cssi/SciSciGPT-SciSciNet huggingface dataset:
The connectivity of silicon sites in silicate glasses, as determined by two-dimensional 29Si nuclear magnetic resonance spectroscopy☆

Abstract The application of two-dimensional silicon-29 homonuclear shift correlated magic angle spinning nuclear magnetic resonance (COSY MAS NMR) spectroscopy to silicate glasses prepared using silica isotopically enriched in silicon-29 is reported. Two sodium silicate glass compositions and a sodium phospho-silicate glass were examined. The results suggest that a substantial proportion of the four coordinate silicate sites in sodium silicate glasses Q2/Q3 and Q3/Q4 are interconnected on a nearest neighbor level. Experiments with the sodium silicate glasses prepared with varying levels of isotopic enrichment reveal a correlation between the intensity of the cross peak and the percentage of silicon-29 in the sample, confirming this observation. No cross peaks were observed for the sodium phospho-silicate glass, implying that the Q4 and six coordinate silicate sites present are not linked together at the nearest neighbor level.
A 77-Year-Old Farmer With Respiratory Failure and Thrombocytopenia

A 77-year-old farmer presented with a 3-month history of progressive dyspnea. His symptoms started with anorexia, malaise, fever, and dry cough. He was initially treated with azithromycin and a short course of oral corticosteroids for COPD exacerbation. Two days after finishing the treatment, his symptoms progressed, and he was admitted to a local hospital with respiratory distress, altered mental status, hypotension, and abnormal chest radiograph findings. Bronchoscopy showed normal airways, and the BAL fluid sample revealed lymphocytosis with negative culture results. The patient was treated with doxycycline, ceftriaxone, and corticosteroids for presumed hypersensitivity pneumonitis and showed some improvement. He was subsequently discharged from the hospital while receiving therapy with prednisone, 20 mg. Five days later, he was readmitted to the hospital with worsening malaise, fever, altered mental status, and severe respiratory distress that required mechanical ventilation. He was then transferred to our facility for further management. His medical history was significant for hypertension and diabetes. He was a lifelong nonsmoker and had worked his whole life as a farmer. He denied the use of alcohol or illegal drugs. The patient lived in Ohio, and no recent travels or contacts with sick persons were reported by the family. Physical Examination The patient arrived intubated and receiving mechanical ventilation. His temperature was 97.4°F, BP was 90/68 mm Hg, heart rate was 120 beats/min, respiratory rate was 22 breaths/min, and oxygen saturation was 98% with a fraction of inspired oxygen of 80%. The findings of examinations of the head, eyes, nose, and throat were unremarkable. His neck was supple with no lymphadenopathy. A chest examination revealed bilateral ronchi. The findings of a cardiovascular examination were significant only for tachycardia. His abdomen was soft, nontender, and there was no hepatosplenomegaly. There were no skin lesions or lower-extremity edema.
A UNIFICATION-BASED PARSER FOR RELATIONAL GRAMMAR

We present an implemented unification-based parser for relational grammars developed within the stratified feature grammar (SFG) framework, which generalizes Kasper-Rounds logic to handle relational grammar analyses. We first introduce the key aspects of SFG and a lexicalized, graph-based variant of the framework suitable for implementing relational grammars. We then describe a head-driven chart parser for lexicalized SFG. The basic parsing operation is essentially ordinary feature-structure unification augmented with an operation of label unification to build the stratified features characteristic of SFG.
The Effect of Acute and Chronic Asthma Severity on Pediatric Emergency Department Utilization

OBJECTIVE. Our goal was to teach emergency department (ED) physicians how to use standardized criteria for diagnosing and classifying asthma severity and to describe the patterns of pediatric ED utilization of these criteria for classification of both acute and chronic severity. METHOD. A health care provider education module was developed and implemented in 4 participating EDs in southeast Texas to educate ED physicians and health care providers on the diagnosis and acute and chronic severity classification of pediatric asthma patients. We undertook both retrospective (medical chart extraction) and prospective surveillance over a 2-year period of all children presenting to 1 of 4 EDs with acute asthma. Demographic characteristics, classification of severity, health care resource utilization, and primary physician contact information were collected. RESULTS. The health care provider educational intervention was provided for 84 different physicians. A subset of 16 physicians was randomly tested preintervention and postintervention. Mean mock-scenario scores at 2 weeks showed an improvement of 55.6%, which was sustained at retesting at 6 months. Over the 2-year period, 6222 individual pediatric ED encounters were entered into the surveillance database. The median age of presentation was 5 years. More than 32% of the patients in the study were uninsured. The majority of the patients in each category had asthma of mild severity: mild intermittent chronic (58.7%) and mild acute (53.9%). CONCLUSIONS. Physicians who completed a health care provider education module learned to effectively diagnose asthma and recognize standardized acute and chronic severity classifications. The majority of children with asthma who presented to the Texas Emergency Department Asthma Surveillance project9s participating EDs were classified as having mild acute severity and mild intermittent chronic disease. Almost one third of these patients did not have health insurance.
Survival and Recovery Rate of Canada Geese Staging in Interior Alaska

Abstract Lesser Canada geese (Branta canadensis parvipes) are indistinguishable from other subspecies of small Canada geese on the wintering grounds using current survey methods. Consequently, managers are unable to adequately measure their abundance. Without direct estimates of abundance, researchers often use estimates of vital rates that influence abundance (e.g., annual survival) to monitor potential impact of harvest on the population. Based on capture and re-sighting data records of 567 geese marked from 1994 through 1998, we calculated annual survival and recovery rates for different age and sex classes of white-cheeked geese staging in interior Alaska. We compared those survival and recovery rates with those of other neck-collared white-cheeked geese. The best approximating model allowed survival to vary by age class while holding Seber's recovery probability (r) constant over sex, age class, and time. We estimated annual survival to be 0.49 (SE = 0.05) for hatch-year geese and 0.68 (SE = 0.03) f...
Lattice Location of Ta in Ni3Ai by Ion Channeling and Nuclear Reaction Analysis

We have investigated the lattice location of Ta in Ni3Al using Rutherford backscattering with channeling, and nuclear reaction analysis. An 8 MeV 4He ion beam was directed along the crystallographic axis of the Ni75Al24Ta single crystal. A silicon surface barrier detector was used to analyze 4He ions backscattered from Ni and Ta atoms. Neutrons generated from Al by the 27Al(4He,n)30P reaction were detected by a large volume liquid scintillator placed outside of the scattering chamber. Essentially all of the Ta atoms were found to be substitutional, as determined by the Ta channeling minimum yield. A comparison of the width of the channeling angular scan for Al, Ni and Ta indicated that the Ta atoms are predominantly distributed on the Ni sites. This result is in conflict with expectations based on the ternary phase diagram.
A cytoplasmic quaking I isoform regulates the hnRNP F/H-dependent alternative splicing pathway in myelinating glia

The selective RNA-binding protein quaking I (QKI) plays important roles in controlling alternative splicing (AS). Three QKI isoforms are broadly expressed, which display distinct nuclear-cytoplasmic distribution. However, molecular mechanisms by which QKI isoforms control AS, especially in distinct cell types, still remain elusive. The quakingviable (qk(v)) mutant mice carry deficiencies of all QKI isoforms in oligodendrocytes (OLs) and Schwann cells (SWCs), the myelinating glia of central and peripheral nervous system (CNS and PNS), respectively, resulting in severe dysregulation of AS. We found that the cytoplasmic isoform QKI-6 regulates AS of polyguanine (G-run)-containing transcripts in OLs and rescues aberrant AS in the qk(v) mutant by repressing expression of two canonical splicing factors, heterologous nuclear ribonucleoproteins (hnRNPs) F and H. Moreover, we identified a broad spectrum of in vivo functional hnRNP F/H targets in OLs that contain conserved exons flanked by G-runs, many of which are dysregulated in the qk(v) mutant. Interestingly, AS targets of the QKI-6-hnRNP F/H pathway in OLs are differentially affected in SWCs, suggesting that additional cell-type-specific factors modulate AS during CNS and PNS myelination. Together, our studies provide the first evidence that cytoplasmic QKI-6 acts upstream of hnRNP F/H, which forms a novel pathway to control AS in myelinating glia.
Near-field analysis of spherical loop arrays

In a recent paper (see ibid., vol.42, p473-7, April 1994), the authors presented the development of an algorithm for the reconstruction of element currents of a spherical loop array given the far-field pattern data in an azimuthal plane, and demonstrated the validity of the method with several computational examples. In this letter, it is shown that the same algorithm can be applied to the reconstruction of the spherical loop-array currents from the near-field data by application of spherical wave expansion of the electric field integral of the array. The main feature of the reconstruction algorithm is that the array currents are obtained recursively through the solution of a triangular equation set.
Hypertonicity-Induced Projections Reflect Cell Polarity in Mouse Metaphase II Oocytes: Involvement of Microtubules, Microfilaments, and Chromosomes

A previous study showed that with hypertonic sucrose treatment, a projection is formed in mouse metaphase II (MII) oocytes in proximity to the spindle and chromosomes, where a polarized cortical domain is located. However, little is known about the mechanisms involved in this process. Here, we designed a series of experiments to test the hypothesis that hypertonicity is the induction factor for the formation of projections in mouse MII oocytes. Our hypothesis was supported by the following evidence: 1) different concentrations of sucrose affected the formation and shape of projections, whereas serum or basic media had little effect; 2) other hypertonic sugar solutions could also induce projection formation; and 3) projections could also be induced by hypertonic NaCl solution. We then tested the hypothesis that the cytoskeleton was involved in the formation of hypertonicity-induced projections. This was investigated by culturing MII- and germinal vesicle-stage mouse oocytes in the presence or absence of cytoskeletal inhibitors, including cytochalasin B (disruption of actin filaments), nocodazole (disruption of microtubules), and taxol (polymerization of tubulin molecules). We found that none of the cytoskeletal inhibitors alone could prevent hypertonicity-induced projection formation, whereas the combination of cytochalasin B with nocodazole or with taxol blocked the formation of these projections in most matured oocytes. When immature oocytes were incubated in cytochalasin B, but not in nocodazole or taxol, the formation of an actin-rich domain and the peripheral positioning of the spindle were blocked during maturation; hence, no projections were formed, even after hypertonic sucrose treatment. Based on these observations, we propose that three components are necessary for projection formation: 1) a polarized cortical patch (e.g., an actin-rich domain), 2) rigid submembrane structures (e.g., a spindle and/or chromosomes), and 3) solid connections between the above. Any disturbance of one of these factors will affect the hypertonicity-induced projection formation. Hypertonicity-induced projection in mouse oocytes thus provides an experimental model for studies regarding cell polarity and the interaction between membrane and submembrane components.
Temperature gradients drive mechanical energy gradients in the flight muscle of Manduca sexta

SUMMARY A temperature gradient throughout the dominant flight muscle (dorsolongitudinal muscle, DLM 1 ) of the hawkmoth Manduca sexta , together with temperature-dependent muscle contractile rates, demonstrates that significant spatial variation in power production is possible within a single muscle. Using in situ work-loop analyses under varying muscle temperatures and phases of activation, we show that regional differences in muscle temperature will induce a spatial gradient in the mechanical power output throughout the DLM 1 . Indeed, we note that this power gradient spans from positive to negative values across the predicted temperature range. Warm ventral subunits produce positive power at their in vivo operating temperatures, and therefore act as motors. Concurrently, as muscle temperature decreases dorsally, the subunits produce approximately zero mechanical power output, acting as an elastic energy storage source, and negative power output, behaving as a damper. Adjusting the phase of activation further influences the temperature sensitivity of power output, significantly affecting the mechanical power output gradient that is expressed. Additionally, the separate subregions of the DLM 1 did not appear to employ significant physiological compensation for the temperature-induced differences in power output. Thus, although the components of a muscle are commonly thought to operate uniformly, a significant within-muscle temperature gradient has the potential to induce a mechanical power gradient, whereby subunits within a muscle operate with separate and distinct functional roles.
Efficient techniques for telephone company line drawing interpretation

In this paper we present the idea of using customizable tools to develop systems to interpret telephone company drawings. These drawings are composed primarily of horizontal and vertical lines. By selecting the intersections as primitives, routines are developed to establish spatial relations of the primitives which are used to describe the structures. Another aspect that as presented is the benefit of using run length encoding to reduce the amount of memory and the processing time needed to process the large files resulting from scanning the forementioned drawings. Examples of the interpretation of telephone company distributing frame and front equipment drawings are presented.
MicroRNA Biogenesis: Drosha Can't Cut It without a Partner

Abstract The ribonuclease Drosha requires a dedicated double-stranded RNA binding protein to convert long, nuclear primary microRNA transcripts into shorter pre-microRNA stem–loops, the cytoplasmic precursors from which mature microRNAs are ultimately excised.
NORTH AMERICAN DESERT RODENTS: A TEST OF THE MID-DOMAIN EFFECT IN SPECIES RICHNESS

Many biological theories have been proposed to explain latitudinal and elevational gradients of species richness, but only recently have theories been proposed that suggest that these patterns may be due solely to geographic constraints. These null models predict mid-domain peaks in species richness as a consequence of geometric patterns resulting from overlapping species ranges between 2 geographic boundaries. Desert rodents exhibit a marked middomain peak in species richness for boundaries defined by the latitudinal extent of North American deserts (19 8N‐458N). Empirical patterns are compared with predictions of 2 null models: an analytical‐stochastic model and the binomial model. Empirical species richness occurs almost entirely within 95% prediction curves of the analytical‐stochastic model. Observed species richness is highly correlated with predictions of the binomial model (r 2 5 93%) but does not generally occur within 95% confidence intervals, in part because empirical range-size distributions differ from predicted distributions. Other diversity theories, species‐area relationships, productivity gradients, latitudinal gradients, and Rapoport’s rule are evaluated; none is consistent with empirical patterns. These results demonstrate that the mid-domain effect is a consequence of overlap of variably sized ranges within a bounded region for both ecologically defined hard boundaries and boundaries determined by the shape of the earth. The significant deviations from null-model predictions become the biological points of interest: skewed or localized (or both) pulses or depressions of species richness. Deviations in the present analysis demonstrated a localized pulse in richness caused by a local hard boundary, the Baja peninsula.
Stability of the superconductive operating mode in high current-density devices

The superconductive operating mode represents a thermal equilibrium that can tolerate a certain amount of disturbance before it is lost. The basin of attraction (BOA), in many ways equivalent to a potential well, is a measure of the size of disturbance needed to lift the device from the superconductive into a resistive operating mode. The BOA for a simple geometry is calculated and discussed. Experimental results are reported, showing how the concept is used to gain information on the disturbances occurring in a superconducting device.
Multiple mechanisms contribute to the synergistic anti-myeloma activity of the pan-histone deacetylase inhibitor LBH589 and the rapalog RAD001

We examined the pre-clinical activity of pan-histone deacetylase inhibitor LBH589 in combination with mTORC1 inhibitor RAD001 and observed that the drug combination strongly synergized in inducing cytotoxicity in multiple myeloma (MM) cells. LBH589 caused an increase in acetylated histones and RAD001 inhibited mTORC1 activity. RAD001 caused potent G0/G1 arrest while LBH589 induced pronounced apoptosis, both of which were enhanced when the drugs were used in combination. LBH589/RAD001 combination led to down regulation of pStat3, cyclins, CDKs and XIAP and up regulation of pro-apoptotic Bcl-2 family proteins. A clinical trial is underway using LBH589/RAD001 combination in relapsed MM patients.
Constitutionalism and Identity in Eastern Europe: Uncovering Philosophical Fragments

The author would like to gratefully acknowledge the comments of Karen Dawisha and Venelin Ganev. An earlier version of this paper was presented as part of the Project on Minorities and Tolerance in Central and Eastern Europe and the NIS (Newly Independant States) at the Woodrow Wilson International Center for Scholars.
ADAPTIVE GRID SOLUTION FOR BUOYANCY-INDUCED FLOW IN VERTICAL SLOTS

ABSTRACT This paper considers the flows induced by symmetrical heating of two vertical parallel surfaces for a Grashof number range of l03-105, a Prandtl number of 0.7, and slot height-to-width ratios of 1.0 and 2.0. A nonorthogonal curvilinear coordinate system in conjunction with an adaptive grid method and second-order accurate discretization schemes were employed in the numerical method. The entire flow field is modeled, including the region beneath the parallel surfaces, the region between the parallel surfaces, the outflow region above, and the downstream wake. The adaptive grid method, based on the concept of equidistribution of a weighting function, clearly shows the evolution of the grid distribution pattern with respect to the change of Grashof number in a way that cannot be prescribed a priori. The resulting improvements of the length scale resolution make the temperature and the velocity fields vary as the Grashof number changes. A converging/diverging convection pattern can be identified with...
Characterization of the impact of interconnect design on the capacitive load driven by a global clock distribution

Power reduction techniques are a critical issue in the design of today's ULSI chips. This paper is concerned with methods to characterize the capacitive load on the POWER4 on-chip global clock distribution [1], which is a large contributor to the overall chip power dissipation. A characterization of the capacitive load is needed because the contributions of the on-chip devices and interconnections are typically overestimated and are not well understood for high performance microprocessors. One problem that results from the lack of this information is excessively high power dissipation in the chip global clock distribution; the global clock distribution is over-designed and stronger than necessary to drive the actual (lower) chip load. Information about the capacitive load is difficult to obtain because the data volume is large, and extracting the interconnect data is a complex task. Sophisticated computer software is needed to extract the circuit and physical design data for hundreds of devices and wire segments within the chip design schedule.This paper presents the first comprehensive characterization of the clock load for ASIC-like control logic designs in the 1.3GHz POWER4 microprocessor core [1], [2]. This characterization was achieved with the use of sophisticated software written for this study to accomplish the task of extracting the data from these designs. Analysis of the data shows that the wire contribution to the chip capacitive load is significant and can increase the capacitive load of a design by 30% on average and by as much as 130% for some designs. The results also suggest that the wire load contribution on each metal layer can be reduced if an alternate interconnect design style is selected. Two alternate design styles are presented and show that a capacitive load reduction of 8.4% to 20% is expected for each design. Extended to the entire chip, the results show that the load reduction for the core is expected to be as high as 10%. These values are large enough that one alternate design style has been implemented in the design methodology of future chips.
3-D Silicon Integration and Silicon Packaging Technology Using Silicon Through-Vias

System-on-Chip (SOC) and System-on-Package (SOP) technologies each have advantages depending on application needs. As system architects and designers leverage ever-increasing CMOS technology densities, a range of two- and three-dimensional silicon integration technologies are emerging which will likely support next-generation high-volume electronic applications and may serve high-performance computing applications. This paper will discuss a few emerging technologies which offer opportunities for enhanced circuit performance, or reduced power as one example. Silicon-on-silicon integration may include three-dimensional (3-D) integration on-chip or may leverage chip stacking or chip integration on package. Common technology features include silicon through-vias, high-I/O interconnection and silicon-on-silicon either as 3-D integrated circuits, integrated chip stacks or silicon-on-silicon packages with passive function or high-bandwidth wiring. Silicon chips on silicon interposers with integrated function such as decoupling capacitors may provide a better module architecture compared to increased on-chip decoupling or off chip discrete capacitors mounted on package at the chip perimeter or underside of the package. Advanced silicon carrier package technology with fine pitch (50 mum) interconnection is described. This silicon carrier package contains silicon through-vias and offers >16times increase over standard chip I/O, a 20times to 100times increase in wiring density over traditional organic and ceramic packaging, and allows for integrated high-performance passives. Silicon carrier technology supports lithographic scaling and provides a basis for known good die (KGD) wafer testing. It may be considered for use in a number of applications including optoelectronic (OE) transceivers, silicon interposers with integrated decoupling capacitors, and mini-multi-chip modules (MMCMs) which integrate heterogeneous dies forming a single "virtual chip."
An appraisal of stock car racing's economic and geographic development in North America: NASCAR as flexible accumulation

Despite the growing popularity of NASCAR stock car racing throughout North America, it has remained largely ignored in the sport management research literature. This article suggests that unlike other major spectator sports, which formed cartel systems based on the principles of industrial Fordism, NASCAR organised within a capitalist system more characteristic of Harvey's theory of flexible accumulation. Using NASCAR as a case study, we describe its organisation within an ideal type methodology. The unique characteristics of NASCAR include fragmentation of production systems, new dimensions of labour practises, new consumption processes, and geographical manipulation and re-configuration. Because of its economic system, NASCAR is better positioned than other North American sports to break free from geographic constraints and exploit emerging markets. However, approaching NASCAR within the framework of flexible accumulation reveals that the sport may be more vulnerable to future crises than other major North American spectator sports.
Mapping stellar content to dark matter haloes – II. Halo mass is the main driver of galaxy quenching

We develop a simple yet comprehensive method to distinguish the underlying drivers of galaxy quenching, using the clustering and galaxy-galaxy lensing of red and blue galaxies in SDSS. Building on the iHOD framework developed by Zu & Mandelbaum (2015a), we consider two quenching scenarios: 1) a "halo" quenching model in which halo mass is the sole driver for turning off star formation in both centrals and satellites; and 2) a "hybrid" quenching model in which the quenched fraction of galaxies depends on their stellar mass while the satellite quenching has an extra dependence on halo mass. The two best-fit models describe the red galaxy clustering and lensing equally well, but halo quenching provides significantly better fits to the blue galaxies above $10^{11} M_\odot/h^2$. The halo quenching model also correctly predicts the average halo mass of the red and blue centrals, showing excellent agreement with the direct weak lensing measurements of locally brightest galaxies. Models in which quenching is not tied to halo mass, including an age-matching model in which galaxy colour depends on halo age at fixed $M_*$, fail to reproduce the observed halo mass for massive blue centrals. We find similar critical halo masses responsible for the quenching of centrals and satellites (~$1.5\times10^{12} M\odot/h^2$), hinting at a uniform quenching mechanism for both, e.g., the virial shock-heating of infalling gas. The success of the iHOD halo quenching model provides strong evidence that the physical mechanism that quenches star formation in galaxies is tied principally to the masses of their dark matter halos rather than the properties of their stellar components.
Resettling Vietnamese refugees: the service agency's role

Nearly seven years have passed since the first refugees from Vietnam began arriving in the United States, and data suggest a positive relationship between the length of time they have been in this country and the levels of employment and income they have attained. This article assesses how the refugees have adjusted to life in the United States and discusses the role of social work agencies in their resettlement.
Scalable Kernel Methods for Uncertainty Quantification

Kernel methods are a broad class of algorithms that find application in approximation theory and non-parametric statistics. In this article, we review the literature with a focus on methods for uncertainty quantification and we discuss computational challenges related to kernel methods. In particular, we focus on approximating kernel matrices, one of the main computational bottlenecks in kernel methods. The most popular method for constructing approximations of kernel matrices is the Nystrom method, which uses randomized sampling to construct a low-rank factorization of a kernel matrix. We present a parallel implementation of the Nystrom method using the Elemental parallel linear algebra library and discuss an efficient variant called the one-shot Nystrom method. We conclude with examples of a regression problems for binary classification in high dimensions that illustrate the capabilities and limitations of Nystrom methods. In our largest test, we consider a dataset from high-energy physics in 28 dimensions with ten million points.
Effects of T-2 Toxin on Turkey Herpesvirus–Induced Vaccinal Immunity Against Marek's Disease

SUMMARY T-2 toxin, a very potent immunotoxic Type A trichothecene, is a secondary metabolite produced primarily by Fusarium spp., which grows on cereal grains and can lead to contaminated livestock feed. Repeated exposure to T-2 toxin has been shown to cause immunosuppression and decrease the resistance of exposed animals to a variety of infectious diseases; however, the effects of T-2 toxin on Marek's disease (MD) vaccinal immunity have not been reported. Four trials were conducted to determine the effects of T-2 toxin on vaccinal immunity against MD. Day-old, white leghorn chicks of Avian Disease and Oncology Laboratory line 15I5 × 71 were treated daily for 7 days via crop gavage with T-2 toxin at a sublethal dose of 1.25 mg/kg body weight. Treated and untreated chicks were also vaccinated with turkey herpesvirus (HVT) at hatch and were challenged with the JM strain of MD virus (MDV) at 8 days of age. Chickens were tested for HVT viremia at 1 wk postvaccination immediately before challenge, and for HVT ...
Selectivity of Ligand-Receptor Interactions between Nanoparticle and Cell Surfaces

Selectivity of interactions between nanoparticles functionalized by tethered ligands and cell surfaces with different densities of receptors plays an essential role in biorecognition and its implementation in nanobiomedicine. We show that the onset of nanoparticle adsorption has a universal character for a range of nanoparticles: the onset receptor density decreases exponentially with the energy of ligand-receptor binding and inversely with the ligand density. We demonstrate that a bimodal tether distribution, which permits shielding ligands by longer nonfunctional tethers, leads to extra loss of entropy at the adsorption onset, enhancing the selectivity.
Abstract 3911: Infrared vibrational frequency as a novel molecular descriptor for lead optimization of PKB/Akt inhibitors

We report the use of a novel molecular descriptor used for lead optimization of PKB inhibitors. Lead optimization remains a major rate limiting step in drug discovery. Current methods for lead optimization that leads to a clinical candidate often fail during clinical trials with attrition rate as high as 9 out of 10. We re-investigated the lock and key theory by incorporating the vibrational frequency of small molecules. The vibrational frequency is calculated based on the summation of all theoretical infrared vibrational frequency of each bond and normalized via division by its molecular weight. We term this molecular descriptor as MDIR. The MDIR is utilized as a rapid lead optimization computational chemistry method. The MDIR correlation to affinity/inhibition at several molecular targets shows a parabolic relationship. Quinoxalines with MDIR values near 135 provide the best inhibition (19% INH at 10 uM) at PKB/Akt as assessed via the Cisbio HTRF KinEASE assay. An internal control, 10-DEBC, known to have 100 % inhibition of PKB at 2.5 uM, had only a 6 % INH @ 10 uM in the KinEASE assay. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3911. doi:1538-7445.AM2012-3911
Further characterization of suckling mouse cataract agent (SMCA): a slow, persistent infection of the nervous system.

SummaryExperiments were designed to further characterize the nature of suckling mouse cataract agent (SMCA). The agent is sensitive to heat, trypsin and ultraviolet inactivation, but is stable over the pH range 5.8 to 10. Penicillin, kanamycin, streptomycin and rifampin have no effect on the replication of the agent while BUdR, actinomycin D and hydroxyurea are inhibitory. By filtration the size of the infectious particle was determined to be between 200 and 500 nm. Ultra-structural studies upon infected allantoic fluids reveal unique particles not present in fluids infected with a series of RNA and DNA viruses.The response of the agent to drugs indicates that it is not a bacterial agent and is probably viral. Filtration experiments and ultrastructural studies favor a viral nature.The authors acknowledge the expert technical assistance of Eva Nagy as electron microscopy technician and James E. Pounds who grew and titered the agent.
A New Development in Complex Multiparty-Multicontract Proceedings: Classwide Arbitration

IN OTHER articles, we have examined the issues and problems arising from arbitrations which have been (or are purported to be) initiated by or against a limited number of individuals or companies which have in common being (or having been) involved in the same or related project(s) or transaction(s). In contrast, this article will be devoted to another aspect of complex arbitrations: that is, arbitrations initiated by groups of individuals (which may be thousands) or in other words, group actions.1 For obvious reasons, explained below, it will mainly focus on the US practice of class actions. Group actions may be injunctive or remedial, meaning that they can seek injunctive relief as well as money damages. They are still relatively rare and unknown in civil law countries. Most of the statutes authorizing multiparty actions in Europe concern consumer protection. For example, in a number of countries,2 independent administrative authorities or consumer organizations have for many years been recognized as having locus standi to apply to the courts for an injunction or a prohibition order in relation to forbidden or unfair commercial practices. On the other hand, the legislation of EU Member States has also been (or is about to be) amended to incorporate the provisions of Directive 98/27/EC which permits consumer organizations to apply to courts in fellow Member States for an injunction against an infringement of any of a number of consumer trading Directives, covering areas such as misleading advertising, unfair contract terms, consumer credit, package holidays, and consumer guarantees, that are committed in the organization’s own state by an entity in the fellow state. But these actions are representative proceedings, quite different from group actions. Although some EU and non-EU states also have legislation on group litigation,3 its scope and impact remains quite limited. The only …
Book review segment

CONTEMPORARY HOSPITALITY MARKETING: A SERVICE MANAGEMENT APPROACH Authors: William Lazer and Roger A. Layton Publisher: Educational Institute of the American Hotel & Motel Association, 1999, 409 pp.
Orientation Dependence of Photochemical Reduction Reactions on SrTiO3 Surfaces

Polished and annealed surfaces of randomly oriented crystallites were used to study the orientation dependence of the photochemical activity of SrTiO3 surfaces. Silver cations reduced from an aqueous solution produce solid silver metal at the reaction site. The amounts of silver produced by a fixed exposure were used as a relative measure of each grain's activity. The surface structure of the grains was observed using atomic force microscopy and the surface orientation of each grain was determined by electron backscattered diffraction. Surfaces annealed in air for 6h at 1200° C were bound by some combination of the following three planes: {110}, {111}, and a complex facet inclined approximately 24° from {100}. By correlating the orientations of individual grains to the amount of deposited silver, we conclude that surfaces with the complex {100} facet are the most active.
Developments in accounting regulation: A synthesis and annotated bibliography of evidence and commentary in the 2008 academic literature

Abstract In this paper we synthesize in annotated bibliography form, selected regulation-related findings and commentaries which appear in the 2008 academic literature. We annotate results of regulation-related research studies and key points from regulation-related commentaries. This annotated bibliography contributes to the existing series appearing in recent volumes of this journal beginning in volume 18 and appearing regularly in each volume thereafter covering the research literature from 1999 through 2007. We have included academic outlets such as The Accounting Review, Journal of Accounting Research, Journal of Accounting and Economics, Accounting Horizons, Journal of Accounting, Auditing & Finance, Journal of Accounting and Public Policy, Journal of Business, Finance & Accounting, Auditing: A Journal of Practice and Theory, and Research in Accounting Regulation. Other journals, most recently Contemporary Accounting Research, are added as the debate and materials have increased and matured.
Research on Evaluation System of Enterprise's Soft Power Based on ANP

Enterprise's soft power is more and more important in enterprise's development and construction. Evaluating soft power scientifically and rationally is prerequisite for constructing it, which can provide decision-making for the enterprise to abstain sustainable development. This article established enterprise's soft power evaluation index system which based on the theory of national soft power and the enterprise's competitive theory from the enterprise's image, enterprise's culture, innovation capability, management capability and enterprise's public relations. We employed the Analytic Network Processes (ANP) to establish evaluation system model of the enterprise's soft power. The example illustrated how to use Super Decisions software evaluate the enterprise's soft power.
Analysis of influence factors of rabies among 416 cases

Objective To investigate human rabies cases and explore the influence factors of rabies.Methods Data from 416 questionnaires for human rabies cases occurred during 2005~2011 in Anhui province were put into EpiData3.1 to build a data base.SPSS 10.0 was used for statistic analysis.Influence factors of rabies incubation period were analyzed with chi-square test,ordinal regression and multiple linear stepwise regression.Results All of the cases,93.99% were caused by dog bites,95.67% were with II and III degree wound,and only 19.47% received treatment from medical institutions.Rabies inoculation rate of the patients after being exposed was 14.42%,and the usage rate of antiserum immunoglobulin was only 0.48%.The median of rabies incubation period was 72 days(ranging from 2 days to 15 years).Exposure position,wound disposal Methods whether or not receiving post-exposure vaccination were main influence factors of rabies incubation period.Conclusion Strengthening health education,and improving wound disposal rate and rabies vaccination rate in rural targeted population are the effective prevention and control measures for rabies after exposure.
The Least of the Sentient Beings

Rats and mice are very much more likely to be experimented on today in biomedical research than dogs, cats, or primates. Rats and mice, however, are explicitly excluded from the federal Animal Welfare Act's protections against animal pain and suffering in a research setting. This paper is a response to an invitation to reflect on how medical and scientific researchers should think about the rats and mice they use, in light of ongoing legal developments in the human-animal relationship. The invitation was extended by the Michigan Society for Biomedical Research, an organization for the promotion of biomedical research and defense of the use of animals in research. It was extended to a teacher of Animal Law at the University of Michigan Law School who was serving as the non-scientist member from the University on the University's Institutional Animal Care and Use Committee. Considerations to which attention is directed include developments in experimentation on humans paralleling and connected with developments in experimentation on animals, developments in the science of animals beyond the biomedical field, general movements in the legal treatment of animals that are not the outcome of conflicts between animal activists and research institutions, and the importance of attitude as a focus in any regulation of experimentation, animal or human.
Obeticholic Acid: A Farnesoid X Receptor Agonist for Primary Biliary Cholangitis

Objective: To review the pharmacology, efficacy, and safety of obeticholic acid (OCA) and determine its clinical role relative to other agents in the treatment of patients with primary biliary chol...
TRC8 (RNF139), the t(3;8) hereditary RCC gene, is a polytopic RING protein whose E3 ubiquitin ligase activity is necessary for tumor suppression

3323 TRC8 encodes an ER-resident E3-ubiquitin ligase disrupted in a family with the (3;8)(p14.2;q24.1) translocation and hereditary kidney and thyroid tumors. TRC8 encodes a 664 amino acid protein with 10 transmembrane segments and a C-terminal RING-H2 domain, a feature common to many E3 ubiquitin ligases. The (3;8) translocation, which was one of the first genetic abnormalities identified in a familial form of cancer, disrupted TRC8 in its second transmembrane segment. The Drosophila homolog of TRC8 (DTrc8) inhibited growth when over-expressed in selected fly tissues yet provided an essential function since universal under-expression by RNAi was lethal. We have now extended these findings into mammalian cells utilizing a TET-on system in HEK293 cells. In vitro cell growth was strongly inhibited when wild type TRC8 was expressed in this system. However, several independent mutations in the RING-H2 domain blocked growth inhibitory activity. Cells expressing wild type (but not RING-mutant) TRC8 accumulated in G2/M. Tumor formation by HEK293 cells in nude mice was completely blocked by wild type TRC8 induction but not when the RING domain was mutated. Wild type TRC8 catalyzed in vitro ubiquitination reactions while RING-mutant proteins lost this function. In vitro analysis of multiple ubiquitin conjugating enzymes (E2s) indicated that TRC8 effectively utilized Ube2g2 (Ubc7) but not the closely related Ube2g1. Both E2s are implicated in ER-associated protein degradation (ERAD). Genetic screens for modifiers of the DTrc8 growth-inhibition phenotype in Drosophila identified several MPN-domain subunits of the COP9 signalosome and related subunits of the translation initiation factor eIF3. In vitro GST-pulldowns demonstrated strong interactions between DTrc8 and these eIF3 subunits. Ectopic DTrc8 expression yielded cuticular phenotypes consistent with Minute mutations that impair protein translation. Induction of human TRC8 in HEK293 cells suppressed polysome loading in general and selectively reduced ribosome loading of specific mRNAs. In summary, TRC8 is an E3 ubiquitin ligase whose tumor suppressor activity resides, in part, by modulating translation initiation, possibly in conjunction with the COP9 signalosome.
Diego de Torres Villarroel, La barca de Aqueronte (1731). Édition critique d'un autographe inédit par Guy Mercadier. Centre de Recherches Hispaniques, Paris, 1969; 465 pp. (Theses, mémoires et travaux, 13).

Se reseno el libro: La barca de Aqueronte (1731). Edition critique d'un autographe inedit par Guy Mercadier.
Measuring rent-seeking

Some 30 years ago Gordon Tullock, in his capacity as Editor of Public Choice, made a pointed effort to motivate researchers to measure and quantify resource investments in rent-seeking activities. Despite Tullock’s identification of this aspect of rent-seeking as a significant gap in the literature and call to arms, this remains an under-studied topic of importance. Why is this? In our opinion, the answer is that, for a variety of reasons, measuring rent-seeking turns out to be very difficult. In this paper we identify and discuss several of the difficulties, both theoretical and empirical, although we concede that our treatment surely is not exhaustive.
Prolog: Die Geschichte der Psychologie

Owen Gingerich (2006), Astronom in Harvard, berichtet, dass es uber 100 Milliarden Galaxien gibt. Eine davon, unsere eigene im Verhaltnis dazu staubkornchengrose Galaxie, umfasst ungefahr 200 Milliarden Sterne, von denen viele, wie unser Sonnenstern, von Planeten umkreist werden. In der Grosenordnung des Weltalls sind wir weniger als ein einzelnes Sandkorn an den Stranden aller Ozeane und unsere Lebenszeit entspricht lediglich einer Nanosekunde.
HYPOTHESIS TESTS AND OPTIMALITY PROPERTIES IN DISCRETE MULTIVARIATE ANALYSIS

Publisher Summary This chapter presents the hypothesis tests and optimality properties in discrete multivariate analysis. The level of the LRT test is obtained as a limit when one parameter is set equal to zero and all other parameters tend to +∞. Linear combinations of the ω's can be tested provided the coefficient vector of the linear combination contains both positive and negative elements. The chapter describes admissibility of tests for Poisson sampling. A chi-square test for independence in an r × s contingency table with multinomial sampling is admissible as it has convex acceptance sections. The chapter also discusses the admissibility of likelihood ratio, Pearson chi-square, and other tests.
PrlA suppressor mutations cluster in regions corresponding to three distinct topological domains.

Abstract The SecY protein of Escherichia coli and its homologues in other organisms, are integral components of the cellular protein translocation machinery. Suppressor mutations that alter SecY (the prlA alleles) broaden the specificity of this machinery and allow secretion of precursor proteins with defective signal sequences. Twenty-five prlA alleles have been characterized. These suppressor mutations were found to cluster in regions corresponding to three distinct topological domains of SecY. Based on the nature and position of the prlA mutations, we propose that transmembrane domain 7 of SecY functions in signal sequence recognition. Results suggest that this interaction may involve a right-handed supercoil of alpha-helices. Suppressor mutations that alter this domain appear to prevent signal sequence recognition, and this novel mechanism of suppression suggests a proofreading function for SecY. We propose that suppressor mutations that alter a second domain of SecY, transmembrane helix 10, also affect this proof-reading function, but indirectly. Based on the synthetic phenotypes exhibited by double mutants, we propose that these mutations strengthen the interaction with another component of the translocation machinery, SecE. Suppressor mutations were also found to cluster in a region corresponding to an amino-terminal periplasmic domain. Possible explanations for this unexpected finding are discussed.
Balancing formation time and electrochemical performance of high energy lithium-ion batteries

Abstract Most lithium-ion batteries still rely on intercalation-type graphite materials for anodes, and the formation process for them typically takes several days or even more to provide a stable solid electrolyte interphase (SEI). The slow formation step results in lower LIB production rates, requires a large number of battery cyclers, and constitutes the second highest cost during battery manufacturing. In an effort to decrease the high manufacturing cost associated with long formation times, we studied five different formation protocols in nickel-rich LiNi0.8Mn0.1Co0.1O2 (NMC811)/graphite cells where the total formation time varied from 10 to 86 h. Electrochemical characterization and post mortem analysis show that very long formation time do not necessarily improve long-term performance while very short formation protocols result in lithium plating and poorer electrochemical performance. We find the optimum formation cycling protocol is intermediate in length to minimize impedance growth, improve capacity retention, and avoid lithium plating.