cssi/SciSciGPT-SciSciNet huggingface dataset:
Coast-wide evidence of low pH amelioration by seagrass ecosystems

Global-scale ocean acidification has spurred interest in the capacity of seagrass ecosystems to increase seawater pH within crucial shoreline habitats through photosynthetic activity. However, the dynamic variability of the coastal carbonate system has impeded generalization into whether seagrass aerobic metabolism ameliorates low pH on physiologically and ecologically relevant timescales. Here we present results of the most extensive study to date of pH modulation by seagrasses, spanning seven meadows (Zostera marina) and 1000 km of U.S. west coast over 6 years. Amelioration by seagrass ecosystems compared to non-vegetated areas occurred 65% of the time (mean increase 0.07 ± 0.008 SE). Events of continuous elevation in pH within seagrass ecosystems, indicating amelioration of low pH, were longer and of greater magnitude than opposing cases of reduced pH or exacerbation. Sustained elevations in pH of >0.1, comparable to a 30% decrease in [H+ ], were not restricted only to daylight hours but instead persisted for up to 21 days. Maximal pH elevations occurred in spring and summer during the seagrass growth season, with a tendency for stronger effects in higher latitude meadows. These results indicate that seagrass meadows can locally alleviate low pH conditions for extended periods of time with important implications for the conservation and management of coastal ecosystems.
Absorption by Double-Centered D3-Branes and the Coulomb Branch of N=4 SYM Theory

We calculate the classical cross-section for absorption of a minimally coupled scalar in the double-centered D3-brane geometry. The dual field theory has gauge symmetry broken to S(U(N_1)*U(N_2)) and is on the Coulomb branch of N=4 Super Yang-Mills theory. Our analysis is valid at energy scales much smaller than the W particles mass, giving logarithmic corrections to the cross section calculated at the IR conformal fixed points. These corrections are associated with deformations of the N=4 Super Yang-Mills theory by irrelevant operators that break conformal invariance and correspond to processes where a virtual pair of gauge particles or a virtual pair of W bosons interact with the incident wave to create a pair of gauge particles.
Bacterial invasion across the human skin barrier - mechanisms and ensuing tissue degradation.

Atopic Dermatitis (AD) is associated with a deficiency of skin lipids, increased populations of Staphylococcus aureus in the microbiome, and structural defects in the stratum corneum (SC), the outermost layer of human skin. However, the pathogenesis of AD is ambiguous as it is unclear whether observed changes are the result of AD or contribute to the pathogenesis of the disease. Previous studies have shown that S. aureus is capable of permeating across isolated human SC tissue when lipids are depleted to levels consistent with AD conditions. In this study, we expand upon this discovery to determine the mechanisms of bacterial penetration into the SC barrier. Specifically, we establish whether bacteria are permeating intercellularly, between corneocytes, or employing a combination pathway of both inter- and intra-cellular travel. The mechanical implications of bacterial invasion, lipid depletion, and media immersion are also evaluated using a newly developed, physiologically relevant, temperature-controlled drip chamber. Results reveal that S. aureus can be internalized by corneocytes, indicating transcellular movement through the tissue during permeation, consistent with previous theoretical models. S. aureus also degrades the mechanical integrity of human SC, particularly when the tissue is partially depleted of lipids. These observed mechanical changes are likely the cause of broken or ruptured tissue seen as exudative lesions in AD flares. This work further highlights the necessity of lipids in skin microbial barrier function. ImportanceMillions of people suffer from the chronic inflammatory skin disease Atopic Dermatitis (AD), whose symptoms are associated with a deficiency of skin lipids that exhibit antimicrobial functions, and increased populations of the opportunistic pathogen Staphylococcus aureus. However, the pathogenesis of AD is ambiguous, and it remains unclear if these observed changes are merely the result of AD, or contribute to the pathogenesis of the disease. In this article, we demonstrate the necessity of skin lipids in preventing S. aureus from penetrating the outermost barrier of human skin thereby causing a degradation in tissue integrity. In terms of AD, this bacterial permeation into the viable epidermis could act as an inflammatory trigger of the disease and could also explain tissue fragility and lesion formation seen with AD patients. Moreover, bacterial induced degradation could lead to increased pathways and further allergen intervention creating chronic irritation.
Variation in baiting intensity among CO2-baited traps used to collect hematophagous arthropods.

Hematophagous arthropods transmit the etiological agents of numerous diseases and as a result are frequently the targets of sampling to characterize vector and pathogen populations. Arguably, the most commonly used sampling approach involves traps baited with carbon dioxide. We report results of a laboratory study in which the performance of carbon dioxide-baited traps was evaluated using measures of baiting intensity, the amount of carbon dioxide released per unit time during trap deployment. We evaluated the effects of trap design, carbon dioxide source, and wind speed on baiting intensity and documented significant effects of these factors on the length of sampling (time to baiting intensity = 0), maximum baiting intensity, and variation in baiting intensity during experimental trials. Among the three dry ice-baited trap types evaluated, traps utilizing insulated beverage coolers as dry ice containers sampled for the longest period of time, had the lowest maximum but most consistent baiting intensity within trials and were least sensitive to effects of wind speed and dry ice form (block vs. pellet) on baiting intensity. Results of trials involving traps baited with carbon dioxide released from pressurized cylinders suggested that this trap type had performance comparable to dry ice-baited insulated cooler traps but at considerably higher cost.
Nevi in the Oral Cavity

Nevi in the oral cavity are rare and dermatopathologists are not really familiar with them; moreover, the ratio between oral nevi and oral melanomas is much more well-balanced than in the skin and differential diagnosis should be discussed virtually in every single case. Problems are also caused by the peculiar anatomy of the oral mucosa which explains why the nevi of the oral cavity have a different architecture than that of their cutaneous counterparts.
Cholesterol metabolism in cancer cells in monolayer culture. VI. Metabolism of high-density lipoprotein.

Abstract The metabolism of high-density lipoprotein (HDL) in cells of five human cancer cell lines maintained in monolayer culture was investigated. In cells of some of the lines there was evidence of high-affinity binding sites for HDL, whereas in others this could not be demonstrated. However, in one cell line, viz., HEC-B-296 (human endometrial carcinoma), degradation of the protein component of HDL was demonstrated. The proteolytic activity was specific for HDL in so far as human serum albumin was not degraded by these cells. However, this degradative process did not involve internalization of the HDL molecule and degradation was not mediated by lysosomal proteolytic enzymes. HDL, when present in the medium, did not affect the degradation of low-density lipoprotein and low-density lipoprotein did not affect the degradation of HDL. HDL did not affect significantly cholesterol biosynthesis or cholesteryl ester biosynthesis as estimated from the activity of the regulatory enzymes, 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl-CoA:cholesterol acyltransferase. The degradation of HDL by HEC-B-296 cells was inhibited, to various degrees, when trypsin inhibitor or a protease inhibitor such as leupeptin, was present in the culture medium. It is concluded that degradation of the protein component of HDL by human neoplastic cells of the HEC-B-296 line was the result of activity of a proteolytic enzyme that is present on the external surface of the cells.
SIMPLIFICATION OF THE ANTHRONE METHOD FOR THE DETERMINATION OF INULIN IN CLEARANCE STUDIES.

Abstract The anthrone method of Young and Raisz 1 was modified by a decrease in the concentration of anthrone in the reagent from 0.4 per cent to 0.08 per cent and by a reduction of the temperature for color development from 75 °C. to 38 °C. Under these conditions, interference by glucose is minimized so that inulin can be determined directly without prior removal of glucose by incubation of samples with yeast or sodium hydroxide. The modified anthrone method was compared with a standard diphenylamine method for inulin in a series of clinical studies. The mean ratio of clearances (C In anthrone/C In diphenylamine) in 12 patients was 0.996 (S.D. = ± 0.026). These data confirm the earlier findings of Walser, Davidson, and Orloffs that alkali-stable inulin has the same clearance as alkali-labile inulin.
Minimizing signal detection time in postmarket sequential analysis: balancing positive predictive value and sensitivity.

Purpose Outcome misclassification in retrospective epidemiologic analyses has been well-studied, but little is known about such misclassification with respect to sequential statistical analysis during surveillance of medical product-associated risks, a planned capability of the US Food and Drug Administration's Sentinel System. Methods Using a vaccine example, we model and simulate sequential database surveillance in an observational data network using a variety of outcome detection algorithms. We consider how these algorithms, as characterized by sensitivity and positive predictive value, impact the length of surveillance and timeliness of safety signal detection. We show investigators/users of these networks how they can perform preparatory study design calculations that consider outcome misclassification in sequential database surveillance. Results Non-differential outcome misclassification generates longer surveillance times and less timely safety signal detection as compared with the case of no misclassification. Inclusive algorithms characterized by high sensitivity but low positive predictive value outperform more narrow algorithms when detecting rare outcomes. This decision calculus may change considerably if medical chart validation procedures were required. Conclusions These findings raise important questions regarding the design of observational data networks used for pharmacovigilance. Specifically, there are tradeoffs involved when choosing to populate such networks with component databases that are large as compared with smaller integrated delivery system databases that can more easily access laboratory or clinical data and perform medical chart validation. Copyright © 2014 John Wiley & Sons, Ltd.
Biosynthesis of Bacterial Lipopolysaccharide VII. ENZYMATIC FORMATION OF THE FIRST INTERMEDIATE IN BIOSYNTHESIS OF THE O-ANTIGEN OF SALMONELLA TYPHIMURIUM

Abstract The initial step in biosynthesis of the O-antigen of Salmonella typhimurium is the formation of a lipid-linked derivative of galactose 1-phosphate, according to the reaction UDP-galactose + P-lipid ⇌ galactose-1-PP-lipid + UMP. The enzyme activity has been detected in the cell envelope fraction of Citrobacter strain 139 (0–4, 5, 12) as well as in wild type S. typhimurium strain LT-2, but is most readily demonstrated in cell envelope fractions obtained from a mutant strain of S. typhimurium lacking UDP-galactose 4-epimerase following growth in the presence of galactose. The enzyme catalyzes transfer of the entire galactose 1-phosphate moiety of UDP-galactose to the lipid acceptor with concomitant formation of stoichiometric amounts of UMP. The reaction is readily reversible, with an apparent equilibrium constant of approximately 0.5.
Gauss Mixture Quantization: Clustering Gauss Mixtures

Gauss mixtures are a popular class of models in statistics and statistical signal processing because Gauss mixtures can provide good fits to smooth densities, because they have a rich theory, because they can yield good results in applications such as classification and image segmentation, and because the can be well estimated by existing algorithms such as the EM algorithm. We here use high rate quantization theory to develop a variation of an information theoretic extremal property for Gaussian sources and its extension to Gauss mixtures. This extends a method originally used for LPC speech vector quantization to provide a clustering approach to the design of Gauss mixture models. The theory provides formulas relating minimum discrimination information (MDI) selection of Gaussian components of a Gauss mixture and the mean squared error resulting when the MDI criterion is used in an optimized robust classified vector quantizer. It also provides motivation for the use of Gauss mixture models for robust compression systems for random vectors with estimated second order moments but unknown distributions.
Comparison of body composition and body mass index on health status indicators (1031.13)

Employees (n=176) from three Midwest companies completed a worksite health assessment. Mean age was 40 years (range 20-76) with equal distribution by gender. Weight status was assessed by Bioelectrical Impedance Analysis (BIA) and Body Mass Index (BMI) with results classified as underweight, healthy/normal, overweight, or obese.Weight status classifications by BIA and BMI were: underweight (2 vs. 3); healthy/normal (28 vs. 35); overweight (45 vs. 57); and obese (100 vs. 78), respectively. Classifications were significantly different (p<0.05) with BIA identifying more as overweight and obese.Both methods identified differences by weight classification in MET scores, LDL, non-HDL, HDL/LDL ratio, flexibility, and disease risk (waist to hip ratio). Weight classification by BIA identified differences in blood glucose, food security, and muscular endurance. In contrast, BMI classification identified differences in age, HDL, triglycerides, and diastolic blood pressure.Results confirm previous findings that weigh...
The role of human metapneumovirus in the critically ill adult patient

Abstract Purpose The purpose of the study is to describe the role of human metapneumovirus (hMPV) infection in critical illness and acute respiratory distress syndrome (ARDS). Materials and methods We collected clinical and demographic information from a retrospective chart review, comparing patients with and without an intensive care unit (ICU) admission. Among patients admitted to the ICU, we assessed whether hMPV was “unlikely,” “possibly,” or “likely” the reason for ICU admission, based on a prespecified definition, and whether the patient met criteria for ARDS. Results We identified 128 hospitalized adults with hMPV infection. Forty hospitalized patients (31%) with hMPV infection required admission to the ICU. Among patients cared for in the ICU, hMPV was “possibly” the reason for ICU admission in 55% of patients and “likely” the reason in 38%. Forty-eight percent of ICU patients met criteria for ARDS. Although most patients admitted to the ICU had significant comorbidities or were immunosuppressed, 6 patients requiring ICU admission had more minor comorbidities and no underlying immunosuppression. Conclusions Although most patients hospitalized with hMPV had chronic cardiac or pulmonary disease, hMPV can also be associated serious respiratory illness and ARDS in adult patients without significant comorbidities or immunosuppression.
ACP Journal Club. After source control in intraabdominal infections, 4-day and longer-duration antibiotics did not differ at 30-days.

Source Citation Sawyer RG, Claridge JA, Nathens AB, et al.Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015;372:1996-2005. 25992746
Prolactin-stimulated ovarian androgen metabolism

Abstract Activities of 5α, 3α, and 3β reductases were studied with the use of microsomal fractions isolated from the ovaries of immature female rats after treatment with pregnant mares' serum (PMS) followed by human chorionic gonadotropin (hCG). The effect of exogenous prolactin treatment was similarly assessed by comparing enzymic activity in prolactin-treated rat ovaries to that in cotrol rat ovaries, after pretreatment with PMS. With the use of 3 H-testosterone as substrate, reductase activities were determined by measuring the production of dihydrotestosterone and the 3α- and 3β-epimers of androstanediol. The rate of formation of tritiated androstanediol from radiolabeled testosterone was ten times higher than that of tritiated dihydrotestosterone during the follicular phase. After ovulation, the metabolism of testosterone to both androstanediol and dihydrotestosterone decreased markedly. Negligible amounts of estrogen and androsterone were formed, and most of the androstanediol was found to be 5α-androstane-3β,17β-diol. The Michaelis-Menten constant (Km) for 5α-reductase was 1.3 × 10 −5 M. During the follicular phase, the sum of 3 H-dihydrotestosterone and 3 H-androstanediol produced from radiolabeled testosterone was found to be 30% greater in prolactin-treated animals than in control animals. Implications of increased ovarian androgen metabolism as a consequence of hyperprolactinemia are discussed.
Channeling Science Information Seekers' Attention? A Content Analysis of Top-Ranked vs. Lower-Ranked Sites in Google

Researchers have suggested that search engines shape portrayals of information by making large and popular websites more prominent while discriminating against smaller sites. Despite the possible skew of information sources, little empirical work has examined whether there is consistent dominance of content representative of that in highly ranked web links provided by search engines. We conducted a content analysis of a particular issue-nanotechnology-in Google and found that the very top-ranked Google results are likely to feature the technical-, environmental-, and risk-related aspects of nanotechnology. We compared this to lower-ranked search results and found emphasis on significantly different themes. The implications of Google as a market-dominant search engine on the diversity of online science content are discussed.
The developmental emergence of coupled activity as cooperative aggregation in rat pups

Rat pups (Rattus norvegicus) are born blind and deaf yet manage to wriggle about in a huddle, dynamically adjusting their positions and thereby displaying thermoregulation and energy conservation at the level of the group. As pups develop, their activity and mobility outpace the development of their visual and auditory systems making it increasingly difficult to aggregate and maintain aggregation while still blind and deaf. The developmental emergence of coupled activity may be one mechanism that facilitates aggregation. Our previous research has shown that the activity of a seven-day-old pup is independent of the activity of the litter mates it contacts. However, we hypothesized that, by day 10, more active and mobile pups will exhibit coupled activity, becoming increasingly quiescent when in contact with other behaviourally quiescent pups. In order to test this hypothesis, we used individual-based modelling. Because the structure of the model was complex, we used a Darwinian algorithm for evolving a model that behaved like ten-day-old pups aggregating in an arena. Sensitivity to quiescent individuals was manifested in some litters by the transitory spreading of quiescence across aggregates of both real and virtual pups (a contagion effect). As pups develop, individual behaviour becomes increasingly contingent on the behaviour of others revealing what may be a basic component in the development of cooperative behaviour.
A new approach for local intravascular drug delivery. Iontophoretic balloon.

BACKGROUNDCatheter-based systems are being developed to deliver drugs directly into the vessel wall. Pressure-mediated trauma and lack of homogeneous delivery are key limitations of these approaches.METHODS AND RESULTSWe studied a new catheter-based delivery system that uses electrical current to force the drug into the vessel wall. The in vivo feasibility of this approach has been assessed by delivering 125I-hirudin into porcine carotid arteries. Vascular levels of hirudin after active iontophoresis (4 mA/cm2, 5 minutes) were 80-fold greater than those achieved by passive diffusion (without electricity). Tissue hirudin levels declined over time; by 1 hour after delivery, 80% of the drug had left the vessel wall, and by 3 hours later, the levels of hirudin within the wall were similar to those achieved by passive diffusion. Autoradiography revealed distribution of the drug throughout the entire circumference of the arterial wall within the intima, media, and adventitia. Iontophoresis-mediated vessel wall ...
Résumé Content: Applicants’ Perceptions

The authors have reviewed many applications for academic library vacancies and have examined sources in the literature which instruct applicants in proper resume construction. Having received resumes that were not well prepared, the authors surveyed academic librarians in the early years of their careers regarding items they perceive as important to include in a resume. Results of the current study are compared with those of Thomas M. Gaughan’s study, and a resume model for academic applicants is suggested.
Modeling of touch mode capacitive sensors and diaphragms

The understanding of deflection, stress and strain of thin diaphragms with clamped edges under various loads including when the diaphragm touches the substrate is of great importance for designing and fabricating sensors and actuators. This article reports the finite element analysis (FEA) of these diaphragms for computer-aided design of touch mode capacitive pressure sensors. The advantages of the touch mode operation are good linearity in touched range, mechanically robust and large overload protection. These simulation results predict the change of the performance when the device parameters are varied and can be served as a design tool to arrive at a set of desired performance. The results also are useful for designing actuators with diaphragms.
GI Drug Absorption in Rats Exposed to Cobalt-60 γ-Radiation III: In Situ Intestinal Absorption

The absorption rate of sulfanilamide, bretylium tosylate, sulfisoxazole acetyl, and riboflavin from the in situ small intestine was studied in rats exposed to 850 rad of cobalt-60 γ-radiation. Compared to absorption from the intestine of sham-irradiated animals, the absorption rate of sulfanilamide declined following irradiation. It declined to a minimum that was 65% of the control value at 4 days postirradiation before it began to return toward the control value. The reduced absorption rate of sulfanilamide in irradiated animals was accompanied by, and appeared to result from, a reduction in the absorption rate of water from the intestinal drug solution. The sulfisoxazole acetyl absorption rate was reduced compared to the control rate at both 1 and 5 days postirradiation. While this reduced absorption rate at 5 days postirradiation may have resulted from a reduced absorption rate of water, postirradiation water absorption rates at 1 day were similar in irradiated and control animals. The absorption rates of bretylium and riboflavin were not affected by exposure of animals to radiation 1 or 5 days previously. The permeability of the small intestinal epithelium to the drugs studied appeared to be reduced slightly following its exposure to ionizing radiation. The reduced permeability is apparently an indirect effect of the reduced absorption rate of water.
Somatic mutations in GNAQ in amelanotic/hypomelanotic blue nevi

A recent study indicates that somatic mutations in codon 209 of GNAQ, a gene encoding the signaling protein G-protein α subunit q, may be present in up to 80% of blue nevi. Given that mutations in GNAQ represent dominant dark skin (Dsk) mutations caused by increased dermal melanin, the primary aim of this study was to ascertain whether amelanotic/hypomelanotic blue nevi exhibited somatic mutations in GNAQ like their melanotic counterpart. Genomic DNA was isolated for genotyping per protocol using techniques including laser capture microdissection to isolate nevus cells from amelanotic/hypomelanotic blue nevi (n = 8). The positive control group comprised regular blue nevi (n = 10, all melanotic) and cellular blue nevi (n = 9, all melanotic), whereas the negative control group comprised other dermal-based nevomelanocytic proliferations such as intradermal melanocytic nevi (n = 9, 7 of which were amelanotic) and metastatic melanoma (n = 9, 5 of which were amelanotic). DNA sequencing analysis was performed on GNAQ spanning codon 209, BRAFV600E, NRAS1, NRAS2, and KRAS genes. Mutations in GNAQ were noted in 12.5% (1/8) of amelanotic/hypomelanotic blue nevi. In the control group 40% (4/10) of blue nevi and 44% (4/9) of cellular blue nevi demonstrated the GNAQ mutation, with no cases of metastatic melanoma or intradermal melanocytic nevi exhibiting the mutation. All GNAQ mutations were A/T point mutations, and statistically significant differences were not noted among the amelanotic/hypomelanotic blue nevi, blue nevi, and cellular blue nevi subgroups. Although additional mutations were not noted in cases of amelanotic/hypomelanotic blue nevi, one blue nevus exhibited a mutation in KRAS alone; one cellular blue nevus, a concurrent NRAS2 mutation; one cellular blue nevus, a concurrent KRAS mutation; and a third cellular blue nevus, a mutation in KRAS alone. The presence of GNAQ mutations in the amelanotic/hypomelanotic blue nevus indicates that mechanisms underlying pigment homeostasis in this variant appear to be similar to those of its melanotic counterparts, although it is not clear why activation of the q class of the G-protein α subunit should cause an abundance of dermal pigment in one variant and not in another. Given that dermal melanocytes are present since birth, one possible explanation is that their melanin-synthesizing pathway is usually in a dormant state. Activation of this pathway is a consequence of multiple triggers-one of which is a mutation in the GNAQ gene, whereas the other is yet to be identified.
Thermodynamics of the partition of chondroitin sulfate–hexadecylpyridinium complexes in butanol/aqueous salt biphasic solutions

The thermodynamics of the partition of chondroitin sulfate–hexadecylpyridinium complexes wee studied in order to gain further insight into the mechanisms responsible for the sensitivity of the relative solubility of these complexes in aqueous slat and butanol phases to small changes in slat concentration. The dependence of the partition coefficient was measured as a function of temperature at three different salt concentrations. Increasing the temperature was found to favor the form of the complex which was soluble n the aqueous phase. Although the transition could be induced by temperature changes, he transition occurred over a 20°C range in temperature. The transition from the aqueous phase to the butanol phase was strongly exothermic, with ΔH = −22.3 kcal/mol polymer. The value of ΔS was found to be dependent on the salt concentration, ranging from −72.7 e.u./mol polymer in 0.05125M NaCl to −77.1 e.u./mol polymer in 0.05375M MaCl. When placed on a disaccharide basis, the corresponding values are ΔH = −402 cal/mol and ΔS = −1.31 to −1.3 e.u./mol. The sharpness of he transition was found to be due t the similarity in magnitude of ΔH and TΔS, and on the dependence of the later upon the salt concentration.
The interaction of triton X-100 with soluble proteins: Possible implications for the transport of proteins across membranes

Abstract Dodecyl sulfate complexes of two soluble proteins, serum albumin and fumarase, have been “renatured” with large excesses of the nonionic detergent Triton X-100. The resulting complexes, essentially free of dodecyl sulfate, differ in their sedimentation properties relative to the native protein and in their interaction with Triton X-100. Albumin molecules refold to a form binding only very small amounts of Triton and have a sedimentation coefficient similar to that of the non-denatured protein. On the other hand, refolded fumarase molecules have a lower sedimentation coefficient than that of the native enzyme and bind up to 1.06 mg of Triton/mg protein. It is postulated that the fumarase molecule has been turned “inside-out” by the dodecyl sulfate/Triton treatment, and the implications of such large conformational changes for protein transport across membranes are discussed.
Effects of 5,7-dihydroxytryptamine lesions of the prefrontal cortex on consumption of sucrose-ethanol solutions: relationship to prefrontal monoamines.

Thirty adult male Wistar rats received 8 micrograms bilaterally of 5,7-dihydroxytryptamine into the medial prefrontal cortex (mPFC). Rats were then trained, via a sucrose, fading paradigm, to consume increasing concentrations of alcohol. After death, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were measured in the mPFC, nucleus accumbens (NA), and raphe nucleus. The lesioned group demonstrated a reduction in 5-hydroxyindoleacetic acid (5-HIAA), DA, and NE in the mPFC (p < 0.05), and a trend toward reduction of 5-HT in the NA. In comparison with controls, lesioned animals consumed less of all solutions containing sucrose and alcohol. On regression analyses, monoamines in the mPFC (i.e., 5-HIAA, dihydrophenylacetic acid and NE) predicted consumption of the 5% ethanol solution (p = 0.009), 10% ethanol solution (p = 0.0006), and the 5% sucrose solutions (p = 0.0006), but not the 20% sucrose solutions. In each case, monoamine levels were positively correlated with consumption. No relationships were seen between monoamine levels in the NA and raphe, and in consummatory behavior.
Decreased peripheral nerve damage after ischemia–reperfusion injury in mice lacking TNF-alpha

We sought to explore the role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of peripheral nerve ischemia-reperfusion (IR) injury. We established an ischemia-reperfusion model in wild type (WT) and TNF-alpha knockout (KO) mice. Electrophysiology, behavioral score and morphological indices (edema and ischemic fiber degeneration [IFD]) were examined to determine the influence of TNF-alpha on peripheral nerve structure and function following ischemia followed by reperfusion. TNF-alpha and nuclear factor-kappa B (NF-kappaB) expression were evaluated using immunohistochemistry. TNF-alpha KO mice, compared to WT had, in sciatic nerve, marked improvement in nerve pathology. This is a region subject to moderate ischemia-reperfusion injury. There was also a significant improvement in electrophysiological and some behavioral indices. TNF-alpha and NF-kappaB expression were abundant in sciatic-tibial nerves of WT mice subjected to IR, but there was less, or complete lack of, expression in ischemic nerve of TNF-alpha KO mice. We conclude that TNF-alpha plays an essential role in the pathogenesis of peripheral nerve ischemia-reperfusion injury, possibly partly through the activation of NF-kappaB.
Discovery of (R)-6-Cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor

The HCV RNA-dependent RNA polymerase has emerged as one of the key targets for novel anti-HCV therapy development. Herein, we report the optimization of the dihydropyrone series inhibitors to improve compound aqueous solubility and reduce CYP2D6 inhibition, which led to the discovery of compound 24 (PF-00868554). Compound 24 is a potent and selective HCV polymerase inhibitor with a favorable pharmacokinetic profile and has recently entered a phase II clinical evaluation in patients with genotype 1 HCV.
A personal computer based environmental control system for the disabled

In order to facilitate the daily lifestyle of disabled individuals, a general purpose environmental control system using a personal computer was designed. The system utilizes a number of commercial devices such as standard relay boards, X-1O and infrared controllers. The system provides the user with the capability to answer the telephone and control lights, appliances, television, stereo, and other household devices. A number of devices have been fabricated to facilitate infrared control of shades, intercom, home temperature, and windows. The entire system is menu driven from the keyboard and is also configured to run with the Intravoice VI voice recognition system so that the device may be used conveniently by a quadriplegic individual. Currently plans are underway to adapt the system for a Dragon Systems Dictate voice recognition system and extend the system for input using eye movements to enable use by stroke victims.
Site-specific photochemistry

We present results on `site-specific' H-atom production in photolysis experiments conducted under collisionless conditions. H and D atoms are used as labels to investigate the site(s) at which C-H (or C-D) bond cleavage occurs in a variety of haloalkane systems. Experiments using two photolysis lasers clearly indicate that photon absorption by an intermediate, presumably an alkyl radical, is important in many of the systems studied. The site(s) (e.g., (alpha) , (beta) , or (gamma) ) at which C-H (or C-D) bond cleavage occurs is dependent not only on the nature of the molecule, but also on the photolysis wavelength. As a diagnostic tool, H- and D-atom Doppler spectroscopy allows us to gain insight into the energetics associated with the various dissociation processes. Our overall aim is to gain a further understanding of the photolysis properties of a variety of simple molecules and their associated radicals.
Control of systems with jump Markov disturbances

Abstract-Control of stochastic differential equations of the form dot{x}=f^{r(t)}(t,x,u) in which r(t) is a fiie-state Markov p n m s is discussed Dynamic programming optimalityconditions are shown to be necessary and sufficient for oplimality. A stochastic minimom principle whose adjoints satisfy deterministic integral equations is defiied and shorn to be necessary and snffiaent for optimality.
The superior mesenteric artery syndrome and acute gastric dilatation in eating disorders: A report of two cases and a review of the literature

Objective The pathophysiology and symptomatology of the superior mesenteric artery syndrome (SMA syndrome) is discussed. A review of much of the available literature concerning the SMA syndrome and the associated condition acute gastric dilatation is offered. Results: Two new cases of acute gastric dilatation in patients with eating disorders, one of whom was diagnosed with SMA syndrome, are presented, along with a discussion of these conditions in reference to the eating disorders. Conclusion: The SMA syndrome and gastric dilatation are rare but potentially a very serious complication of eating disorders, and clinicians who work with these patients should be aware of such problems. © 1997 by John Wiley & Sons, Inc. Int J Eat Disord 21: 103–114, 1997.
Modelling the sensitivity of cells in the anteroventral cochlear nucleus to spatiotemporal discharge patterns

This study investigates a potential mechanism for the processing of acoustic information that is encoded in the spatiotemporal discharge patterns of auditory nerve (AN) fibres. Recent physiological evidence has demonstrated that some low-frequency cells in the anteroventral cochlear nucleus (AVCN) are sensitive to manipulations of the phase spectrum of complex sounds (Carney 1990b). These manipulations result in systematic changes in the spatiotemporal discharge patterns across groups of low-frequency AN fibres having different characteristic frequencies (CFS). One interpretation of these results is that these neurons in the AVCN receive convergent inputs from AN fibres with different CFS, and that the cells perform a coincidence detection or cross-correlation upon their inputs. This report presents a model that was developed to test this interpretation.
Age-related spatial reference and working memory deficits assessed in the water maze

Aged rats have spatial memory deficits relative to young rats. The extent of these deficits in intermediate-aged rats is not well established. The present study examined the pattern of age-related changes in spatial reference and working memory in four ages of Fischer-344 rats. Place discrimination (PD) in the Morris water maze measured spatial reference memory. Repeated acquisition (RA), a discrimination in which the escape platform location varied from session to session, measured spatial working memory. Fischer-344 rats, 4 months, 11 months, 17 months, and 24 months of age, were tested. Compared to 4-month-olds, 24-month-olds were significantly impaired on all six PD measures of performance, 17 months were significantly impaired on five PD measures, and 11 months were significantly impaired on only one PD measure. Only 24-month-olds had a significant working memory impairment in RA relative to 4 months. Reference and working memory measures were distinct as assessed by a principal components analysis. The results indicate a nonlinear age-related spatial memory decline in Fischer-344 rats from 4 to 24 months of age.
Escalation of Commitment and Nonorthogonal Analysis of Variance Revisited: A Comment on Schoorman, Bobko, and Rentsch

Schoorman, Bobko, and Rentsch (1991) reanalyzed previously published data (Schoorman, 1988) and claimed that, in contrast to the original analysis, the data supported Schoorman's negative escalation hypothesis. We contend that this reanalysis was conceptually and technically flawed, and that Schoorman's original analysis yielded the correct (negative) conclusion. Schoorman et al. also discussed a variety of alternatives for conducting a factorial analysis of variance with unequal cell sizes, demonstrating that different procedures can lead to different statistical conclusions. However, their discussion is misleading and overlooks recent literature that has removed much of the mystery from the unequal-n problem. We offer a brief review of the fundamental problems, and their solutions, in analysis of variance with unequal ns.
Crystallographic and Spectroscopic Studies of Native, Aminoquinol, and Monovalent Cation-bound Forms of Methylamine Dehydrogenase from Methylobacterium extorquens AM1

Various monovalent cations influence the enzymatic activity and the spectroscopic properties of methylamine dehydrogenase (MADH). Here, we report the structure determination of this tryptophan tryptophylquinone-containing enzyme from Methylobacterium extorquens AM1 by high resolution x-ray crystallography (1.75 A). This first MADH crystal structure at low ionic strength is compared with the high resolution structure of the related MADH from Paracoccus denitrificans recently reported. We also describe the first structures (at 1.95 to 2.15 A resolution) of an MADH in the substrate-reduced form and in the presence of trimethylamine and of cesium, two competitive inhibitors. Polarized absorption microspectrophotometry was performed on single crystals under various redox, pH, and salt conditions. The results show that the enzyme is catalytically active in the crystal and that the cations cause the same spectral perturbations as are observed in solution. These studies lead us to propose a model for the entrance and binding of the substrate in the active site.
Endothelin-1 increases arterial sensitivity to 5-hydroxytryptamine.

Abstract Rings of rabbit abdominal aorta were pretreated with endothelin-1 (ET-1) or vehicle and then isometric contractions to cumulative additions of 5-hydroxytryptamine (5-HT) were recorded. ET-1 at concentrations of 0.4, 1 and 2 nM produced contractions of 7, 15 and 35% of maximal potassium chloride-induced contractions, respectively. Pretreatment of aortic rings with these concentrations of ET-1 increased (P 50 ) to 5-HT 1.9-, 2.4- and 3.5-fold, respectively, without affecting peak 5-HT-induced force. Acetylcholine-induced, endothelium-dependent aortic relaxations were not affected by pretreatment with ET-1. Removal of the endothelium potentiated aortic responses to ET-1 and to 5-HT-induced contractions of ET-1-pretreated but not untreated aortic rings. These results suggest that ET-1 could promote arterial vasospasm by sensitizing the artery to 5-HT released from platelets.
Critical analysis and applications of a quasi-resonant theory of pressure broadening of linear molecules☆

Abstract A simplified Anderson theory of the pressure broadening of linear molecules has been critically analyzed and applied to five common types of molecular interactions. It has been shown that the simplified theory is equivalent to assuming that all partial cross sections of the exact Anderson theory are of the same order of magnitude as the resonant partial cross sections. Quantitative estimates of the errors introduced in the partial cross sections of the exact theory by making this simplifying assumption are given.
High speed stripline coils for magnetic bubble devices

In magnetic bubble technology, high speed operation in practical systems has been hampered by the lack of suitable coil designs for in-plane fields. These coils should produce 20-40 Oe per ampere, have uniform fields over a large area, have low inductances, and be practical to fabricate. A close-wrapped, large area multistrip line approach, with the large areas being separated by only tens of mils (≥30 mils), is proposed. The normalized data allow handbook-type designs of a large range of coil sizes. A model, design equations, field uniformity contours, and useful coil area plots are presented. Results calculated using probable fabrication tolerances show that uniform fields with a tolerance of ±5 percent can be provided over an area covering 70 percent of the coil and with field strengths up to 45 Oe per ampere. Inductances range from 200 nh to 10 μh for 1/4 to 2 1/4 inch wide coils.
Effects of heart failure on baroreflex control of sympathetic neural activity

Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean +/- SEM 21 +/- 1 years) and in 11 patients with moderate to severe heart failure (age 48 +/- 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 +/- 2%, pulmonary capillary wedge pressure 27 +/- 2 mm Hg, cardiac index 2.04 +/- 0.22 liters/min/m2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 micrograms/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 micrograms/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01) and in patients with heart failure (90 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01). The patients with heart failure exhibited significantly attenuated (p less than 0.01 for normal vs heart failure) decreases in heart rate (93 +/- 5 to 90 +/- 6 beats/min, p = not significant [NS]) compared with normal subjects (67 +/- 3 to 58 +/- 4 beats/min, p less than 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 +/- 2 to 80 +/- 3 mm Hg, p less than 0.001) and right atrial (4 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01) pressures with a resultant reflex increase in heart rate (68 +/- 3 to 81 +/- 4 beats/min, p less than 0.001) and muscle sympathetic nerve activity (326 +/- 74 to 746 +/- 147 U/min, p less than 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 +/- 2 to 77 +/- 2 mm Hg, p less than 0.001) and right atrial (6 +/- 1 to 1 +/- 1 mm Hg, p less than 0.001) pressures, but did not significantly alter heart rate (91 +/- 6 to 97 +/- 4 beats/min, p = NS) or sympathetic nerve activity (936 +/- 155 to 1179 +/- 275 U/min, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)
Molecular cloning and characterization of a novel Rel/NF-kappa B family member displaying structural and functional homology to NF-kappa B p50/p105.

ABSTRACT The NF-χB transcription factor has been implicated in the inducible expression of many genes, including inflammatory, immune, and acute-phase response genes. NF-χB consists of two subunits...
Appendiceal fecalith is associated with early perforation in pediatric patients

Abstract Purpose A fecalith is a fecal concretion that can obstruct the appendix leading to acute appendicitis. We hypothesized that the presence of a fecalith would lead to an earlier appendiceal perforation. Methods Between January 2001 and December 2005, the charts of all patients younger than 18 years old who underwent appendectomy at our institution were reviewed. Duration of symptoms and timing between presentation and operation were noted along with radiologic, operative, and pathologic findings. Results There were 388 patients who met the study criteria. A fecalith was present in 31% of patients (n = 121). The appendix was perforated in 57% of patients who had a fecalith vs 36% in patients without a fecalith ( P P = .036). Conclusion The presence of fecalith is associated with earlier and higher rates of appendiceal perforation in pediatric patients with acute appendicitis. An expedient appendectomy should therefore be performed in the pediatric patient with a radiologic evidence of fecalith.
Tropical origins of North and South Pacific decadal variability

[1] The origin of the Pacific Decadal Oscillation (PDO), the leading mode of sea surface temperature variability for the North Pacific, is a matter of considerable debate. One paradigm views the PDO as an independent mode centered in the North Pacific, while another regards it as a largely reddened response to El Nino-Southern Oscillation (ENSO) forcing from the tropics. We calculate the Southern Hemisphere equivalent of the PDO index based on the leading mode of sea surface temperature variability for the South Pacific and find that it adequately explains the spatial structure of the PDO in the North Pacific. A first-order autoregressive model forced by ENSO is used to reproduce the observed PDO indices in the North and South Pacific. These results highlight the strong similarity in Pacific decadal variability on either side of the equator and suggest it may best be viewed as a reddened response to ENSO.
Odor thresholds of various branched esters

A series of branched esters (methyl 2,2-dimethylpropanoate to ethyl 2-ethylhexanoate) were purified by preparative gas chromatography and their odor thresholds were determined using sensory panel methods. The odor thresholds reached a minimum with the butanoate and pentanoate esters. In general, the branched esters have much lower odor thresholds than their straight chain counterparts. Replacing methyl and ethyl branch substituents with mercapto- or hydroxy-groups resulted in higher odor thresholds.