cssi/SciSciGPT-SciSciNet huggingface dataset:
Multiplexed Surrogate Analysis of Glycotransferase Activity in Whole Biospecimens

Dysregulated glycotransferase enzymes in cancer cells produce aberrant glycans--some of which can help facilitate metastases. Within a cell, individual glycotransferases promiscuously help to construct dozens of unique glycan structures, making it difficult to comprehensively track their activity in biospecimens--especially where they are absent or inactive. Here, we describe an approach to deconstruct glycans in whole biospecimens then analytically pool together resulting monosaccharide-and-linkage-specific degradation products ("glycan nodes") that directly represent the activities of specific glycotransferases. To implement this concept, a reproducible, relative quantitation-based glycan methylation analysis methodology was developed that simultaneously captures information from N-, O-, and lipid linked glycans and is compatible with whole biofluids and homogenized tissues; in total, over 30 different glycan nodes are detectable per gas chromatography-mass spectrometry (GC-MS) run. Numerous nonliver organ cancers are known to induce the production of abnormally glycosylated serum proteins. Thus, following analytical validation, in blood plasma, the technique was applied to a group of 59 lung cancer patient plasma samples and age/gender/smoking-status-matched non-neoplastic controls from the Lung Cancer in Central and Eastern Europe (CEE) study to gauge the clinical utility of the approach toward the detection of lung cancer. Ten smoking-independent glycan node ratios were found that detect lung cancer with individual receiver operating characteristic (ROC) c-statistics ranging from 0.76 to 0.88. Two glycan nodes provided novel evidence for altered ST6Gal-I and GnT-IV glycotransferase activities in lung cancer patients. In summary, a conceptually novel approach to the analysis of glycans in unfractionated human biospecimens has been developed that, upon clinical validation for specific applications, may provide diagnostic and/or predictive information in glycan-altering diseases.
Crystal structure of reovirus attachment protein σ1 reveals evolutionary relationship to adenovirus fiber

Reovirus attaches to cellular receptors with the sigma1 protein, a fiber-like molecule protruding from the 12 vertices of the icosahedral virion. The crystal structure of a receptor-binding fragment of sigma1 reveals an elongated trimer with two domains: a compact head with a new beta-barrel fold and a fibrous tail containing a triple beta-spiral. Numerous structural and functional similarities between reovirus sigma1 and the adenovirus fiber suggest an evolutionary link in the receptor-binding strategies of these two viruses. A prominent loop in the sigma1 head contains a cluster of residues that are conserved among reovirus serotypes and are likely to form a binding site for junction adhesion molecule, an integral tight junction protein that serves as a reovirus receptor. The fibrous tail is mainly responsible for sigma1 trimer formation, and it contains a highly flexible region that allows for significant movement between the base of the tail and the head. The architecture of the trimer interface and the observed flexibility indicate that sigma1 is a metastable structure poised to undergo conformational changes upon viral attachment and cell entry.
Deploying Information and Communication Technologies (ICT) to Enhance Participation in Local Governance for Citizens with Disabilities

Information and Communication Technologies (ICT) offer a promising technology for citizens with disabilities to participate in local e-governance planning and implementation, provided that underlying issues of social exclusion and technology accessibility are properly addressed. Existing research suggests that for citizens with disabilities gateway issues such as technology access, usability, community- and government-receptivity are barriers to participation in local e-governance. Results from a pilot study indicate that the e-governance landscape for people with disabilities is heterogeneous; likely reflecting both differences within the disability community, as well as among the online governance entities. Systematic changes to the development, implementation, and evaluation of local e-governance for people with disabilities are recommended, informed by an analytical model suitable for empirical testing.
Effect of 1D Cu Nanostructures on Heat Transfer Characteristics of Single Phase Microchannel Heat Sink

This study experimentally assesses single phase heat transfer characteristics of a shallow rectangular microchannel heat sink whose surface is enhanced with copper nanowires (CuNWs). The hydraulic diameter of the channel is 672 μm and the bottom wall is coated with Cu nanowires (CuNWs) of 200 nm in diameter and 50 μm in length. CuNWs are grown on the Cu heat sink by electrochemical synthesis technique which is inexpensive and readily scalable. The heat transfer and pressure drop results of CuNWs enhanced heat sink are compared with that of bare copper heat sink using deionized (DI) water as the working fluid at Reynolds Number (Re) ranging from 106–636. The experimental results indicate an enhancement in Nusselt Number (Nu) at all Re with a maximum enhancement of 24% at Re = 106. The enhanced thermal performance is attributed to two properties of Cu nanowire arrays — improvement in surface wettability characteristics and increased heat transfer surface area.Copyright © 2011 by ASME
Fructan Precipitation from a Water/Ethanol Extract of Oats and Barley

Fructan was precipitated from a water and ethanol extract of oat (Avena sativa L.) and barley (Hordeum vulgare L.). The degree of polymerization and response on a differential refractometer, based on peak area and height, was compared to fructan collected from a lead-based HPLC column and to commercially available inulin. Statistically significant differences are discussed.
Role of CT in the evaluation of children with foregut cyst

The presentation of a foregut cyst may vary from an asymptomatic mass discovered as an incidental finding in a chest radiograph, to signs or symptoms secondary to airway compression by the cyst. The radiographic evaluation of a child with a possible foregut cyst usually consists of a chest radiograph and barium esophagogram. Although this approach is often sufficient, in other instances delay of treatment occurs or unnecessary workups are performed due to the inadequacy of the approach. CT is useful for (a) depicting cryptic foregut cysts, (b) clarifying abnormal radiographs, (c) avoiding unnecessary workup of patients by establishing the precise location of the mass, and (d) defining the cystic nature of the mass and excluding other etiologies.
A Stochastic Dynamic Analysis of Parental Sex Preferences and Fertility

The author has developed a stochastic dynamic model of fertility to examine assumptions which form the basis of often used econometric tests for parental sex preferences. These assumptions included the use of fertility data to test for sex preferences and to test for son preference based on the effect of the number of males on fertility. The Heckman and Willis stochastic model of reproduction was used to formulate this model. This new model allowed some tractable and testable predictions. It was able to predict income and wage effects without sex preferences. Further it can accurately describe life cycle dynamic fertility behavior. The model demonstrated the existence of a quantity quality interaction which influence parents decisions on fertility. For example higher quality measured by the effective number of children substituted for a higher quantity (number of children). The model proved that sex preferences can indeed be tested but it could not differentiate empirically between son preference and daughter preference from fertility data. Perhaps data on intrafamily allocation of resources as used by Rosenzweig and Schultz; Behrman Pollak and Taubman; and Behrman would better be able to test for son versus daughter preference since allocation is based on existing children. The results of this newly formulated stochastic dynamic model of fertility challenge the validity of traditional econometric tests for son preference.
Effect of oviductal condition on the development of one-cell porcine embryos in mouse or rat oviducts maintained in organ culture

Abstract To determine the effect of varying oviductal conditions on porcine embryo development in mouse oviducts in organ culture, one-cell porcine embryos from each donor female were randomly assigned to the following treatments: medium alone, mouse oviducts obtained from females mated to fertile males or vasectomized males, mouse oviducts from mated fertile females flushed with culture medium, and rat oviducts. Of the embryos cultured in medium alone, 17.3% (n = 52) developed to the morula or blastocyst stage. For porcine embryos cultured in mouse oviducts, 77.1% (n = 35) developed to the morula or blastocyst stage in mouse oviducts obtained from fertile matings; 74.5% (n = 51) in mouse oviducts obtained from females mated to vasectomized males; and 58.7% (n = 46) in flushed mouse oviducts obtained from mated fertile females. Development of porcine embryos in rat oviducts from mated fertile females was limited (17.8% morula or blastocyst; n = 45). Mouse oviducts obtained from females mated to fertile or vasectomized males and not flushed supported one-cell porcine embryo development to a greater extent than flushed mouse oviducts (P 0.90). Cell numbers were similar for embryos reaching the morula or blastocyst stage across all treatments, except for embryos reaching the blastocyst stage in rat oviducts, where cell numbers were significantly lower (P
Predictive effects of mother and peer influences on increases in adolescent eating disorder risk factors and symptoms: a 3-year longitudinal study.

Objective: To investigate the relation of maternal and peer attitudes and behaviors to changes in eating disorder risk factors and symptoms in adolescent females. Method: We tested whether maternal and peer eating attitudes, behaviors, and deficits in social support at baseline predicted subsequent increases in eating disorder risk factors and symptoms among 483 late adolescent females followed over 3 years. Results: Data provide partial support for hypotheses, as eating disorder risk factors and symptoms increased over time and maternal thin ideal internalization significantly predicted a future increases in adolescent bulimic symptoms. There were no significant predictors of adolescent thin ideal internalization or body dissatisfaction. Discussion: Findings only partially support the hypothesis that unhealthy attitudes and behaviors of mothers increase risk for eating disorder symptoms in their late adolescent daughters. These results underscore why eating disorder prevention programs should be based on risk factor research that has used prospective and rigorous designs. © 2011 by Wiley Periodicals, Inc.
THE INTERMOLECULAR INTERACTION MECHANISMS IN LIQUID CS2 AT 295 AND 165 K PROBED WITH TWO-DIMENSIONAL RAMAN SPECTROSCOPY

Abstract Two-dimensional Raman spectroscopy is used to probe the intermolecular interaction dynamics of CS 2 at 295 and 165 K. The influence of nonlinear polarizability and liquid anharmonicity on the observable is discussed. It is found that the response at both temperatures is dominated by the nonlinear polarizability, which is most likely due to interaction-induced effects. A model using three Brownian oscillators to represent the collective motions on three time scales is unable to reproduce the 295 K data. At low temperature, the model presumably works better as a result of the time-scale separation between the inertial and diffusive dynamics.
Mechanical Properties of 3C-SiC Films for MEMS Applications

There is a technological need for hard thin films with high elastic modulus and fracture toughness. Silicon carbide (SiC) fulfills such requirements for a variety of applications at high temperatures and for high-wear MEMS. A detailed study of the mechanical properties of single crystal and polycrystalline 3C-SiC films grown on Si substrates was performed by means of nanoindentation using a Berkovich diamond tip. The thickness of both the single and polycrystalline SiC films was around 1-2 μm. Under indentation loads below 500 μN both films exhibit Hertzian elastic contact without plastic deformation. The polycrystalline SiC films have an elastic modulus of 457 GPa and hardness of 33.5 GPa, while the single crystalline SiC films elastic modulus and hardness were measured to be 433 GPa and 31.2 GPa, respectively. These results indicate that polycrystalline SiC thin films are more attractive for MEMS applications when compared with the single crystal 3C-SiC, which is promising since growing single crystal 3C-SiC films is more challenging.
Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers.

Background Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates.
Long-term endoscopic management for primary recurrent pyogenic cholangitis

Background: Primary recurrent pyogenic cholangitis (RPC) is characterized by relentless suppurative cholangitis in those with a suspected parasitic injury of the biliary tree. Prior work has demonstrated that the infections recur following "definitive" biliary surgery and long-term percutaneous biliary catheters are poorly tolerated. The aim of this study was to assess whether scheduled surveillance endoscopic retrograde cholangiopancreatography (ERCP) prevents cholangitis in those with RPC. Materials and Methods: Following initial biliary decompression and stone clearance, patients with RPC were offered serial ERCP every 3-6 months to remove accumulating stony debris and to dilate incipient strictures. Review of a large series managed using this approach at the University of California, San Francisco Medical Center was performed. The principle outcome was the development of acute cholangitis requiring hospitalization and whether the episode occurred, while the RPC patient was in compliance with endoscopic surveillance recommendations. Results: Over a period of 10 years, 66 patients with primary RPC were managed for RPC at the University of California, San Francisco. The patients were comprised primarily of first-generation immigrants from Asia though one-quarter had migrated from Latin America and Russia. Episodes of cholangitis were significantly less likely to occur in those undergoing surveillance biliary endoscopy than in those who were not (odds ratio 5.3; P = 0.005) . The mean follow-up was 36.1 months. Conclusions: Serial endoscopic treatment of RPC may be used to systematically clear biliary debris and decreases the risk of cholangitis requiring hospitalization. It represents a reasonable initial management strategy for these patients. Surgery and percutaneous management may also be required, but are best performed as part of a multidisciplinary approach.
The reaction of α-crystallin with the cross-linker 3,3′-dithiobis(sulfosuccinimidyl propionate) demonstrates close proximity of the C termini of αA and αB in the native assembly

The chaperone-like activity of human lens α-crystallin in inhibiting the aggregation of denatured proteins suggests a role for α-crystallin in cataract prevention. Although a variety of techniques have generated structural information relevant to its chaperone-like activity, the size and heterogeneity of α-crystallin have prevented determination of its crystal structure. Even though synthetic cross-linkers have provided considerable information about protein structures, they have not previously been used to study the proximity and orientation of subunits within human α-crystallin. Cross-linkers provide structural insight into proteins by binding the side chains of amino acids within close proximity. To identify the cross-linked residues, the modified protein is digested and the resulting peptides are analyzed by mass spectrometry. Analysis of products from the reaction of α-crystallin with 3,3′dithiobis(sulfosuccinimidyl propionate), DTSSP, identified several modifications to both αA and αB. The most structurally informative of these modifications was a cross-link between lysine 166 of αA and lysine 175 of αB. This cross-link provides experimental evidence supporting theoretical structural models that place the C termini of αA and αB within close proximity in the native aggregate.
Cognitive artifacts: an art-science engagement

'Cognitive Artifacts' is a theoretical framework that may allow a common evaluation of the impact of the products of science and art. Describes need for transformations of science that engage emotional, aesthetic, social and spiritual cognitive processes. Artist describes current work investigating 'Social Architectures.'.
Anti-arthritic effect of astragaloside IV and its molecular mechanism

Abstract The anti-inflammatory drugs and biological agents have been commonly used for the treatment of rheumatoid arthritis (RA) and other chronic inflammatory joint diseases. However, the prolonged use of such drugs may lead to severe side effects. Therefore, there is a growing need for newer drugs that are effective and less toxic for the treatment of these diseases. Natural plant extracts and purified bioactive compounds offer a promising resource for potential anti-arthritic agents. The saponin astragaloside IV (AST) is one of major active components purified from Astragalus membranaceus, which has been widely used in traditional Chinese medicine to treat immune disorders including RA. This review summarizes our recent findings on anti-arthritic effect of AST and its molecular mechanism. Key words Astragaloside IV; arthritis; macrophage; chondrocyte; inflammation
Hospitality leaders: Do they know how their employees feel about them?

Abstract Hospitality organizations may have a disparity between the way employees view their leaders and the leaders' own view—to the detriment of the organization.
Intraterminal Ca2+ concentration and asynchronous transmitter release at single GABAergic boutons in rat collicular cultures

Neurotransmitter release in response to a single action potential has a precise time course. A significant fraction of the releasable vesicles is exocytosed synchronously, within a few milliseconds after the arrival of an action potential. If repeatedly activated, stimulus-locked phasic synchronous release declines, but synaptic transmission can be maintained through tonic asynchronous transmitter release. The desynchronisation of release during repetitive activation is generally attributed to a build-up of intraterminal Ca2+ concentration. However, the precise relationship between presynaptic Ca2+ level and asynchronous release rate at small central synapses has remained unclear. Here we characterise this relationship for single GABAergic terminals in rat collicular cultures. In the presence of tetrodotoxin, inhibitory postsynaptic currents (IPSCs) and presynaptic Ca2+ transients were recorded in response to direct presynaptic depolarisation of individual boutons. Repetitive stimulation indeed resulted in a shift from phasic to asynchronous neurotransmitter release. A clear dominance of the asynchronous release mode was observed after 10 pulses. The steady-state asynchronous release rate showed a third-power dependency on the presynaptic Ca2+ concentration, which is similar to that of evoked release. The Ca2+ sensor for asynchronous release exhibited a high affinity for Ca2+ and was far from saturation. These properties of the Ca2+ sensor should make the asynchronous release very sensitive to any modification of presynaptic Ca2+ concentration, including those resulting from changes in presynaptic activity patterns. Thus, asynchronous release represents a powerful but delicately regulated mechanism that ensures the maintenance of appropriate inhibition when the readily releasable pool of vesicles is depleted.
Toward a Multi-Scale Computational Model of Arterial Adaptation in Hypertension: Verification of a Multi-Cell Agent Based Model

Agent-based models (ABMs) represent a novel approach to study and simulate complex mechano chemo-biological responses at the cellular level. Such models have been used to simulate a variety of emergent responses in the vasculature, including angiogenesis and vasculogenesis. Although not used previously to study large vessel adaptations, we submit that ABMs will prove equally useful in such studies when combined with well-established continuum models to form multi-scale models of tissue-level phenomena. In order to couple agent-based and continuum models, however, there is a need to ensure that each model faithfully represents the best data available at the relevant scale and that there is consistency between models under baseline conditions. Toward this end, we describe the development and verification of an ABM of endothelial and smooth muscle cell responses to mechanical stimuli in a large artery. A refined rule-set is proposed based on a broad literature search, a new scoring system for assigning confidence in the rules, and a parameter sensitivity study. To illustrate the utility of these new methods for rule selection, as well as the consistency achieved with continuum-level models, we simulate the behavior of a mouse aorta during homeostasis and in response to both transient and sustained increases in pressure. The simulated responses depend on the altered cellular production of seven key mitogenic, synthetic, and proteolytic biomolecules, which in turn control the turnover of intramural cells and extracellular matrix. These events are responsible for gross changes in vessel wall morphology. This new ABM is shown to be appropriately stable under homeostatic conditions, insensitive to transient elevations in blood pressure, and responsive to increased intramural wall stress in hypertension.
DTVS: a distributed trace visualization system

We present a straightforward and sample method of visualizing the execution of a distributed system as it is recorded in a collection of per-process traces. The technique is based directly on Lamport's space-time diagrams and the notion of causal precedence as embodied in vector time. Timestamping trace events with vector time provides the leverage required for the rapid display of the space-time diagram. It also allows us to define and display concurrent regions of the trace and to implement a fast algorithm for the evaluation of global state predicates over those regions. We describe an implementation of DTVS for distributed systems in which synchronous communication is used. >
The performance of nanocrystalline CuInS 2 /In 2 S 3 /SnO 2 heterojunction solar cells prepared by chemical spray pyrolysis

CuxIn2-xS3-x thin films with various compositions were prepared by chemical spray pyrolysis to investigate Cu-In-S chalcopyrite semiconductor materials for photovoltaic applications. Nanocrystalline grains with sizes ranging from 30 to 80 nm were identified from XRD and SEM measurements. The CuInS2/In2S3/SnO2 heterojunction was formed to study photovoltaic effects with the sprayed Cu-chalcopyrite thin films. Best results of η=1.32%, VOC=421 mV, JSC=5.35 mA/cm2 and FF=58.5% were found for solar cells with a Cu1.1In0.9S1.9 absorber layer. Through analysis of the film and device parameters, factors that limited the photovoltaic performance are identified and discussed.
A conceptual model of the multiple stages of communication necessary to support patient-centered care

Patient-centered care requires that both healthcare providers and patients have access to comparative effectiveness research (CER), which provides direct comparisons of the risks and benefits of available clinical options. However, insufficient attention has been paid to developing the comprehensive communication systems necessary to ensure that CER reaches patients and healthcare providers. In this review, we propose a model of the multiple stages of CER communication necessary for patient-centered care and review the existing research and gaps in knowledge relevant to each stage. These stages include: promotion of the underlying concepts and value of CER; translation of CER results; dissemination of CER results; and utilization of the results of CER in shared decision-making between patients and providers. A comprehensive approach to CER communication is necessary to ensure that the growing interest in and availability of CER is able to support a more patient-centered model of healthcare.
Maximally permissive deadlock avoidance for multithreaded computer programs (Extended abstract)

Multicore architectures in computer hardware bring an unprecedented need for parallel programming. In the work considered in this presentation, we are especially interested in multithreaded programs with shared data. In this widelyused programming paradigm, “lock” primitives are employed to control access to the shared data within the program threads. For example, mutual exclusion locks (mutexes) are used to protect shared data from concurrent inconsistent updates. However, improper use of mutexes can lead to the familiar “deadly embrace” problem, where a set of threads are waiting for one another and no further progress can be made. These situations are called Circular-Mutex-Wait (CMW) deadlocks and the tale of the dining philosophers [4], [3] is an amusing way to illustrate CMW-deadlocks. As parallel programs are becoming more and more complex, reasoning about deadlock is becoming more and more difficult for programmers. Significant effort has to be spent to detect and fix intricate deadlock bugs. Therefore, there is an emerging need for more systematic methodologies that will enable the programmers of these environments to effectively characterize, analyze, and resolve these deadlock problems.
Phase reconstruction using machine learning for wireless tomography

This is the following paper in a series on a new initiative of wireless tomography. The goal is to combine two areas: wireless communication and radio tomography. This paper primarily focuses on phase reconstruction using machine learning for wireless tomography. When only communication components instead of sophisticated equipment are exploited to perform wireless tomography, phase information of the received field is hard to obtain. Thus self-coherent tomography is proposed, which has two main steps. First, phase reconstruction is achieved using the received amplitude only data. Second, the standard radio tomographic imaging algorithms are used for data analysis. However for the real application, the effect of noise can not be ignored. In order to improve the performance of phase reconstruction with the consideration of noise, a hybrid system for wireless tomography is proposed in this paper. Meanwhile, machine learning is explored here to execute the noise reduction.
BENTHIC STUDIES IN BUZZARDS BAY II. THE MEIOFAUNA1

During the summer of 1957 a study of the small metazoans (meiofauna), based on a series of Phleger core samples, Massachusetts. was undertaken at three stations in Buzzards Bay, The number of animals ranged from 1.69 x lo5 to 1.86 x 106/m2, the dry weights varied from approximately 100 to 600 mg/m2. The nematodes and kinorhynchs, which comprised between 89 and 99% of the total mieofauna, were studied in detail. The sandy localities ( stations P and J ) were characterized by a number of nematodes restricted to this habitat, particularly by three representatives of the genus Odontophora and by all representatives of the genus LeptonemeZZa. The locality rich in fine deposits (station R) was characterized by the relative abundance of several nematodes, particularly of Terschellingia Zongicaudata, and the three kinorhynch species. It was possible to recognize an Odontophora-LeptonemeZZu community in the sandy habitats, and a TerschelZingia Zongicaudata-Trachydemus mainensis (kinorhynch) community in the silty habitat, the former being equivalent to the Ampelisca community, the latter to the Nucula proximaNephthys in&a community described for the macrofauna in the same area. However, these “communities” can also be considered as two ecological groups of species, the former dependent on the presence of sand, the latter on that of fine deposits, which actually live side by side, forming an intricate meshwork of faunal combinations. Each combination is determined by the relative amounts of sand and fine deposits present. The uniformity of the nematode fauna within each station was greater than that between two different stations. Most important in determining the degree of faunal uniformity between paired samples is the similarity in their silt-clay content. However, other mechanical factors also play a role. An analysis of the total species composition of the nematode fauna revealed that Terschellingia Zongicaudata was the most abundant species at station R, whereas at the stations P and J there were three or four equally dominant species. This is interpreted as indicating a splitting up of the sandy habitat into subhabitats. The simultaneous occurrence of closely related species in this environment further supports the conjecture. The distribution of “buccal types” amongst nematodes is correlated with the distribution of sediments.
CHANGE IN THE ETHNOGRAPHY AND LAND USE OF THE ILI VALLEY AND REGION, CHINESE TURKESTAN

ABSTRACT The dry Ili Valley lies on the Soviet borderlands of Chinese Central Asia, where irrigation is a requirement for agriculture. This valley is a classic example of a geographical region, providing a case study of change in landuse over time owing to the introduction of differing ethnic groups and political policies. These changes may be classified into six stages: A nomad, pastoral stage from prehistoric times to 1755 when the Manchu armies defeated and dispersed the Dzungar Mongols; the pastoral-military farm stage with the introduction and extension of agriculture through soldier farmers and soldier ranches, and the construction of fixed settlements and walled cities; the stage of temporary agricultural setback and ethnic change during and following the Muslim rebellions of the 1860's when Manchu and Han Chinese inhabitants were decimated and Turkic Uighurs became the chief agriculturalists; the stage of agricultural expansion and consolidation and increased Chinese settlement, with the organizat...
A Social History and Analysis of the Lsd Controversy

The evolution of LSD use and the controversy surrounding it are reviewed. LSD is treated as a powerful drug whose mind-revealing effects embodied the potential for both psychological harm and personal insight. Predominant motives for LSD use appear to have shifted from desire for self-exploration to a desire for fun. Early LSD use, stimulated by curiosity and adventure seeking, focused on the personal, existential, and spiritual insights attributed (sometimes erroneously) to the drug. Opposition to LSD developed as LSD became a focus or symbol for generational conflict, parental worries, political dissent, irrational behavior and violence, personal cognitive dissonance, and threat to traditional values and institutions. LSD use declined because changes in the social conditions confronting youth created a desire for a type of drug experience LSD was ill-suited to provide, and because changes in users' attitudes and preparations changed the nature of the LSD experience. The relation of drug preference to so...
What made possible the accurate calculations of NMR spin–spin coupling constants?

The 1990s were an exciting time at the Quantum Theory Project of the University of Florida, during which several new developments in coupled cluster (CC) theory took place. One in particular is the development of the equation of motion coupled cluster (EOM-CC) method. It was realized that the EOM-CC excited states could be used to compute second-order properties in a sum over state formulation and the benchmark molecular polarizability calculations have since shown that EOM-CC performs remarkably well. The NMR spin–spin coupling is also a second-order property, and thus calculable by the new EOM-CC methodology. It was a common observation of reviews published at the time that a need existed for accurate nuclear magnetic resonance (NMR) indirect spin–spin coupling constants for medium-size molecules. This article is a first-hand account of the development of the EOM-CC methods for NMR spin–spin coupling constants and their successful applications to problems of interest.
Niaspan® in the management of dyslipidaemia: the evidence

Simultaneous correction of hyperlipidaemia and low HDL-cholesterol may provide superior cardiovascular protection than a single pharmacological lipid-modifying strategy. Combinations of nicotinic acid (the most effective HDL-raising agent currently available) and a statin have been especially well studied. The HDL Atherosclerosis Treatment Study (HATS) demonstrated regression of atherosclerosis and a 60-90% reduction in cardiovascular event rates in patients with cardiovascular disease and low HDL-cholesterol who were randomized to receive a combination of immediate-release nicotinic acid and a statin when compared with patients randomized to placebo. Niaspan®, a prolonged-release formulation of nicotinic acid with superior tolerability to the immediate-release version also reduced the progression of atherosclerosis, in the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER 2) study, although this trial was not powered to evaluate outcomes. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL-C/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) study will test the hypothesis that treatment with Niaspan® plus a statin will provide superior cardiovascular outcomes to a statin given alone in a population of >3000 patients with vascular disease and atherogenic dyslipidaemia (low HDL-cholesterol and hypertriglyceridaemia). The results of AIM-HIGH will be available in 2010. However, the current clinical evidence base supports intensive intervention to correct low HDL-cholesterol today.
Aldehyde oxidase importance in vivo in xenobiotic metabolism: Imidacloprid nitroreduction in mice

Aldehyde oxidase (AOX) metabolizes many xenobiotics in vitro, but its importance in vivo is usually unknown relative to cytochrome P450s (CYPs) and other detoxification systems. Currently, the most important insecticides are neonicotinoids, which are metabolized in vitro by AOX on reduction of the nitroimino group and by CYPs via oxidation reactions. The goal of this study was to establish the relative importance of AOX and CYPs in vivo using the mouse model. The procedure was to reduce liver AOX activity by providing tungsten or hydralazine in the drinking water or to use the AOX-deficient DBA/2 mouse strain. None of these approaches reduced CYP activity measured in vitro with an isozyme nonspecific substrate. Liver AOX activity was reduced by 45% with tungsten and 61% with hydralazine and 81% in AOX-deficient mice relative to controls. When mice were treated ip with the major neonicotinoid imidacloprid (IMI), metabolism by CYP oxidation reactions was not appreciably affected, whereas the AOX-generated nitrosoguanidine metabolite was decreased by 30% with tungsten and 56% with hydralazine and 86% in the AOX-deficient mice. The other IMI nitroreduction metabolite, desnitro-IMI, was decreased by 55%, 65%, and 81% with tungsten, hydralazine, and in the AOX-deficient mice, respectively. Thus, decreasing liver AOX activity by three quite different procedures gave a corresponding decrease for in vivo reductive metabolites in the liver of IMI-treated mice. Possible AOX involvement in IMI metabolism in insects was evaluated using AOX-expressing and AOX-deficient Drosophila, but no differences were found in IMI nitroreduction or sensitivity between the two strains. This is the first study to establish the in vivo relevance of AOX in neonicotinoid metabolism in mammals and one of the first for xenobiotics in general.
Immune checkpoint blockade: a common denominator approach to cancer therapy

The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions. The complex biology of immune checkpoint pathways still contains many mysteries, and the full activity spectrum of checkpoint-blocking drugs, used alone or in combination, is currently the subject of intense study.
Mechanical control of tissue morphogenesis during embryological development

Twenty years ago, we proposed a model of developmental control based on tensegrity architecture, in which tissue pattern formation in the embryo is controlled through mechanical interactions between cells and extracellular matrix (ECM) which place the tissue in a state of isometric tension (prestress). The model proposed that local changes in the mechanical compliance of the ECM, for example, due to regional variations in basement membrane degradation beneath growing epithelium, may result in local stretching of the ECM and associated adherent cells, much like a "run-in-a-stocking". Cell growth and function would be controlled locally though physical distortion of the associated cells, or changes in cytoskeletal tension. Importantly, experimental studies have demonstrated that cultured cells can be switched between different fates, including growth, differentiation, apoptosis, directional motility and different stem cell lineages, by modulating cell shape. Experiments in whole embryonic organ rudiments also have confirmed the tight correlation between basement membrane thinning, cell tension generation and new bud and branch formation during tissue morphogenesis and that this process can be inhibited or accelerated by dissipating or enhancing cytoskeletal tension, respectively. Taken together, this work confirms that mechanical forces generated in the cytoskeleton of individual cells and exerted on ECM scaffolds, play a critical role in the sculpting of the embryo.
INFERTILITY AND THE ROLE OF PSYCHOTHERAPY

Infertility affects 6 million American women and their partners, about 10% of the reproductive age population. Recent improvements in medication, microsurgery, and assisted reproductive technology (ART) make pregnancy possible for more than half the couples pursuing treatment, yet infertility is more than a medical condition. Infertility touches all aspects of a person's life. It affects how individuals feel about themselves, their relationships, and their life perspective. Stress is only one of a myriad of emotional realities that couples facing infertility deal with, often for extended periods of time. In addition to ongoing stress, infertility creates issues of guilt, anxiety, tension within the relationship, and feelings of depression and isolation. Treating couples and individuals who are involved in the journey of dealing with infertility is an opportunity for clinical specialists in psychiatric mental health nursing. The expertise of clinical specialists both in providing psychotherapy services as ...
A robust method using propensity score stratification for correcting verification bias for binary tests

Sensitivity and specificity are common measures of the accuracy of a diagnostic test. The usual estimators of these quantities are unbiased if data on the diagnostic test result and the true disease status are obtained from all subjects in an appropriately selected sample. In some studies, verification of the true disease status is performed only for a subset of subjects, possibly depending on the result of the diagnostic test and other characteristics of the subjects. Estimators of sensitivity and specificity based on this subset of subjects are typically biased; this is known as verification bias. Methods have been proposed to correct verification bias under the assumption that the missing data on disease status are missing at random (MAR), that is, the probability of missingness depends on the true (missing) disease status only through the test result and observed covariate information. When some of the covariates are continuous, or the number of covariates is relatively large, the existing methods require parametric models for the probability of disease or the probability of verification (given the test result and covariates), and hence are subject to model misspecification. We propose a new method for correcting verification bias based on the propensity score, defined as the predicted probability of verification given the test result and observed covariates. This is estimated separately for those with positive and negative test results. The new method classifies the verified sample into several subsamples that have homogeneous propensity scores and allows correction for verification bias. Simulation studies demonstrate that the new estimators are more robust to model misspecification than existing methods, but still perform well when the models for the probability of disease and probability of verification are correctly specified.
Spontaneous Remission of Primary Hyperparathyroidism Related to an Autoimmune Disease: A Case Report

ABSTRACT Objective: To report the unusual case of a woman with unequivocal primary hyperparathyroidism (PHPT) for 13 years who experienced spontaneous remission of her disease concomitant with the diagnosis of psoriatic arthritis. Methods: Clinical presentation, clinical course over 23 years of follow-up, and review of the pertinent literature are presented. Results: A 42-year-old woman was referred for evaluation of persistent hypercalcemia 2 months after unsuccessful parathyroid surgery for PHPT, in which a single, hyperplastic parathyroid gland was removed. Further evaluation confirmed persistent PHPT evidenced by hypercalcemia (12.1 mg/dL), elevated parathyroid hormone (PTH) level (118 pg/mL), normal calcium urinary excretion, and increased bone turnover markers. Persistent hypercalcemia and serum levels of PTH above normal were observed for 11 years after the parathyroid surgery. Thereafter, the patient experienced a downward trend and ultimate normalization of her serum calcium and PTH, which was as...
Sucrose produces withdrawal and dopamine-sensitive reinforcing effects in planarians

Sucrose produces physical dependence and reinforcing effects in rats. We hypothesized that similar effects could be demonstrated in planarians, the earliest animal with a centralized nervous system. We used two assays, one that quantifies withdrawal responses during drug absence as a reduction in motility and another that quantifies reinforcing effects using a conditioned place preference (CPP) design. In withdrawal experiments, planarians exposed to sucrose (1%) for 60 min and then tested in water for 5 min displayed reduced motility compared to water controls. Acute or continuous sucrose (1%) exposure did not affect motility. CPP experiments used a biased design to capitalize upon planarians' natural preference for the dark (pretest, sucrose conditioning in the light, posttest). Planarians conditioned with sucrose (1%) displayed a greater preference shift than sucrose-naive planarians. Glucose (0.1, 1%), but not the non-digestible disaccharide lactulose (0.1, 1%), also produced a greater preference shift than water-exposed planarians. Development of sucrose-induced CPP was inhibited when sucrose (1%) conditioning was conducted in combination with dopamine receptor antagonists SCH 23390 (1 μM) or sulpiride (1 μM). These results suggest that the rewarding and reinforcing effects of sugar are highly conserved across species and that planarians offer an invertebrate model to provide insight into the pharmacological effects of sucrose and related sweeteners.
Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus.

Phosphatidylinositol 4-kinase, Pik1, is essential for viability. GFP-Pik1 localized to cytoplasmic puncta and the nucleus. The puncta colocalized with Sec7-DsRed, a marker of trans-Golgi cisternae. Kap95 (importin-β) was necessary for nuclear entry, but not Kap60 (importin-α), and exportin Msn5 was required for nuclear exit. Frq1 (frequenin orthologue) also is essential for viability and binds near the NH2 terminus of Pik1. Frq1-GFP localized to Golgi puncta, and Pik1 lacking its Frq1-binding site (or Pik1 overexpressed in frq1Δ cells) did not decorate the Golgi, but nuclear localization was unperturbed. Pik1(Δ10-192), which lacks its nuclear export sequence, displayed prominent nuclear accumulation and did not rescue inviability of pik1Δ cells. A Pik1-CCAAX chimera was excluded from the nucleus and also did not rescue inviability of pik1Δ cells. However, coexpression of Pik1(Δ10-192) and Pik1-CCAAX in pik1Δ cells restored viability. Catalytically inactive derivatives of these compartment-restricted Pik1 constructs indicated that PtdIns4P must be generated both in the nucleus and at the Golgi for normal cell function.
Wavelet galerkin algorithms for ground penetrating radar imaging

A new algorithm for fixed-offset Ground Penetrating Radar imaging is derived. The forward model of this inversion scheme is based on the Born approximation and the dyadic Green function for a two-layer medium. The forward model is inverted using the Wavelet Galerkin Algorithms for solving integral equations. We use the Laplacian operator to regularize the ill-posedness of the inverse problem. Numerical results are provided to illustrate performance of the inversion scheme.
WNT-SHH Antagonism Specifies and Expands Stem Cells prior to Niche Formation

Adult stem cell (SC) maintenance and differentiation are known to depend on signals received from the niche. Here, however, we demonstrate a mechanism for SC specification and regulation that is niche independent. Using immunofluorescence, live imaging, genetics, cell-cycle analyses, in utero lentiviral transduction, and lineage-tracing, we show that in developing hair buds, SCs are born from asymmetric divisions that differentially display WNT and SHH signaling. Displaced WNT(lo) suprabasal daughters become SCs that respond to paracrine SHH and symmetrically expand. By contrast, basal daughters remain WNT(hi). They express but do not respond to SHH and hence maintain slow-cycling, asymmetric divisions. Over time, they become short-lived progenitors, generating differentiating daughters rather than SCs. Thus, in contrast to an established niche that harbors a fixed SC pool whose expelled progeny differentiate, asymmetric divisions first specify and displace early SCs into an environment conducive to expansion and later restrict their numbers by switching asymmetric fates.
Cooperative Enterprise as a Structural Dimension of Farm Markets

This article reports on a theoretical analysis of cooperative marketing under alternative sets of assumptions regarding market structure. For some major results, consider a market where raw material is sold by a perfectly competitive industry to a processing industry. If the processing industry has an atomistic structure and no barriers to entry, cooperative marketing—where some processors are cooperatively organized by raw material producers—may cause departures from perfectly competitive equilibrium in the short run, but not in the long run. Where there is but one processor and blockaded entry, cooperative organization of that firm leads to smaller departures from competitive equilibrium than that associated with pure monopsony under many circumstances. Restricted membership cooperation, however, can give rise to market results that are undesirable from the viewpoint of all except the member producers. If the finished product is sold in perfect competition and scale diseconomies do not exist, cooperative marketing tends to lead to competitive equilibrium regardless of other structural conditions that would support monopsony elements.