cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase I Study of Noninvasive Imaging of Adenovirus-mediated Gene Expression in the Human Prostate

To monitor noninvasively potentially therapeutic adenoviruses for cancer, we have developed a methodology based on the sodium iodide symporter (NIS). Men with clinically localized prostate cancer were administered an intraprostatic injection of a replication-competent adenovirus, Ad5-yCD/utTKSR39rep-hNIS, armed with two suicide genes and the NIS gene. NIS gene expression (GE) was imaged noninvasively by uptake of Na99 mTcO4 in infected cells using single photon emission–computed tomography (SPECT). The investigational therapy was safe with 98% of the adverse events being grade 1 or 2. GE was detected in the prostate in seven of nine (78%) patients at 1 × 1012 virus particles (vp) but not at 1 × 1011 vp. Volume and total amount of GE was quantified by SPECT. Following injection of 1 × 1012 vp in 1 cm3, GE volume (GEV) increased to a mean of 6.6 cm3, representing, on average, 18% of the total prostate volume. GEV and intensity peaked 1–2 days after the adenovirus injection and was detectable in the prostate up to 7 days. Whole-body imaging demonstrated intraprostatic gene expression, and there was no evidence of extraprostatic dissemination of the adenovirus by SPECT imaging. The results demonstrate that noninvasive imaging of adenovirus-mediated gene therapy in humans is feasible and safe.
The Classificational Distribution by Weight of the Meteoritic Falls of the World

The classificational distribution by weight of 1495 meteoritic falls of the world inventoried in the recent (1953: 2nd) edition of the Prior-Hey Catalogue of Meteorites is presented statistically in a table bearing that caption and graphically by means of 7 line diagrams. The system of classification used is the simplified classification of meteorites in its latest form. The integrated weight of the 1495 falls—which together constitute almost the entire known meteoritic increment of the Earth—is, in round numbers, between 450 and 500 metric tons.
Vitamin E and adiponectin: proposed mechanism for vitamin E‐induced improvement in insulin sensitivity

Insulin resistance and type 2 diabetes have been treated with the PPARγ agonists thiazolidinediones, or TZDs, since the 1990s. One mechanism by which these drugs may work is through PPARγ-mediated upregulation of adiponectin, an endogenous adipokine that has been shown to increase insulin sensitivity. Interestingly, α- and γ-tocopherol, two vitamin E vitamers, have structural similarities to the TZDs and have also been linked to enhanced insulin sensitivity. A recent study identified a novel function of α- and γ-tocopherol in 3T3-L1 preadipocytes: upregulation of an endogenous ligand involved in activating PPARγ. This study also found that tocopherols dramatically enhanced adiponectin expression and that this effect was mediated through a PPARγ-dependent process. These findings illustrate a possible mechanistic link between vitamin E and insulin sensitivity.
Systems theory and its application to research on human sexuality

Systems theory has been applied and influential in a variety of disciplines. Within the field of human sexuality it has been used most often in the clinical areas of sexual dysfunction and abuse. I...
Identification and Ranking of Phenomena Leading to Peak Cladding Temperatures in Boiling Water Reactors During Large Break Loss of Coolant Accident Transients

In the licensing and validation process of best estimate codes for the analysis of nuclear reactors and postulated accident scenarios, the identification and quantification of the calculational uncertainty is required. One of the most important aspects in this process is the identification and recognition of the crucial contributing phenomena to the overall code uncertainty. The establishment of Phenomena Identification and Ranking Tables (PIRT) provides a vehicle to assist in assessing the capabilities of the computer code, and to guide the uncertainty analysis of the calculated results. The process used in this work to identify the phenomena was reviewing both licensing and best estimate calculations, as well as experiments, which had been performed for BWR LOCA analyses. The initial PIRT was developed by a group of analysts and was compared to existing BWR LOCA PIRTs as well as BWR LOCA analyses. The initial PIRT was then independently reviewed by a second panel of experts for the selected ranking of phenomena, identification of phenomena which were ignored, as well as the basis and rationale for the ranking of the phenomena. The differences between the two groups were then resolved. PIRTs have been developed for BWR types 4 and5/6 for the Large Break Loss of Coolant Accidents (LB-LOCA). The ranking and the corresponding rationale for each phenomenon is included in tables together with the assessed uncertainty of the code capability to predict the phenomena.Copyright © 2002 by ASME
Two novel automatic frequency tracking loops

Two automatic-frequency-control loops are introduced and analyzed in detail. The algorithms are generalizations of the well-known cross-product automatic-frequency-control loop with improved performance. The first estimator uses running overlapping discrete Fourier transforms (DFTs) to create a discriminator curve proportional to the frequency estimation error, whereas the second one preprocesses the received data and then uses an extended Kalman filter to estimate the input frequency. The algorithms are tested by computer simulations in a low carrier-to-noise-ratio (CNR) and highly dynamic environment. The algorithms are suboptimum tracking schemes with a larger frequency error variance compared to an optimum strategy, but they offer simplicity of mechanization and a CNR with a very low operating threshold. >
In situ toxicity tests of fishes in acid waters

Toxicity of waters within the North Branch of the Moose River to various life stages of lake trout (Salvelinus namaycush), brook trout (Salvelinus fontinalis), creek chub (Semotilus atromaculatus), and blacknose dace (Rhinichthys atratulus) were examined in situ. Study sites were selected that were expected to range from toxic to favourable water quality. For example, pH varied from 4.25 to 7.17, inorganic monomeric Al ranged from ND (< 0.01 mg/l) to 0.40 mg/l, and Ca, from 0.41 to 4.27 mg/l. Toxicity tests were conducted at times when the life stages would naturally occur in these waters and were continued until a range of mortality was observed at the various sites. These experiments suggested that the extent of the drainage system that is toxic to fish increases during snowmelt and major runoff events. Summer base flow water quality was generally the least toxic. Critical life stages were upon hatching and as early feeding fry. In general, young of the year fish were the most tolerant life stage tested. Yearling and adult fish, however, were very sensitive. Blacknose dace were the most sensitive fish of the four species tested, and brook trout were the most tolerant. Hydrogen ion (H+) concentration was the most toxic variable in the majority of tests. Inorganic monomeric Al was the most toxic in several, and the combination of H+ and Al seemed to cause increased toxicity in many instances. A three-variable model employing hours of exposure, H+ concentration, and inorganic monomeric Al predicted mortality quite well. A simple two-variable model using H+ and color was nearly as good (R2 from 0.49 to 0.94). Documented differences in toxicity among sites and species agreed with observed patterns of fish distribution. These in situ results indicated that laboratory estimates of safe levels of pH and concentrations of Al can result in mortality of fishes in surface waters subject to acidification.
Barometric Sensitive Coatings Based upon Osmium Complexes Dissolved in a Fluoroacrylic Polymer

Pressure sensitive paints (PSP) that measure the changes in air pressure have proved to be useful in the design of aircraft and other vehicles. In this study we incorporate highly luminescent divalent osmium complexes into PSP. The divalent osmium complexes were heptafluorobutyrate salts of [Os(N−N)2(L−L)]2+ or [Os(L−L)2(N−N)]2+, where N−N is a derivative of 1,10-phenanthroline, and L−L is a diphosphine or diarsine ligand. The complexes were dissolved into poly(1,1,1,3,3,3-hexafluoroisopropylmethacrylate-co-1H,1H-dihydroperflurobutylmethacrylate) (FIB) at a concentration of 0.002 g of complex to 1.000 g of polymer. The luminescence of the coatings was tested for pressure sensitivity, temperature dependence, and photodegradation. The paints featured strong pressure response, and the temperature dependence of the luminescence was measured as low as −0.11% °C−1. Several of the complexes exhibited little photodegradation upon prolonged exposure to 400 nm light. These attributes make the complexes very desirab...
Microwave conductivity measurements on insulating Si:P near the metal-insulator transition

Abstract The microwave electrical conductivity σ(ω,N,T) of insulating Si:P has been measured for frequencies between 100 MHz and 2.1 GHz in the density range 0.46 c c =3.74×10 18 /cm −3 ) for the temperature range 1.5 T T s(N) with s(N) increasing rapidly with increasing donor density from s∼1 to s > 2. These results can be explained with the Shklovskii-Efros theory, but only if the magnitude of the Coulomb interaction energy E c is drastically reduced as suggested by the 400 MHz σ(N,T) Si:P results of Hess et al .
Effect of PMA optical isomers and 4-MTA in PMMA-trained rats☆

1-(4-Methoxyphenyl)-2-aminopropane (PMA) and its sulfur analog, 1-(4-methylthiophenyl)-2-aminopropane (4-MTA), have been misrepresented as the controlled substance analog, N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; "Ecstasy"). Because MDMA has been shown to produce both amphetamine-like and N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA)-like stimulus effects in rats, we examined S(+)PMA, R(-)PMA and 4-MTA in rats trained to discriminate either PMMA (1.25 mg/kg) or (+)amphetamine (1.0 mg/kg) from saline vehicle. The sulfur analog of PMMA (i.e., 4-MTMA) was also examined. The PMMA stimulus generalized to R(-)PMA (ED50=0.4 mg/kg), whereas S(+)PMA produced a maximum of 72% PMMA-appropriate responding. 4-MTA (ED50=0.3 mg/kg) also substituted for PMMA, but 4-MTMA produced a maximum of only 36% PMMA-appropriate responding. None of the four agents substituted for (+)amphetamine. Hence, like MDMA, R(-)PMA and 4-MTA are capable of producing PMMA stimulus effects in rats, but unlike MDMA, neither agent substituted for (+)amphetamine.
Knowledge and Attitudes of Early Childhood Preservice Teachers Regarding the Inclusion of Children With Autism Spectrum Disorder

Limited research exists on what preservice teachers know and believe about children with Autism Spectrum Disorders (ASD) and their inclusion in general education classrooms, especially in early childhood education. In this preliminary study, knowledge and attitudes of 15 early childhood preservice teachers at a large southeastern university were surveyed using a modified version of the Autism Inclusion Questionnaire (Segall, 2008); four of these participants also engaged in subsequent in-depth interviews. Results indicated preservice teachers lacked knowledge and held basic misconceptions about ASD and the needs of children with ASD in inclusive classrooms. While participants wanted to learn more in this area and were generally supportive of inclusion, they had mixed attitudes about inclusion of children with more severe disabilities and their own future roles in an inclusive classroom. Implications for both collegiate and noncollegiate preparation and in-service training of early childhood educators are ...
Effect of hot rolling on superplasticity of a SiC/6061 aluminum alloy composite made by a vortex method

High strain rate superplasticity (HSRS) in ceramic whisker or particulate reinforced aluminum alloy composites is expected to offer an efficiently near-net shape forming technique for automobile, aerospace, and even semi-conductor industries, because the HSRS materials usually exhibit lower flow stress and higher total elongation of 250--600% at a high strain rate such as 0.1 {approximately} 10 s{sup {minus}1}. The purpose of this study is to make clear an effect of hot rolling after extrusion and squeeze casting to HSRS behavior of a SiC particulate reinforced aluminum alloy composite fabricated by a vortex method. In addition, the deformation mechanism of the HSRS in the composite will also be discussed.
Formalizing Service-Oriented Architectures

Service-oriented architecture (SOA) is defined as a paradigm for organizing and using distributed capabilities that might be under the control of different ownership domains. SOA is also known as a methodology for achieving application interoperability and reuse of IT assets in distributed computing environments characterized as transformable by the visibility, interaction, and effect dimensions.
Factors associated with the prevalence of non-ROPS tractors on farms in the U.S

Rollover protective structures (ROPS) are an effective engineering control known to prevent tractor overturn deaths, the leading cause of occupational fatalities for farmers and farm workers in the U.S. However, the use of ROPS is known to vary greatly from farm to farm. A national sample of 11,458 farm operators from the 2004 Occupational Injury Surveillance of Production Agriculture (OISPA) survey was used to assess the association between the prevalence of ROPS and ten farm operator and farm demographic variables using logistic regression. The variable were: operator's age, operator's sex, operator's education, farm sales, full- or part-time farming, acreage, type of operation, number of hired workers, number of injuries, and region. All ten variables were found to have significant associations with the prevalence of non-ROPS tractors on farms in the univariate logistic regressions. For the multivariate model, all variables except for the sex of the farm operator remained significant. Farms with less than three adult injuries, no hired workers, less than 300 acres in size, a Midwest location, and a primary farm type of tobacco, fruit and nuts, dairy, or poultry and eggs all had adjusted odds ratios of 2 or greater. Increasing the prevalence of ROPS-equipped tractors is essential for reducing the leading cause of death on farms, tractor overturns. Economic factors play a major role in the prevalence and distribution of non-ROPS tractors on farms. The identified associations can be used to effectively target areas of the U.S. for ROPS promotion activities.
Lobeline augments and inhibits cocaine-induced hyperactivity in rats

Lobeline has high affinity for nicotinic receptors and alters presynaptic dopamine storage and release in brain. Moreover, lobeline decreases the reinforcing and locomotor-activating properties of methamphetamine, suggesting that lobeline may be a pharmacotherapy for psychostimulant abuse. This study determined if lobeline alters cocaine-induced hyperactivity and if lobeline alters the induction and/or expression of sensitization to cocaine. On Days 1-12, male rats were administered lobeline (0.3 or 1.0 mg/kg) or saline, placed in an automated activity monitor for 20 min, administered cocaine (10, 20 or 30 mg/kg) or saline and returned to the monitor for 60 min. On Day 13, the effect of lobeline on the induction and expression of sensitization to cocaine was determined. Lobeline did not alter the effect of cocaine after acute injection. However, 1.0 mg/kg lobeline attenuated cocaine (10 and 20 mg/kg)-induced hyperactivity after repeated administration and prevented the development of sensitization to these cocaine doses. Interestingly, 0.3 mg/kg lobeline augmented cocaine (10 mg/kg)-induced hyperactivity after repeated administration. Lobeline did not alter the effect of 30 mg/kg cocaine. The present results indicate a complex interaction of lobeline with cocaine and support other research indicating a role for nicotinic receptors in the development of sensitization to psychostimulants.
A DYNAMIC PROGRAMMING MODEL FOR PERIODICAL SELECTION

This paper presents a model for choosing the periodical collection in a reading room. The model consists of two stages. In the first stage the probability distribution of contacts by users with a given periodical is developed and employed to determine the utility of the periodical. In the second stage the problem of choosing an optimum periodical collection is formulated as a capital budgeting problem and solved with the aid of dynamic programming. The implementation of this model at the University of Connecticut is described in detail.
Multiple transcripts from a 3'-UTR reporter vary in sensitivity to nonsense-mediated mRNA decay in Saccharomyces cerevisiae.

Nonsense-mediated mRNA decay (NMD) causes accelerated transcript degradation when a premature translation termination codon disrupts the open reading frame (ORF). Although endogenous transcripts that have uninterrupted ORFs are typically insensitive to NMD, some can nonetheless become prone to NMD when translation terminates at out-of-frame premature stop codons. This occurs when introns containing stop codons fail to be spliced, when translation of an upstream ORF (uORF) terminates in the 5′-untranslated region (5′-UTR) or the coding region, or when the 5′-proximal AUG initiation codon is bypassed and translation initiates at a downstream out-of-frame AUG followed by a stop codon. Some 3′-untranslated regions (3′-UTRs) are also known to trigger NMD, but the mechanism is less well understood. To further study the role of 3′-UTRs in NMD, a reporter system was designed to examine 3′-UTRs from candidate genes known to produce NMD-sensitive transcripts. Out of eight that were tested, the 3′-UTRs from MSH4 and SPO16 caused NMD-dependent mRNA destabilization. Both endogenous genes produce multiple transcripts that differ in length at the 3′ end. Detailed studies revealed that the longest of six reporter MSH4-3′-UTR transcripts was NMD-sensitive but five shorter transcripts were insensitive. NMD-dependent degradation of the long transcript required Xrn1, which degrades mRNA from the 5′ end. Sensitivity to NMD was not associated with extensive translational read-through past the normal stop codon. To our knowledge, this is the first example where multiple transcripts containing the same ORF are differentially sensitive to NMD in Saccharomyces cerevisiae. The results provide a proof of principle that long 3′-UTRs can trigger NMD, which suggests a potential link between errors in transcription termination or processing and mRNA decay.
Desensitization of the pancreatic β-cell: effects of sustained physiological hyperglycemia and potassium

The impact of modest but prolonged (3 h) exposure to high physiological glucose concentrations and hyperkalemia on the insulin secretory and phospholipase C (PLC) responses of rat pancreatic islets...
Apolipoprotein A5 and Lipoprotein Lipase Interact to Modulate Anthropometric Measures in Hispanics of Caribbean Origin

Apolipoprotein A5 (APOA5) and lipoprotein lipase (LPL) proteins interact functionally to regulate lipid metabolism, and single-nucleotide polymorphisms (SNPs) for each gene have also been associated independently with obesity risk. Evaluating gene combinations may be more effective than single SNP analyses in identifying genetic risk, but insufficient minor allele frequency (MAF) often limits evaluations of potential epistatic relationships. Populations with multiple ancestral admixtures may provide unique opportunities for evaluating genetic interactions. We examined relationships between LPL m107 (rs1800590) and APOA5 S19W (rs3135506) and lipid and anthropometric measures in Caribbean origin Hispanics (n = 1,019, aged 45–75 years) living in the Boston metropolitan area. Significant interaction terms between LPL m107 and APOA5 S19W were observed for BMI (P = 0.003) and waist circumference (P = 0.019). Higher BMI (P = 0.001), waist (P = 0.011) and hip (P = 0.026) circumference were observed in minor allele (G) carriers for LPL m107 who also carried the APOA5 S19W minor allele (G). Additionally, extreme obesity (BMI ≥ 40 kg/m2) risk was higher (odds ratio = 4.02; 95% confidence interval: 1.81–8.91; global P = 0.008) for minor allele carriers for both SNPs (LPL TG+GG, APOA5 CG+GG) compared to major allele carriers for both SNPs. In summary, we identified significant interactions for APOA5 S19W and LPL m107 for obesity in Caribbean Hispanics. Population-specific MAFs increase the difficulties of replicating gene–gene interactions, but may support the hypothesis that combinations of frequencies in selected genes could heighten obesity susceptibility in a given population. Analyses of gene–gene interactions may improve understanding of genetically based obesity risk, and underscore the need for further study of groups with multiple ancestral admixtures.
A 19-Year-Old Man With Nonresolving Pneumonia

(CHEST 2004; 125:330 –333) A 19-year-old white man was referred to the pulmonary clinic with a 2-month history of refractory cough, low-grade fevers, night sweats, and 30-lb weight loss. He had right-sided pleuritic pain and episodic scant hemoptysis. He denied smoking and using illicit drugs. He was single and had protected sex with two female partners over the past several years. He worked as a pipe fitter and denied any unusual hobbies, hunting, or recent travel. He would frequently go on camping and fishing trips near his hometown lake in southern Indiana. Chest radiographs and CT scans over 2 months showed progressive right upper lobe consolidation. He had negative findings on purified protein derivative and HIV screening. He had undergone bronchoscopy with normal results, and BAL specimens and brushes were culture negative for acid-fact bacilli, fungi, and cytology. He had been treated with multiple antibiotics, including amoxicillin, azithromycin, ciprofloxacin, clindamcyin, and cephalexin.
Mass spectra of diverse organic species utilizing the liquid sampling-atmospheric pressure glow discharge (LS-APGD) microplasma ionization source

This laboratory has demonstrated the analytical versatility of the liquid sampling-atmospheric pressure glow discharge (LS-APGD) ionization source. Demonstrations have included elemental analysis of solutions and laser ablation (LA)-produced aerosols, ambient desorption of small organic molecules on substrates, and direct speciation of organometallic complexes in solution. Here we present initial efforts in mapping the operation space of the device as it applies to obtaining molecular mass spectra from diverse organic molecules. An initial parametric evaluation is performed using caffeine as the test molecule, with a preliminary limit of detection of 5.9 × 10−9 M (43 pg) for 20 μL injections. Conditions optimum for that molecule are applied in assessing the qualitative nature of spectra from caffeine, sinapinic acid, daidzin (a flavonoid), a FITC-labeled lipid tethered ligand, the mass marker Ultramark 1621, and the heme-protein myoglobin. The product spectra for the small molecules are very much like what would be obtained from electrospray and atmospheric pressure chemical ionization sources, predominately the production of the protonated pseudomolecular ion of the form (M + H)+. The mid-range molecules show ion signatures of the thermally stable fragments. Finally, the macromolecules yield mass spectra that are very much like those from electrospray, producing a range of protonated charged states. While much optimization and understanding are needed to best apply the source to such solutes, the fact that the same ion source can be used across the spectrum from elemental/isotopic analysis to perhaps proteomics is totally unique and is worthy of continued development.
A Mechanism of Oxygen Free Radical Production in the Dahl Hypertensive Rat

Objective:To determine if oxygen free radicals derived from xanthine oxidase are involved in the development of salt-induced hypertension. Enhanced production of oxygen free radicals may play a role in hypertension by affecting vascular smooth muscle contraction and provide a mechanism for lesion formation. Methods:Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed either a low-salt, high-salt or high-salt + tungsten diet for 4 wk. In vivoproduction of superoxide (O2−) was detected by the reduction of a tetranitroblue tetrazolium (TNBT) dye in the rat mesentery, while plasma hydrogen peroxide (H2O2) production levels were determined using a modified electrochemical electrode technique. Results:The tungsten diet lowered the blood pressure of Dahl-S rats compared to high-salt-treated Dahl-S rats, but had no effect on blood pressure in Dahl-R rats. Light absorption of formazan deposits revealed that tungsten-treated Dahl-S rats had reduced TNBT staining along the endothelium of arterioles...
Dielectric Interface Conditions for General Fourth-Order Finite Difference

In this letter, two dielectric interface conditions, for narrow- and broad-band simulations, are presented for the general fourth-order finite-difference stencil in the space domain. The effectiveness of both conditions is verified by numerical simulations.
Adhesives Prepared from Vegetal and Animal Sources Used by Iconographers

Glues prepared from natural materials of vegetal and animal origin were used by iconographers in different applications: primer recipes for painting on wood with tempera paints, on textiles, on dry mortar, in oil paints to make them shine, in adhesive primers used for gilding in manuscripts, in inks, and in some restorations and impregnations. All these adhesive preparations were similar to those used in Western Europe and in the Middle as well as the Far East.
Interactions between temperature and nutrients across levels of ecological organization.

Temperature and nutrient availability play key roles in controlling the pathways and rates at which energy and materials move through ecosystems. These factors have also changed dramatically on Earth over the past century as human activities have intensified. Although significant effort has been devoted to understanding the role of temperature and nutrients in isolation, less is known about how these two factors interact to influence ecological processes. Recent advances in ecological stoichiometry and metabolic ecology provide a useful framework for making progress in this area, but conceptual synthesis and review are needed to help catalyze additional research. Here, we examine known and potential interactions between temperature and nutrients from a variety of physiological, community, and ecosystem perspectives. We first review patterns at the level of the individual, focusing on four traits – growth, respiration, body size, and elemental content – that should theoretically govern how temperature and nutrients interact to influence higher levels of biological organization. We next explore the interactive effects of temperature and nutrients on populations, communities, and food webs by synthesizing information related to community size spectra, biomass distributions, and elemental composition. We use metabolic theory to make predictions about how population-level secondary production should respond to interactions between temperature and resource supply, setting up qualitative predictions about the flows of energy and materials through metazoan food webs. Last, we examine how temperature–nutrient interactions influence processes at the whole-ecosystem level, focusing on apparent vs. intrinsic activation energies of ecosystem processes, how to represent temperature–nutrient interactions in ecosystem models, and patterns with respect to nutrient uptake and organic matter decomposition. We conclude that a better understanding of interactions between temperature and nutrients will be critical for developing realistic predictions about ecological responses to multiple, simultaneous drivers of global change, including climate warming and elevated nutrient supply.
Hypocholesterolemic effects of cholestyramine and colestipol in patients with familial defective apolipoprotein B-100

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor. To date, patients with FDB have been heterozygous for this disorder and their plasma contains both normal and defective-binding LDL particles, with a predominance of the latter. In the present report, we have compared the hypocholesterolemic effects of bile acid sequestrant therapy (cholestyramine or colestipol) in eight patients with FDB, to the response seen in sixteen patients with heterozygous familial hypercholesterolemia (FH), treated with the same drugs. Concentrations of LDL cholesterol fell by 32.0% in the patients with FDB and by 21.6% in the patients with FH. The results indicate that the hypercholesterolemia of both FDB and FH responds to treatment with bile acid sequestrants.
Adipokinetic Actions of Adrenocorticotropin, Thyroid-Stimulating Hormone, Vasopressin, α- and β-Melanocyte-Stimulating Hormones, Fraction H, Epinephrine and Norepinephrine in the Rabbit, Guinea Pig, Hamster, Rat, Pig and Dog

Several naturally occurring polypeptide and amine hormones possess adipokinetic activity. The present investigation compares the adipokinetic activity of these hormones in the rabbit, guinea pig hamster, rat, pig and dog. Activity was assayed by measuring the effect of various concentrations of hormone upon the production of free fatty acids (FFA) by slices of perirenal adipose tissue incubated in Krebs-Ringer phosphate solution. As described by previous investigators, when the medium does not contain albumin, the FFA produced by lipolysis accumulate only within the tissue slice; when albumin is present in the medium, the FFA produced by lipolysis accumulate in the medium as well as in the tissue slice. In the albumin- free assay system, the concentration of FFA in the tissue after 3 hours' incubation is linearly related to the logarithm of the concentration of hormone in the medium. The following 6 components of the pituitary gland possess adipokinetic activity upon the adipose tissue of one or more mamm...
Role of transient receptor potential and pannexin channels in cigarette smoke-triggered ATP release in the lung

Background COPD is an inflammatory disease usually associated with cigarette smoking (CS) with an increasing global prevalence and no effective medication. Extracellular ATP is increased in the COPD affected lung and may play a key role in driving CS-induced airway inflammation, but the mechanism involved in ATP release has eluded researchers. Recently, the transient receptor potential (TRP) and pannexin-1 channels have been suggested to play a role in other experimental paradigms. Thus, the aim of this work is to investigate if these channels are involved in CS-induced ATP release in the lung. Methods Primary human cells were exposed to CS and extracellular ATP levels measured. Mice were exposed to mainstream CS and airway inflammation assessed. TRPV1/4 mRNA expression was assessed in human lung parenchyma. Results CS exposure caused a dose-related increase in ATP from primary airway bronchial epithelial cells. This was attenuated by blockers of TRPV1, TRPV4 and pannexin-1 channels. Parallel data was obtained using murine acute CS-driven model systems. Finally, TRPV1/4 mRNA expression was increased in lung tissue samples from patients with COPD. Conclusions Extracellular ATP is increased in the COPD affected lung and may play a key role in driving disease pathophysiology. These experiments uncover a novel mechanism which may be responsible for CS-induced ATP release. These findings highlight novel targets that could lead to the development of medicine to treat this devastating disease.
Regulation of neuregulin/ErbB signaling by contractile activity in skeletal muscle

Putative roles of neuregulin (NRG) and the ErbB receptors in skeletal muscle biology include myogenesis, ACh receptor expression, and glucose transport. To date, however, the physiological regulation of NRG/ErbB signaling has not been examined. We tested the hypothesis that contractile activity in vivo induces NRG/ErbB activation. Rat hindlimb muscle contraction was elicited with a single bout of electrical stimulation (RX) or treadmill running (EX). Western blot and immunofluorescence confirmed the expression of multiple NRG isoforms and the ErbB2, ErbB3, and ErbB4 receptors in adult skeletal muscle. Both RX and EX significantly increased phosphorylation of all NRG receptors. Furthermore, contraction induced a shift in the expression profile of NRG, consistent with proteolytic processing of a transmembrane isoform. Thus two distinct modes of exercise activated processing of NRG with concomitant stimulation of ErbB2, ErbB3, and ErbB4 signaling in vivo. To our knowledge, this is the first demonstration of physiological regulation of NRG/ErbB signaling in any organ and implicates this pathway in the metabolic and proliferative responses of skeletal muscle to exercise.
Expression and function of KV2-containing channels in human urinary bladder smooth muscle

The functional role of the voltage-gated K+ (KV) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of KV2.1, KV2.2, and the electrically silent KV9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of KV2.1, KV2.2, and KV4.2 homotetrameric channels and of KV2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca2+ imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of KV2.1, KV2.2, and KV9.3 (but not KV4.2) channel subunits in human isolated DSM cells. KV2.1 and KV2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced KV current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca2+ level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5–30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive KV2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.
A planar IrO multichannel stimulating electrode for use in neural prostheses

This paper describes a multisite stimulating probe capable of the precise delivery of sophisticated charge waveforms to neural structures on a chronic basis. The fabrication process for passive probes requires only four masks and is very high yield. Activated iridium oxide stimulating sites are shown to be compatible with the delivery of over 3 mC/cm2/phase in biphasic charge-balanced operation. In order to minimize the number of external probe leads, on-chip circuitry has been defined to allow per-channel current control at the 8-bit level using serial input data and a total of five external leads. densities, and the design of system electronics, including on-chip interface circuitry, to improve system reliability and minimize interconnects to the external world.
Marital Status Integration, Suicide Disapproval, and Societal Integration as Explanations of Marital Status Differences in Female Age‐Specific Suicide Rates

Sociological analyses of suicide have often neglected female suicide rates. Three competing explanations are tested to determine why the suicide rates of married women are, typically, lower than the suicide rates of women who are not married: (1) marital status integration, (2) societal integration, and (3) a nation's normative order about disapproval of suicide. Data refer to age and marital status-specific female suicide rates from 12 developed countries. The results provide the strongest support for the marital status integration theory and consistent support for the social integration perspective. There is also mixed support for the cultural disapproval of suicide hypothesis.
SALIGN: a web server for alignment of multiple protein sequences and structures

Summary: Accurate alignment of protein sequences and/or structures is crucial for many biological analyses, including functional annotation of proteins, classifying protein sequences into families, and comparative protein structure modeling. Described here is a web interface to SALIGN, the versatile protein multiple sequence/structure alignment module of MODELLER. The web server automatically determines the best alignment procedure based on the inputs, while allowing the user to override default parameter values. Multiple alignments are guided by a dendrogram computed from a matrix of all pairwise alignment scores. When aligning sequences to structures, SALIGN uses structural environment information to place gaps optimally. If two multiple sequence alignments of related proteins are input to the server, a profile–profile alignment is performed. All features of the server have been previously optimized for accuracy, especially in the contexts of comparative modeling and identification of interacting protein partners. Availability: The SALIGN web server is freely accessible to the academic community at http://salilab.org/salign. SALIGN is a module of the MODELLER software, also freely available to academic users (http://salilab.org/modeller). Contact: gro.balilas@ilas; gs.ude.rats-a.iib@nahdusuhdam
Turbulent diffusion in the geostrophic inverse cascade

Motivated in part by the problem of large-scale lateral turbulent heat transport in the Earth's atmosphere and oceans, and in part by the problem of turbulent transport itself, we seek to better understand the transport of a passive tracer advected by various types of fully developed two-dimensional turbulence. The types of turbulence considered correspond to various relationships between the streamfunction and the advected field. Each type of turbulence considered possesses two quadratic invariants and each can develop an inverse cascade. These cascades can be modified or halted, for example, by friction, a background vorticity gradient or a mean temperature gradient. We focus on three physically realizable cases: classical two-dimensional turbulence, surface quasi-geostrophic turbulence, and shallow-water quasi-geostrophic turbulence at scales large compared to the radius of deformation. In each model we assume that tracer variance is maintained by a large-scale mean tracer gradient while turbulent energy is produced at small scales via random forcing, and dissipated by linear drag. We predict the spectral shapes, eddy scales and equilibrated energies resulting from the inverse cascades, and use the expected velocity and length scales to predict integrated tracer fluxes.When linear drag halts the cascade, the resulting diffusivities are decreasing functions of the drag coefficient, but with different dependences for each case. When β is significant, we find a clear distinction between the tracer mixing scale, which depends on β but is nearly independent of drag, and the energy-containing (or jet) scale, set by a combination of the drag coefficient and β. Our predictions are tested via high- resolution spectral simulations. We find in all cases that the passive scalar is diffused down-gradient with a diffusion coefficient that is well-predicted from estimates of mixing length and velocity scale obtained from turbulence phenomenology.
When do Buyers and Targets Draw on Related Resources? A Test of Between-firm Measures of Industry Relatedness in Acquisitions

The received view is that related acquisitions have more potential to create value than unrelated acquisitions. However, there are very few measures of relatedness between two firms. Existing measures are very crude relative to those used in diversification research (e.g., diversity of a single firm's portfolio). In addition, they do not reflect recent advances in resource-based theory. Relatedness is critical in acquisitions because it may indicate asymmetric information as well as buyer objectives. These, in turn, are factors that investors may respond to when an offer is announced. We develop and test between-firm relatedness measures based on products, technology, and human expertise. While all measures had some predictive validity, the expertise measure was slightly better at predicting investor response.
Does Salient Financial Information Affect Academic Performance and Borrowing Behavior among College Students

The rising incidence and amount of student loan debt among young adults has significant implications for their economic well-being. However, students are generally provided little information on how to finance postsecondary education and how much to borrow. This paper studies how information can change student loan behavior among college students. We exploit a natural experiment across two large public colleges in which some students at one institution above a specific loan amount received "Know Your Debt" letters with information about their student loan debt, suggestions on how to manage their debt, and incentivized offers for one-on-one financial counseling, while the remainder did not. Using a difference-in-difference-in-difference strategy and a rich administrative dataset on individual-level academic records and financial aid packages, we find that students receiving the letters borrow an average of $1,360 less in the subsequent semester -- a reduction of one-third. This reduction in borrowing does not adversely affect academic performance. In fact, those who receive the intervention take more credits and have higher GPAs in the subsequent semester.
Effects of microbial supplements containing yeast and lactobacilli on roughage-fed ruminal microbial activities

Effects of two microbial feed supplements on microbial activities in rumen-stimulating cultures and the rumens of steers fed a fescue hay-based roughage diet were evaluated. The yeast culture supplement contained Saccharomyces cerevisiae (1.4 to 4.2 x 10(9) colony-forming units [cfu]/g), whereas the mixed microbial supplement contained yeast, lactobacilli and enterococci (1.4 to 2.7 x 10(9) cfu/g, 1.2 to 2.3 x 10(9) cfu/g, and 1.5 to 2.6 x 10(10) cfu/g, respectively). Concentrations of viable yeast cells were increased consistently in continuous cultures and rumens of steers receiving either supplement (1 g/kg of feed). However, neither supplement consistently altered the relative concentrations of volatile fatty acids or ammonia in continuous cultures and rumens of steers. The pH tended to be greater (P = .13) in continuous cultures receiving yeast culture supplement than in cultures receiving the unsupplemented diet (6.50 vs 6.36), but pH in the rumens of steers was not affected by the supplements. Concentrations of cellulolytic microorganisms in cultures and the rumens of steers receiving supplements containing only yeast were from 5 to 40 times greater than those observed in cultures or steers receiving the unsupplemented diet. Supplements that had been treated with heat (121 degrees C for 15 min) to inactive yeast cells did not alter the concentrations of cellulolytic bacteria in rumen-stimulating cultures. These results suggest that live yeast culture supplements stimulate growth of cellulolytic microorganisms in the rumen.
Limits in the evolution of biological form: a theoretical morphologic perspective

Limits in the evolution of biological form can be empirically demonstrated by using theoretical morphospace analyses, and actual analytic examples are given for univalved ammonoid shell form, bivalved brachiopod shell form and helical bryozoan colony form. Limits in the evolution of form in these animal groups can be shown to be due to functional and developmental constraints on possible evolutionary trajectories in morphospace. Future evolutionary-limit research is needed to analyse the possible existence of temporal constraint in the evolution of biological form on Earth, and in the search for the possible existence of functional alien life forms on Titan and Triton that are developmentally impossible for Earth life.
Ferryl Protonation in Oxoiron(IV) Porphyrins and Its Role in Oxygen Transfer

Ferryl porphyrins, P–FeIV═O, are central reactive intermediates in the catalytic cycles of numerous heme proteins and a variety of model systems. There has been considerable interest in elucidating factors, such as terminal oxo basicity, that may control ferryl reactivity. Here, the sulfonated, water-soluble ferryl porphyrin complexes tetramesitylporphyrin, oxoFeIVTMPS (FeTMPS-II), its 2,6-dichlorophenyl analogue, oxoFeIVTDClPS (FeTDClPS-II), and two other analogues are shown to be protonated under turnover conditions to produce the corresponding bis-aqua-iron(III) porphyrin cation radicals. The results reveal a novel internal electromeric equilibrium, P–FeIV═O ⇆ P+–FeIII(OH2)2. Reversible pKa values in the range of 4–6.3 have been measured for this process by pH-jump, UV–vis spectroscopy. Ferryl protonation has important ramifications for C–H bond cleavage reactions mediated by oxoiron(IV) porphyrin cation radicals in protic media. Both solvent O–H and substrate C–H deuterium kinetic isotope effects are ...
Type Variation of Strains of Streptococcus pneumoniae in Capsular Serogroup 15

The repeated finding of two capsular types of Streptococcus pneumoniae in serogroup 15 in infected exudate from the middle ear led to the demonstration of type variation in pneumococcal types 15B and 15C. Determination of the chemical composition of the capsular polysaccharides of the pneumococci in serogroup 15 showed that the observed variation was related to the presence of an O-acetyl group in the capsular polysaccharide of type 15B which was lacking from the otherwise identical polysaccharide of type 15C. The phenomenon appears similar to that reported in several other bacterial species in which it has been ascribed to labile inversion of a segment of DNA.
Revision of the affinity constant for perchlorate binding to the sodium-iodide symporter based on in vitro and human in vivo data

A series of previously published physiologically based pharmacokinetic (PBPK) models describe the effect of perchlorate on iodide uptake by the thyroid, with the mechanism being competitive inhibition of iodide transport by the sodium-iodide symporter (NIS). Hence a key parameter of these models is the affinity of perchlorate for the NIS, characterized as the Michaelis-Menten kinetic constant, Km . However, when model predictions were compared to published results of a human study measuring radio-iodide uptake (RAIU) inhibition after controlled perchlorate exposures, it was found to only fit the lowest exposure level and underpredicted RAIU inhibition at higher levels. Published in vitro data, in which perchlorate-induced inhibition of iodide uptake via the NIS was measured, were re-analyzed. Km for binding of perchlorate to the NIS originally derived from these data, 1.5 μm, had been obtained using Lineweaver-Burk plots, which allow for linear regression but invert the signal-noise of the data. Re-fitting these data by non-linear regression of the non-inverted data yielded a 60% lower value for the Km , 0.59 μm. Substituting this value into the PBPK model for an average adult human significantly improved model agreement with the human RAIU data for exposures <100 μg kg-1 day-1 . Thus, this lower Km value both fits the in vitro NIS kinetics and provides better predictions of human in vivo RAIU data. This change in Km increases the predicted sensitivity of humans to perchlorate over twofold for low-level exposures. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.