cssi/SciSciGPT-SciSciNet huggingface dataset:
Continuous downstream processing for high value biological products: A Review

There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations.
Discriminative Gaussian process latent variable model for classification

Supervised learning is difficult with high dimensional input spaces and very small training sets, but accurate classification may be possible if the data lie on a low-dimensional manifold. Gaussian Process Latent Variable Models can discover low dimensional manifolds given only a small number of examples, but learn a latent space without regard for class labels. Existing methods for discriminative manifold learning (e.g., LDA, GDA) do constrain the class distribution in the latent space, but are generally deterministic and may not generalize well with limited training data. We introduce a method for Gaussian Process Classification using latent variable models trained with discriminative priors over the latent space, which can learn a discriminative latent space from a small training set.
Commutative discrete filtering on unstructured grids based on least-squares techniques

The present work is concerned with the development of commutative discrete filters for unstructured grids and contains two main contributions. First, building on the work of Marsden et al. [J. Comp. Phys. 175 (2002) 584], a new commutative discrete filter based on least-squares techniques is constructed. Second, a new analysis of the discrete commutation error is carried out. The analysis indicates that the discrete commutation error is not only dependent on the number of vanishing moments of the filter weights, but also on the order of accuracy of the discrete gradient operator. The results of the analysis are confirmed by grid-refinement studies.
Protozoans of Minor Medical Importance

Babesiosis, or piroplasmosis, in humans is a rare, zoonotic, protozoan infection transmitted by ticks. Infections can also be acquired by blood transfusion.1 The parasite infects erythrocytes, and the disease that results is similar to malaria, although it has been confused with Rocky Mountain spotted fever. It has two clinical patterns. Patients without spleens are likely to have fatal infections caused by species of Babesia associated with cattle: B. bigemina, B. diver gens, and B. bovis. Normal individuals, who develop a self-limited disease, tend to be infected by a parasite of rodents, B. microti, the most common species of Babesia infecting humans in the United States. In the northeastern United States, B. microti is transmitted by the same deer tick (Ixodes scapularis) that transmits Lyme disease. However, in areas where Lyme disease and babesiosis overlap, the former usually has a higher prevalence.2
BioAcoustica: a free and open repository and analysis platform for bioacoustics.

We describe an online open repository and analysis platform, BioAcoustica (http://bio. acousti.ca), for recordings of wildlife sounds. Recordings can be annotated using a crowdsourced approach, allowing voice introductions and sections with extraneous noise to be removed from analyses. This system is based on the Scratchpads virtual research environment, the BioVeL portal and the Taverna workflow management tool, which allows for analysis of recordings using a grid computing service. At present the analyses include spectrograms, oscillograms and dominant frequency analysis. Further analyses can be integrated to meet the needs of specific researchers or projects. Researchers can upload and annotate their recordings to supplement traditional publication.
In vivo regulation of the fetal rhesus monkey adrenal gland.

Fetal adrenal function in utero was studied in chronically catheterized rhesus monkey fetuses (129–154 days gestational age). Measurements of fetal pH, pCO2, pO2, heart rate, and fetal and maternal blood pressure were normal by 24 h after surgery. Maternal cortisol levels were 484.6 ± 60.7 ng/ml (mean ± SE) after surgery, decreasing to 300 ± 26.9 and 227.8 ± 30.6 ng/ml by the second and third day after surgery and stabilizing thereafter. No consistent pattern in fetal cortisol was seen after surgery. A significant increase in fetal concentration was observed between 145 and 149 and 150 and 154 days' gestation (87.9 ± 9.3 and 123.8 ± 20.0 ng/ml, respectively). A significant diurnal variation of cortisol levels was found in the fetal, but not maternal, circulation (fetal levels: AM, 167 ± 13.4 ng/ml, PM, 115 ± 8.9 ng/ml; maternal levels: AM, 326 ± 18.8 ng/ml, PM, 319 ± 38.5 ng/ml). Seven fetuses were challenged with bolus injections of 0.5 IU ACTH. An increase in circulating cortisol levels in response to A...
A flexible simulation framework for evaluating multi-level, heuristic-based production control strategies

A flexible simulation framework (FSF) is described which greatly reduces changeover time between scenarios and allows the rapid examination of multiple heuristic alternatives. The effectiveness of the framework is tested in the development phase of a heuristic-based, three-level FCS (flexible control strategy). The production basis for this experimentation is a mixed technology printed circuit board assembly plant. The performance of the flexible framework is discussed with a focus on the advantages and limitations of the approach in this challenging environment. Through the inclusion of specific interfacing mechanisms between control subroutines, and through standardization of inputs and outputs to those subroutines, the FSF helps to isolate operational control problems and helps to minimize the management task associated with operational flexibility. This feature is especially important as additional operational flexibility is made available. >
Gamma Interferon Controls Mouse Polyomavirus Infection In Vivo

Human polyomaviruses are associated with substantial morbidity in immunocompromised patients, including those with HIV/AIDS, recipients of bone marrow and kidney transplants, and individuals receiving immunomodulatory agents for autoimmune and inflammatory diseases. No effective antipolyomavirus agents are currently available, and no host determinants have been identified to predict susceptibility to polyomavirus-associated diseases. Using the mouse polyomavirus (MPyV) infection model, we recently demonstrated that perforin-granzyme exocytosis, tumor necrosis factor alpha (TNF-α), and Fas did not contribute to control of infection or virus-induced tumors. Gamma interferon (IFN-γ) was recently shown to inhibit replication by human BK polyomavirus in primary cultures of renal tubular epithelial cells. In this study, we provide evidence that IFN-γ is an important component of the host defense against MPyV infection and tumorigenesis. In immortalized and primary cells, IFN-γ reduces expression of MPyV proteins and impairs viral replication. Mice deficient for the IFN-γ receptor (IFN-γR(-/-)) maintain higher viral loads during MPyV infection and are susceptible to MPyV-induced tumors; this increased viral load is not associated with a defective MPyV-specific CD8(+) T cell response. Using an acute MPyV infection kidney transplant model, we further show that IFN-γR(-/-) donor kidneys harbor higher MPyV levels than donor kidneys from wild-type mice. Finally, administration of IFN-γ to persistently infected mice significantly reduces MPyV levels in multiple organs, including the kidney, a major reservoir for persistent mouse and human polyomavirus infections. These findings demonstrate that IFN-γ is an antiviral effector molecule for MPyV infection.
The Detection of Chemical Vapors in Air Using Optical Emission Spectroscopy of Pulsed Microdischarges From Two- and Three- Electrode Microstructures

Emission spectroscopy of plasma-excited chemical species is widely used for generalized chemical analyses in bench-top systems. This paper explores the use of pulsed microdischarges between two and three electrode microstructures, which operate in air at atmospheric pressure, for use in handheld chemical analyzers. Pulsed microdischarges are fired between two-electrodes spaced apart by 0.2-2 mm. Synchronized optical sampling and time resolved spectroscopy are performed to capture the emission spectra from the microdischarge and its afterglow. The discharge spectra in air consist mainly of wide-band background spectra and line spectra from the nitrogen, and water vapor in air. The detection of vapors in air is limited by the relative strengths of representative lines compared to background spectra rather than by their absolute strength. The separate temporal characteristics of the line and background spectra present opportunities to improve detection. This concept is evaluated using isopropyl alcohol vapors (100 ppm) for which lines corresponding to CH fragments are detected with a handheld spectrometer despite the presence of air spectra. This paper also introduces a three-electrode (flashFET) configuration, which further reduces power consumption and electrode wear. Occupying an active area < 1 mm2, it employs a strategically located high-impedance gate electrode that permits the use of pulses < 100 V between the source and drain. The device consumes only 2.5 muJ/pulse at 140 Torr and 22.5 muJ/pulse at atmosphere, as compared to 470 muJ/pulse for two-electrode discharges. The operation of the flashFET as a gas sensor is evaluated using acetone vapors in air ambient. A response curve is obtained by measuring the 388.1 nm emission from acetone fragments for acetone concentrations ranging from 50 to 1000 ppm.
Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

During acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. Hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype. Salmonella enterica serovar Typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. The mechanism(s) that triggers a macrophage to become hemophagocytic is unknown, but it has been reported that the proinflammatory cytokine gamma interferon (IFN-γ) is responsible. We show that primary macrophages become hemophagocytic in the absence or presence of IFN-γ upon infection with Gram-negative bacterial pathogens or prolonged exposure to heat-killed Salmonella enterica, the Gram-positive bacterium Bacillus subtilis, or Mycobacterium marinum. Moreover, conserved microbe-associated molecular patterns are sufficient to stimulate macrophages to hemophagocytose. Purified bacterial lipopolysaccharide (LPS) induced hemophagocytosis in resting and IFN-γ-pretreated macrophages, whereas lipoteichoic acid and synthetic unmethylated deoxycytidine-deoxyguanosine dinucleotides, which mimic bacterial DNA, induced hemophagocytosis only in IFN-γ-pretreated macrophages. Chemical inhibition or genetic deletion of Toll-like receptor 4, a pattern recognition receptor responsive to LPS, prevented both Salmonella- and LPS-stimulated hemophagocytosis. Inhibition of NF-κB also prevented hemophagocytosis. These results indicate that recognition of microbial products by Toll-like receptors stimulates hemophagocytosis, a novel outcome of prolonged Toll-like receptor signaling, suggesting hemophagocytosis is a highly conserved innate immune response.
Authoritarianism and Polarization in American Politics

Although politics at the elite level has been polarized for some time, a scholarly controversy has raged over whether ordinary Americans are polarized. This book argues that they are and that the reason is growing polarization of worldviews - what guides people's view of right and wrong and good and evil. These differences in worldview are rooted in what Marc J. Hetherington and Jonathan D. Weiler describe as authoritarianism. They show that differences of opinion concerning the most provocative issues on the contemporary issue agenda - about race, gay marriage, illegal immigration, and the use of force to resolve security problems - reflect differences in individuals' levels of authoritarianism. Events and strategic political decisions have conspired to make all these considerations more salient. The authors demonstrate that the left and the right have coalesced around these opposing worldviews, which has provided politics with more incandescent hues than before.
Geometric Topology & Visualizing 1-Manifolds

Ambient isotopic approximations are fundamental for correct representation of the embedding of geometric objects in R 3, with a detailed geometric construction given here. Using that geometry, an algorithm is presented for efficient update of these isotopic approximations for dynamic visualization with a molecular simulation.
Plasminogen activators and thrombolytic therapy

The mechanism of plasminogen activation by streptokinase, tissue and urokinase-type plasminogen activators (PAs) were reviewed. The regulatory role of fibrin in plasminogen activation involving its direct interaction with tissue-type PA and indirect interaction with streptokinase and urokinase-type PAs was demonstrated. Recent information on the development of new PAs is also displayed. The result of studies of PA mutant derivatives synthesized by recombinant DNA techniques are discussed. Date on chimeric (hybrid) forms of PAs and their chemically synthesized conjugates are presented. The trend in search for PAs is analysed. A new direction in the study of PAs for combined plasminogen activation and the further development of the methods of thrombolytic therapy was outlined.
Grid connected solar photovoltaic in island states: Challenges, opportunities and waste management

Small island developing states (SIDS) strive to continue economic growth, mitigate climate change and reduce their dependence on imported fossil fuels. They offer a geographical landscape which encourages distributed generation in order to provide power to end users that are located in remote areas. Often times, this distributed generation is accomplished through grid connected solar photovoltaic (PV) systems. Because they do not emit greenhouse gas, and they use the free light from the sun to generate electricity, solar PV systems provide renewable energy in a sustainable way. This paper will respectively discuss the challenges and opportunities associated with grid connected solar PV in island states. It will also propose potential waste management strategies of such solar PV systems from cradle to grave.
Microengineered embryonic stem cells niche to induce neural differentiation

A major challenge in therapeutic use of embryonic stem cells (ESCs) for treating neurodegenerative diseases is creating a niche in vitro for controlled neural-specific differentiation of ESCs. We employ a niche microengineering approach to derive neural cells from ESCs by mimicking embryonic development in terms of direct intercellular interactions. Using a polymeric aqueous two-phase system (ATPS) microprinting technology, murine ESCs (mESCs) are precisely localized over a monolayer of supporting stromal cells to allow formation of individual mESC colonies. Polyethylene glycol (PEG) and dextran (DEX) are dissolved in culture media to form two immiscible aqueous solutions. A robotic liquid handler is used to print a nanoliter-volume drop of the denser DEX phase solution containing mESCs onto a confluent layer of supporting PA6 stromal cells submerged in the aqueous PEG phase. mESCs proliferate into isolated colonies of uniform size. For the first time, a comprehensive protein expression analysis of individual mESC colonies is performed over a two-week culture period to track temporal progression of cells from a pluripotent stage to specific neural cells. Starting from day 4, the expression of nestin, neural cell adhesion molecule (NCAM), and beta-III tubulin shows a significant increase but then levels off after the first week of culture. The expression of specific neural cell markers glial fibrillary acidic protein (GFAP), 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase), and tyrosine hydroxylase (TH) is elevated during the second week of culture. This microengineering approach to control ESCs differentiation niche combined with the time-course protein expression analysis of individual differentiating colonies facilitates understanding of evolution of specific neural cells from ESCs and identifying underlying molecular markers.
Population parameter estimates for performance and reproductive traits in Polish Large White nucleus herds.

Performance test records from on-farm tests of young Polish Large White boars and reproductive records of Polish Large White sows from 94 nucleus farms during 1978 to 1987 were used to estimate population parameters for the measured traits. The number of boar performance records after editing was 114,347 from 3,932 sires, 21,543 dams, 44,493 litters and 1,075 herd-year-seasons. Reproductive performance records of sows involved 41,080 litters from 2,348 sires, 18,683 dams and 1,520 herd-year-seasons. Both data sets were analyzed by using restricted maximum-likelihood programs. The model used for the performance records included fixed herd-year-seasons, random sires, dams and error effects, and covariances for the year of birth of sire and year of birth of dam. The model used for the reproduction data set was the same as the performance data with parity as an additional fixed effect. Estimated heritabilities were .27, .29, .26, .07, .06, .06 for average daily gain standardized to 180 d (ADG), backfat thickness standardized to 110 kg BW (BF), days to 110 kg (DAYS), litter size at birth born alive (NBA), litter size at 21 d (N21) and litter weight at 21 d (W21), respectively. Estimated common environmental effects for the same traits were .09, .10, .09, .06, .07 and .08, respectively. Genetic correlations were .25 (ADG and BF), -.99 (ADG and DAYS), -.21 (BF and DAYS), .91 (NBA and N21), .68 (NBA and W21) and .80 (N21 and W21). The respective phenotypic correlations were .23, -.99, -.20, .88, .75, .86. These population parameters for Polish Large White pigs are similar to those for breeds in other countries.
Species-related antigens of mammalian cell strains as determined by immunofluorescence.

SummaryA procedure has been described whereby species-associated antigens were directly identified in cultured mammalian cells by fluorescent antibody techniques. Guinea pig anti-cellular globulin fractions were conjugated with fluorescein isothiocyanate. Dispersed cells were prepared from monolayer cultures or frozen cell suspensions and the resulting wet cell suspensions were treated with the labeled antibodies. Staining specificity was recognized by presence or absence of peripheral fluorescence of the treated cells. Four cell strains derived from human tissues, 3 from mouse, and one from Chinese hamster, reacted specifically with homologous but not with heterologous labeled antibodies. Antibodies to monkey- and human-derived strains exhibited reciprocal cross-reactions that were eliminated by absorption procedures.
Effect of Drugs on Myokinase Activity of Coronary Arteries.

SummaryTransphosphorylation reactions mediated by the adenylic acid system are involved in energy transfer for muscle activity. These experiments were designed to study the influence of vaso-active drugs upon two such systems, adenylate kinase (myokinase) and adenosine triphosphatase from coronary tissue. These results indicate that the constriction and dilatation of coronary arteries elicited by these drugs do not involve the inhibition of these enzyme systems.
Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: Testing an experimental medicine strategy

Pro-cognitive agents for chronic psychotic disorders (CPDs) might be detected via experimental medicine models, in which neural targets engaged by the drug predict sensitivity to the drug’s pro-cognitive effects. This study aims to use an experimental medicine model to test the hypothesis that “target engagement” predicts pro-cognitive effects of the NMDA antagonist, memantine (MEM), in CPDs. MATRICS Consensus Cognitive Battery (MCCB) performance was assessed in CPD (n = 41) and healthy subjects (HS; n = 41) in a double-blind, randomized cross-over design of acute (single dose) MEM (placebo vs. 10 or 20 mg p.o.). Measures of prepulse inhibition (PPI) and mismatch negativity previously reported from this cohort substantiated target engagement. Biomarkers predicting MEM neurocognitive sensitivity were assessed. Testing confirmed MCCB deficits associated with CPD diagnosis, age, and anticholinergic exposure. MEM (20 mg p.o.) reduced MCCB performance in HS. To control for significant test order effects, an “order-corrected MEM effect” (OCME) was calculated. In CPD subjects, greater age, positive MEM effects on PPI, and SNP rs1337697 (within the ionotropic NMDA receptor gene, GRIN3A) predicted greater positive OCME with 20 mg MEM. An experimental medicine model to assess acute pro-cognitive drug effects in CPD subjects is feasible but not without challenges. A single MEM 20 mg dose had a negative impact on neurocognition among HS. In CPD patients, age, MEM effects on PPI, and rs1337697 predicted sensitivity to the neurocognitive effects of MEM. Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients cannot be inferred without a validating clinical trial.
Persistent ectopic pregnancy following laparoscopic linear salpingostomy.

As the surgical approach for ectopic pregnancies evolves from radical to conservative procedures, the potential hazard of persistent ectopic pregnancy has become increasingly pertinent. From September 1, 1986 to August 31, 1989, 11 women with persistent ectopic pregnancy after laparoscopic salpingostomy were diagnosed and treated at Yale-New Haven Hospital. Persistent ectopic pregnancy was suspected in nine cases because of symptoms and in two because of plateauing beta-hCG titers. Ten of 11 patients underwent repeat surgery. Eight had partial or complete salpingectomy of the involved ipsilateral tube, two had repeat salpingostomies, and one was treated with methotrexate. When the 11 women with persistent ectopic pregnancies were compared with 70 patients treated successfully by laparoscopic salpingostomy using multivariate stepwise logistic regression, smaller size of the ectopic (P less than .01) and fewer days of amenorrhea (P less than .05) predicted persistent ectopic pregnancy after laparoscopic salpingostomy. Based upon our experience, we believe that earlier-treated ectopic pregnancies (ie, fewer than 42 days of amenorrhea) and/or smaller ectopics (ie, 2.0 cm or less in diameter) require treatment with particular caution and close postoperative surveillance.
The Use of Pulsed Doppler Ultrasound to Identify Arterial Flow Abnormalities

The Pulsed Doppler Ultrasound Instrument (1) has a feature which distinguishes it from other Doppler Ultrasound blood velocity detectors. It can range across a blood vessel and record the flow velocities in a small sample of blood at a defined position in the cross-sectional diameter of the vessel. This feature makes determinations of the flow condition independent of incident angle since a small sample size is used (approx. 2 mm). Sound spectrograms of Pulsed Doppler signals obtained from a flow model and from the center of the flow stream of human arteries are identical in pattern over a wide range of incident angles (30° to 80°).
Seismic design of bridge columns incorporating mechanical bar splices in plastic hinge regions

Abstract The application of prefabricated bridge elements dates back to more than half a century. Several prefabrication techniques have been developed thereafter for capacity protected bridge elements. However, the application of precast bridge columns in moderate and high seismic regions is scarce mainly because of a lack of performance data pertaining to their connections. One of the precast column connections that has been recently emphasized for accelerated bridge construction (ABC) utilizes mechanical bar splices, which are commonly referred to as couplers. For ABC, couplers have to be generally used in the plastic hinge region of precast columns. This would violate the current bridge seismic design codes ban on the application of couplers in the plastic hinge regions of ductile members. The present study was conducted to (a) identify suitable mechanical bar splices for precast column connections through a state-of-the-art review, (b) develop a generic material model for all coupler types, (c) quantify the coupler effects on the column seismic performance, and (d) develop simple design equations for plastic hinges to facilitate the design and field application of mechanically spliced columns in moderate and high seismic regions. It is proposed that the current code limitation on couplers in plastic hinges be revised based on the findings of the present study.
Design of Peptide Ligands that Interact with Specific Membrane Receptors

Peptide hormones and neurotransmitters are carriers of biological information that initiate their biological effects by binding to receptors found on the surface of cells. A basic assumption of modern molecular biology is that the information content of a peptide hormone or neurotransmitter is related to the stereostructural and conformational properties of the peptide. However, the properties of most small (<20 residues) polypeptide hormones and neurotransmitters makes the rational design of such ligands difficult. These properties include: 1) a high degree of conformational flexibility with many conformations accessible at physiological temperatures; 2) a lack of high receptor selectivity; 3) ready biodegration; and 4) the complexity of peptide structures compared with most natural products that have been developed as potential drugs. Despite these difficulties, we and others have developed approaches that show great potential for the systematic rational design of peptide ligands. In this paper we outline some of the approaches that can lead to peptide ligands with high potency, high receptor selectivity, agonist or antagonist activity, high stability against enzymatic breakdown, and conformationally constrained structural properties that provide templates for topographical design and receptor mapping.
Validation of procedures for elemental impurities

In recent years, the concern about the toxicity of trace elements in foods and drugs has increased significantly. Four elements—mercury, arsenic, cadmium, and lead—have been specifically targeted for increased levels of control because of this toxicity. To measure these elemental impurities, the application of advanced spectroscopic procedures has been necessary. The procedures provide tremendous gains in sensitivity, but may suffer from specificity and precision issues. The choice of the procedure often will involve a trade-off between these important parameters and the United States Pharmacopeia (USP) has provided a means by which to evaluate this trade-offs without giving up the data quality. This chapter examines the two different validation approaches as applied to the evaluation of a sample for the trace elemental impurity contamination. These approaches examined include the traditional validation approach and the USP approach. In addition, the chapter provides some best practices and common sense approaches to validation of these types of procedures.
Migration: A Theological Vision

Migration is a global phenomenon that is a defining issue of our times. Scholars study migration’s multidimensionality, but behind the complex and often contentious realities are people and their stories—stories of what is most important in the human heart, namely relationships. A theological perspective on migration begins with the notion that justice involves the search for right relationships. The theological concepts, of human dignity, solidarity, communion, and conversion, address four critical obstacles to right relationships, specifically negativism, narcissism, nationalism, and ultimately nihilism. A theological vision of migration challenges us to move beyond an identity based on a narrow sense of national, racial, or psychological territoriality. It offers the possibility of defining life on the expansive spiritual terrain consistent with the kingdom of God.
Sturge-Weber Syndrome Linked to GNAQ Mutation

Investigators from Johns Hopkins School of Medicine, the Hugo W Moser Research Institute at Kennedy Krieger, Baltimore; Duke University; and Medical College of Wisconsin, Milwaukee, performed whole-genome sequencing of DNA from paired samples of tissue from 3 persons with the Sturge-Weber syndrome (SWS).
Electrostatic forces drive poleward chromosome motions at kinetochores.

Recent experiments regarding Ndc80/Hec1 in force generation at kinetochores for chromosome motions have prompted speculation about possible models for interactions between positively charged molecules at kinetochores and negative charge at and near the plus ends of microtubules. A clear picture of how kinetochores and centrosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The current paradigm of molecular cell biology requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to explain several different mitotic motions—including poleward force production at kinetochores—within a classical electrostatics approach in terms of experimentally known charge distributions, modeled as surface and volume bound charges interacting over nanometer distances. We propose here that implicating Ndc80/Hec1 as a bound volume positive charge distribution in electrostatic generation of poleward force at kinetochores is most consistent with a wide range of experimental observations on mitotic motions, including polar production of poleward force and chromosome congression.
Abstract 244: Why Registries Matter: Impact of a Comprehensive Telestroke Data Collection Process on Clinical Quality Improvement

Introduction: Evaluating patient care within a telestroke network is challenging due to lack of appropriate data. The AHA/ASA’s Target Stroke helps address QI programming in larger hospitals, typically PSCs, but may not be appropriate for smaller facilities that lack specialty knowledge and data collection tools. Telestroke has only heightened this need for smaller facilities to measure and track performance to ensure quality care. Goal: In an effort to narrow this disparity and incorporate similar data-driven QI projects in our partner sites and therefore network as a whole, the Providence Telestroke Network sought to develop a novel comprehensive registry. Clinical performance measures, such as IV tPA treatment rates, door to CT and door to needle times, were collected to inform our quality improvement processes. Methods: The Providence Telestroke Network consists of two PSC hubs and 17 partner sites. Network participants utilize the American Stroke Association’s Get With The Guidelines (GWTG) data collection tool to capture stroke quality measures. Once entered, quality data from all sites are consolidated into a single cloud-based registry. For patients that transfer, clinical information from the partner hospital is automatically matched to the corresponding hub record within the registry. Aggregate patient information is then summarized for quality reviews and performance improvement planning. Results: The registry includes information on 1264 patients who received a neurologic consult by hub-based neurologists, of which 37% (n=470) received a formal telemedicine consult and 20% (n=274) resulted in a transfer to our hub facility for a higher level of care. We identified several partner sites that had patient arrival to initiation of IV tPA (door to needle) times in excess of the recommended goal of 60 minutes and door to CT times in excess of the recommended goal of 25 minutes. Initial data review at the start of network participation also found overall treatment rates at the spokes were between 0 to 6%. Quality improvement processes and ED staff education from our hub PSCs were provided to partner facilities to improve door to CT and door to needle times as well as overall IV tPA treatment rates. Door to CT times were changed by up to 54% and door to needle times were changed by up to 24%. IV tPA treatment rates in the partner sites increased by 5-32%. Implications: Our comprehensive registry enabled us to identify quality improvement opportunities at partner hospitals and implement appropriate QI processes. As a result, significant improvement in acute stroke care metrics were realized in our partner facilities.
Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs

3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive component of so-called bath salts products that has caused serious medical consequences in humans. In this chapter, we review the neuropharmacology of MDPV and related analogs, and supplement the discussion with new results from our preclinical experiments. MDPV acts as a potent uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET) in nervous tissue. The MDPV formulation in bath salts is a racemic mixture, and the S isomer is much more potent than the R isomer at blocking DAT and producing abuse-related effects. Elevations in brain extracellular dopamine produced by MDPV are likely to underlie its locomotor stimulant and addictive properties. MDPV displays rapid pharmacokinetics when injected into rats (0.5–2.0 mg/kg), with peak plasma concentrations achieved by 10–20 min and declining quickly thereafter. MDPV is metabolized to 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) in vivo, but motor activation produced by the drug is positively correlated with plasma concentrations of parent drug and not its metabolites. 3,4-Catechol-PV is a potent uptake blocker at DAT in vitro but has little activity after administration in vivo. 4-OH-3-MeO-PV is the main MDPV metabolite but is weak at DAT and NET. MDPV analogs, such as α-pyrrolidinovalerophenone (α-PVP), display similar ability to inhibit DAT and increase extracellular dopamine concentrations. Taken together, these findings demonstrate that MDPV and its analogs represent a unique class of transporter inhibitors with a high propensity for abuse and addiction.
Masculinity and the culture of rising sea-levels in a mangrove lagoon in Papua New Guinea

In the wake of rising sea-levels, dialogue about climate change and resettlement took on new urgency among the Murik, a lagoon-dwelling, coastal people in Papua New Guinea. A theoretical question is raised by their discourse: how to conceptualize the relationship among multiple perspectives of climate change that does not pre-empt local voices? Bakhtin’s concept of the chronotope and Lacan’s notion of the symbolic phallus in the time and space of the other are utilized in this analysis. In particular, chronotopes of modernity and global risk contest a chronotope of local masculinity. These concepts, in turn, are challenged by a chronotope of doubt, and the latter seems to be winning the argument, as it were. The four chronotopes, I argue, combine in dialogue to constitute an otherwise ignored view of rising sea-levels, not only in Papua New Guinea but in climate-change discourse, more broadly. Multi-sited ethnography is analyzed in support of this argument.
Applying the lessons of developmental psychology to the study of juvenile interrogations: New directions for research, policy, and practice.

Police interrogation of criminal suspects is a core function of the American justice system that involves numerous cognitive, social, and other psychological processes. While a robust psycholegal literature on police interrogation has emerged, the subset of that literature focusing on adolescent sus
Inferior vena cava filters in patients with cancer and venous thromboembolism (VTE) does not improve clinical outcomes: A population-based study

Abstract Background There are few studies that have determined clinical outcomes following inferior vena cava filter (IVCF) insertion in cancer patients hospitalized for acute deep-vein-thrombosis (DVT) or pulmonary embolism (PE). Methods and results We analyzed hospital discharge records of all patients with active cancer who were admitted to a California hospital specifically for acute DVT or PE between 2005 through 2009. Propensity and competing risk methodology were used to determine if IVCF-use lowered either 30-day mortality or the risk of recurrent PE, DVT, and major bleeding within 180 days. Among 14,000 patients, an IVCF was placed in 2747 (19.6%), but only 577 (21%) of these IVCF patients had an apparent indication for filter use because of acute bleeding or undergoing major surgery. Data on anticoagulation use was not available. Filter-use provided no reduction in either 30-day mortality (HR = 1.12, 95% CI: 0.99–1.26, p = 0.08) or the adjusted 180-day risk of subsequent PE (± DVT) (HR = 0.81, 95% CI: 0.52–1.27, p = 0.36). Filter use was, however, associated with an increase in the adjusted180-day risk of recurrent DVT (HR = 2.10, 95% CI: 1.53–2.89, p Conclusions We conclude that in this population-based study, approximately 20% of cancer patients with acute VTE received an IVCF, but only 21% of these had an indication for IVCF use. Overall, IVCF use provided neither a short-term survival benefit nor a reduction in risk of recurrent PE, but IVCF use was associated with a higher risk of recurrent DVT.
From Shame to Guilt: The Remediation of Bullying Across Cultures and the US

When shame becomes guilt, individuals change their focus from blaming others to acknowledging personal responsibility. This piece reports on findings that show how aspects of shame are correlated with bullying behaviors and how reducing those behaviors can be achieved by remediating shame through the promotion of guilt or by using interconnected harmony strategies. Though this study primarily tested US (individualistic) participants, these findings are compared with extant studies carried out in collectivistic cultures because it is important to focus on remediating shame to reduce bullying in multiple contexts. Shame prompts the desire to amend the threatened social self and improve self-esteem. A common maladaptive method of amending the threatened social self and improving self-esteem is bullying, because bullying gives the perpetrator an illusion of power and importance. Addressing and remediating shame could have a positive effect on reducing bullying by establishing an ethical climate within bullying environments that encourages mutual respect, shared responsibility, and social inclusion. Results of this study support the notion that correlates of shame established in previous research on convicts, extends to individuals with a propensity to bully others. Analysis of cross-cultural literature and US findings illuminates how shame leads to a resource-orientation through the desire for harmonious mediation and the acceptance of responsibility through guilt.
The Evolutionary Origin of Epithelial Cell–Cell Adhesion Mechanisms

Abstract A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell–cell adhesion proteins comprising the classical cadherin/β-catenin/α-catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: (1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. (2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and β-catenin in metazoa. (3) The α-catenin-binding domain in β-catenin appears to be the favored mutation site for disrupting β-catenin function in the CCC. (4) The ancestral function of the α/β-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of α-catenin were gained by sequence divergence in the non-actin-binding (N-, M-) domains. (5) Allosteric regulation of α-catenin may have evolved for more complex regulation of the actin cytoskeleton.
Structural investigation of phase segregation in Mn2CrGa-based alloys

Abstract Alloys with nominal compositions of Mn2CrGa1-xAlx (x = 0.0, 0.2, 0.5, 1.0) have been studied by X-ray powder diffraction (XRD). Detailed structural investigation of the alloys with x = 0.2 and 0.5 has been further carried out using transmission electron microscopy (TEM). The alloys, in the typical Heusler composition, were prepared using rapid quenching and subsequent annealing. The XRD analysis revealed that a disordered cubic phase was present in the alloys with x = 0.0 and 1.0 while a spinodal decomposition with phase separation has been observed in the alloys with x = 0.2 and 0.5. TEM study confirms a segregation of two crystalline phases, one of them a cubic phase with the β–Mn prototype structure and the other a new crystalline phase with a tetragonal structure. Energy-dispersive X-ray spectroscopy (EDS) analysis was used to determine the compositions of the two crystalline phases. The mass ratio of the tetragonal phase and the β–Mn prototype cubic phase is derived as t/c ≈ 2.41 by fitting the average compositions of the two crystalline phases to the nominal composition. The orientational relationship of two crystalline structures has been determined by selected-area electron diffraction (SAED) and stereogram analysis. The structures of the two crystalline phases have been investigated by high-resolution transmission electron microscopy (HRTEM) and image simulation. The structural model of the tetragonal phase is proposed and compared with the experimental results in SAED and HRTEM studies.
Help Wanted: Realigning Journalism Education to Meet the Needs of Top U.S. News Companies:

Journalism programs working to stay current with industry practice often struggle to do so without forgoing traditional journalism skills and attributes. This longitudinal study involves content an...
Barcelona'92 postolímpica : esport i multiculturalisme

En aquest article, Kennett aborda el paper dels Jocs, dels processos globalitzadors i de l'esport en el dialeg intercultural, i despres se centra en aspectes relacionats amb la realitat de la cultura de l'esport a la Barcelona posterior als Jocs Olimpics.
Early post-hatch survival and humoral immune response of layer chickens when in ovo vaccinated with strain F Mycoplasma gallisepticum,.

Commercial layer hens reared on multi-age hen complexes are vaccinated during pullet rearing to combat production losses due to the bacteria Mycoplasma gallisepticum (MG). In this study, the potential to in ovo vaccinate layer chickens against MG was investigated. Layer embryos were administered a dosage of a live attenuated strain F MG (FMG) vaccine at 18 d of incubation and raised for 6 wk for initial post-hatch evaluation in 2 replicate trials. Treatments included control non-injected eggs, eggs injected with diluent, a non-diluted dosage, a 10-2 dilution, a 10-4 dilution, and a 10-6 dilution. A subset of chicks were swabbed for detection of FMG in the trachea at hatch. At 6 wk of age, birds were swabbed again for FMG detection and a blood sample was tested for MG antibody production. Hatch was depressed in the non-diluted dose group (P 50%). Birds in the in ovo FMG treatments had detectable FMG and antibody production at 6 wk. There were no differences in percentage positive birds (P > 0.3 for all tests) or ELISA titers (P = 0.079) between the FMG treatments. Body weight at 6 wk of age was diminished with increasing FMG dose (P < 0.0001). The lowest dose tested was found to be the most practical, causing the least mortality, least weight loss, and a humoral immune response in the majority of the birds. Further work is needed to evaluate how this in ovo vaccine, promoting immunity earlier, would compare to a standard post-hatch vaccination against an MG challenge scenario through a lay cycle.
Anthelmintic efficacy against equine strongyles in the United States

Abstract Equine strongyle parasites are ubiquitous in grazing equids across the world. Anthelmintic resistance is widely developed in cyathostomin populations, but very few surveys have evaluated anthelmintic efficacy in equine populations in the United States, and most of these are over 15 years old. The present study was carried out as part of the National Animal Health Monitoring Systems (NAHMS) Equine 2015–2016 study. The aims were to investigate anthelmintic treatment efficacy by means of the fecal egg count reduction test (FECRT) and identify parameters associated with decreased efficacy. Data were collected from equine operations in 28 states via questionnaires and fecal samples submitted for fecal egg count analysis. Participants were instructed to collect samples from six equids at the day of anthelmintic treatments and 14 days later, and they were asked to include an empty syringe with a legible label of the anthelmintic product used in the shipment. Overall, dewormer treatment was effective for 76.3% of operations (84.6% of animals). Macrocyclic lactone use was effective for 88.7% of operations (95.0% of animals) while pyrimidine/benzimidazole use was effective for 21.4% of operations (43.5% of animals). Univariate analysis revealed that overall, macrocyclic lactones exhibited significantly higher efficacy than the pyrimidine and benzimidazole drug classes (p
Energy Efficient Approaches in Wireless Networking

Wireless networking is one of the fastest growing segments of the computer industry, being the platform of many critical applications in the military or in disaster recovery situations, where deployment of traditional wired networks is infeasible. Wireless devices are battery powered and therefore have a limited operational time. Recently, the optimization of energy utilization of wireless terminals has received significant attention. Different techniques for power management have been proposed at all layers of the network protocol stack. In this paper we survey recent advances in energy efficiency for Medium Access Control (MAC) protocols, ad-hoc routing and topology control mechanisms.
Large-eddy simulation of the Mississippi River under base-flow condition: hydrodynamics of a natural diffluence-confluence region

We conduct large-eddy simulation (LES) to investigate the turbulent flow in a 3.2 km long reach of the Mississippi River. The digital elevation model of the study reach was reconstructed from remot...