cssi/SciSciGPT-SciSciNet huggingface dataset:
Complete Haplotype Determination and Single-Chromosome Analysis

Haplotype phase represents the collective genetic variation between homologous chromosomes and is an essential feature of non-haploid genomes. Although shotgun sequencing can reveal genotypes at variant sites, it cannot resolve linkage between variant genotypes on each chromosome as most sequencing fragments (≤ 1kb) span at most one variant site (∼1 per 1.5 kb in human genomes). Long-range sequencing can generate variant linkage information, but whether such information can determine whole-chromosome haplotype phase remains unclear. Here we describe a general framework for haplotype inference from variant linkage data using a one-dimensional spin model. Building on this model, we design and implement algorithms that can determine complete chromosomal haplotypes of diploid human genomes using 60x linked-reads sequencing in combination with 60x Hi-C sequencing. The computationally inferred haplotypes show high completeness (>98%) and accuracy (>99%) when compared to reference haplotypes determined from sequencing of single chromosomes. We further present examples of single-chromosome analysis enabled by whole chromosome haplotype information.
Kernel classification using a linear programming approach

A support vector machine (SVM) classifier corresponds in its most basic form to a quadratic programming problem. Various linear variations of support vector classification have been investigated such as minimizing the L1-norm of the weight-vector instead of the L2-norm. In this paper we introduce a classifier where we minimize the boundary (lower envelope) of the epigraph that is generated over a set of functions, which can be interpreted as a measure of distance or slack from the origin. The resulting classifier appears to provide a generalization performance similar to SVMs while displaying a more advantageous computational complexity. The discussed formulation can also be extended to allow for cases with imbalanced data.
Pharmacologic, Breastfeeding, and Nutritional Considerations During Pregnancy and Postpartum

Careful consderation should be given to medications administered pre and post partum. For the duration of the pregnancy, one must make sure that the medications are not teratogenic. Postpartum, one must make sure that medications are not passed through to the breastmilk. This chapter discusses various pharmacologic management strategies for management of hypertension in pregnancy, lupus nephritis during pregnancy, various electrolyte disorders during pregnancy, diabetic and renal transplant medications and their safety during pregnancy, medications used when dialyzing a pregnant woman, and breastfeeding and postpartum care.
No Pain, More Gain: Reduced Postoperative Opioid Consumption with a Standardized Opioid-Sparing Multimodal Analgesia Protocol in Opioid-Tolerant Patients Undergoing Colorectal Surgery.

The utility of opioid-sparing multimodal analgesia protocols (OSMMAPs) in opioid-tolerant (OT) patients is unknown. We sought to determine the impact of a standardized OSMMAP in OT versus opioid-naive (ON) patients after major colorectal surgery. Consecutive patients undergoing surgery before (January 2015-March 2017) and after OSMMAP implementation (April 2017-March 2018) were identified from a single-institution prospective colorectal surgery registry. OT was defined by the presence of an opioid on the preadmission medication record. Opioid use (measured in oral morphine equivalents (OMEs)) and surgical outcomes were compared between OT and ON patients pre- and post-OSMMAP. The study cohort of 201 patients included 59 OT patients (25 pre- and 34 post-OSMMAP) and 142 ON controls (34 pre- and 108 post-OSMMAP). The median age was 47.5 years (IQR 32), and 50% were male. 185 patients (92%) had a laparoscopic/robotic resection and 16 (8%) open. There were statistically significant reductions in OME required post-OSMMAP on each postoperative day (days 1 to 4) and cumulative OME for both OT and ON patients. The reduction in opioid requirements was significantly larger in OT than ON patients. We present the first study highlighting a larger opioid usage reduction in OT than in ON patients after OSMMAP implementation.
The role of negative affect in the association between attention bias to threat and posttraumatic stress: An eye-tracking study.

Abstract Biased processing of threatening stimuli, including attention toward and away from threat, has been implicated in the development and maintenance of PTSD symptoms. Research examining theoretically-derived mechanisms through which dysregulated processing of threat may be associated with PTSD is scarce. Negative affect, a transdiagnostic risk factor for many types of psychopathology, is one potential mechanism that has yet to be examined. Thus, the present study (n = 92) tested the indirect effect of attention bias on PTSD via negative affect using rigorous eye-tracking methodology in a sample of urban-dwelling, trauma-exposed African-American women. We found support for the hypothesis that attention bias toward threat was indirectly associated with PTSD symptoms through increased negative affect. These results suggest that negative affect may be an important etiological process through which attention bias patterns could impact PTSD symptom severity. Implications for psychological and pharmacological therapeutic interventions targeting threat-related attention biases and negative affect are discussed.
Exosomal Long Non-Coding RNA (LNCRNA) in Lung Cancer

ABSTRACT Background Long noncoding RNAs (lncRNAs) are master regulators of pluripotency, differentiation, body axis patterning and promoting developmental transitions. Dysregulation of lncRNA expression has been shown to be associated with a wide range of pathologies. Study Design lncRNA within exosomes of lung cancer cell line (H838) and derived from patients with NSCLC were analyzed. After 10,000xg centifugation, microvesicles were isolated by chromatography (CT). Trizol isolated total RNA, which was analyzed for specific lncRNAs using the LncRNA profiler qPCR array (Systems Biosciences). RNA and ln RNA from tumor cells and the vesicles from NSCLC patient (n = 8) sera were analyzed the same way. Results Microvesicles' size, 50-200nm, was consistent with exosomes (CD63 confirmed). Exosomes contained RNA and lncRNA. Comparison of lncRNA between tumor cells and their released exosomes revealed selectivity on the lncRNAs appearing in the exosomes. Three of 90 examined lncRNAs had a 10-fold increase within exosomes. Representative lncRNAs were compared between the cells and their released exosomes. For lncRNAs exhibiting epigenetic silencing, splicing regulation, regulating apoptosis and translational control the CT values of lncRNA within cells and the lncRNA within exosomes were the same (ANRIL cells 23.80 vs. 26.44 exosomes. MALAT-1 cells 31.84 vs. 32.85 exosomes. BACE1AS cells 34.14 vs 34.86 exosomes). The lncRNA profiles of cancer patients were distinct from normal.An increase of greater than 20-fold was observed in 58 lncRNAs in cancer patient-derived exosomes. In contrast, a decrease of 10-fold or greater was observed in 20 lncRNAs in cancer patients. LncRNAs exhibiting epigenetic silencing, In lncRNAs exhibiting splicing regulation and lncRNAs regulating apoptosis,were elevated 20-40 fold in cancer patient-derived exosomes versus controls. Conclusions: Misexpression of lncRNAs contributes to cancer development and progression. Cancer patients' exosomes contain lncRNA distinct from non-cancer controls.Some lncRNAs, such as MALAT-1 (metastasis-associated in lung adenocarcinoma transcript) were identified in serum of NSCLC patients. The stability of exosomes in the peripheral circulation and the unique profile of lncRNAs suggest their ideal utility as a diagnostic biomarker. Disclosure All authors have declared no conflicts of interest.
Interventions to Improve Antiretroviral Therapy Adherence Among Adolescents and Youth in Low- and Middle-Income Countries: A Systematic Review 2015-2019.

Adolescents and youth living with HIV have poorer antiretroviral treatment (ART) adherence and viral suppression outcomes than all other age groups. Effective interventions promoting adherence are urgently needed. We reviewed and synthesized recent literature on interventions to improve ART adherence among this vulnerable population. We focus on studies conducted in low- and middle-income countries (LMIC) where the adolescent and youth HIV burden is greatest. Articles published between September 2015 and January 2019 were identified through PubMed. Inclusion criteria were: [1] included participants ages 10–24 years; [2] assessed the efficacy of an intervention to improve ART adherence; [3] reported an ART adherence measurement or viral load; [4] conducted in a LMIC. Articles were reviewed for study population characteristics, intervention type, study design, outcomes measured, and intervention effect. Strength of each study’s evidence was evaluated according to an adapted World Health Organization GRADE system. Articles meeting all inclusion criteria except being conducted in an LMIC were reviewed for results and potential transportability to a LMIC setting. Of 108 articles identified, 7 met criteria for inclusion. Three evaluated patient-level interventions and four evaluated health services interventions. Of the patient-level interventions, two were experimental designs and one was a retrospective cohort study. None of these interventions improved ART adherence or viral suppression. Of the four health services interventions, two targeted stable patients and reduced the amount of time spent in the clinic or grouped patients together for bi-monthly meetings, and two targeted patients newly diagnosed with HIV or not yet deemed clinically stable and augmented clinical care with home-based case-management. The two studies targeting stable patients used retrospective cohort designs and found that adolescents and youth were less likely to maintain viral suppression than children or adults. The two studies targeting patients not yet deemed clinically stable included one experimental and one retrospective cohort design and showed improved ART adherence and viral suppression outcomes. ART adherence and viral suppression outcomes remain a major challenge among adolescents and youth. Intensive home-based case management models of care hold promise for improving outcomes in this population and warrant further research.
Ethics as Usual? Unilateral Withdrawal of Treatment in a State of Exception

Do extraordinary crisis situations requiring life-and-death decisions create a “state of exception” in which ordinary social, political, and ethical norms must be altered or suspended altogether (A...
OOxytetracycline Hydrochloride (OTC-HCl) Application for Control of Palm Phytoplasmas

Phytoplasma diseases of palms are a major threat to the Florida nursery and landscaping industries. Historically, lethal yellowing (LY) has been responsible for the death of millions of coconut palms throughout the Caribbean. LY, introduced into Florida sometime in the first half of the 20th century, has been causing decline of over 30 species of palm (Harrison and Elliott 2015). In 2006, lethal bronzing disease (LBD) was discovered on the west coast of Florida near Tampa. Currently, the only two management options available for control of phytoplasmas is an aggressive sampling strategy followed by consistent tree removal and injections of OTC. This document seeks to provide a source of information and instruction on the injection of OTC into palm trunks.
Genetic analysis of rice seedling traits related to machine transplanting under different seeding densities

Due to the diversity of rice varieties and cropping systems in China, the limitation of seeding density and seedling quality makes it hard to improve machine-transplanted efficiency. Previous studies have shown that indica and japonica varieties varied in machine transplanting efficiency and optimal seeding density. In this study, a RIL population derived from ‘9311’ and ‘Nipponbare’ were performed to explore the seedling traits variations and the genetic mechanism under three seeding densities. The parents and RIL population exhibited similar trends as the seeding density increased, including seedling height and first leaf sheath length increases, shoot dry weight and root dry weight decreases. Among the 37 QTLs for six traits detected under the three seeding densities, 12 QTLs were detected in both three seeding densities. Five QTL hotspots identified clustered within genomic regions on chromosomes 1, 2, 4, 6 and 11. Specific QTLs such as qRDW1.1 and qFLSL5.1 were detected under low and high seeding densities, respectively. Detailed analysis the QTL regions identified under specific seeding densities revealed several candidate genes involved in phytohormones signals and abiotic stress responses. Whole-genome additive effects showed that ‘9311’ contributed more loci enhancing trait performances than ‘Nipponbare’, indicating ‘9311’ was more sensitive to the seeding density than ‘Nipponbare’. The prevalence of negative epistasis effects indicated that the complementary two-locus homozygotes may not have marginal advantages over the means of the two parental genotypes. Our results revealed the differences between indica rice and japonica rice seedling traits in response to seeding density. Several QTL hotspots involved in different traits and specific QTLs (such as qRDW1.1 and qFLSL5.1) in diverse seeding densities had been detected. Genome-wide additive and two-locus epistasis suggested a dynamic of the genetic control underlying different seeding densities. It was concluded that novel QTLs, additive and epistasis effects under specific seeding density would provide adequate information for rice seedling improvement during machine transplanting.
Excess mortality associated with the COVID-19 pandemic among Californians 18-65 years of age, by occupational sector and occupation: March through October 2020

Abstract Background Though SARS-CoV-2 outbreaks have been documented in occupational settings and though there is speculation that essential workers face heightened risks for COVID-19, occupational differences in excess mortality have, to date, not been examined. Such information could point to opportunities for intervention, such as workplace modifications and prioritization of vaccine distribution. Methods and findings Using death records from the California Department of Public Health, we estimated excess mortality among Californians 18–65 years of age by occupational sector and occupation, with additional stratification of the sector analysis by race/ethnicity. During the COVID-19 pandemic, working age adults experienced a 22% increase in mortality compared to historical periods. Relative excess mortality was highest in food/agriculture workers (39% increase), transportation/logistics workers (28% increase), facilities (27%) and manufacturing workers (23% increase). Latino Californians experienced a 36% increase in mortality, with a 59% increase among Latino food/agriculture workers. Black Californians experienced a 28% increase in mortality, with a 36% increase for Black retail workers. Asian Californians experienced an 18% increase, with a 40% increase among Asian healthcare workers. Excess mortality among White working-age Californians increased by 6%, with a 16% increase among White food/agriculture workers. Conclusions Certain occupational sectors have been associated with high excess mortality during the pandemic, particularly among racial and ethnic groups also disproportionately affected by COVID-19. In-person essential work is a likely venue of transmission of coronavirus infection and must be addressed through strict enforcement of health orders in workplace settings and protection of in-person workers. Vaccine distribution prioritizing in-person essential workers will be important for reducing excess COVID mortality.
Fecal incontinence

Fecal incontinence is a socially devastating clinical condition. Initial symptomatic treatment includes exclusion of foods that precipitate the problem, increased use of fiber, and drug therapy with loperamide. Persistence of incontinence after these lifestyle modifications requires the physician to evaluate the internal and external anal sphincters. Anal endosonography and manometry provide an evaluation of sphincter structure and function. If an isolated muscle defect is seen, sphincteroplasty can be tried. If this surgical procedure is not indicated, biofeedback may be an option. Biofeedback should be considered for patients with neurogenic fecal incontinence, a weak but structurally intact external sphincter, or a decreased ability to perceive rectal distention. Muscle transposition to create a neosphincter should be offered only by surgeons with extensive experience performing this surgery. Because of the cosmetic sequela of colostomy, this surgery is often considered as a last-step procedure, despite being safe and effective.
A Phase 1 first-in-human study of the safety, tolerability, and pharmacokinetics of the ROBO2 fusion protein PF-06730512 in healthy participants.

Proteinuria associated with podocyte effacement is a hallmark of focal segmental glomerulosclerosis (FSGS). Preclinical studies implicated ROBO2/SLIT2 signaling in the regulation of podocyte adhesion, and inhibition of this pathway is a novel target to slow FSGS disease progression. This first‐in‐human dose‐escalation study evaluated the safety, tolerability, pharmacokinetics, and immunogenicity of PF‐06730512, an Fc fusion protein that targets the ROBO2/SLIT2 pathway, in healthy adults. In this Phase 1, double‐blind, sponsor‐open study, single ascending dose (SAD) cohorts were randomized to receive up to 1000 mg or placebo intravenously (IV); multiple ascending dose (MAD) cohorts were randomized to receive up to 400 mg subcutaneous (SC) doses, 1000 mg IV dose, or matching placebo. Safety evaluations were performed up to 71 (SAD) and 113 (MAD) days after dosing; blood samples were collected to measure serum PF‐06730512 concentrations and antidrug antibodies (ADA) to PF‐06730512. Seventy‐nine participants (SAD, 47; MAD, 32) were enrolled. There were 108 mild (SAD, 46; MAD, 62) and 21 moderate (SAD, 13; MAD, 8) treatment‐emergent adverse events (TEAEs); no deaths, treatment‐related serious AEs, severe TEAEs, or infusion reactions were reported. PF‐06730512 exposure generally increased in an approximately dose‐proportional manner; mean t 1/2 ranged from 12–15 days across 50–1000 mg doses. Immunogenicity incidence was low (SAD, 0 ADA+; MAD, 2 ADA+). In conclusion, single IV doses of PF‐06730512 up to 1000 mg and multiple IV and SC dosing up to 1000 and 400 mg, respectively, were safe and well tolerated in healthy participants. Further trials in patients with FSGS are warranted. Clinical trial registration: Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT03146065","term_id":"NCT03146065"}}NCT03146065.
Activation of a G protein-coupled receptor through indirect antibody-mediated tethering of ligands

Antibodies raised against many cell surface proteins, including G protein-coupled receptors, remain important tools for their functional characterization. By linking antibodies to ligands for cell surface proteins, such adducts can be targeted to the surface of a cell type of choice. Site-specific functionalization of full-size antibodies with synthetic moieties remains challenging. Here we present new approaches in which single domain antibodies (known as VHHs or nanobodies) that target either cell surface proteins or conventional antibodies are used to indirectly deliver ligands for GPCRs to their sites of action. The combination of high yield production of nanobodies, facile site-specific functionalization, and compatibility with commercially available mouse and rabbit antibodies should enable wide application of this approach.
REGIONAL RELATIONSHIPS BETWEEN DEVELOPMENT AND GROWTH IN LARVAE OF ANTARCTIC KRILL, EUPHAUSIA SUPERBA, FROM FIELD SAMPLES

ABSTRACT Larvae of Euphausia superba were sampled during January-March 1981 in three Antarctic areas: the Scotia Sea (twice), waters near Elephant Island in the South Shetlands (twice), and Bransfield Strait. January-February larvae in the Scotia Sea averaged 250/m3 and 99% were calyptopes, dominated by stage 1. The oldest stages, Furcilia 3 and 4, had grown at slow rates, determined by comparisons of body lengths with larvae from other areas. Progressively younger stages reflected better growth, associated with a contemporary highly variable distribution of chlorophyll. Most rapid growth was inferred in a low density of larvae south of Elephant Island in March, where chlorophyll was at highest observed levels. Intermediate growth had occurred in larvae from north and east of Elephant Island, and Bransfield Strait, where chlorophyll concentrations were intermediate. During March, larvae averaged 3-6 stages older than during January-February. Abundances were 100–500/m3 along 250 km in the same area sampled in January. To the north and east of Elephant Island, principal modes in larval abundances were at younger stages (by 2-4 stages, respectively, = about 16-32 days of growth) than near the South Orkneys. An intermediate region showed an intermediate mode, implying intermediate timing of peak recruitment. Inferred development times of about 8 days per calyptopis and furcilia stage are shorter than previous estimates. In Scotia Sea areas having the highest densities of larvae in March, there were numerous developmental forms (variants) of furcilia stages 1 and 2, without clearly dominant forms. This evidence of indirect pathways during larval development and of slow growth was borne out by body-length measurements. Chlorophyll was near depletion in these areas of high densities of larvae. Data from earlier years indicate that absence of dominant forms in Furciliae 1 and 2 during March in the southern Scotia Sea may occur regularly, possibly contributing to the substantial range of body size of older year classes. Pathways of larval development observed in March were direct in coastal areas, compared with oceanic, in spite of variable ambient chlorophyll. Extremes in growth rate, population density, and food seem to interrelate, whereas intermediate states do not.
Kant and Capital Punishment Today

Even if a civil society were to be dissolved by the consent of all its members (e.g., if a people inhabiting an island decided to separate and disperse throughout the world), the last murderer remaining in the prison would first have to be executed, so that each has done to him what his deeds deserve and blood guilt does not cling to the people for not having insisted upon this punishment; for otherwise the people can be regarded as collaborators in this public violation of justice.1
Performance analysis and middleware assisted adaptation for quantum chemistry computations

Quantum chemistry applications such as General Atomic and Molecular Electronic Structure System(GAMESS) that can execute on a complex peta-scale parallel computing environment have a large number of input parameters that affect the overall performance. The application characteristics vary according to the input parameters. This is due to the difference in the usage of resources like network bandwidth, I/O and main memory according to the input parameters. Effective execution of applications in a parallel computing environment that share such resources require some sort of adaptive mechanism to enable efficient usage of these resources. The adaptation adjusts the most computationally intensive part of the application thus leading to sizable gains. General Atomic and Molecular Electronic Structure System (GAMESS), used for ab-initio molecular quantum chemistry calculations, utilizes NICAN (Network Information Conveyer and Application Notification) for dynamically making adaptations so as to improve the application performance in heavy load conditions. The adaptation mechanism has the ability to modify the application execution in a very simplistic yet effective manner. In this work, we have explored methods to expand the structure of NICAN in order to include other input parameters based on which the application performance can be controlled. The application performance has been analyzed on different architectures to otain fine grained performance data and a tuning strategy has been identified. A generic database framework has been incorporated in the existing NICAN mechanism.
Model minimization in Markov decision processes

We use the notion of stochastic bisimulation homogeneity to analyze planning problems represented as Markov decision processes (MDPs). Informally, a partition of the state space for an MDP is said to be homogeneous if for each action, states in the same block have the same probability of being carried to each other block. We provide an algorithm for finding the coarsest homogeneous refinement of any partition of the state space of an MDP. The resulting partition can be used to construct a reduced MDP which is minimal in a well defined sense and can be used to solve the original MDP. Our algorithm is an adaptation of known automata minimization algorithms, and is designed to operate naturally on factored or implicit representations in which the full state space is never explicitly enumerated. We show that simple variations on this algorithm are equivalent or closely similar to several different recently published algorithms for finding optimal solutions to (partially or fully observable) factored Markov decision processes, thereby providing alternative descriptions of the methods and results regarding those algorithms.
torsion of genus two curves over _

We determine the isogeny classes of abelian surfaces over F q whose group of F q -rational points has order divisible by q 2 . We also solve the same problem for Jacobians of genus-2 curves.
An Overview of Integral Quadratic Constraints for Delayed Nonlinear and Parameter-Varying Systems.

A general framework is presented for analyzing the stability and performance of nonlinear and linear parameter varying (LPV) time delayed systems. First, the input/output behavior of the time delay operator is bounded in the frequency domain by integral quadratic constraints (IQCs). A constant delay is a linear, time-invariant system and this leads to a simple, intuitive interpretation for these frequency domain constraints. This simple interpretation is used to derive new IQCs for both constant and varying delays. Second, the performance of nonlinear and LPV delayed systems is bounded using dissipation inequalities that incorporate IQCs. This step makes use of recent results that show, under mild technical conditions, that an IQC has an equivalent representation as a finite-horizon time-domain constraint. Numerical examples are provided to demonstrate the effectiveness of the method for both class of systems.
Rank-aware cache replacement and write buffering to improve DRAM energy efficiency

DRAM power and energy efficiency considerations are becoming increasingly important for low-power and mobile systems. Using lower power modes provided by commodity DRAM chips reduces power consumption but comes at a performance penalty to return to full power for servicing requests. We propose a novel cache replacement policy and write buffer that prevents cache blocks going to certain DRAM chips from being replaced, resulting in less requests going to these chips, and allowing them to remain idle for longer periods of time. Our proposed modifications improve DRAM energy efficiency by 10% on average (up to 30%) compared to a base case that utilizes low power modes, and by 76% compared to a base case that does not utilize power saving modes.
Contraint-based polymorphism in Cecil: towards a practical and static type system

We present a static type system for object-oriented languages which strives to provide static typechecking without resorting to dynamic "type casts," restricting what code the programmer can write, or being too verbose or difficult to use in practice. The type system supports bounded parametric polymorphism where the bounds on type variables can be expressed using general recursive subtype or signature constraints, with F-bounded polymorphism and covariant type parameters being special cases.We implemented this type system in the Cecil language and used it to successfully typecheck a 100,000-line Cecil program, the Vortex optimizing compiler. Our experience was very good: dynamically-typed code needed very little rewriting. We also observed several common programming situations that presented a challenge for our type system. We discuss these situations and ways to typecheck them statically.
Multiple description scalable coding for error-resilient video transmission over packet networks

Two types of scalabilities exist in current scalable video streaming schemes: (1) nested scalability, in which different representations (i.e., descriptions) of each frame are generated using layered scalable coding and have to be decoded in a fixed sequential order, and (2) parallel scalability, which is used in multiple description coding (MDC) where different descriptions are mutually refinable and independently decodable. In this paper, we present a general framework that includes both scalabilities and demonstrate the similarity between the leaky prediction based layered coding and an MDC scheme that uses motion compensation. Based on this framework, we introduce nested scalability into each description of the MDC stream and propose a fine granularity scalability (FGS) based MDC approach. We also develop a scalable video coding structure that is characterized by the dual-leaky prediction to balance the trade-off between coding efficiency and the error resilience performance of the coded bit stream.
Diacylglycerol Enrichment of Endoplasmic Reticulum or Lipid Droplets Recruits Perilipin 3/TIP47 during Lipid Storage and Mobilization

Fatty acid-induced triacylglycerol synthesis produces triacylglycerol droplets with a protein coat that includes perilipin 3/TIP47 and perilipin 4/S3-12. This study addresses the following two questions. Where do lipid droplets emerge, and how are their coat proteins recruited? We show that perilipin 3- and perilipin 4-coated lipid droplets emerge along the endoplasmic reticulum (ER). Blocking membrane trafficking with AlF4− during fatty acid-induced triacylglycerol synthesis drove perilipin 3 to the tubular ER. Forskolin, which like AlF4− activates adenylate cyclase, did not redistribute perilipin 3, but when added together with AlF4− perilipin 3 was recruited to lipid droplets rather than the ER. Thus inhibiting trafficking with AlF4− redistributed perilipin 3 differently under conditions of triacylglycerol synthesis (fatty acid addition) versus hydrolysis (forskolin) suggesting a shared acylglycerol-mediated mechanism. We tested whether diacylglycerol (DG), the immediate precursor of triacylglycerol and its first hydrolytic product, affects the distribution of perilipin 3. Stabilizing DG with the DG lipase inhibitor RHC80267 enhanced the perilipin 3 recruited to lipid droplets and raised DG levels in this fraction. Treating cells with a membrane-permeable DG recruited perilipin 3 to the ER. Stabilizing DG, by blocking its hydrolysis with RHC80267 or its acylation with triacsin C, enhanced recruitment of perilipin 3 to the ER. Expressing the ER enzyme DGAT1, which removes DG by converting it to triacylglycerol, attenuated perilipin 3 DG-induced ER recruitment. Membrane-permeable DG also drove perilipin 4 and 5 onto the ER. Together the data suggest that these lipid droplet proteins are recruited to DG-enriched membranes thereby linking lipid coat proteins to the metabolic state of the cell.
Thyroxine sulfate is a major thyroid hormone metabolite and a potential intermediate in the monodeiodination pathways in fetal sheep.

T3 and rT3 production rates in the fetus account for roughly only a third of the total T4 production rate; thus, the fate of the majority of T4 produced in the fetus is unknown (the "T4 disposal gap"). We developed sensitive and specific T4 sulfate (T4S) and T3 sulfate (T3S) RIAs to investigate the roles of these compounds in fetal T4 metabolism. T3, T4, T3S, and T4S were determined in a variety of tissue fluid and/or serum samples obtained from fetal, newborn (n = 6), and adult (n = 6) sheep. Four groups of fetal animals, with gestational ages of 94 days (n = 5), 110-111 days (n = 6), 130-131 days (n = 6), and 145 days (n = 6; term = 150 days), were studied. In addition, type I 5'-monodeiodinase (5'-MDI) activity was quantified in liver and kidney tissues. 5'-MDI activities were lower in 94- to 131-day-old fetuses than in fetuses near term or in newborn animals. Mean serum T3 concentrations increased progressively from 94 days (19 ng/dl) to term (371 ng/dl), while mean T3S and T4S serum concentrations we...
Kepler Observations of the Seyfert 1 Galaxy II ZW 229.015

The Seyfert 1 galaxy II ZW 229.015 has been observed with the Kepler spacecraft since quarter 4 of Kepler science operations. The results of the quarters 4-7 (1 year) Kepler observations are presented in this paper. We find the source to be highly variable on multiple timescales, with discrete variations occurring on timescales as short as tens of hours with amplitudes as small as 0.5%. Such small amplitude, rapid variability has never before been detected in active galactic nuclei. The presence of a strong galaxy component dilutes the variability determined from the photometric aperture used in the standard Kepler PDC analysis. Using the tools provided by the Kepler Guest Observer Office and simultaneous V-band photometry found in the literature, we determine an optimal customized aperture for photometry of this source with Kepler. The results of a PSRESP analysis reveal tentative evidence of a characteristic variability timescale in the power spectrum. Using this timescale, we estimate the mass of the central supermassive black hole and this estimate is consistent with the virial mass estimate from reverberation mapping studies.
Diagnosis of abnormalities of the human fetus during the first, second, and third trimesters.

Clinical teratologists will have new challenges during the 1990s as birth defects are diagnosed more frequently than in previous decades. Malformations and genetic disorders will be diagnosed in utero during all three trimesters of pregnancy. The teratologist may participate in or lead a multispecialty group to give the involved family optimal interpretation of test results, counseling, and recommendations regarding subsequent clinical management. © 1992 Wiley-Liss, Inc.
A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition.

The PI3K (phosphoinositide 3-kinase) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110α inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined. In contrast, p110β-selective inhibitors only reduced PKB/Akt phosphorylation in PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing cell-cycle arrest in the G 1 phase, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell-cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signalling pathways. Taken together, our data indicate that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts.
A VIGILANCE TASK SENSITIVE TO THE EFFECTS OF STIMULANTS, HYPNOTICS, AND ENVIRONMENTAL STRESS : THE SCANNING VISUAL VIGILANCE TEST

The Scanning Visual Vigilance Test is a variable-length detection test designed to assess the ability of individuals to maintain visual alertness for sustained periods of time. The test was designed to be sensitive to changes in vigilance produced by subtle variations in performance, such as those produced by low doses of centrally acting food constituents, drugs, or environmental stress. The test has been shown to be sensitive to the effects of stimulants and sedatives, as well as cold stress and sleep loss. It requires the subject to continuously scan a video monitor to detect the occurrence of infrequent stimuli that are difficult to detect. The number of stimuli correctly detected, false alarms, and reaction times are recorded. The stimulus is a small rectangle displayed for 2 sec at random locations on a darker region of a video monitor at random or pseudo-random times. The brightness of the stimulus can be adjusted for each subject individually on an automated threshold detection test. Training and test session length are defined by the experimenter. Hardware requirements are an IBM-compatible personal computer (286 or higher) with a color or grayscale VGA monitor.
Evaluation of Currencies in the Foreign Exchange Market: Attitudes and Expectations of Foreign Exchange Traders

Summary: This article examines whether there is a connection between the attitudes of traders in the foreign exchange market and their expectations of future exchange rate developments. A psycholog...
Evidence order and belief revision in management accounting decisions

Abstract One of the primary functions of management accounting is to provide inputs for management decisions. These inputs, or pieces of evidence, are used in making judgements about an organization's activities. We focus on situations in which an individual's degree of belief in a specific cause, or hypothesis, is sequentially revised as additional evidence is received. These types of situations are numerous in management accounting contexts (e.g. performance evaluation, variance analysis, and resource allocation). Effects of evidence order and currently held beliefs (anchors) on judgements and decisions are investigated using Hogarth & Einhorn's belief-adjustment model (Order Effects in Belief Updating: The Belief-Adjustment Model, Working paper, 1990). Business students taking a management accounting course processed eight cases, four “generic” (i.e. nonaccounting) and four “management accounting”. Model predictions were supported for both groups: recency effects were present for mixed evidence; anchor size did not affect the magnitude of the recency effect; and anchor size had the predicted impact on changes in belif. For generic cases, as predicted. no order effect existed for consistent evidence. For accounting cases, some recency effects were found for consistent evidence, whereas the model predicts none. Mixed evidence order effects (i.e. recency) did not consistently impact action-oriented decisions in either generic or accounting cases. Prior research is reinterpreted in light of these findings. Implications of these findings for developing descriptive models of accounting judgements and decisions, as well as applications within management accounting contextsm are discussed.
From the politics of accommodation to adversarial politics in the Netherlands: A reassessment

(1989). From the politics of accommodation to adversarial politics in the Netherlands: A reassessment. West European Politics: Vol. 12, Politics in the Netherlands: How much change?, pp. 139-153.
Comparison of pattern recognition approaches for multisensor detection and discrimination of anti-personnel and anti-tank landmines

In this work we explore and compare several statistical pattern recognition techniques for classification and identification of buried landmines using both electromagnetic induction and ground penetrating radar data. In particular we explore application of different feature extraction approaches to the problem of landmine/clutter classification in blind- and known- ground truth scenarios using data from the NIITEK ground penetrating radar and the Vallon EMI sensor as well as the CyTerra GPR and Minelab EMI sensors. We also compare and contrast the generalization capabilities of different kernels including radial basis function, linear, and direct kernels within the relevance vector machine framework. Results are presented for blind-test scenarios that illustrate robust classification for features that can be extracted with low computational complexity.
Effects of impurities on the lattice parameters of GaN

The effects on the lattice parameters due to incorporation of impurities in GaN are evaluated using first-principles pseudopotential-density-functional calculations. Both the size effect, due to the relaxation of host atoms around the impurity, and the deformation-potential effect, due to placing free carriers in the conduction or valence band, are investigated. The incorporation of silicon and beryllium causes contraction of the lattice, while oxygen and magnesium cause expansion. Consequences for experimental observations are discussed; in particular, the presence of impurities in bulk crystals that are used as standards for the lattice parameters of GaN can have a sizable effect on the measured values.
Cocaine-primed craving and its relationship to depressive symptomatology in individuals with cocaine dependence.

Several lines of evidence suggest a link between cocaine-primed craving and depressive symptomatology. The purpose of this study was to directly relate these two clinical phenomena. Thirty-three cocaine-dependent subjects were rated on the Hamilton Rating Scale for Depression (HRSD) at baseline and then administered an i.v. bolus of cocaine (0.2 mg/kg). Multiple regression analysis revealed that only the HRSD score was an independent predictor of cocaine-primed craving (F= 4.09; d.f. = 10,22; r = 0.81, p < 0.003) when baseline spontaneous craving during early withdrawal, age, gender, frequency of use, time since last use, monetary expenditure on cocaine and the Addiction Severity Index Drug Composite Scores were considered. These data support the hypothesis that depressive symptomatology affects cocaine-primed craving and that this relationship is relatively specific to symptoms defined by the HRSD and is not seen with a number of other clinical and demographic variables.
Altered voiding after the tension-free vaginal tape procedure: is increased resistance the mechanism of therapy?

Abstract Objective: Tension–free vaginal tape (TVT) is gaining popularity as an effective treatment for genuine stress urinary incontinence. To better understand the procedure’s mechanism, we prospectively assessed voiding indices in a cohort of patients undergoing TVT for stress incontinence. Methods: We compared the preoperative and postoperative pressure flow studies of women who underwent TVT between November 1998 and July 1999. From the maximal flow rate (Qmax) and detrusor pressure at maximal flow rate (Pdet), the urethral resistance (R = P/Q 2 ) was calculated. Results were compared using one-tailed t test for paired values. Results: At a mean follow-up of 4 months, 10 of 18 women undergoing TVT had adequate voiding studies. All were both subjectively and objectively cured of their stress incontinence. Both mean detrusor pressure and mean urethral resistance increased significantly postoperatively. Cotton swab tests results for hypermobility remained positive postoperatively in 9 of 10 patients. Conclusions: Urethral resistance during voiding increases when TVT corrects stress incontinence. A surgical procedure may correct stress incontinence without affecting proximal urethral mobility. Qmax 1 Qmax 2 Pdet 1 Pdet 2 R 1 R 2 Mean 25.08 21.94 20.1 41.8 0.048 0.216 SD 10.029 11.186 14.587 15.697 0.051 0.266 P = NS P = 0.0002 P = 0.0357
Inflammation in asthma: the cornerstone of the disease and target of therapy.

Asthma is a chronic disease associated with variable levels of airflow obstruction. Considerable evidence has been obtained to show that airway inflammation is a major factor in the pathogenesis of asthma in associated bronchial hyperresponsiveness, and in the level of disease severity. The inflammatory pattern in asthma is multicellular in nature, with mast cells, neutrophils, eosinophils, T lymphocytes, and epithelial cells participating in the response. Furthermore, it is known that mediators, cytokines, and chemokines from these cells contribute to the orchestration of the inflammatory process. Because airway inflammation appears to be a critical etiologic feature of asthma, it has become the target of therapy. In this review the features of airway inflammation will be examined, and the effect of therapeutic agents on markers of airway injury will be discussed. Establishing, understanding, and finally controlling the features of airway inflammation have given insight to disease pathogenesis and the effectiveness of various treatments. The integral role of inhaled corticosteroids in modifying the complex inflammatory component of asthma will be explored, with special focus on the high degree of efficacy associated with this treatment--vis-a-vis other therapeutic agents--in preventing or blocking specific proinflammatory markers.
Anxiolytic activity of the progesterone metabolite 5α-pregnan-3α-ol-20-one

Abstract 3α-hydroxylated pregnane steroids have been shown to possess anesthetic, hypnotic, anticonvulsant and anxiolytic properties. In this study, metabolites of progesterone and deoxycorticosterone, 5α-pregnan-3α-ol-20-one (3α-OH-DHP) and 5α-pregnan-3α,21-diol-20-one (5α-THDOC), respectively, were tested for anxiolytic effects in N.I.H. Swiss-Webster mice using the light/dark transition, open-field and lick-suppression tests. Similar to the benzodiazepine (BZ) diazepam, 3α-OH-DHP (5–40 mg/kg) and 5α-THDOC (5–40 mg/kg) significantly increased the number of light/dark transitions. 3α-OH-DHP's effects were stereospecific as its diasteriomer, 3β-OH-DHP was devoid of activity. The benzodiazepine antagonist CGS-8216 (10 mg/kg) blocked diazepam's (1.0 mg/kg) anxiolytic effects, but did not have any effect against 3α-OH-DHP (20 mg/kg). The data indicate that the pregnane steroids produce their anxiolytic effects through a separate mechanism than the BZs. 3α-OH-DHP (20 mg/kg), 5α-THDOC (20 mg/kg) and diazepam (1.0 mg/kg) increased activity in a open-field test. 3β-OH-DHP had no effect in the open-field test. Furthermore, 3α-OH-DHP produced a 235% increase in punished responding in a lick-suppression test. These results demonstrate that the endogenous pregnane steroids possess anxiolytic effects that may be clinically relevant.
Reverse bifurcations in a quartic family

Abstract We show a family of real quartic maps exhibits reverse bifurcations. Also called cycle-annihilating transitions, reverse bifurcations have been known for the Henon map for several years, but are not present in the logistic map. We use trapping squares to explain these quartic reverse bifurcations.
Capital-biased subsidies, bureaucratic monitoring, and bus scrapping

Abstract A model of bus scrapping yields the hypothesis that a capital-biased subsidy increases the scrapping probability and reduces the expected life for urban transit buses and hence wastes resources. Governments have instituted bureaucratic approval requirements to prevent capital-biased subsidies from leading to “premature” scrapping of buses. If effective, these requirements would reduce the impact of capital-biased subsidies on the scrapping probability for buses that are less than 15 years old. Estimates of a probit model using data for Ontario, Canada, during 1963–1981 are consistent with the hypothesis that capital-biased subsidies increase the scrapping probability, but not with the hypothesis that bureaucratic monitoring has prevented premature scrapping.