cssi/SciSciGPT-SciSciNet huggingface dataset:
A glutamic acid 3-methyltransferase encoded by an accessory gene locus important for daptomycin biosynthesis in Streptomyces roseosporus

In many peptide antibiotics, modified amino acids are important for biological activity. The amino acid 3-methyl-glutamic acid (3mGlu) has been found only in three cyclic lipopeptide antibiotics: daptomycin and the A21978C family produced by Streptomyces roseosporus, calcium-dependent antibiotic produced by Streptomyces coelicolor and A54145 produced by Streptomyces fradiae. We studied the non-ribosomal peptide synthetase genes involved in A21978C biosynthesis and the downstream genes, dptG, dptH, dptI and dptJ predicted to encode a conserved protein of unknown function, a thioesterase, a methyltransferase (MTase) and a tryptophan 2,3-dioxygenase respectively. Deletion of dptGHIJ reduced overall lipopeptide yield and led to production of a series of novel A21978C analogues containing Glu12 instead of 3mGlu12. Complementation by only dptI, or its S. coelicolor homologue, glmT, restored the biosynthesis of the 3mGlu-containing compounds in the mutant. Compared with A21978C, the Glu12-containing derivatives were less active against Staphylococcus aureus. Further genetic analyses showed that members of the dptGHIJ locus cooperatively contributed to optimal A21978C production; deletion of dptH, dptI or dptJ genes reduced the yield significantly, while expression of dptIJ or dptGHIJ from the strong ermEp* promoter substantially increased lipopeptide production. The results indicate that these genes play important roles in the biosynthesis of daptomycin, and that dptI encodes a Glu MTase.
Risk factors for leptomeningeal carcinomatosis in patients with brain metastases who have previously undergone stereotactic radiosurgery

Our objective was to explore the hypothesis that the risk of leptomeningeal dissemination (LMD) in patients who underwent stereotactic radiosurgery (SRS) for brain metastases is influenced by the site of the primary cancer, the addition of whole brain radiation therapy (WBRT), surgical resection, and control over their sys- temic disease. We conducted a retrospective cohort ana- lysis of 805 patients who were treated with SRS for brain metastases between 1999 and 2012 at the Wake Forest Baptist Medical Center, and excluded all patients with evidence of LMD before SRS. The primary outcome was LMD. Forty-nine of 795 patients developed LMD with a cumulative incidence of 6.2 % (95 % Confidence Interval (CI), 4.7-8.0). Median time from SRS to LMD was 7.4 months (Interquartile Range (IQR), 3.3-15.4). A colorectal primary site (Hazard Ratio (HR), 4.5; 95 % CI 2.5-8.0; p \ 0.0001), distant brain failure (HR, 2.0; 95 % CI 1.2-3.2; p = 0.007), breast primary site (HR, 1.6; 95 % CI 1.0-2.7; p = 0.05), the number of intracranial metas- tases at time of initial SRS (HR, 1.1; 95 % CI 1.0-1.2; p = 0.02), and age (by 5-year interval) (HR, 0.9; 95 % CI 0.8, 0.9; p = 0.0006) were independent factors associated with LMD. There was no evidence that surgical resection before SRS altered the risk of LMD (HR, 1.1; 95 % CI 0.6-2.0, p = 0.78). In patients who underwent SRS for brain metastases, a colorectal or breast primary site, distant brain failure, younger age, and an increased number of intracranial metastases were independently associated with LMD. Given its relative rarity as an outcome, multi-insti- tutional prospective studies will likely be necessary to validate and quantify these relationships.
Regulation of rat luteinizing hormone beta gene expression in transgenic mice by steroids and a gonadotropin-releasing hormone antagonist.

Transcriptional regulation of the rat LHβ (rLHβ) gene was studied through the use of transgenic mice bearing a region of the rLH gene (from - 2 kb to + 41 bp) linked to a luciferase (LUC) reporter gene. All 7 founder mice were successfully bred with B6SJLF1 mates and exhibited germ line transmission of the LHβLUC transgene. Levels of rLHβLUC activity were highest in the pituitary, but activity was also detected in ovary, testis, and hypothalamus. Pituitary rLHβLUC activity was found to be regulated by gender, gonadectomy, gonadal steroid replacement, and GnRH antagonist administration. Females had higher basal pituitary rLHβLUC activity than males. This activity was increased 2- to 4-fold seven days postovariectomy, and stimulated activity was suppressed to intact levels by daily injections of 17β-estradiol (E 2 ; 300 ng). In males, castration increased pituitary LUC activity 2- to 4-fold, and this was suppressed to intact levels by daily injections of 25 μg dihydrotestosterone (DHT). The postgonadectomy rise in pituitary rLHβLUC activity in females and males was blocked by daily administration of the GnRH antagonist Antide (60 μg), which also suppressed serum LH and LHβ mRNA levels to a similar extent. Rat LHβLUC activity measured in the hypothalamus was not altered by gonadectomy or gonadal steroid or Antide treatment, demonstrating that this regulation is pituitary-specific. These results indicate that feedback regulation of pituitary rLHβLUC gene expression is operational in this transgenic mouse model. The region of the rLHβ gene within 2 kb upstream from the transcriptional start site contains sequences that confer transcriptional responses to GnRH, which may contribute to the changes in LHβ gene expression after gonadectomy and after gonadal steroid replacement.
The ‘Alternative Quality Contract,’ Based On A Global Budget, Lowered Medical Spending And Improved Quality

Seven provider organizations in Massachusetts entered the Blue Cross Blue Shield Alternative Quality Contract in 2009, followed by four more organizations in 2010. This contract, based on a global budget and pay-for-performance for achieving certain quality benchmarks, places providers at risk for excessive spending and rewards them for quality, similar to the new Pioneer Accountable Care Organizations in Medicare. We analyzed changes in spending and quality associated with the Alternative Quality Contract and found that the rate of increase in spending slowed compared to control groups, more so in the second year than in the first. Overall, participation in the contract over two years led to savings of 2.8 percent (1.9 percent in year 1 and 3.3 percent in year 2) compared to spending in nonparticipating groups. Savings were accounted for by lower prices achieved through shifting procedures, imaging, and tests to facilities with lower fees, as well as reduced utilization among some groups. Quality of care...
Weighted Nonnegative Matrix Tri-Factorization for Co-clustering

Nonnegative matrix tri-factorization and spectral co-clustering are two popular techniques that allow simultaneous clustering of the rows and columns of a matrix. In this paper, by adding a weighting scheme derived from spectral co-clustering into the objective function of nonnegative matrix tri-factorization, we show that the normalized cut information for co-clustering can be incorporated into nonnegative matrix tri-factorization. With the weighting scheme, a weighted nonnegative matrix tri-factorization algorithm for co-clustering is proposed, and extensive experiments show that our method statistically outperforms state-of-the-art co-clustering algorithms.
Collaborative security architecture for black hole attack prevention in mobile ad hoc networks

An ad hoc network is a group of wireless mobile computers (or nodes) wherein individual nodes cooperate by forwarding packets for each other to allow nodes to communicate beyond direct wireless transmission range. The Black hole attack is an important problem that could happen easily in ad hoc networks especially in popular on-demand protocols like the ad hoc on-demand distance vector routing (AODV). Prior research in ad hoc networking has generally looked into the routing problem in a non-adversarial network setting, assuming a reasonably trusted environment. This paper proposes a collaborative architecture to detect and exclude malicious nodes that act in groups or alone. The focus is on the network layer, using the ad hoc on-demand distance vector routing (AODV) protocol as an example. This paper describes an extension to the watchdog method to incorporate a collaborative architecture to tackle collusion among nodes.
Raman spectroscopic study of spodumene (LiAlSi2O6) through the pressure-induced phase change from C2/c to P21/c

High-pressure Raman spectroscopy was used to follow the effects of a phase transition on the Raman spectrum of a natural specimen of the pyroxene spodumene, from its low-pressure (C2/c) to its high-pressure (P21/c) phases. The transition occurred at 3.2 GPa and was accompanied by an increase from 15 to 23 observed peaks, owing to a decrease in symmetry. Comparisons were made with other pyroxenes with the same space groups. The change in Raman shift with pressure of all peaks observed is reported. An additional change in the spectrum is observed between 7.7 and 8.9 GPa, possibly due to the formation of an additional bond between Li and O3 or some other transition that retained the mineral's P21/c space group. Splitting of the peak appearing at ∼700 cm−1, used to characterize the P21/c phase in other studies, was not observed. Copyright © 2003 John Wiley & Sons, Ltd.
Implications of the tobacco industry documents for public health and policy

▪ Abstract The release of previously secret internal tobacco industry documents has given the public health community unprecedented insight into the industry's motives, strategies, tactics, and data. The documents provide information that is not available from any other source and describe the history of industry activities over the past 50 years. The documents show that the tobacco industry has been engaged in deceiving policy makers and the public for decades. This paper begins with a brief history of the tobacco industry documents and describes the methodological challenges related to locating and analyzing an enormous number of poorly indexed documents. It provides an overview of selected important findings of document research conducted to date, including analyses of industry documents on nicotine and addiction, product design, marketing and promotion, passive smoke, and internal activities. The paper concludes with a discussion of the implications of tobacco document research for public health and t...
Genome-wide decoding of hierarchical modular structure of transcriptional regulation by cis -element and expression clustering

Motivation: A holistic approach to the study of cellular processes is identifying both gene-expression changes and regulatory elements promoting such changes. Cellular regulatory processes can be viewed as transcriptional modules (TMs), groups of coexpressed genes regulated by groups of transcription factors (TFs). We set out to devise a method that would identify TMs while avoiding arbitrary thresholds on TM sizes and number. Method: Assuming that gene expression is determined by TFs that bind to the gene's promoter, clustering of genes based on TF binding sites (cis-elements) should create gene groups similar to those obtained by gene expression clustering. Intersections between the expression and cis-element-based gene clusters reveal TMs. Statistical significance assigned to each TM allows identification of regulatory units of any size. Results: Our method correctly identifies the number and sizes of TMs on simulated datasets. We demonstrate that yeast experimental TMs are biologically relevant by comparing them with MIPS and GO categories. Our modules are in statistically significant agreement with TMs from other research groups. This work suggests that there is no preferential division of biological processes into regulatory units; each degree of partitioning exhibits a slice of biological network revealing hierarchical modular organization of transcriptionalregulation. Contact: dleyfer@gnsbiotech.com
A historical analysis of the international business perspectives of Mexican industrial groups

Based on an analysis of Mexican industrial history, the objective of this study was to identify the historical events and factors which shaped the international business perspectives and management strategies of Mexican industrial groups (MIGs). To this end, the evolution of MIGs is traced over the course of 170 years and through three distinct phases of Mexican political and economic history: pre‐industrial era (1821‐1940); industrial boom (1940‐1970); and economic crisis and reform (1970‐1990). The subsequent analysis indicates a combination of historical factors resulting in two conditions ‐ domestic orientation and dependent development ‐ which caused MIGs to focus almost exclusively on the Mexican market and to shun international markets and competition.
Optimal control of linear systems with parameter uncertainty

A class of infinite-horizon regulator problems is formulated for families of time-invariant linear systems with parameter uncertainty. Under a regularity assumption, the optimal linear, state-feedback control is shown to exist and is defined via a positive-definite solution of a family of Riccati-type, algebraic equations. The solvability of these equations is equivalent to the stabilizability of the family of linear systems by a constant, linear feedback.
The lexical interface in L1 acquisition: What children have to say about radical concept nativism

In the ongoing philosophical debate over the origins and nature of lexical concepts stemming from the work of Fodor (1970, 1998, 2000, 2008), the potential of first language acquisition studies as a source of evidence has been somewhat overlooked. At the lexical interface with syntax, a restricted set of lexical conceptual elements can be shown to play a pivotal role in the generation of syntactic representations, and patterns of syntactic development can elucidate the nature of such elements. An experiment is described which reveals mature knowledge of interface principles in this domain in early syntactic production. It is argued that first language research of this type can provide much-needed observable evidence for lexical semantic decomposition and against radical concept nativism.
Early Events in Mycobacterium tuberculosis Infection in Cynomolgus Macaques

Little is known regarding the early events of infection of humans with Mycobacterium tuberculosis. The cynomolgus macaque is a useful model of tuberculosis, with strong similarities to human tuberculosis. In this study, eight cynomolgus macaques were infected bronchoscopically with low-dose M. tuberculosis; clinical, immunologic, microbiologic, and pathologic events were assessed 3 to 6 weeks postinfection. Gross pathological abnormalities were observed as early as 3 weeks, including Ghon complex formation by 5 weeks postinfection. Caseous granulomas were observed in the lung as early as 4 weeks postinfection. Only caseous granulomas were observed in the lungs at these early time points, reflecting a rigorous initial response. T-cell activation (CD29 and CD69) and chemokine receptor (CXCR3 and CCR5) expression appeared localized to different anatomic sites. Activation markers were increased on cells from airways and only at modest levels on cells in peripheral blood. The priming of mycobacterium-specific T cells, characterized by the production of gamma interferon occurred slowly, with responses seen only after 4 weeks of infection. These responses were observed from T lymphocytes in blood, airways, and hilar lymph node, with responses predominantly localized to the site of infection. From these studies, we conclude that immune responses to M. tuberculosis are relatively slow in the local and peripheral compartments and that necrosis occurs surprisingly quickly during granuloma formation.
Educating Pharmacy Students About Nutrition and Physical Activity Counseling

Abstract The current study provides measures of association between self-reported beliefs of currently practicing pharmacists and pharmacy students' beliefs about, willingness to provide, and preparedness to provide counseling on nutrition and physical activity following completion of a health education unit. A 3-week health education unit focusing on the pharmacists' role in nutrition and physical activity counseling was developed and implemented in a required nonprescription drug therapy pharmacy course for fifth-year doctor of pharmacy students. As expected, the majority of pharmacy students postintervention believed that diet and physical activity health-related behaviors were very important for the average adult. Furthermore, significantly more pharmacy students believed that it was their professional responsibility to educate patients about diet and physical activity, felt more prepared to educate on diet modification and physical activity, and felt more comfortable with implementing behavioral-modi...
Formation Criterion for Synthetic Jets

Af ormation criterion for synthetic jets is proposed and validated. A synthetic jet actuator is a zero-net mass-flux device that imparts momentum to its surroundings. Je tf ormation is defined as the appearance of a time-averaged outward velocity along the jet axis and corresponds to the generation and subsequent convection or escape of a vortex ring. It is shown that over a wide range of operating conditions synthetic jet formation is governed by the jet Strouhal number Sr (or Reynolds number Re and Stokes number S). Both numerical simulations and experiments are performed to supplement available two-dimensional and axisymmetric synthetic jet formation data in the literature. The data support the jet formation criterion 1/Sr = Re/S 2 > K, where the constant K is approximately 1 and 0.16 for two-dimensional and axisymmetric synthetic jets, respectively. In addition, the dependence of the constant K on the normalized radius of curvature of a rounded orifice or slot is addressed. The criterion is expected to serve as a useful design guide for synthetic jet formation in flow control, heat transfer, and acoustic liner applications, in which a stronger jet is synonymous with increased momentum transfer, vorticity generation, and acoustic nonlinearities.
Cloning and Mapping of Human Rab7 and Rab9 cDNA Sequences and Identification of a Rab9 Pseudogene

Rab GTPases reside in specific intracellular compartments and are key regulators of vesicular transport. To facilitate studies of the mechanism of lysosomal integral membrane protein (LAMP-1) transport, cDNAs for human Rab7 and Rab9 were isolated, and their nucleotide sequences were determined. During isolation and characterization of these cDNAs a Rab9 pseudogene was identified. The sequences are highly homologous to other mammalian Rab proteins and also share homology with proteins of the Rab GTPase family. Rab7 and the Rab9 pseudogene were mapped to chromosomes 3 and 5, respectively, by amplification of their sequences from human monochromosomal somatic cell hybrids. In addition, preliminary studies using antisense expression indicate that down-regulation of either Rab7 or Rab9 proteins induces severe cell vacuolation that resembles the phenotype seen in fibroblasts from patients with Chediak-Higashi syndrome.
Science and Sovietology: Bridging the Methods Gap in Soviet Foreign Policy Studies

Specialists in the study of Soviet foreign policy increasingly feel torn between the positivist culture of political science departments and the holistic traditions of the Soviet area-studies programs. In fact, these approaches are largely complementary. Examples taken from literature on Soviet security policy and on the domestic sources of Soviet expansionism show how positivist theories and methods can be used to clarify holist (or traditionalist) arguments, to sharpen debates, to suggest more telling tests, and to invigorate the field's research agenda.
OPTIMIZING THE USE OF THE FISCAL STIMULUS FOR HEALTH IT IN THE U.S.

The fiscal stimulus of 2009 allocated about $19 billion over five years to advance the country’s push for a nationwide health information network. Information sharing among public health agencies and private health care providers has the potential for reducing public health threats and increasing public access to measures of provider quality. It can also help build and disseminate a database of cost-effective best practices in health care delivery. An analysis of existing evidence on enablers and barriers to adoption and effective use of electronic health records suggest that government intervention is justified. The market system will result in low utilization because of scale economies, externalities, network effect, and a need for national standards to ensure interoperability, privacy and data security,. However, optimal use of the fiscal stimulus requires that financial and technical assistance be targeted on smaller physician practices and independent hospitals. Such assistance must be made conditional on adoption and effective use of a certified, interoperable system. The public health benefits will also be maximized the more health care providers participate in the national health IT network. Thus, in addition to awarding financial incentives, electronic submission of aggregated or de-identified health information must be mandated of all health care providers, not only those that are participants of Federal health programs.
Discovery of unfixed endogenous retrovirus insertions in diverse human populations

Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from 0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity.
Use of Adenine–ACD Solution in Long Term Storage of Blood

This report of the long term storage of blood preserved in adenine–ACD solution presents the 51Cr survival of such blood stored from 1 to 42 days at 4 C. in plastic bags. Results of survival studies performed 24 hours and 15 days after transfusion indicate that this solution is satisfactory and provides more than 70% posttransfusion survival of the erythrocytes. The problem of sensitive erythrocytes for crossmatching is solved by using the plasma and cells of the integral tubing of the bag, because the antigen reactivity of these cells is identical to that of the contents of the bag. Preliminary studies revealed normal survival of freshly collected erythrocytes suspended in ACD–adenine after transfusion. This was followed by studies of 21-day-old stored blood, and finally blood stored for 21 to 42 days was studied. Hematologic and chemical studies performed both pre- and post-transfusion showed no deleterious effects. The increases in hemoglobin and hematocrit values recorded were expected. The better utilization of blood under conditions that permit storage for 42 days would be of benefit in Blood Bank logistics.
New American Literary History

Until I sat down to think about this paper, I didn't realize just how schizophrenic my professional career has been. On the one hand, as an editor of a so-called standard anthology of American literature, as Textual General Editor of a CEAA sanctioned author, as general editor of a series of enumerative bibliographies devoted to so-called major American writers, I have been part of what Florence Howe and Steven Tabachnick have recently characterized as a conspiracy to celebrate, preserve, and perpetuate the canonical American writers to the neglect and exclusion of enormous amounts of worthwhile writing by women, popular, and minority writers. On the other hand, as a literary scholar, I have devoted most of my research to Upton Sinclair (certainly not among the elect or elected of our writers), have written a pioneering piece on Agnes Smedley, and have raised more than one set of eyebrows with my enthusiasm for film and popular culture studies. My teaching has been schizophrenic as well. I have taught conventional great writer courses at prestigious institutions with traditional departments of English, and I have offered such courses as Protest and Prophecy at radically experimental and blue-collar colleges. I believe that this intellectual divison is not all that uncommon for people of my generation, and I further believe that this division even confusion bears on the problem I am addressing here. Many of us, in short, are conservative in our desire to preserve the best writing of the past and radical in our wish to be responsive to the best of the new work that has emerged or been rediscovered. My own experience is, to put it another way, a version of a profoundly American theme: the difficulty of reconciling the real to the ideal. Dexter Fisher, among others, has put very well what is real: "America is pluralistic, but traditional literary studies and the educational system have been based upon an ethnocentric and homogenous set of values that reveal only one aspect of man and society, greatly limiting knowledge of cultures and literatures outside the dominant group." David Dorsey has put very well what is ideal what our challenge is as editors and as teachers of literature: "we must consciously create an American ethos from a confusion of articulated and contradictory priorities." Two generations ago the task of critics was to uncov-
Massacres as process: A micro-sociological theory of internal patterns of mass atrocities:

Mass atrocities are episodes of violence that do not unfold at random: (a) there are recurrent patterns in the forms that violent behavior takes; (b) the chain of events in which violence unfolds is patterned internally, that is, there are processual patterns. These patterns are not the mere outcome or reflection of larger structures such as ethnic conflict; violence instead has patterns (including processual patterns) with a logic of their own. By tracing the onset and early phases of massacres in Srebrenica and Rwanda, it is shown that patterns of violence are shaped by local emotional dynamics. The paper builds on recent findings in the micro-sociology of violence by Collins and others and on Horowitz’s research on the processual character of violence in riots.
THE UNUSUAL STORMS OF FEBRUARY 1992 IN SOUTHERN CALIFORNIA

During February 1992, a series of relatively warm storms passed eastward across southern California, yielding intense precipitation that triggered widespread mass movement, flooding, property damage, and loss of life. These storms were triggered by an intense low pressure system (976 mb) off northern California which deepened as its eastward progress was initially blocked by a high pressure ridge (1040 mb) across western North America. Between February 10 and 13, large areas of Ventura and Los Angeles counties experienced cumulative precipitation of 200–400 mm with intensities reaching 40–50 mm hr-1. Mass movement, mainly as soil slips that transformed downslope into debris flows, occurred where cumulative precipitation exceeded 300 mm and when sustained intensities exceeded 25 mm hr-1. Stream response was rapid, particularly in urban areas where impermeable surfaces and storm drains fed concrete stream channels. The canalized upper Los Angeles River and Arroyo Simi exceeded all previous discharges for ov...
First Amendment at Its Third Century: Reckoning with the Ravages of Time

Freedom of speech and freedom of the press have been explicit constitutional commands for precisely two hundred years. Despite its prominence in the Bill of Rights and status as an essential condition of ratification, the First Amendment did not begin to figure meaningfully in the nation's jurisprudence until this century.
A New Genus of Perientomine Psocids (Psocoptera : Lepidopsocidae) with a Review of the Perientomine Genera

A new genus of psocids, Papuapsocus, of subfamily Perientominae is described based on a new species from New Guinea with the unique character of tailed forewings. Several new characters for the subfamily are recorded, resulting from examination of all genera available, in addition to the new one. These are Lepium Enderlein, Nepticulomima Enderlein, Perientomum Hagen, Proentomum Badonnel, and Soa Enderlein. Several of these genera were originally based on seemingly trivial characters of wing venation and an attempt is made to evaluate them, as well as other described genera not seen, based on all information available. The new subfamily Parasoinae is proposed for the genus Parasoa Thornton. The genus Notolepium Enderlein probably belongs in subfamily Thylacellinae. Nepticulomima pulvillata New, Nepticulomima saltuaria Smithers and Nepticulomima scottiana Enderlein are transferred to the genus Proentomum Badonnel. A key is included to the genera that clearly belong in Perientominae.
Alcohol and Aldehyde Dehydrogenases Contribute to Sex-Related Differences in Clearance of Zolpidem in Rats.

Objectives: The recommended zolpidem starting dose was lowered in females (5mg vs 10mg) since side effects were more frequent and severe than those of males; the mechanism underlying sex differences in pharmacokinetics (PK) is unknown. We hypothesized that such differences were caused by known sex-related variability in alcohol dehydrogenase (ADH) expression. Methods: Male, female, and castrated male rats were administered 2.6 mg/kg zolpidem, +/- disulfiram (ADH/ALDH pathway inhibitor) to compare PK changes induced by sex and gonadal hormones. PK analyses were conducted in rat plasma and rat brain. Key findings: Sex differences in PK were evident: females had a higher CMAX (112.4 vs 68.1 ug/L) and AUC (537.8 vs 231.8 hr*ug/L) than uncastrated males. Castration induced an earlier TMAX (0.25 vs 1 hr), greater CMAX (109.1 vs 68.1 ug/L), and a corresponding AUC increase (339.7 vs 231.8 hr*ug/L). Administration of disulfiram caused more drastic CMAX and TMAX changes in male vs female rats that mirrored the effects of castration on first-pass metabolism, suggesting that the observed PK differences may be caused by ADH/ALDH expression. Brain concentrations paralleled plasma concentrations. Conclusions: These findings indicate that sex differences in zolpidem PK are influenced by variation in the expression of ADH/ALDH due to gonadal androgens.
Extending Shelf Life of Refrigerated Catfish Fillets Using Sodium Acetate and Monopotassium Phosphate.

The effects of sodium acetate (SA) and monopotassium phosphate (MKP) on total aerobic plate counts (APC), pH, odor, and appearance of catfish fillets during storage at 4°C were determined. Use of 0.75% and 1.0% SA lowered (P < 0.05) initial APC by 0.6 to 0.7 log units compared to the control. Microbial counts of SA-treated fillets remained lower than the control during storage, resulting in a 6-day shelf-life increase. MKP alone had no effect on APC values, but it did influence the activity of SA. The results indicate that a combination of SA and MKP could prolong the microbiological shelf life of catfish to 12 days at 4°C. Fillets treated with 1% SA alone or SA-MKP combinations had pH values and odor scores that were similar to fresh controls for up to 9 days; however, appearance scores were lower after 3 days, probably due to a brownish and watery appearance. MKP alone is not recommended for shelf-life extension of catfish fillets. Conversely, SA alone or combined with MKP is recommended to extend the microbiological shelf life of refrigerated catfish fillets.
Empirical Modeling of Control Valve Layer with Application to Model Predictive Control-Based Stiction Compensation*

Abstract: In this work, we develop an empirical modeling procedure for feedback loops comprised of sticky valves and linear controllers for the valves and incorporate the models in a model predictive control (MPC)-based stiction compensation strategy. The empirical models are developed from data on the measured values of the valve outlet flowrates and the set-points for these flowrates. They utilize standard empirical model structures but are defined in a piecewise fashion, with different branches identified for set-point changes that correspond to sticking of the valve and to sliding of the valve, and modifications to account for the effect of the linear controller on the response of the valve outlet flowrate to a set-point change. Through a chemical process example, it is shown that the use of the empirical models in the MPC-based stiction compensation strategy can decrease the computation time of the method without significantly jeopardizing the constraint satisfaction of the closed-loop process, but preventing the need for a valve layer model with parameters and/or details about the valve that are difficult to obtain.
Association of Non-Healing Wounds, Pain and Neurochemical Alterations In Sickle Cell Disease

Abstract Abstract 842 The mechanisms underlying non-healing leg ulcers in sickle cell disease (SCD) remain unknown and their treatment is difficult. We hypothesized that leg ulcers in SCD cause injury to nerve fibers leading to neurogenic inflammation, and peripheral and central sensitization resulting in chronic pain and impairment of wound healing. We examined our hypotheses by creating 4 mm punch biopsies on the lower thigh of the left leg (LL) of 12 wk old BERK and hemizygous BERK (hBERK) mice expressing sickle hemoglobin (HbS). Since BERK did not survive wounding, hBERK and control HbA-BERK, expressing normal human HbA and wild type C57/BL6, were used. hBERK appeared to be a suitable model for this study because we found that >5 mo old BERK and hBERK show deep tissue and cutaneous hyperalgesia similar to pain in human SCD (Blood 116:456-65, 2010). Wounds were treated with topical morphine (3 mg/g Eucerin base cream) or with Eucerin base cream twice a day. Behavioral measures of hyperalgesia were assessed by paw withdrawal frequency (PWF) per 10 applications of a 1.0 g von Frey monofilament and paw withdrawal latency (PWL) in response to a radiant heat stimulus, applied to the plantar surface of the hind paw of wounded left leg and unwounded right leg. No hyperalgesia was observed in 12 wk old hBERK (baseline), but wounding led to a sharp increase in PWF and decrease in PWL, in LL for 24h, suggestive of wound-induced pain. Topical application of morphine significantly decreased mechanical and thermal hyperalgesia after 1h and 24h as compared to the base cream treated wound (p Disclosures: No relevant conflicts of interest to declare.
The Impact of Bariatric Surgery on Type 2 Diabetes Mellitus and the Management of Hypoglycemic Events.

Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus(T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide and duration of the disease), HbA1C, fasting blood glucose, incretins [Glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. Restrictive-malabsorptive procedures are most effective in treating T2DM patients based on changes induced in appetite through regulation of gastro-intestinal hormones, with decreased hunger and increased satiation. We propose a review of bariatric surgery influence on T2DM and post-intervention hypoglycemic events. An extensive literature search was conducted on PubMed and Google Scholar using key words such as gastric bypass, T2DM, bariatric surgery, GLP-1, GIP, and post bariatric hypoglycemia. Conclusion: Post bariatric surgery hypoglycemia (PBH) is a serious complication especially when patients develop life-threatening neuroglycopenia with loss of consciousness and seizure. The avoidance of this adverse event may be achieved by strict dietary modification including a restriction on carbohydrates as well as foods with high glycemic index. Further research will provide more information on post bariatric surgery hyperinsulinemic hypoglycemia pathophysiology and management.
Gradual loading ameliorates maladaptation in computational simulations of vein graft growth and remodelling

Vein graft failure is a prevalent problem in vascular surgeries, including bypass grafting and arteriovenous fistula procedures in which veins are subjected to severe changes in pressure and flow. Animal and clinical studies provide significant insight, but understanding the complex underlying coupled mechanisms can be advanced using computational models. Towards this end, we propose a new model of venous growth and remodelling (G&R) based on a constrained mixture theory. First, we identify constitutive relations and parameters that enable venous adaptations to moderate perturbations in haemodynamics. We then fix these relations and parameters, and subject the vein to a range of combined loads (pressure and flow), from moderate to severe, and identify plausible mechanisms of adaptation versus maladaptation. We also explore the beneficial effects of gradual increases in load on adaptation. A gradual change in flow over 3 days plus an initial step change in pressure results in fewer maladaptations compared with step changes in both flow and pressure, or even a gradual change in pressure and flow over 3 days. A gradual change in flow and pressure over 8 days also enabled a successful venous adaptation for loads as severe as the arterial loads. Optimization is used to accelerate parameter estimation and the proposed framework is general enough to provide a good starting point for parameter estimations in G&R simulations.
An Inexpensive Discrimination Apparatus for Classroom Use with Pigeons

An apparatus for classroom use with pigeons is presented. It is similar in function to the Wisconsin General Test Apparatus.
The effect of substitutional impurity atoms on the diffusivity of an interstitial species

Abstract A model has been developed to treat the problem of the effect of substitutional solute elements on the diffusion of an interstitial species. The calculation applies only to cases where the substitutional solute creates “antitrapping” sites, whose energies are higher than the “normal” interstitial sites in the defect-free solvent lattice. The model predicts that, for sufficiently “high” antitrapping sites, there will be substantially no effect of composition or even solute atom type on the mobility of the interstitial species even up to about 20 atm% of substitutional solute. It is also possible for a given substitutional solute to act both as an accelerator or retarder with respect to the diffusivity of the interstitial species, depending upon temperature.
Nutrition: joint responsibility of agriculture and medicine.

The need for good nutrition is given “lip service” by almost every lay or professional person but the ultimate responsibihty for adequate nutrition and its role in maintaining human health can be said to rest squarely on the sister disciplines of agriculture and medicine.
Detecting the sub-states of grating superhydrophobic surfaces with naked eyes

We propose a convenient method to detect the detailed wetting states of grating-type superhydrophobic (SHPo) surfaces under water. Although the silvery plastron makes the nonwetted state easily discernable from the wetted, which appears black, various sub-states of the nonwetted state have so far been indistinguishable without special techniques such as confocal microscopy. For certain applications, however, different sub-states within the nonwetted state may have dramatically different effects. Applied for drag reduction experiments, here we develop an observation strategy that reveals the sub-states of plastron on grating SHPo surface to naked eyes for the first time. The results are confirmed by visualizing the liquid-air interfaces on the submerged surface with optical microscope.
What Is the Institutional Duty of Trauma Systems to Respond to Gun Violence

In the past, trauma centers have almost exclusively focused on caring for patients who suffer from physical trauma resulting from violence. However, as clinicians' perspectives on violence shift, violence prevention and intervention have been increasingly recognized as integral aspects of trauma care. Hospital-based violence intervention programs are an emerging strategy for ending the cycle of violence by focusing efforts in the trauma center context. These programs, with their multipronged, community-based approach, have shown great potential in reducing trauma recidivism by leveraging the acute experience of violence as an opportunity to introduce services and assess risk of re-injury. In this article, we explore the evolving role of trauma centers and consider their institutional duty to address violence broadly, including prevention.
Do health promotion messages integrate unintended pregnancy and STI prevention? A content analysis of online information for adolescents and young adults.

Abstract Objective Recently there have been calls to strengthen integration of unintended pregnancy and sexually transmitted infection (STI) prevention messages, spurred by increasing use of long-acting reversible contraception. To assess the extent to which public health/clinical messages about unintended pregnancy prevention also address STI prevention, we conducted a content analysis of web-based health promotion information for young people. Study Design Websites identified through a systematic Google search were eligible for inclusion if they were operated by a United States-based organization with a mission related to public health/clinical services and the URL included: 1) original content; 2) about sexual and reproductive health; 3) explicitly for adolescents and/or young adults. Using defined protocols, URLs were screened and content was selected and analyzed thematically. Results Many of the 32 eligible websites presented information about pregnancy and STI prevention separately. Concurrent discussion of the two topics was often limited to statements about (1) strategies that can prevent both outcomes (abstinence, condoms only, condoms plus moderately or highly effective contraceptive methods) and (2) contraceptive methods that confer no STI protection. We also identified framing of condom use with moderately or highly effective contraceptive methods for back-up pregnancy prevention but not STI prevention. STI prevention methods in addition to condoms, such as STI/HIV testing, vaccination, or pre-exposure or post-exposure prophylaxis, were typically not addressed with pregnancy prevention information. Conclusions There may be missed opportunities for promoting STI prevention online in the context of increasing awareness of and access to a full range of contraceptive methods. Implications Strengthening messages that integrate pregnancy and STI prevention may include: describing STI prevention strategies when noting that birth control methods do not prevent STIs; promoting a full complement of STI prevention strategies; and always connecting condom use to STI prevention, even when promoting condoms for back-up contraception.
Imaging features of phosphaturic mesenchymal tumors.

To examine the CT and MR imaging features of phosphaturic mesenchymal tumors (PMTs). With IRB approval, our institutional radiology/pathology database was reviewed for pathologically-proven PMTs. CT and MRI examinations were reviewed in consensus noting several imaging features, and if available, comparative molecular imaging tests were analyzed. We identified 39 patients (21 male, 18 females) with 40 PMTs [mean age, 52.9 ± 14.9 years (range, 14–78)], including 20 bone and 20 soft tissue lesions. Mean maximal lesion diameter was 3.4 ± 2.0 cm (range, 1.1–9.8). 12/18 primary bone lesions (66.6%) were osteolytic and 15/20 (75.0%) had a narrow zone of transition. Internal matrix was present in 18/32 (56.3%) lesions. PMTs were most commonly T1 isointense (31/37, 83.8%), T2 hyperintense (14/36, 38.9%), and solidly enhancing (21/30, 70.0%). The majority (32/36, 88.9%) contained areas of dark T2 signal. 8/9 PMTs were positive by 99mTc-sestamibi scintigraphy, 2/4 by 111In-pentetreotide scintigraphy, 2/2 by 68Ga-DOTATATE PET/CT and 11/13 by 18F-FDG PET/CT. On FDG PET/CT, the mean SUVmax was 4.1 ± 2.5 (range, 1.5–10.8). Osseous PMTs are commonly osteolytic with a narrow zone of transition. Both bone and soft tissue PMTs often contain matrix and areas of dark T2 signal on MRI, independent of the presence of matrix. However, PMTs may mimic other bone and soft tissue neoplasms, including fibrous dysplasia, tenosynovial giant cell tumor, and even atypical lipomatous tumor. As such, clinical presentation and laboratory correlation are critical to PMT recognition and accurate diagnosis.
Periodic and coordinated gene expression between a diazotroph and its diatom host.

In the surface ocean, light fuels photosynthetic carbon fixation of phytoplankton, playing a critical role in ecosystem processes including carbon export to the deep sea. In oligotrophic oceans, diatom–diazotroph associations (DDAs) play a keystone role in ecosystem function because diazotrophs can provide otherwise scarce biologically available nitrogen to the diatom host, fueling growth and subsequent carbon sequestration. Despite their importance, relatively little is known about the nature of these associations in situ. Here we used metatranscriptomic sequencing of surface samples from the North Pacific Subtropical Gyre (NPSG) to reconstruct patterns of gene expression for the diazotrophic symbiont Richelia and we examined how these patterns were integrated with those of the diatom host over day–night transitions. Richelia exhibited significant diel signals for genes related to photosynthesis, N2 fixation, and resource acquisition, among other processes. N2 fixation genes were significantly co-expressed with host nitrogen uptake and metabolism, as well as potential genes involved in carbon transport, which may underpin the exchange of nitrogen and carbon within this association. Patterns of expression suggested cell division was integrated between the host and symbiont across the diel cycle. Collectively these data suggest that symbiont–host physiological ecology is strongly interconnected in the NPSG.
Priority Queues

Customers of different priorities are arriving at a counter in accordance with a Poisson process. The customers are served by a single server in order of priority and for each priority in order of arrival. Two cases are considered: i service with privileged interruptions and ii service without interruption. It is supposed that the service times are mutually independent random variables having a prescribed distribution for each priority and independent of the arrival times. In both cases i and ii a simple method is given for finding the Laplace-Stieltjes transform and the moments of the stationary distribution of the waiting time for each priority level.
Male Sexual Dysfunction

Life can be defined as an autonomous self-replicating system that evolves by natural selection. The penile erection is a requisite for the propagation of the human species. One could say that when one loses the ability to attain an erection, one loses life.
Pervasive Charge Solvation Permeates Native-like Protein Ions and Dramatically Influences Top-down Sequencing Data.

Post-translational modifications create a diverse mixture of proteoforms, leading to substantial challenges in linking proteomic information to disease. Top-down sequencing of intact proteins and m...