cssi/SciSciGPT-SciSciNet huggingface dataset:
Anti-tumor effect of a novel PI3-kinase inhibitor, SF1126, in 12?V-Ha-Ras transgenic mouse glioma model

Background: Growth factor mediated activation of RAS-MAP-kinase and PI3-kinase-AKT pathways are critical for the pathogenesis of glioblastoma. The attenuation of PI3-kinase/AKT signaling will be effective in regulating the tumorigenic phenotypes of the glioma cells. Methods: Glioma cells derived from the brain of the 12 V-Ha-Ras transgenic mice were used to study the effect of PI-3 kinase inhibitor SF1126 on activation of AKT and ERK signaling, proliferation, vitronectin mediated migration and changes in the distribution of cortical actin on vitronectin in the glioma cells in vitro. The anti-tumor effects of SF1126 were also tested in vivo using pre-established tumors (subcutaneous injection of the glioma cells from 12 V-Ha-Ras transgenic mice) in a mouse xenograft model. Results: Our results demonstrate that treatment of LacZ+, GFAP + and PCNA + 12 V-Ras Tg transformed astrocytes with SF1126 and LY294002 blocked the activation of AKT as well as EGF-induced phospho-ERK. Most notably, treatment of SF1126 blocked integrin-dependent migration in transwell and scratch assays and caused a significant change in the organization and distribution of cortical actin on vitronectin in the glioma cells. Moreover, SF1126 treatment inhibited in vitro proliferation of these cells and in vivo growth of pre-established subcutaneous tumors in a xenograft model. Conclusion: The present study validate the potent anti-proliferative and anti-migratory activity of SF1126, in a V 12 Ras oncogene driven glioma model and suggest that this effect is mediated potentially through a combined
Nano/Microporous Materials: Mesoporous and Surface-Functionalized Mesoporous Carbon

Mesoporous carbon materials, a category of porous carbons with pore size between 2 and 50 nm, have attracted considerable attention owing to their wide applications. There are many conventional methods available for the preparation of mesoporous carbons. Generally, the resulting mesoporous carbon materials have a broad pore size distribution. Carbon materials with uniform pore size can be prepared using porous silica gels or colloidal silica nanoparticles as hard templates. Periodically ordered mesoporous carbons are a recent addition to this category. Ordered mesoporous carbons can be made by a hard template method using ordered mesoporous silicas with three-dimensionally connected pore structures (e.g., SBA-15) as the templates. Self-assembly of thermal decomposable block copolymers with thermosetting resol or novalac resin into mesostructured nanocomposites provides an alternative approach for the synthesis of ordered mesoporous carbons. The carbon materials obtained exhibit high Brunauer–Emett–Teller (BET) surface areas, controllable pore diameters with narrow pore size distribution, and large pore volumes. Efforts aimed toward surface modification of mesoporous carbons that integrate unique mesoporosity with other functionalities have led to many interesting materials and some promising results for applications. With the development of mesoporous and surface-functionalized mesoporous carbon materials, numerous applications are awaiting the exploration of materials research scientists. Herein we summarize the recent progress in the synthesis and surface modification of mesoporous carbons, mainly on the carbon materials with uniform pore size and/or ordered structures. Keywords: mesoporous carbons; ordered structures; synthesis; functionalization; hard template; soft template
Molecular-Imaging Probe 2-(1-{6-[(2-Fluoroethyl)(Methyl) Amino]-2-Naphthyl}Ethylidene) Malononitrile Labels Prion Plaques In Vitro

The study aimed to evaluate the fluorescent molecular-imaging probe 2-(1-{6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) for its ability to selectively and reproducibly label prion plaques in fixed, paraffin-embedded cerebellar sections from patients of confirmed Gerstmann-Straussler-Scheinker disease, sporadic Creutzfeldt-Jacob disease (CJD) with kuru plaques, and variant CJD (vCJD). FDDNP is a highly hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent substance, whose radiofluorinated analog [ 18 F]FDDNP has recently been successfully used to label senile plaques and neurofibrillary tangles in the living brain of Alzheimer9s disease patients with positron emission tomography. Our results show that FDDNP reliably identifies all prion plaques, including small cluster-plaques in vCJD. This finding may open new in vivo diagnostic possibilities for vCJD.
Protein Destabilization as a Common Factor in Diverse Inherited Disorders

Protein destabilization by amino acid substitutions is proposed to play a prominent role in widespread inherited human disorders, not just those known to involve protein misfolding and aggregation. To test this hypothesis, we computationally evaluate the effects on protein stability of all possible amino acid substitutions in 20 disease-associated proteins with multiple identified pathogenic missense mutations. For 18 of the 20 proteins studied, substitutions at known positions of pathogenic mutations are significantly more likely to destabilize the native protein fold (as indicated by more positive values of ∆∆G). Thus, positions identified as sites of disease-associated mutations, as opposed to non-disease-associated sites, are predicted to be more vulnerable to protein destabilization upon amino acid substitution. This finding supports the notion that destabilization of native protein structure underlies the pathogenicity of broad set of missense mutations, even in cases where reduced protein stability and/or aggregation are not characteristic of the disease state.
A Comparison of Physiological and Morphological Properties of Deciduous and Wintergreen Ferns in Southeastern Pennsylvania

Physiological and morphological properties of a deciduous, perennial fern (Onoclea sensibilis) and three wintergreen, perennial ferns (Polystichum acrostichoides, Polypodium virginianum, and Dryopteris intermedia) were examined using leaf fluorescence, chlorophyll a:b ratios, total chlorophyll content, water potential, and leaf edge to surface area ratios. Onoclea sensibilis differed significantly from the wintergreen ferns in morphology and physiology for almost every parameter measured. Interspecific differences were also observed within the wintergreen group. Dryopteris intermedia differed most within the wintergreen group and showed more similarity in physiology to O. sensibilis. Dryopteris intermedia was found occupying the same high-light, higher soil moisture habitat as O. sensibilis, which may indicate that inherent leaf morphology, physiological characteristics, and a wintergreen or perennial life cycle, play im- portant roles in determining habitat preference.
HABITAT USE OF A FRAGMENTED LANDSCAPE BY FEMALES IN A SMALL POPULATION OF DESERT MULE DEER

Abstract We examined use of vegetation associations by female desert mule deer (Odocoileus hemionus eremicus) and proximity to human developments to determine whether human activity and developments influenced habitat use. We hypothesized that use of habitats in disturbed areas would be reduced with increasing human activity. We radiocollared 14 deer and monitored their distribution from March 1996 to March 1997. Female desert mule deer generally used the mesquite-burroweed (Prosopis velutina-Isocoma tenuisecta) vegetation association more than it was available and the palo verde (Cercidium)-mixed cacti association less than it was available. Female deer were generally closer to housing, roads, permanent water, and the Central Arizona Project than random points. Our prediction that desert mule deer would avoid human activity was not supported.
Inhaled nitric oxide does not alter endotoxin-induced nitric oxide synthase activity during rat lung perfusion

Nitric oxide (NO) has been demonstrated to decrease its own synthesis in tissue preparations. We tested the hypothesis that endogenous NO synthesis induced by lipopolysaccharides (LPS) would be decreased by exogenous NO during isolated lung perfusion. Rats were pretreated with either saline or LPS 48 h before lung harvest. Endogenous NO synthase activity was measured as conversion of L-[14C]-arginine to L-[14C]citrulline during 90 min of perfusion. NO (100 ppm) was added to the ventilating gas during perfusion of lungs from one group of control or LPS-treated rats. A second group of control or LPS-treated rats was exposed chronically to 100 ppm NO for the 48 h before lung harvest, in addition to receiving 100 ppm NO added to the ventilating gas during lung perfusion. We conclude that conversion of L-[14C]arginine to L-[14C]citrulline was minimal in control lungs and increased in response to LPS pretreatment. NO added to the ventilating gas for the 90 min of ex vivo perfusion did not alter the rate of L-[14C]citrulline production. In vivo exposure to 100 ppm NO for 48 h did not alter the induction of inducible NO synthase activity as measured during ex vivo lung perfusion. This indicates that inhaled NO does not exert negative-feedback inhibition on inducible NO synthase in the ex vivo rat lung.
Enterocyte alpha 2-adrenergic receptors: yohimbine and p-aminoclonidine binding relative to ion transport

We previously reported that alpha 2-adrenergic agonists enhance absorption and inhibit secretion of electrolytes in small intestine. The present study was undertaken to characterize and localize the relevant receptors. Plasma membranes derived from isolated rabbit ileal epithelial cells were incubated with either [3H]yohimbine (Yo), an alpha 2-antagonist, or p-[3H]aminoclonidine (PAC), an alpha 2-agonist. Scatchard analysis of [3H]Yo binding suggests a single receptor. Competitive displacement of Yo from this receptor by other ligands had a potency order characteristic for alpha 2-receptors in other tissue systems. A Scatchard plot of [3H]PAC binding was curvilinear and best fit by assuming two independent site. Competitive displacement of [3H]PAC by PAC in the presence of 140 mM Na+ or 0.1 mM GTP increased the IC50 for PAC binding from 10 nM to 100 and 105 nM, respectively, and the Hill coefficient from 0.7 to 1.2 and 1.0, respectively. The ED50 for PAC effect on short-circuit current (200 nM) does not differ significantly from these values. We conclude that alpha 2-receptors are present on ileal enterocytes and that these receptors mediate enterocyte fluid and electrolyte transport function.
Complementary and Alternative Medicine Use by Normal Weight, Overweight, and Obese Patients with Arthritis or Other Musculoskeletal Diseases.

Abstract Objectives: The Centers for Disease Control and Prevention estimates that 50 million Americans have been diagnosed with arthritis and other musculoskeletal diseases. The purpose of the current study was to (1) estimate the prevalence of overall complementary and alternative medicine (CAM) use and (2) examine the role of body mass index (BMI) on CAM use among normal weight, overweight, and obese persons with chronic lower back pain, chronic neck pain, chronic/rheumatoid arthritis, or musculoskeletal diseases, while controlling for other covariates. Design: Cross-sectional design using secondary data for 9724 adults from the 2007 National Health Interview Survey. Data were weighted and analyzed by using Stata 12 for Windows (Stata Corp., College Station, TX). Descriptive, bivariate, and multivariate logistic regression statistics were computed. Participants: The participants were randomly surveyed from U.S. households. Outcome measures: CAM use was measured as reported use of any modality within th...
Recent Advances in Application of Pharmacogenomics for Biotherapeutics

Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of their relatively high specificity, low off-target effects, and biocompatible metabolism, in addition to legal and logistic advantages. However, their clinical utility is limited, among other things, by their high immunogenic potential and/or variable therapeutic efficacy in different patient populations. Both of these issues, also commonly experienced with small molecule drugs, have been addressed effectively in a number of cases by the successful application of pharmacogenomic tools and approaches. In this introductory article of the special issue, we review the current state of application of pharmacogenomics to BTs and offer suggestions for further expansion of the field.
Amides as ligands—IV: Spectrochemical studies of ε-thiocaprolactam cobalt (II) complexes

Abstract The syntheses and properties of the crystalline compounds, [CoL 2 X 2 ] (L = e-thiocaprolactam) (X = Cl, Br, I) and [CoL 4 ](ClO 4 ) 2 ; are reported. The spectral parameters Dq , B ′ and β are calculated for the sulphur-co-ordinated complexes. The data indicate tetrahedral stereochemistry for these complexes. e-Thiocaprolactam is assigned a position relative to the other sulphur-containing donors in the spectrochemical series. Infra-red spectra indicate that Co ← S bond in these complexes appears at 390 cm −1 .
SERF: optimization of socially sourced images using psychovisual enhancements

Online communities and social networks are the most popular sites on the Internet, and have exploded with multimedia content in the last decade. Most web designers recognize that site images can be saved with lower fidelity to reduce bandwidth consumption and increase capacity, though many are reluctant to do so for aesthetic concerns. However, there are many images that site designers have little direct control over---socially sourced images. Many social networks automatically reduce the fidelity of uploaded images in order to conserve bandwidth. Social networks also contain a vast archive of images with popularity indicators, such as likes and shares, which recent work has correlated with psychovisual features within the images. In this paper, we investigate the trade-off between fidelity reduction and selected psychovisual enhancements. We demonstrate that even simple enhancements can be used to enable more aggressive optimization of socially sourced content, which has implications for static content delivery networks and image servers. Through user testing on real images, we validate the efficacy of our proposed approach.
Microfluidic systems for cell pairing and fusion

Cell fusion has become a routine laboratory technique for generating hybrids with diverse genetic and epigenetic properties, and has been used for many different applications. Here, we describe a microfluidics based cell pairing and fusion method that affords controllable formation of cell pairs and high efficiency fusion. The microfluidic device uses passive hydrodynamics and multistep cell loading procedure to immobilize and pair thousands of cells in a dense array of weir-based traps. Once paired, cells can be fused either using chemical or electrical fusion protocols, and provide twofold to tenfold improvement in fusion yields in comparison to commercial systems. The hybrids can be harvested from the device for culture and further studies.
Polarographic reduction of aldehydes and ketones: Part XXVIII. 1,2-cyclohexanedione

Abstract 1,2-Cyclohexanedione exists in aqueous solutions partly as a monoenol. The protonated form of the monoenol (I) is reduced polarographically at H0 = −2.5 to pH 7 in the wave i3, the unprotonated form (IIa) at pH > 6 in the wave i4. Wave i3 at pH 7 at potentials almost 1.0 V more positive than those of the monoenol form. The diketo form (IIb) is strongly hydrated. Waves i1 and i2 are small reaching maximum height at pH about 12 corresponding to 13% of the total current. Their height is limited by the rate of dehydration. The pH dependence of height of waves i1 and i2 is attributed to the base catalysis of dehydration.
Cyber Collateral Damage

Abstract Unintended damage to non-military targets is typically straightforward to characterize and weigh against anticipated benefits because of well-established definitions, technical assessments, and legal conventions. In a kinetic military context, collateral damage occurs when a hostile action causes physical or property damage to a civilian target. However, collateral effects caused by cyber operations lack formal recognition when they are limited to electronic data, information technology and computing systems, whether caused by conventional military operations, or the result of law enforcement, or private sector operations. Even though there may be tangible consequences stemming from the loss or destruction of data, conventional norms are ill equipped to formally recognize them. Uniquely in the cybersecurity context, tactical operations may have broad systemic “collateral” effects on other important policy priorities that must be accounted for. In short, we lack a clear conceptual vocabulary for cyber operations for both the military operations, as well as for non-military operations, where many cyber activities occur. This research examines this discontinuity by first examining conventional military definitions of “cyber operations,” “collateral damage” and international norms governing operations conducted by lawful participants against military targets. It then examines a number of important similarities and differences between conventional and cyber operations as they relate to damage and injury. Finally, it introduces other contexts for considering collateral damage in the cyber realm, and the way in which other legal and strategic regimes have handled the concept, providing specific examples of these outcomes and guidance for how to think about collateral damage in a range of contexts.
The Polycomb Group Transcriptional Repressor Bmi-1 Is Constitutively Expressed in Multiple Myeloma (MM) Cells and Modulates Proliferation through a Mechanism Independent of the Ink4a/ARF Locus.

The polycomb group protein Bmi-1 is required for self-renewal of adult hematopoietic stem cells by inhibiting cell senescence and apoptosis through repression of p16 INK4a and p14/p19 ARF expression. Based on gene expression profile studies showing absence of Bmi-1 expression in normal plasma cells versus upregulation in all MM cell lines and primary patient MM cells, we evaluated its role in MM pathobiology. Bmi-1 expression in MM cell lines is constitutive, and is not modulated by IL-6 and IGF-1. Immunoprecipitation and immunoblotting studies confirmed both Bmi-1 overexpression and nuclear localization. Bmi-1 was found to be tyrosine- and serine-phosphorylated. We next inhibited Bmi-1 expression in MM cell lines (ARP and MM.1S) by stably transfecting a PU6 vector expressing siRNA targeting Bmi-1. Following G418 selection, cell growth, as measured by H 3 thymidine incorporation and MTT assay, was stimulated 1.4 fold in MM.1S and 2 fold in ARP cells compared to control cells transfected with a PU6 vector. Gene expression profiling showed: up-regulation of IL-6 and IGF-1 receptors, as well as Gab-1, which plays a critical role in MM cell proliferation and survival induced by IL-6; Phospholipase D1 and proteinase 3 which potentiate cell proliferation by repression and cleavage of p21 cip1/waf1 ; stem cell growth factor, HOXA9, which modulate bone marrow stem cell survival and proliferation. In contrast, p21 cip1/waf1 and GADD45a, GADD45b which moderate cell growth arrest were down regulated. However, no change in expression of either p16 INK4a or p14/p19 ARF was detected by microarray and immunoblotting. We therefore conclude that Bmi-1 is abnormally expressed in MM cells and contrary to its classic action, modulates MM cell growth and survival by modulating cytokine signaling rather than INK4a/ARF. Our studies further suggest that Bmi-1 represents a promising target for novel MM therapeutics.
Investigations of skeletal layer microstructure in the context of remote sensing of oil in sea ice

ABSTRACT (2017-159) The Arctic Oil Spill Response Technology – Joint Industry Program (JIP) funded a controlled basin experiment in November 2014 to assess the relative capabilities of a variety of...
Pain, Psychological Comorbidities, Disability, and Impaired Qualify of Life in Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic, painful dermatologic disease characterized by recurrent inflammatory nodules and abscesses of intertriginous areas such as the axilla and groin. People with HS suffer from greater pain and associated psychological comorbidities, including depression, anxiety, disability, and impairments in quality of life (QoL), compared to those with other dermatologic conditions. Our review focuses on the occurrence of pain and these relationships. The existing literature indicates that acute and chronic pain, depression, anxiety, and disability all contribute to poor quality of life in individuals with HS. Despite the central role of pain and distress in the presentation of HS, few studies have empirically evaluated the impact of pain and gaps remain in the existing psychosocial literature. There are no formal guidelines for treating HS-specific pain or psychological comorbidities. The results of this review show a clear and pressing need to develop treatment recommendations and effective interventions for addressing acute and chronic pain, psychological comorbidities, disability, and impaired quality of life among people with HS. This review outlines a multidisciplinary approach to treating and managing pain and psychological comorbidities.
Classification of Single-Cell Gene Expression Trajectories from Incomplete and Noisy Data

This paper studies classification of gene-expression trajectories coming from two classes, healthy and mutated (cancerous) using Boolean networks with perturbation (BNps) to model the dynamics of each class at the state level. Each class has its own BNp, which is partially known based on gene pathways. We employ a Gaussian model at the observation level to show the expression values of the genes given the hidden binary states at each time point. We use expectation maximization (EM) to learn the BNps and the unknown model parameters, derive closed-form updates for the parameters, and propose a learning algorithm. After learning, a plug-in Bayes classifier is used to classify unlabeled trajectories, which can have missing data. Measuring gene expressions at different times yields trajectories only when measurements come from a single cell. In multiple-cell scenarios, the expression values are averages over many cells with possibly different states. Via the central-limit theorem, we propose another model for expression data in multiple-cell scenarios. Simulations demonstrate that single-cell trajectory data can outperform multiple-cell average expression data relative to classification error, especially in high-noise situations. We also consider data generated via a mammalian cell-cycle network, both the wild-type and with a common mutation affecting p27.
Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis.

Background and Aims: Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma (CCA) and gallbladder carcinoma (GBCa). Surveillance for GBCa is recommended, but the clinical utility of surveillance for other hepatobiliary cancers (HBCa) in PSC, namely CCA and hepatocellular carcinoma (HCC), is unclear. We aimed to determine whether surveillance is associated with better survival after diagnosis of HBCa in patients with PSC. Methods: Medical records of PSC patients seen at Mayo Clinic Rochester from 1995-2015 were reviewed. Patients were included if they had ≥1 year of follow-up and developed HBCa. Patients were categorized according to their surveillance status (abdominal imaging and carbohydrate antigen 19-9 and alpha-fetoprotein). The primary endpoints were HBCa recurrence, HBCa-related death, and all-cause mortality. Overall survival was assessed by the Kaplan-Meier survival method. HBCa-related survival was assessed using the competing risks regression model. Tests of significance were 2-tailed, and a p-value < 0.05 was considered statistically significant. Results: From 1995-2015, a total of 79 of 830 PSC patients were diagnosed with HBCa. Cumulative follow-up was 712 and 283 person-years pre- and post-HBCa diagnosis, respectively. Seventy-eight percent (54/79) developed CCA, 21% (17/79) HCC, 6% (5/79) GBCa, 3% (2/79) both CCA and HCC, and 1% (1/79) both HCC and GBCa. Fifty-one percent (40/79) were under surveillance and 49% (39/79) were not. Patients in the surveillance group had significantly higher 5-year overall survival (68% vs. 20%, respectively; p<0.001) and significantly lower 5-year probability of experiencing an HBCa-related adverse event (32% versus 75%, respectively; p<0.001), compared with the no-surveillance group. Conclusion: This study demonstrates that surveillance for HBCa significantly improves outcomes, including survival, in patients with PSC. This article is protected by copyright. All rights reserved.
Gender morality and emotion work in Taiwanese immigrant in-law relations

AbstractThis study examines major social, economic, and cultural factors that sustain in-law inequality in Taiwanese transnational families. Data are based on life-history interviews with 16 Taiwanese immigrant women and ethnographic observations in a Midwest urban area. Findings suggest that middle-class immigrants’ abilities to host in-laws for lengthy periods and parents-in-law’s financial support for immigrant couples lead to the living arrangement of three-generation households in many immigrant families. Daughters-in-law in these households experience enormous stress because their mothers-in-law demand obedience. Traditional gender norms become moralized when the women’s husbands, mothers, and fellow immigrants reinforce Confucian cultural values of filial piety and respect for the elderly. Considering the importance of securing a stable family and children’s well-being, the women hesitate to challenge the power imbalance in their in-law relations. In a single ethnic household and a private domestic...
Spectrum of activity testing for therapeutics against all four dengue virus serotypes in AG129 mouse models: Proof-of-concept studies with the adenosine nucleoside inhibitor NITD-008.

Abstract Dengue is a mosquito-borne disease of global public health importance caused by four genetically and serologically related viruses (DENV-1 to DENV-4). Efforts to develop effective vaccines and therapeutics for dengue have been slowed by the paucity of preclinical models that mimic human disease. DENV-2 models in interferon receptor deficient AG129 mice were an important advance but only allowed testing against a single DENV serotype. We have developed complementary AG129 mouse models of severe disseminated dengue infection using strains of the other three DENV serotypes. Here we used the adenosine nucleoside inhibitor NITD-008 to show that these models provide the ability to perform comparative preclinical efficacy testing of candidate antivirals in vivo against the full-spectrum of DENV serotypes. Although NITD-008 was effective in modulating disease caused by all DENV serotypes, the variability in protection among DENV serotypes was greater than expected from differences in activity in in vitro testing studies emphasizing the need to undertake spectrum of activity testing to help in prioritization of candidate compounds for further development.
Pharmacological Factors in Drug Dependence

I would like to state my bias as being that of internal medicine, pharmacology and 30 years of association with opiate type dependence in the United States. I will now attempt the impossible by trying to discuss the pharmacological factors in drug dependence in ten minutes. This is impossible because there is such a large number of different substances with markedly varying chemical structures, and markedly varying pharmacological actions that are used non-medically and frequently to a degree causing dependence. Some of the most important drugs are listed in the following Table in which substances causing specific types of dependence are grouped together regardless of chemical configuration. Because of the diversity and number of kinds of drugs of dependence, the WHO Expert Committee on Addiction Producing Drugs (1964) defined drug dependence as “a state arising from repeated administration of a drug on a periodic or continuous basis.” “The characteristics of such a state will vary with the agent involved and the characteristics must be made clear by designating the particular type of drug dependence in each specific case; for example, drug dependence of the morphine type, of the barbiturate type, of the amphetamine type, etc.” (Eddy, et al. 1965)
Understanding Cultural Policy

It is rare to find a cultural policy reference book that successfully bridges the distinct academic traditions stemming from anthropology, sociology, public administration, and political science th...
The use of the STEP assessment with infants with Congenital Heart Defects (CHD)

Date Presented 04/05/19 Primary Author and Speaker: Patty Coker-Bolt Additional Authors and Speakers: Rachel Fleming, Evie Needle, Turki Aljuhani, Dorothea Jenkins
Characterization of recirculating structures in the near field of underexpanded swirling jets

Recirculation in underexpanded supersonic jet flow with varying degrees of swirl was experimentally investigated due to its potential for enhanced flame holding in supersonic combustion engines. Recirculation caused by swirl is free of solid walls, avoiding the challenge of wall cooling due to high heat fluxes. Schlieren imaging, planar laser Mie scattering, and planar particle image velocimetry were used to observe and quantify shock cell and vortex structure, and where applicable, to map velocity in and around the recirculation zone. Case study showed that different patterns of tangential injection, pressure ratios, and nozzle sizes were more or less favorable to flow recirculation. Various metrics of recirculation and shock structure were correlated with the onset, variability, characteristic length, and characteristic time of recirculation vortex. Statistical analysis of instantaneous velocities indicated that (1) recirculation velocity and recirculation zone width had standard deviations of ~ 30% and ~ 20%, respectively (in part due to unsteady precession of the vortex around the axis of mean flow); and (2) the average velocity within the recirculation zone was seen to be insensitive to the pressure ratio (and hence, to the fully expanded Mach number). The recirculation zone width was slightly increased by doubling the pressure ratio, within the range investigated. Thus, under conditions that most favored recirculation, the net effect of (1) and (2) was the formation of a toroidal vortex structure within which the average velocity was sufficiently slowed (by a factor of 3 relative to the bulk velocity) to measurably enhance flame holding in supersonic combustor applications.
Involvement of Chromosomally Encoded Homologs of the RRNPP Protein Family in Enterococcus faecalis Biofilm Formation and Urinary Tract Infection Pathogenesis.

ABSTRACT Enterococcus faecalis is an opportunistic pathogen capable of causing infections, including endocarditis and urinary tract infections (UTI). One of the well-characterized quorum-sensing pathways in E. faecalis involves coordination of the conjugal transfer of pheromone-responsive plasmids by PrgX, a member of the RRNPP protein family. Members of this protein family in various Firmicutes have also been shown to contribute to numerous cellular processes, including sporulation, competence, conjugation, nutrient sensing, biofilm formation, and virulence. As PrgX is a plasmid-encoded RRNPP family member, we surveyed the genome of the multidrug-resistant strain V583 for additional RRNPP homologs using computational searches and refined those identified hits for predicted structural similarities to known RRNPP family members. This led us to investigate the contribution of the chromosomally encoded RRNPP homologs to biofilm processes and pathogenesis in a catheter-associated urinary tract infection (CAUTI) model. In this study, we identified five such homologs and report that 3 of the 5 homologs, EF0073, EF1599, and EF1316, affect biofilm formation as well as outcomes in the CAUTI model. IMPORTANCEEnterococcus faecalis causes health care-associated infections and displays resistance to a variety of broad-spectrum antibiotics by acquisition of resistance traits as well as the ability to form biofilms. Even though a growing number of factors related to biofilm formation have been identified, mechanisms that contribute to biofilm formation are still largely unknown. Members of the RRNPP protein family regulate a diverse set of biological reactions in low-G+C Gram-positive bacteria (Firmicutes). Here, we identify three predicted structural homologs of the RRNPP family, EF0073, EF1599, and EF1316, which affect biofilm formation and CAUTI pathogenesis.
Quantifying cytoskeletal heterogeneity via single-cell protein-complex fractionation

Abstract Multimeric cytoskeletal protein complexes, including filamentous F-actin, orchestrate normal cellular function. However, protein-complex distributions in stressed, heterogeneous cell populations remain unknown. Cell staining and proximity-based methods have limited selectivity and/or sensitivity for robust endogenous multimeric protein-complex quantification from single cells. We introduce micro-arrayed differential detergent fractionation to simultaneously detect protein complexes in 100s of individual cells. Fractionation occurs by 60s size-exclusion electrophoresis with protein complex-stabilizing buffer that minimizes depolymerization. Validating with actin-destabilizing Latrunculin A (LatA), we quantify 2.7-fold lower median F-actin complex-levels in LatA-treated single cells. Further clustering analysis of U2OS cells treated with LatA detects a subpopulation (∼11%) exhibiting downregulated F-actin, but upregulated microtubule and intermediate filament protein complexes. Thus, some cells upregulate other cytoskeletal complexes to counteract the stress of LatA treatment. We also sought to understand the effect of non-chemical stress on cellular heterogeneity of F-actin, and find heat shock dysregulates F and monomeric G-actin correlation. The assay overcomes selectivity limitations of existing methods to biochemically quantify single-cell protein complexes perturbed with diverse stimuli.
Alzheimer disease biomarker profiles in dementia with Lewy bodies: Does A plus T spell D-L-B?

The advent of biofluid and molecular imaging biomarkers to reliably detect Alzheimer disease (AD) neuropathology in vivo has led to the increasing recognition of the complexity of clinicopathologic associations in neurodegenerative disease. For example, the clinical syndrome of dementia with Lewy bodies (DLB)1 is relatively specific to identify individuals with dementia due to underlying neocortical α-synuclein “Lewy” pathology; however, the majority of patients with DLB have sufficient additional plaque and tangle pathology at autopsy for a secondary diagnosis of AD neuropathologic change associated with poor clinical outcomes.2 Moreover, at least 50% of patients with clinical AD have additional α-synuclein pathology at autopsy.2 Thus, there is a current paradigm shift to define AD and related neurodegenerative disorders in living patients on a biological basis, rather than on a syndromic one alone. This is exemplified by the recent National Institute on Aging/Alzheimer’s Association (NIA/AA) research framework3 for biomarker classification of patients based on categorical biomarker evidence for β-amyloid plaque (A), tau neurofibrillary tangles (T), and resultant neurodegeneration (N); i.e., A/T(N) classification scheme. The purpose of this approach is to provide a common nomenclature to test hypotheses on the biological underpinnings of neurodegenerative disorders and to improve therapeutic trials by creating more biologically homogenous cohorts.3 In this issue of Neurology ®, Ferreira et al.4 apply and test clinical associations of A/T biomarker profiles in a large international cohort of 417 patients with DLB from 10 centers in the European DLB Consortium and from the Mayo Clinic.
Membrane-based optomechanical accelerometry

Optomechanical accelerometers promise quantum-limited readout, high band- width, self-calibration, and radiation-pressure stabilization. We present a simple, scalable platform that enables these benefits with sub-µg sensitivity and 10 kHz bandwidth, based on a pair of vertically integrated SiN membranes.
Evaluation of bovine viral diarrhea virus (BVDV) transmission from a persistently infected goat to pregnant goats and calves

Infections with bovine viral diarrhea virus (BVDV) occur in various artiodactyls. Persistent infections occur in non-bovine species, but rarely in goats. Recently, a persistently infected (PI) goat was born following experimental infection of pregnant goats. The present study evaluated the potential of BVDV transmission from the PI goat to pregnant goats and calves.
Scattering resonances for a three-dimensional subwavelength hole

This work aims to investigate scattering resonances and the field amplification at resonant frequencies for a subwavelength hole of width $$\varepsilon $$ embedded in a sound hard slab. We apply the integral equation approach and asymptotic analysis to derive the asymptotic expansions of scattering resonances and quantitatively analyze the corresponding field amplifications. It is shown that the complex-valued scattering resonances attain imaginary parts of order $$O(\varepsilon ^2)$$ . The field enhancement inside the hole and in the far field is of order $$O({1/\varepsilon ^2})$$ at the resonant frequencies, which is much stronger the enhancement order in the two-dimensional subwavelengt hole of the same width.
Neutron radiography through a SIFaN instrument

Neutron radiography through Spectroscopic Imaging by Fast Neutrons (SIFaN) is described. The fast neutron tracking principle [1] has been extended to include neutron-induced fissions in actinide perovskites. The design and performance of a new SIFaN instrument, called SIFaN-perovskite (or SIFaN-P), are studied by a combination of MCNP and semi-analytical models. Hybrid organic-inorganic and actinide perovskites are considered and compared with gas and silicon for neutron detection and tracking. The Los Alamos LANSCE facility provides access to the initial SIFaN-P testing and demonstration.
Ophthalmology's future in the next decade: a historical and comparative perspective.

Abstract PURPOSE: To gain a historical and comparative perspective about the future of ophthalmology within the profession of medicine. METHODS: A literature search is made of disciplines other than medicine (history, sociology, philosophy, economics, and ethics) in order to assess factors responsible for survival and healthiness of a profession. The "learned" professions (medicine, law, and theology) are assessed. Other "professional" careers valued by society (sports and classical music) are reviewed. RESULTS: From the perspective of other disciplines, the future of ophthalmology is seen as vulnerable and fragile. Survival of professions, be they classically or economically defined, is linked to societal needs, a profession's unique commitment and ability to provide services to society, and the profession's maintenance of knowledge as well as skill-based services. Historical evidence has shown erosion of a profession's power consequent to capitalist influences, government influences, access of skills by less trained individuals, and elitist posturing by a profession. Comparative evidence has shown societal acceptance of an escalation of salaries for designated superstars, increasing roles and influence of managerial personnel, and trivialization of values other than economic ones. CONCLUSION: Attention to historical and comparative trends by individual ophthalmologists as well as associations representing ophthalmologists is mandatory if ophthalmology as we know it is to survive within the profession of medicine.
Load‐Sharing Models

Load sharing describes how the failure probabilities of components within a system depend on the working status of the other components. For example, if a component fails in the system, the other components may experience an increase in failure rate by inheriting an extra “load” from the failed one. Load sharing has its roots in stress-strength models for fiber bundles, but extends to many time-to-failure test environments, including software reliability and materials testing. Load-share rules characterize how the load changes after a component within the system fails, and can be estimated if unknown. Keywords: stochastic dependence; shock model; order restricted inference; nonparametric estimation
Bounded Ethicality in Negotiations

Most negotiators think of themselves as good people, and most negotiators act in ethically questionable ways at times. How can these two descriptions be reconciled? This paper follows Bazerman and Tenbrunsel (2011) in arguing that good people often engage in unethical acts without their own awareness of doing so. This paper specifically explores how negotiators may be prejudiced, favor in-groups, and overclaim in negotiation, without knowing that they are doing anything wrong.
Molecular Pathology of α-Thalassemia

The different classes of mutations found in the alpha- and beta-thalassemia syndromes are summarized in FIGURE 5. Mutations affecting almost every stage of globin gene expression have been described. The only lesion not yet characterized is one affecting enhancing sequences, although such sequences have not yet been identified in the globin gene system. The clinically important alpha-thalassemias are the deletion types, which occur with much higher frequency than the nondeletion lesions. In contrast, apart from one deletion beta-thalassemia lesion found in Pakistan, all the clinically significant beta-thalassemia lesions are not caused by gene deletion. The common beta-thalassemia lesions in the Mediterranean region and Asia are caused by defective mRNA synthesis, processing, or translation. Why deletion lesions predominate in the alpha-thalassemias and nondeletion ones in the beta-thalassemias remains an enigma.
Characterization of a newIr-GLT gene and its location in theI-region of theH-2 complex

The data presented in this paper characterize the immune responses in mice to the two related random terpolymers, poly(Glu57Lys38Tyr5) (GLT5) and poly (Glu55Lys34Tyr15) (GLT15), which are similar to the previously reported response against the terpolymer poly(Glu58Lys38Phe4) (GLO). Responsiveness is linked to theH-2d,H-2ja,H-2q andH-2r haplotypes. The observed responsiveness of the recombinant strain B10.A(5R)tentatively maps theIr-GLT gene to the right of theIB subregion, i. e., in theIC subregion which codes for lymphocyte alloantigens. If confirmed this would be the firstIr gene to be mapped in theIC subregion.
The Superior Colliculus and Visual Function

The sections in this article are: 1 Anatomy of Superior Colliculus 1.1 Methods 1.2 Intrinsic Organization 1.3 Inputs to Superior Colliculus 1.4 Outputs of Superior Colliculus 1.5 Summary 2 Physiology of Superior Colliculus: Electrical Recording Studies 2.1 Methods 2.2 Recordings from Paralyzed Animals 2.3 Recordings from Alert Animals 2.4 Summary 3 Physiology of Superior Colliculus: Stimulation Studies 3.1 Methods 3.2 Electrical Stimulation of Primate Superior Colliculus 3.3 Electrical Stimulation of Cat and Rodent Superior Colliculi 3.4 Summary 4 Physiological Studies of Inputs to Superior Colliculus 4.1 Methods 4.2 Retinal Input 4.3 Cortical Input 4.4 Subcortical Input 4.5 Summary 5 Physiological Studies of Outputs of Superior Colliculus 6 Behavioral Effects of Superior Colliculus Ablation 7 Developmental Studies of Superior Colliculus 7.1 Methods 7.2 Development of Mammalian Superior Colliculus 7.3 Effect of Surgical Interference on Retinotectal Pathway 7.4 Effect of Selective Rearing on Collicular Functions 7.5 Summary 8 Concluding Remarks
Flash photolysis absorption spectroscopy of xenon fluoride . Vibrational analysis of the B-X transition

Kinetic spectroscopy of a flash-photolyzed mixture of Xe and UF6 yielded the B-X transition (300–355 nm) of XeF in absorption. Vibrational assignments were made for 22 bands (0 ≤ v′ ≤ 12, 0 ≤ v″ ≤ 3), and were confirmed by computer modeling of the relative absorption intensities. Spectroscopic constants for XeF (B-X) are: Te = 28 813.9 ± 0.5 cm−1, ω′e = 308.23 ± 0.5 cm−1, ωeχ′e = 1.4266 ± 0.03 cm−1, ω″e = 225.06 ± 1.4 cm−1, ωeχ″e = 10.568 ± 0.4 cm−1, and ΔRe = R′e - R″e = 0.35 ± 0.02 A. A linear Birge-Sponer extrapolation yields a ground state XeF dissociation of about 1200 cm−1.
Effect of Ribavirin on Junin Virus Infection in Guinea Pigs

Junin virus (JUNV) is the aetiological agent of Argentine haemorrhagic fever. The pathogenesis of the infection is not well understood, no licensed vaccines exist and no specific antiviral therapy is available. Previous studies have demonstrated the ability of ribavirin to delay and reduce JUNV disease and virus burden in guinea pigs without preventing death. Based on available data, we performed three different studies to determine the efficacy of ribavirin against JUNV in the guinea pig model with a focus on survival. Different doses and treatment schedules of ribavirin were tested in a lethal model of JUNV infection. Our results show that prolonged treatment with high doses of ribavirin significantly reduces the mortality in guinea pigs infected with JUNV. These results may be useful in future experimental studies or clinical testing.
The Corrosion Behavior of Stainless Steels and Copper Alloys Exposed to Natural Seawater

Abstract : The corrosion behavior of stainless steels, titanium, and copper alloys exposed to flowing Pacific Ocean water was characterized using surface analytical and electrochemical techniques. Biofilm formation on stainless steels and titanium resulted in thin films of bacteria and diatoms that did not cause significant changes of the corrosion Potential (E corr) or surface properties. Rotating cylinder experiments indicated that both E. and corrosion rates for stainless steels and titanium were independent of mass transport. Four surface layers were identified on copper-containing materials: substratum metal; and inorganic chloride corrosion layer that contained alloying elements; a biofilm; and crystalline, spherical phosphate-rich deposits. All copper surfaces were colonized by bacteria independent of alloy composition. The complexity of the impedance spectra for copper-containing materials was attributed to formation of surface layers and contributions of charge transfer and mass transport controlled reactions mediated by the layers. Both anodic and cathodic reactions for copper-based materials were affected by mass transport. Biofouling, Corrosion, Biodeterioration, Electrochemistry.
Neural network detection of antiepileptic drugs from a single EEG trace

Three systems-a Bayes quadratic classifier (BQ), a self-organizing polynomial network (PN), and a backpropagation neural network (NN)-were created for subject-independent classification into either no-drug or antiepileptic drug categories from a single 2.1-second EEG trace at the Pz/A1+A2 channel. Spectral features were derived from the raw signals, and then preprocessed using singular value decomposition prior to their classification. Recognition rates on an independent data set were 63.5%, 60.4%, and 74.0% for the BQ, PN, and NN respectively. >
Fault tree analysis-using spreadsheet

Design considerations are given for fault-tree analysis (FTA) using spreadsheet software. The objective is to demonstrate, by means of examples, how microcomputer spreadsheet software can be used as an alternative to the mainframe commercial FTA package for designing the fault tree and performing tedious computations. Experiences in using this approach for fault tree analysis are described, and the sensitivity analysis of fault-tree research is addressed. >