cssi/SciSciGPT-SciSciNet huggingface dataset:
P418 Correlates of immune protection in the rabbit model of syphilis vaccination

Background An effective syphilis vaccine will be integral to efforts to eradicate this disease. Promising vaccine candidates are surface antigens of the syphilis spirochete, Treponema pallidum subsp. pallidum (T. pallidum). These antigens can be targeted by vaccination-induced opsonic antibodies and mediate pathogen immune clearance. Defining correlates of protection will aid in the identification of the best vaccine candidates. Here, we sought to investigate whether immunization with variants of the T. pallidum Repeat C (TprC) protein and the conserved NH2-terminus of the TprK induced protection and whether splenocyte proliferation and IFN-γ production correlated with protection. Methods Rabbits were immunized with either a cocktail of three recombinant, full-length TprC variants, or the NH2-terminus of the TprK protein with a RIBI-like adjuvant. Animals were challenged with T. pallidum intradermally (10 sites; 10^5 bacteria/site). Treponemal burden and progression to ulceration were monitored. To assess for immunogen-specific splenocytes, pools of synthetic peptides corresponding to each immunogen were used to stimulate splenocytes collected ex-vivo in proliferation assays. Supernatants from stimulated splenocytes were used to quantify IFN-γ responses by ELISA. Results Immunizations protected animals significantly albeit not completely. At day 35 post-challenge only 14.1% and 15.5% of lesions ulcerated in immunized rabbits compared to the 95% of lesions in unimmunized rabbits. At day 21, there was a 99.3% and 98.7% reduction in treponemal burden averaged across all challenge sites in TprC- and TprK-immunized rabbits compared to unimmunized animals, respectively. Lymphocyte proliferation and IFN-γ production correlated to reduction in both percent of ulcerated lesions and treponemal burden. Conclusions Lymphocyte proliferation and IFN-γ release assays may serve as surrogates to assess for antigen-specific T-cell responses. TprK and TprC immunizations are able to stimulate cellular immunity in a TH2 environment, which is key to development of an effective syphilis vaccine.
Genome-informed characterisation of antigenic drift in the haemagglutinin gene of equine influenza strains circulating in the United States from 2012 to 2017.

Equine influenza virus (EIV) is a major infectious pathogen causing significant respiratory signs in equids worldwide. Voluntary surveillances in the United States (US) recently reported EIV detection in horses with respiratory signs even with adequate vaccine protocols and biosecurity programs and posed a concern about suboptimal effectiveness of EIV vaccine in the US. This study aims to determine genetic characteristics of 58 field EIV H3N8 strains in the US from 2012 to 2017 using the phylogenetic analysis based on hemagglutinin (HA) gene. Amino acid substitution and acquisition of N-glycosylation of the HA gene were also evaluated. Phylogenetic analysis identified that almost all US field strains belonged to the Florida Clade 1 (FC1) except one Florida Clade 2 strain from a horse imported in 2014. US EIV strains in 2017 shared 11 fixed amino acid substitutions in the HA gene comparing to the vaccine strain (A/equine/Ohio/2003) and two additional amino acid substitutions were detected in 2019. Introduction of foreign EIV strains into the US was not detected, but antigenic drift without acquisition of N-glycosylation in the HA gene were observed in US field strains until 2017. Considering the global dominance of FC1 strains, subsequent antigenic drift of US EIV strains should be monitored for better effectiveness of EIV vaccine in the US and global equine industries. This article is protected by copyright. All rights reserved.
The The Personality and Political Activity of Otto-von-Bismarck in the Russian Conservative, Liberal and Democratic Press in the second half of the 19-th - the beginning of the 20th century

The article is devoted to the personality and the political activity of one of the leading European diplomats of the 19th century, German Chancellor Otto-von-Bismarck reflected in the Russian press of the different political directions, and how these opinions influenced the decision-making in foreign policy by the Russian political elite.
Gateway to the Northern Plains: Railroads and the Birth of Fargo and Moorhead

Review of: "Gateway to the Northern Plains: Railroads and the Birth of Fargo and Moorhead," by Carroll Engelhardt.
Differential expression of Q4 proteins (Qb-1) in fibroblasts and lymphocytes.

The Qb-1 protein is coded for by the Q4 gene. This gene appears to be widely transcribed in murine tissues. We have examined the subcellular localization and processing of Qb-1 in fibroblast cells. This protein has previously been reported to be secreted from activated lymphocytes. However, we report that high levels of Qb-1 are present on the surface of B10.P fibroblast cells. We also observed an unusual intracellular distribution for Qb-1. The protein appears to be highly concentrated in the endoplasmic reticulum, in addition to being on the surface. This distribution is not due to inefficient processing. The kinetics of Qb-1 processing and transport are not unusual for class I molecules. Complete resistance to endo-beta-N-acetylglucosaminidase H is acquired, indicating terminal processing. This unusual localization in fibroblast cells and the differential expression of this protein between cell types may reflect a specific role for Qb-1.
Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells

Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic–sedative agent employed today and is nontoxic to humans at high levels (50 μg/ml). Clinically relevant concentrations of propofol (3 to 8 μg/ml; 20 to 50 μM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA). The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells. At low concentrations (25 μM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells. These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer.
Micromechanical resonators for oscillators and filters

Fully monolithic, high-Q, micromechanical signal processors are described. A completely monolithic high-Q oscillator, fabricated via a combined CMOS plus surface micromachining technology, is detailed, for which the oscillation frequency is controlled by a polysilicon micromechanical resonator to achieve high stability. The operation and performance of mechanical resonators are modelled, with emphasis on circuit and noise modelling. Micromechanical filter design is described, and a prototype two-resonator bandpass filter is demonstrated. An integrated micro-oven that stabilizes the resonance frequency against temperature variations using only 2 mW of power is reviewed. Brownian motion and mass loading phenomena are shown to have a greater influence on short-term stability and dynamic range in this micro-scale. Scaling strategies are proposed to alleviate potential limitations due to Brownian noise.
Gerbil: MPI+YARN

Emerging big data applications comprise rich multi-faceted workflows with both compute-intensive and data-intensive tasks, and intricate communication patterns. While MapReduce is an effective model for data-intensive tasks, the MPI programming model may be better suited for extracting high-performance for compute-intensive tasks. Researchers have recognized this need to employ specialized models for different phases of a workflow, e.g., performing computations using MPI followed by visualizations using MapReduce. However, extant multi-cluster approaches are inefficient as they entail data movement across clusters and porting across data formats. Consequently, there is a crucial need for disparate programming models to co-exist on the same set of resources. In this paper, we address the above issue by designing GERBIL, a framework for transparently co-hosting unmodified MPI applications alongside MapReduce applications on the same cluster. GERBIL exploits YARN as the model agnostic resource negotiator, and provides an easy-to-use interface to the users. GERBIL bridges the fundamental mismatch between YARN and MPI by designing an MPI-aware resource allocation mechanism. We also support five different optimizations: minimizing job wait time, achieving inter-process locality, achieving desired cluster utilization, minimizing network traffic, and minimizing job execution time, all in a multi-tenant environment. Our evaluation shows that GERBIL enables MPI executions with performance comparable to a native MPI setup, and improve compute-intensive applications performance by up to 133% when compared to the corresponding MapReduce-based versions.
Sample entropy analysis of heart rhythm following cardiac transplantation

Pediatric heart transplantation has become a mainstream in the treatment of end-stage heart disease in infants and children. Heart rate variability is a measure of autonomic nervous influence on the heart. After heart transplantation, the donor heart loses its nervous control. Nonlinear analysis of heart rate is a method to study the physiologic mechanisms responsible for the control of heart rate fluctuations, in which the autonomic nervous system appears to play a primary role. This work evaluated the heart rate entropy in children who has undergone heart transplantation. Patients who underwent heart transplantation showed significant decrease in entropy as assessed by sample entropy (0.63 /spl plusmn/ 0.31 vs. 0.90 /spl plusmn/ 0.33, p < 0.05). System complexity as can be assessed by entropy methods decreases in transplanted patients and this may be related to loss of the neural modulation of heart rate.
Adolescent Sexuality in Western Societies: A Research Compendium

As Moore and Rosenthal argue, “There has been an explosion of information and research on adolescent sexuality in the past decade” (p. 1). In an attempt to synthesize these findings, the authors wr...
Technology Creation, Diffusion, and Growth Cycles

Standard macroeconomic models that assume an exogenous stochastic process for multifactor productivity offer the interpretation that recessions are the result of ''bad news'' (technological regress) and expansions are the result of ''good news'' (technological advancement). The view taken here is that both expansions and recessions are the result of ''good news'' in the sense that in both cases, aggregate production possibilities have increased. Recessions can be thought of as the transition from one technological frontier to the next.
Comparison of nanostructured silver-modified silver and carbon ultramicroelectrodes for electrochemical detection of nitrate.

We report the use of silver (Ag)-modified carbon and Ag ultramicroelectrodes (UMEs) for electrochemical detection of nitrate. We investigated several methods for electrodeposition of Ag; our results show that the addition of a complexation agent (ammonium sulfate) in the Ag deposition solution is necessary for electrodeposition of nanostructured Ag that adheres well to the electrode. The electrodeposited Ag on both types of electrodes has branch-like structures that are well-suited for electrocatalytic reduction of nitrate. The use of UMEs is advantageous; the sigmoidal-shaped cyclic voltammogram allows for sensitive detection of nitrate by reducing the capacitive current, as well as enabling easy quantification of the nitrate reduction current. Both cyclic voltammetry and chronoamperometry were used to characterize the electrodes; and independent of the electrochemical interrogation technique, both UMEs were found to have a wide linear dynamic range (4-1000 μM) and a low limit of detection (3.2-5.1 μM). More importantly, they are reusable up to ∼100 interrogation cycles and are selective enough to be used for direct detection of nitrate in a synthetic aquifer sample without any sample pretreatment and/or pH adjustment.
Linear array design using Bayesian parameter estimation

In the course of designing and optimizing antenna arrays, many difficulties are often experienced. Due to the complex nature of modern arrays, finding the optimal configuration from scratch can be a challenging task. Many synthesis options are available for certain array types, however they are not without their problems as well. The paper deals with a technique for optimizing an array using Bayesian sampling and inference techniques. This technique can be applied to any array with any configuration to determine the best fitting parameters for a given radiation pattern. We also discuss how the procedure is implemented in modern programming methods and its applicability to parallelization. Results show that this method allows for the examination of an entire parameter space so that the best parameters for an arbitrary linear array can be quickly and efficiently examined.
Comparative efficacy and safety of antidiabetic drug regimens added to stable and inadequate metformin and thiazolidinedione therapy in type 2 diabetes

SummaryAims Determine the efficacy and safety of antidiabetic agents added-on to metformin and a thiazolidinedione (TZD) in patients with inadequately controlled type 2 diabetes (T2D). Methods MEDLINE and CENTRAL were searched for randomised controlled trials (RCTs) evaluating the addition of an antidiabetic agent in patients with T2D inadequately controlled on stable, optimised metformin and TZD therapy (≥ 1500 mg metformin and ≥ 50% maximum TZD dose for ≥ 4 weeks). Frequentist network meta-analysis was performed on identified studies. Results Eleven RCTs evaluating dipeptidyl peptidase-4 inhibitors (linagliptin, sitagliptin), sulfonylureas (SUs) (glibenclamide, glimepiride), glucagon-like peptide-1 (GLP-1) analogues (exenatide, liraglutide, dulaglutide, taspoglutide) and sodium-glucose cotransporter2 (SGLT2) inhibitors (canagliflozin, empagliflozin) were identified. The mean reduction in HbA1c from baseline was significant for all agents (range, 0.55–1.17%) vs. placebo. SUs were associated with weight gain (range, 3.31–7.29 kg), while weight loss was seen with all GLP-1 analogues (range, 1.53–2.20 kg) and SGLT2 inhibitors (range, 2.08–2.95 kg) vs. placebo. Relative risk of hypoglycaemia was increased with dulaglutide, exenatide and glimepiride vs. placebo (RR range, 2.65–6.17); and trended higher with all other agents except linagliptin. GLP-1 analogues and canagliflozin reduced systolic blood pressure vs. placebo (range, 2.39–5.05 mmHg). No agent with available data increased the risk of urinary or genital tract infection vs. placebo. Conclusion When added to stable, optimised metformin and TZD, all evaluated antidiabetic agents reduced HbA1c; albeit not to the same degree. Moreover, agents differed in their effects on body weight, hypoglycaemia and systolic blood pressure.
Programmable diode/resistor-like behavior of nanostructured vanadium pentoxide xerogel thin film.

Electrical properties of a Cr/V2O5/Cr structure are investigated and switching of the device due to electrochemical reactions is observed at low bias (<1 V). Depending on the polarity of the first applied bias, the switched device can behave like a diode (forward sweep first) or a resistor (reverse sweep first). The switching is irreversible and persistent, lasting for more than one month. By performing environmental tests, we prove that water molecules in the atmosphere and intercalated in the xerogel film are involved in the electrochemical reactions. It is proposed that an interfacial layer with reduced oxidation state forms at the Cr/V2O5 interface, and creates a higher Schottky barrier due to rise of electron affinity. Different interfacial layer thicknesses in forward and reverse first sweeps are responsible for different I–V characteristics in subsequent sweeps. The results suggest future applications of these V2O5 thin films in low-power read-only memory devices and diode-resistor networks.
A time-efficient web-based teaching tool to improve medical knowledge and decrease ABIM failure rate in select residents.

Aim : The American Board of Internal Medicine (ABIM) exam’s pass rate is considered a quality measure of a residency program, yet few interventions have shown benefit in reducing the failure rate. We developed a web-based Directed Reading (DR) program with an aim to increase medical knowledge and reduce ABIM exam failure rate. Methods : Internal medicine residents at our academic medical center with In-Training Examination (ITE) scores ≤35th percentile from 2007 to 2013 were enrolled in DR. The program matches residents to reading assignments based on their own ITE-failed educational objectives and provides direct electronic feedback from their teaching physicians. ABIM exam pass rates were analyzed across various groups between 2002 and 2013 to examine the effect of the DR program on residents with ITE scores ≤35 percentile pre- (2002–2006) and post-intervention (2007–2013). A time commitment survey was also given to physicians and DR residents at the end of the study. Results : Residents who never scored ≤35 percentile on ITE were the most likely to pass the ABIM exam on first attempt regardless of time period. For those who ever scored ≤35 percentile on ITE, 91.9% of residents who participated in DR passed the ABIM exam on first attempt vs 85.2% of their counterparts pre-intervention ( p <0.001). This showed an improvement in ABIM exam pass rate for this subset of residents after introduction of the DR program. The time survey showed that faculty used an average of 40±18 min per week to participate in DR and residents required an average of 25 min to search/read about the objective and 20 min to write a response. Conclusions : Although residents who ever scored ≤35 percentile on ITE were more likely to fail ABIM exam on first attempt, those who participated in the DR program were less likely to fail than the historical control counterparts. The web-based teaching method required little time commitment by faculty. Keywords: teaching tool; web-based; In-Training Examination; internal medicine residency; residents; teaching physicians (Published: 30 October 2015) Citation: Med Educ Online 2015, 20: 29221 - http://dx.doi.org/10.3402/meo.v20.29221
Organizing a research community with SPIRES: Where repositories, scientists and publishers meet

High Energy Physics (HEP) as a discipline has, for decades, embraced the preprint as a means of communicating results within the community. Community services such as SPIRES and arXiv.org have evolved to serve the needs of this community and enable the preprint communication model to be successful. Currently HEP researchers utilize preprints, not journals as their primary mode of communication, while journals are used to provide quality control via peer-review. SPIRES provided the infrastructure that allows researchers to blend the peer-review of journals with the speed of arXiv. Now a new project, INSPIRE, will provide an even more flexible and extensible system to allow publishers, repositories, and researchers themselves to contribute and share information.
Prolactin and gonadotrophin dynamics in response to antagonists of LHRH and dopamine in ovariectornized rhesus monkeys: a dissection of their common secretion

This experiment was designed to study the prolactin (PRL) and gonadotrophin response to an inhibitory analogue of luteinizing hormone releasing hormone (LHRH-A; ORG 30276) and a dopamine antagonist, metoclopramide (MCP), in castrated female rhesus monkeys. The LHRH-A given as an i.v. bolus followed by an infusion 2 h later induced a significant decline in circulating PRL levels reaching a maximum suppression 1 h after initiation of the LHRH-A infusion. Intravenous administration of MCP, performed 1 h after beginning the LHRH-A infusion, resulted in a prompt and abrupt rise in PRL levels in the LHRH-A group as well as in the controls. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels showed a progressive decline during LHRH-A treatment. Injection of MCP did not affect the levels of LH and FSH in either of the groups. The data obtained demonstrate in primates that the prolactin inhibitory effect of LHRH-A is easily overcome by the dopamine antagonist, MCP, whereas the LHRH-A-induced gonadotrophin suppression remains unaffected by MCP.
Vigorous Currents, Painful Archives: The Production of Affect and History in Poe's "Tale of the Ragged Mountains"

A s we turn to the question of pain in Poe, we might return to Walter Benjamin’s Berlin Childhood, which describes how effectively his mother’s stories drained away all of his morbid symptoms.1 Given the relief attributed to the “vigorous current” of those tales, we could ask if the current coursing through Poe’s work also targets some feverish pain abroad in the land of his upbringing. Many scholars now find Poe’s engagement with painful issues of his day undeniable, particularly as they relate to traumas of slavery and the racism driving imperialism at home and abroad. Yet those same scholars continue to debate how to interpret that engagement, particularly when it takes the indirect, ghoulish, and splenetic form so characteristic of his work. If some still question whether Poe was a racist, most assume that some degree or kind of racism was unavoidable for a man of his time. While initially useful, efforts to pinpoint Poe’s position on the spectrum of racist ideologies of his day have been superseded by recognition that his writing constitutes an archive with broad implications for an anatomy of racism’s conflicted and contested operations.2 Poe exposes slavery’s impact well beyond the experience of its most immediate victims and perpetrators, and this extended traumatic environment generates a range of response whose effects are worth studying with care. This last is particularly the case when we discover how often the vigorous currents of Poe’s work invite us to consider the broader traumatic relays alive in their very production. Thus if we consider the deeper resonances of Benjamin’s association between storytelling and pain, we may find another way to approach some of the
Structural and valence properties of the amorphous-metallic high-pressure phase of SnI 4

M\"ossbauer spectroscopy (MS) in $^{119}\mathrm{Sn}$ and $^{129}\mathrm{I}$ was employed to investigate the evolution and properties of the high-pressure amorphous-metallic phase of ${\mathrm{SnI}}_{4}$. Measurements were carried out at pressures up to 27 GPa using diamond-anvil cells. Both MS probes detect the onset of a new high-pressure phase at P\ensuremath{\simeq}10 GPa. The relative abundance of the high-pressure phase increases with pressure, reaching 100% at P\ensuremath{\ge}20 GPa. Whereas the isomer shift ${\ensuremath{\delta}}_{\mathrm{IS}(\mathrm{P})}$ of Sn in the low-pressure phase has a positive slope, that of the high-pressure phase has a negative slope with an unusual plateau in the 15--20-GPa region. In the 0\ensuremath{\le}P\ensuremath{\le}10 GPa range the $^{129}\mathrm{I}$ MS reveals a single site. For P\ensuremath{\ge}10 GPa a spectral component evolves with pressure that coexists with the ``molecular'' phase and reaches an abundance saturation of \ensuremath{\simeq}50% at P\ensuremath{\ge}18 GPa. In contrast to the low-pressure phase this component shows a positive quadrupole coupling constant, whose magnitude is about half that of the low-pressure phase, a large \ensuremath{\eta} value, and nearly identical ${\ensuremath{\delta}}_{\mathrm{IS}}$ values. The high-pressure abundance determined by both $^{119}\mathrm{Sn}$ and $^{129}\mathrm{I}$ shows a dramatic pressure hysteresis. It is unequivocally determined that no ${\mathrm{SnI}}_{4}$\ensuremath{\rightarrow}${\mathrm{SnI}}_{2}$+${\mathrm{I}}_{2}$ dissociation takes place. A model proposed for the high-pressure phase of ${\mathrm{SnI}}_{4}$ consists of randomly oriented chains of ${\mathrm{SnI}}_{4}$ tetrahedral molecules where two bridging iodines per molecule provide for the intermolecular association. The ${\mathrm{Sn}}^{4+}$ ground state in this structure is formed by hybridizing the outer 5s5p with the inner 4p4d tin orbitals. This unique molecular association and the high-pressure ${\mathrm{Sn}}^{4+}$ ground state provide the proper path and mechanism for the one-dimensional charge delocalization.
Micro-coil NMR to monitor optimization of the reconstitution conditions for the integral membrane protein OmpW in detergent micelles

Optimization of aqueous solutions of the integral membrane protein (IMP) OmpW for NMR structure determination has been monitored with micro-coil NMR, which enables the acquisition of NMR spectra using only micrograms of protein and detergent. The detergent 30-Fos (2-undecylphosphocholine) was found to yield the best 2D [15N, 1H]-TROSY correlation NMR spectra of [2H, 15N]-labeled OmpW. For the OmpW structure determination we then optimized the 30-Fos concentration, the sample temperature and long-time stability, and the deuteration level of the protein. Some emerging guidelines for reconstitution of β-barrel integral membrane proteins in structural biology are discussed.
Effects of Hydrogen Addition on Swirl-Stabilized Flame Properties

The role of hydrogen addition to swirl-stabilized methane flames is studied experimentally. Of specific interest are flame properties including flame surface density and curvature. The measurements are based on Particle Image Velocimetry (PIV), Mie-scattering and CH-chemiluminescence imaging. Identification of the flame front and its geometric characterization provides an understanding of the flame properties. Compared to the non-reacting flow, the methane flame broadens the central recirculation zone. Hydrogen enriched flames reduce the central recirculation zone and scales down the characteristic length of the flow. With hydrogen addition, the distribution of the flame front curvature is broadened and flame surface density is increased. This indicates that hydrogen addition increases the reaction front thermo-diffusive instability, causing the flame front to be more wrinkled, and increasing the flame surface area leading to an increase in the burning velocity.Copyright © 2010 by ASME
Increases in heart rate accompanying decreases in activity and defecation: support for a dual process theory of habituation.

Repeated exposure of adult male rats to a small chamber resulted in decreases in general activity and defecation during four 3-min habituation sessions. Heart rate, however, increased both between and within sessions, reaching intrasession asymptotes that were maintained during the last two-thirds of the recording periods. The results are discussed with respect to a dual-process theory of habituation proposed by Groves and Thompson (1970) and possible mechanisms involving changes in arousal level are suggested to account for the data.
Abstract 4968: Chemotherapy up-regulates RANK-RANKL signaling in breast cancer cells.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Chemotherapy has been the mainstay of cancer treatment for so many years and so do the increasing resistance to it. Recent studies emphasize the importance of cytokines in breast cancer therapy resistance and how targeting cytokines or their receptor may prove to be a better therapeutic regimen. This study focuses on the role of receptor activator of NFkB ligand (RANKL), recently been observed to provide survival benefits to cancer cells and helps in mammary stem cell maintenance. To the best of our knowledge the modulations of RANK and RANKL in response to chemotherapy has not been evaluated before. Our preliminary studies with drug-resistant cells showed higher expression of RANK and RANKL both in vitro in cells as well as in vivo in tumors formed by these cells, suggesting a role of this RANKL mediated signaling in breast cancer therapy resistance. Given that RANK and RANKL are expressed in aggressive breast tumors and this signaling provides survival benefits to cancer cells, we hypothesized that chemotherapy up-regulates RANK-RANKL signaling in breast cancer cells which eventually makes breast cancer cells resistant to further chemotherapy providing evasion to therapy. To investigate this, we monitored the expression of RANKL in murine 4T1, CL66 and MDA MB-231, MCF-7; human breast cancer cells lines after treatment with two commonly used drugs doxorubicin and paclitaxel for breast cancer treatment. We observed that both drugs up-regulate RANKL expression in these cells. To examine if the expression of RANK also changes after drug treatment in these cells, we treated 4T1 and Cl66 cells with paclitaxel for 4, 8 and 12 hours. We observed an increase in the expression of RANK in these cells in a dose- and duration-dependent manner. 4T1 and Cl66 along with MDA MB-231 and MCF-7 were also treated with both paclitaxel and doxorubicin to evaluate if the change in receptor and ligand expression was drug-dependent. Our data showed that both the drugs up-regulate RANKL at mRNA (qRT-PCR) and protein levels (Immunofluorescence) in Cl66 and 4T1 cells. This up-regulation was as early as 4hrs (at mRNA level) after drugs treatment and the expression decreases after 8 hrs, suggesting an early transcriptional up-regulation. Our data suggest that increased expression of both RANK and RANKL in the breast cancer cells following chemotherapy may contribute to the activation of RANK-RANKL signaling in breast cancer and targeting this signaling might provide a novel adjuvant therapeutic regimen. Citation Format: Bhawna Sharma, Michelle L. Varney, Rakesh K. Singh. Chemotherapy up-regulates RANK-RANKL signaling in breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4968. doi:10.1158/1538-7445.AM2013-4968
Cecal Amputation Within the Right Ventral Colon for Surgical Treatment of Nonreducible Cecocolic Intussusception in 8 Horses

Objectives— To report a surgical technique for treatment of nonreducible cecocolic intussusception and outcome in 8 horses. Study Design— Retrospective study. Animals— Eight horses with nonreducible cecocolic intussusception treated by cecal amputation through a right ventral colotomy. Methods— Data were obtained from medical records and telephone conversations by using a standardized questionnaire. The large colon was exteriorized and, if necessary, evacuated of its contents through a pelvic flexure enterotomy. A second colotomy was made on the ventral surface of the right ventral colon (RVC) centered over or immediately distal to the intussusceptum. In most horses, attempts to manually reduce the intussusception by pushing the cecum from within the RVC through the cecocolic orifice were unsuccessful. Invaginated cecum was then pulled into the RVC and amputated; the cecum was either ligated with umbilical tape or sutured proximal to the site of amputation. After amputation, the remainder of the invaginated cecum was reduced. After further resection to healthy tissue, the typhlectomy was closed with a double-inverting suture pattern. Results— The median horse age was 2 years (range, 1 to 8 years). Duration of colic ranged from 6 hours to 6 months. Median surgical time was 180 minutes (range, 135 to 300 minutes). Median duration of antibiotic therapy was 7 days (range, 5 to 14 days). Median duration of hospitalization was 12 days (range, 6 to 21 days). All horses survived to hospital discharge. One horse died 3 months postoperatively; however, the remainder survived (median survival, 30 months; range, 6 to 96 months) and returned to or exceeded previous function. Clinical Relevance— Despite some contamination during surgery, horses with nonreducible cecocolic intussusception that underwent this method of surgical treatment had a good prognosis.
Ongoing Deadbeat Observers for Linear Time-Varying Systems

New, computationally efficient design methods are reported for discrete time-varying deadbeat observers. The importance of an ongoing deadbeat property is shown and is incorporated in the design. These results are attractive even for time-invariant systems because of their simplicity.
A single-dose placebo- and moxifloxacin-controlled study of the effects of temsirolimus on cardiac repolarization in healthy adults

Temsirolimus, a selective inhibitor of mammalian target of rapamycin, is an approved treatment for patients with advanced renal cell carcinoma (RCC). This study assessed the effect of intravenous (i.v.) temsirolimus 25 mg, the recommended dose for patients with RCC, on the corrected QT (QTc) interval. This 3-period crossover study enrolled healthy subjects. In periods 1 and 2, subjects received i.v. placebo either alone or with open-label oral moxifloxacin. In period 3, subjects received a single dose of temsirolimus 25 mg. The primary statistical objective was to estimate the effect of temsirolimus compared with placebo on change from time-matched baseline QTc at the end of infusion (0.5 h). Assay sensitivity was evaluated by the effect of moxifloxacin on change from time-matched baseline QTc compared with placebo. In total, 58 subjects were enrolled. Temsirolimus had no effect on QTc interval in the primary analysis. At 11 of 12 secondary time points, the upper bound for the temsirolimus QTc 90% confidence intervals for the time-matched change from baseline difference from placebo was 30 ms. Therapeutic exposure to temsirolimus is not associated with clinically significant changes in QTc intervals in healthy adults.
Preparation for Future Care Needs by Parents Providing Care for their Adult Offspring with Disabilities

Older adults who provide care for an adult child with a disability have rarely been considered when investigating propensity to plan for future care. Families in these circumstances are at risk of experiencing a crisis as these caregiving parents experience personal health challenges. This study investigated influences on the plans made by adults caring for adult offspring with a disability for their own as well their offspring's future care. Results indicated that parents who cared for an adult child with a disability were more likely to plan for their offspring's than their own care and the more planning they did for their adult child, the more they were likely to do for themselves. Implications are discussed.
TSA'09 workshop summary: topic-sentiment analysis

This workshop seeks to bring together researchers in both computer science and social sciences who are interested in developing and using topic-sentiment analysis methods to measure mass opinion, and to foster communications between the research community and industry practitioners as well.
Effects of various denervation techniques on the ATP of the rat vas deferens

Abstract Postganglionic denervation of the vas deferens of the rat by surgical means or pretreatment with 6-hydroxydopamine results in a substantial decrease in the concentration of ATP in the tissue. The loss of ATP cannot entirely be accounted for by the loss of neuronal ATP nor by a compromised blood supply. The results suggest the the postganglionic nerve plays an important role in the regulation of the ATP of the effector cells.
Carboxylesterase-dependent cytotoxicity of dibasic esters (DBE) in rat nasal explants.

Abstract Dibasic esters (DBE) are a solvent mixture of dimethyl adipate (DMA), dimethyl glutarate (DMG), and dimethyl succinate (DMS) used in the paint and coating industry. Subchronic inhalation toxicity studies have demonstrated that DBE induce a mild degeneration of the olfactory, but not the respiratory, epithelium of the rat nasal cavity. Carboxylesterase-mediated hydrolysis of the individual dibasic esters is more efficient in olfactory than in respiratory mucosal homogenates. In the present study, an in vitro system of cultured rat nasal explants was utilized to determine if DBE toxicity is dependent on a metabolic activation by nonspecific carboxylesterase. Explants from both the olfactory and the respiratory regions of the female rat nasal cavity were incubated for 2 hr in Williams' medium E containing 10–100 m m DMA, DMG, or DMS. DBE caused a dose-related increase in nasal explant acid phosphatase release, a biochemical index of cytotoxicity. HPLC analysis demonstrated parallel increases in the carboxylesterase-mediated formation of monomethyl ester metabolites. Diacid metabolite production in the nasal explant system was not entirely concentration-dependent. Metabolite concentrations and acid phosphatase release were generally greater in olfactory than respiratory tissues. DBE-induced cytotoxicity and acid metabolite production were markedly attenuated in nasal tissue excised from rats which were pretreated with bis (p-nitrophenyl)phosphate, a carboxylesterase inhibitor. This study presents a viable in vitro method for assessing organic ester cytotoxicity in the rat nasal cavity. It was shown that DBE are weak nasal toxicants under the conditions of this system. It was further demonstrated that DBE toxicity is dependent on a carboxylesterase-mediated activation. A similar mechanism was proposed for the nasal toxicity induced by other organic esters following inhalation exposure.
Formation of conjugated polymer brushes by surface-initiated catalyst-transfer polycondensation

Electroactive conjugated polymer brushes of poly(thiophene) and poly(phenylene) have been prepared via a surface-initiated Kumada-type polycondensation reaction, yielding films with a thickness up to 42 nm.
Changes in Protein Patterns and In Vivo Protein Synthesis during Presenescence and Senescence of Hibiscus Petals

Summary Senescence of petals from flowers of Hibiscus rosa-sinensis L. cv. Pink Versicolor was associated with a rapid loss in fresh and dry weights, and extractable protein. Changes in the patterns of proteins resolved by one-dimensional SDS-PAGE were noted with petal aging. The intensity of polypeptide bands with molecular weights of 39, 38, 34, and 16 kD increased, while those with molecular weights of 89, 56, 50, and 41 kD decreased with petal age. Protein synthesis during petal aging was investigated by following the uptake and incorporation of 3 H-leucine into the TCA-insoluble fraction of petal discs. Protein synthesis was highest the day before flower opening and declined rapidly as petal tissue senesced. Newly synthesized radiolabeled proteins from different stages of petal development were separated by SDS-PAGE and identified by fluorography. Presenescent petal tissue showed similar protein patterns with radioactivity distributed among several major polypeptides, whereas in senescent tissue, much of the radioactivity was concentrated in the 39 kD polypeptide.
The design of the 88000 RISC family

The design and implementation of the RISC (reduced-instruction-set computer) 88000 system in high-speed, complementary metal-oxide semiconductor (HCMOS) technology is described. The total system consists of the 88100 processor and two 88200 cache memory management units (CMMUs). The various features and components of the 88000 are discussed. >
Long-term use of sildenafil

The treatment of erectile dysfunction (ED) has been revolutionised by new agents to inhibit the enzyme PDE5. The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of PDE5 that breaks down cGMP, the key pathway for the production of erectile function in humans. Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (Viagra™, Pfizer) – the first approved selective PDE inhibitor for the treatment of ED. Sildenafil is inhibitory of PDE5 at a rate tenfold higher than for the next PDE (PDE6), which produces visual changes through the retinal rods. Its clinical effectiveness has been well documented in the majority of men with ED irrespective of aetiology. The aetiology of ED, also, does not appear to effect the function of sildenafil in relaxing corpus cavernosum smooth muscle tissue. Adverse events are usually associated with the vascular changes from PDE5 inhibition. These incl...
Lagtime in psychosomatic medicine consultations for cognitive-disorder patients: association with length of stay.

Background Utilization studies in inpatient psychosomatic medicine have focused on patterns of consultation requests, timing of consultation requests relative to date of hospital admission, and the association between time to initial psychiatric consultation and length of stay. Objective The authors studied the association of time to initial psychosomatic medicine consultation and length of stay for inpatients with cognitive disorders. Method The authors reviewed 157 charts, analyzing effects of age, gender, days from admission until consultation (REFLAG), and length of stay (LOS). Two values were computed: referral lag divided by LOS (REFLAG/LOS) and log(REFLAG)/log(LOS). Results Mean REFLAG was 8.13; mean LOS was 18.6 days; mean REFLAG/LOS was 0.466; and mean log(REFLAG)/log (LOS) was 0.596. REFLAG and log (REFLAG)/log(LOS) correlated significantly with LOS. Conclusion REFLAG is significantly associated with increased LOS. Referring services may need to consider earlier consultation requests.
The Initiation, Propagation, and Arrest of Joints and Other Fractures

The growth of joints is a fundamental issue in structural geology and related disciplines since joints exert a profound influence on the strength, deformability geophysical properties, and hydrologic characteristics of a rock mass. Joints in large igneous intrusions such as granitic plutons can provide exceptionally fine views of joint surface topography that are of interest to studies of joint propagation, interaction, and arrest. On the other hand, layered sedimentary sequences present opportunities to investigate the influence of heterogeneous layer thicknesses on joints, as well as properties involved with geometry and spacing of joints as they attempt to propagate laterally across and vertically through the sequence. Because the geometries and characteristics of subsequent geologic phenomena, such as faults, folds, and fluid-bearing fracture networks, are influenced by those of the joints, field-based studies of joint growth and pattern development are necessary prerequisites to clearly understand the later joint-dependent phenomena.
Effects of Road Pricing on Freight Carrier Behaviors Analyzed with Experimental Economics: Comparison of Peak Hour Delivery and Off-Hour Delivery

This paper uses experimental economics to examine the route choice behavior of freight carriers in peak hours and off-hours. The study finds that carriers tend to choose toll roads in peak hours to ensure on-time delivery, regardless of the type of cargo. In contrast, carriers are reluctant to choose toll roads in off-hours. For a delivery of 50 mi, the receiver’s final cost is lowered by approximately 25% if the receiver switches from peak hour delivery to off-hour delivery. The paper sheds light on the route choice behaviors of freight carriers under the constraint of delivering the cargo within a given time window. Findings of this study reinforce the empirical observation of freight carrier behaviors. The study also offers a data set that can be used for further econometric analysis of the freight sector.
Development of a tripeptide mimetic strategy for the inhibition of protein farnesyltransferase

Abstract This paper describes the development of a novel terphenyl-based tripeptide mimetic of the CAAX carboxy terminal sequence of Ras. We employ a concise synthesis to form a series of differently functionalized terphenyl inhibitors of protein farnesyltransferase (PFTase), exemplified by 5 , 6 and 7 . The key reaction in the synthesis of the terphenyl methyl ester 13 , and therefore 6 and 7 , was the Pd-catalyzed chemoselective Suzuki cross-coupling of 3-bromo-4-chloronitrobenzene 16 with an appropriate boronic acid derivative utilizing a commercially available, electron rich phosphine ligand. We further show that one member of this series is a potent inhibitor of PFTase.
Promutagen activation in parasite-infected organisms: Preliminary observations with Fasciola hepatica-infected mice and aflatoxin B1

Mutagenic activity of aflatoxin B1 (AFB1) was followed in the Ames Salmonella/microsome test using liver S-9 from uninfected and Fasciola hepatica infected mice. The S-9 preparations from parasite-infected animals were capable of inducing significantly greater AFB1 mutagenic activity to strain TA100 than S-9 preparations from either control, uninfected mice or Aroclor 1254-induced mice. The differences in activity between infected and uninfected mice were consistent between sex and strains of mice studied. The observed increase in biological activity was apparently due to an induction phenomenon in the host tissues rather than due to metabolism of AFB1 by F. hepatica enzymes.
Nursing Time Study for the Administration of a PRN Oral Analgesic on an Orthopedic Postoperative Unit

As needed (PRN) oral opioid analgesics are an integral part of many orthopedic postoperative multimodal pain management regimens. However, the unpredictable nature of this dosing method can lead to disruptions in the process of administering the medication, as well as be an interruption to regular nursing activities. This IRB approved quantitative time study tested the hypothesis that a significant amount of nursing time is required in the administration of PRN oral opioid analgesics on a postoperative orthopedic nursing unit. The purpose of this study is to evaluate the time necessary to complete the required steps related to the administration of PRN oral analgesics. Nurses from 28 nursing shifts used a personal digital assistant (PDA) to record the time needed to complete these steps. We determined that 10.9 minutes is the mean time required to administer PRN oral analgesics on this unit. Other time studies have evaluated the medication administration process as a whole. No time studies related to PRN oral analgesic administration have been reported. In phase I of our project, the data were summarized and will be used as a baseline comparison for phase II, in which we will evaluate an oral PCA medication administration system.
Endoscopic colloid cyst surgery.

OBJECTIVE The purpose of this report is to discuss the technical aspects of operating on colloid cysts through a transventricular approach, with rigid endoscopes. METHODS Twelve patients underwent 14 endoscopic operations in attempts to treat their colloid cysts. All patients were symptomatic, with headache being the most common complaint (8 of 12 patients). Six patients in this series exhibited enlarged ventricles associated with their colloid cysts. Using rigid endoscopes of < or =3.5-mm diameter, the cysts were inspected and fenestrated. Both hard and soft cyst contents were evacuated, and then the walls of the cysts were coagulated inside and outside. External ventriculostomy tubes were usually placed. Technical obstacles to successful completion of endoscopic colloid cyst surgery are discussed. RESULTS For 11 of the 12 patients, the colloid cysts could be treated via an endoscopic approach. The mean follow-up time was 173 weeks, and the median follow-up time was 125 weeks. For the 12th patient, bilateral scarring of the foramina of Monro precluded direct surgery; therefore, a septostomy was performed and a ventriculoperitoneal shunt was placed. CONCLUSION Endoscopic transventricular surgery should be considered for the treatment of colloid cysts.