken as 6p3 (4S)np5P3′, n = 7,8,9. The ionization potential of 208Po has been tentatively estimated as 8.414 V. From the measured splittings of the energy levels of the configuration 6p4 of 209Po i, the nuclear magnetic moment of 209Po is estimated to be 0.76 nm. Mrozowski’s identifications of some lines of Po i are examined. It is found that his identifications of the 4611 A and 5940 A lines are confirmed by coincidence of frequencies and by hyperfine-structure patterns, but that his identifications of the other lines and his determination of 6p4 1S0′ could not be confirmed by the data of this investigation.
Asymptotic packing densities for two-dimensional lattice models

Blocks of nodes are randomly packed on torus shaped lattices, and estimates of some random packing densities are obtained by repeated simulation. Using nonlinear regression to fit the estimated densities, an asymptotic approximation formula is obtained for the packing densities which is similar to Mackenzie's result in the analogous one-dimensional setting. Upon taking a limit, the formula yields an estimate of the analog of Renyi's asymptotic packing constant which is in close agreement with some values that have been proposed by others
Stabilization of different types of transition states in a single enzyme active site: QM/MM analysis of enzymes in the alkaline phosphatase superfamily.

The first step for the hydrolysis of a phosphate monoester (pNPP2–) in enzymes of the alkaline phosphatase (AP) superfamily, R166S AP and wild-type NPP, is studied using QM/MM simulations based on an approximate density functional theory (SCC-DFTBPR) and a recently introduced QM/MM interaction Hamiltonian. The calculations suggest that similar loose transition states are involved in both enzymes, despite the fact that phosphate monoesters are the cognate substrates for AP but promiscuous substrates for NPP. The computed loose transition states are clearly different from the more synchronous ones previously calculated for diester reactions in the same AP enzymes. Therefore, our results explicitly support the proposal that AP enzymes are able to recognize and stabilize different types of transition states in a single active site. Analysis of the structural features of computed transition states indicates that the plastic nature of the bimetallic site plays a minor role in accommodating multiple types of tra...
SERS chemical sensors and biosensors: new tools for environmental and biological analysis☆

This paper describes recent advances in chemical sensors and biosensors based on surface-enhanced Raman scattering (SERS) detection. The SERS-active probes involve silver-coated microstructured substrates designed to amplify the Raman signals of adsorbed molecules and to detect trace chemicals in liquid as well as vapor samples. The development and application of several SERS devices such as a fiber-optic remote sensor and a vapor dosimeter are described. The results illustrate the different uses of the SERS method for the identification and quantification of important environmental and biological compounds.
Rit GTPase Regulates a p38 MAPK-Dependent Neuronal Survival Pathway

Rit, along with Rin and Drosophila Ric, comprises the Rit subfamily of Ras-related small GTPases. Although the cellular functions of many Ras family GTPases are well established, the physiological significance of Rit remains poorly understood. Loss of Rit sensitizes multiple mammalian cell lines and mouse embryonic fibroblasts (MEFs) derived from Rit−/− mice to oxidative stress-mediated apoptosis. However, whether Rit-mediated pro-survival signaling extends to other cell types, particularly neurons, is presently unknown. Here, to examine these issues we generated a transgenic mouse overexpressing constitutively active Rit (RitQ79L) exclusively in neurons, under control of the Synapsin I promoter. Active Rit-expressing hippocampal neurons display a dramatic increase in oxidative stress resistance. Moreover, pharmacological inhibitor studies demonstrate that p38 MAPK, rather than a MEK/ERK signaling cascade, is required for Rit-mediated protection. Together, the present studies identify a critical role for the Rit-p38 MAPK signaling cascade in promoting hippocampal neuron survival following oxidative stress.
Sulfur mustard lowers nicotinamide adenine dinucleotide concentrations in human skin grafted to athymic nude mice

Human skin grafted to athymic nude mice shows a decrease in nicotinamide adenine dinucleotide (NAD+) concentrations when exposed to sulfur mustard (HD). The lowering of NAD+ is dependent on both dose of HD and time after exposure. When HD is applied to grafted skin at 127 μg/cm2, the decrease in NAD+ begins immediately after exposure, approaches minimal values by 4 hr. NAD+ returned to normal within 18 hr. With higher concentrations of HD, NAD+ concentrations fall precipitously within 4 hr, reach a minimum value at 18 hr, and seem to remain at this depressed value for at least 72 hr. NAD+ loss appears to precede and be proportional to tissue injury. Pretreatment of mice with 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) polymerase, seems to lessen the effect of HD. At higher concentrations of HD, human grafts from mice pretreated with 3-aminobenzamide show significant protection from loss of NAD+ levels after 4 hr.
Parliament in print: William Caxton and the history of political government in the fifteenth century

This article explores the narrative of parliamentary history in fifteenth-century England, specifically as found in the texts William Caxton printed. It investigates Caxton's approach to history and motivation for choosing texts, his translations and vocabulary, his editorial oversight and his audience. As his confidence in his own skill grew, and as he moved from a continental to an English context, his reading of parliaments changed. Initially it corresponded to his French texts, but by the early 1480s he understood the term ‘parliament’ to mean some variation of the contemporary English Parliament. Caxton's later understanding is reflected in the histories he published. This article emphasises the importance of Caxton's historical narratives to Parliament's legitimacy and to political discourse in a time when few parliaments were held.
From within the thick of it: Human beings doing being human in languaged worlds

In this commentary I note that Lipari and Bertau want to assume that we live immersed in a flowing, stranded, agential reality in which no-“thing” is separate from any-“thing” else. Thus rather than being wholly in control of the unfolding processes of importance to us, we need to see ourselves as essentially living within dialogical and hermeneutical, back-and-forth relations with the others and othernesses around us. So although we may assume our understandings occur as a result of our “thoughts,” “ideas,” or “theories,” the fact is such nameable causal processes can only be seen as having been at work in people’s performances after they have been performed. Something else altogether guides us in the performance of our actions than the nameable “things” whose nature we currently seek to discover in our inquiries. Both Lipari and Bertau go a long way towards describing the nature of this “something else.”
The design, characterization, and comparison of MEMS comb-drive acoustic emission transducers with the principles of area-change and gap-change

Comb-drive transducers are made of interdigitized fingers formed by the stationary part known as stator and the moving part known as rotor, and based on the transduction principle of capacitance change. They can be designed as area-change or gap-change mechanism to convert the mechanical signal at in-plane direction into electrical output. The comb-drive transducers can be utilized to differentiate the wave motion in orthogonal directions when they are utilized with the outof- plane transducers. However, their sensitivity is weak to detect the wave motion released by newly formed damage surfaces. In this study, Micro-Electro-Mechanical System (MEMS) comb-drive Acoustic Emission (AE) transducer designs with two different mechanisms are designed, characterized and compared for sensing high frequency wave propagation. The MEMS AE transducers are manufactured using MetalMUMPs (Metal Multi-User MEMS Processes), which use electroplating technique for highly elevated microstructure geometries. Each type of the transducers is numerically modeled using COMSOL Multiphysics program in order to determine the sensitivity based on the applied load. The transducers are experimentally characterized and compared to the numerical models. The experiments include laser excitation to control the direction of the wave generation, and actual crack growth monitoring of aluminum 7075 specimens loaded under fatigue. Behavior and responses of the transducers are compared based on the parameters such as waveform signature, peak frequency, damping, sensitivity, and signal to noise ratio. The comparisons between the measured parameters are scaled according to the respective capacitance of each sensor in order to determine the most sensitive design geometry.
IUCF Status Report

A report is presented on the status of the Indiana University Cyclotron Facility (IUCF) three years after first operation. The range of accelerator beam characteristics, the beam delivery record for research use and selected observations of unusual features of this facility will be given.
Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective.
Two quantitative assays for chemotaxis inParamecium

We present two new methods to quantify the attraction and repulsion ofParamecium aurelia by chemicals. These are a T-maze assay and a countercurrent separation assay. In the T-maze assay, cells were placed in one arm of a three-way stopcock. The cells were then allowed to enter the other two arms, one of which contained an attractant or repellent. The ratio of cells collected from these two arms was an index of chemotaxis. The reproducibility of this method was demonstrated, using potassium acetate to study attraction (positive chemotaxis), and quinine-HCl to study repulsion (negative chemotaxis). This method is rapid and convenient. The countercurrent separation assay was adapted from the method of Dusenbery (1973), originally used to study behavior in nematodes. Animals were injected into the center of a slanted tube through which two solutions of different densities were pumped in opposite directions. One solution contained an attractant or repellent. Animals emerging from the tube in each of the two solutions were counted. These counts were used to measure the extent of chemotaxis. This method is useful for studying attraction in populations of over 104 paramecia and for isolating mutants defective in chemotaxis.
A 4π Detector Array, NIMROD-ISIS

Fermi energy heavy ion collisions provide a valuable tool to research nuclear reaction dynamics and the hot nuclear matter Equation of State (EOS) at sub/supra-normal densities. In this energy regime, multi-fragmentation becomes important and the ejected light particles and intermediate mass fragments (IMFs) with Z > 2 carry a great deal of information on the thermal and chemical evolution of the reaction system under investigation. Existing detectors [1] include those with excellent isotopic resolution with limited angular coverage or excellent geometric acceptance with moderate isotopic resolution. Much information has been extracted from experiments performed with these detectors [2–9]. Ideally, a detector array with both excellent isotopic resolution and with a nearly 4π angular coverage of discrete telescopes with a high granularity is desirable. NIMROD–ISiS at the Cyclotron Institute, TAMU, is designed for such purposes and provides a powerful detector array capable of both charged particle and neut...
Multidisciplinary Engineering Systems 2nd and 3rd Year College-Wide Courses

Abstract - Undergraduate engineering education today is ineffective in preparing students for multidisciplinary system integration and optimization - exactly what is needed by companies to become innovative and gain a competitive advantage in this global economy. While there is some movement in engineering education to change that, this change is not easy, as it involves a cultural change from the silo approach to a holistic approach. The ABET-required senior capstone multidisciplinary design course too often becomes a design-build-test exercise with the emphasis on just getting something done. Students rarely break out of their disciplinary comfort zone and thus fail to experience true multidisciplinary system design. What is needed are multidisciplinary systems courses, with a balance between theory and practice, between academic rigor and the best practices of industry, presented in an integrated way in the 2nd and 3rd years that prepares students for true multidisciplinary systems engineering at the senior level and beyond. The two courses presented here represent a significant curriculum improvement in response to this urgent need.
Ubiquitin proteasome system-mediated degradation of synaptic proteins: An update from the postsynaptic side

The ubiquitin proteasome system is one of the principle mechanisms for the regulation of protein homeostasis in mammalian cells. In dynamic cellular structures such as neuronal synapses, ubiquitin proteasome system and protein translation provide an efficient way for cells to respond promptly to local stimulation and regulate neuroplasticity. The majority of research related to long-term plasticity has been focused on the postsynapses and has shown that ubiquitination and subsequent degradation of specific proteins are involved in various activity-dependent plasticity events. This review summarizes recent achievements in understanding ubiquitination of postsynaptic proteins and its impact on synapse plasticity and discusses the direction for advancing future research in the field.
Instituting systems-based practice and practice-based learning and improvement: a curriculum of inquiry

Background: The Accreditation Council for Graduate Medical Education (ACGME) requires that training programs integrate system-based practice (SBP) and practice-based learning and improvement (PBLI) into internal medicine residency curricula. Context and setting : We instituted a seminar series and year-long-mentored curriculum designed to engage internal medicine residents in these competencies. Methods : Residents participate in a seminar series that includes assigned reading and structured discussion with faculty who assist in the development of quality improvement or research projects. Residents pursue projects over the remainder of the year. Monthly works in progress meetings, protected time for inquiry, and continued faculty mentorship guide the residents in their project development. Trainees present their work at hospital-wide grand rounds at the end of the academic year. We performed a survey of residents to assess their self-reported knowledge, attitudes and skills in SBP and PBLI. In addition, blinded faculty scored projects for appropriateness, impact, and feasibility. Outcomes : We measured resident self-reported knowledge, attitudes, and skills at the end of the academic year. We found evidence that participants improved their understanding of the context in which they were practicing, and that their ability to engage in quality improvement projects increased. Blinded faculty reviewers favorably ranked the projects’ feasibility, impact, and appropriateness. The ‘Curriculum of Inquiry’ generated 11 quality improvement and research projects during the study period. Barriers to the ongoing work include a limited supply of mentors and delays due to Institutional Review Board approval. Hospital leadership recognizes the importance of the curriculum, and our accreditation manager now cites our ongoing work. Conclusions : A structured residency-based curriculum facilitates resident demonstration of SBP and practice-based learning and improvement. Residents gain knowledge and skills though this enterprise and hospitals gain access to trainees who help to solve ongoing problems and meet accreditation requirements. Keywords: graduate medical education; competencies; longitudinal curriculum (Published: 16 September 2013) Citation: Med Educ Online 2013, 18 : 21612 - http://dx.doi.org/10.3402/meo.v18i0.21612