cssi/SciSciGPT-SciSciNet huggingface dataset:
Cytokines disrupt intracellular patterns of Parkinson's disease-associated proteins alpha-synuclein, tau and ubiquitin in cultured glial cells.

Abstract The purpose of this study was to determine the effects of specific proinflammatory cytokines interleukin-6 (Il-6), interleukin-1β (Il-1β), interferon-gamma (IFN), and tumor necrosis factor-alpha (TNFα), on content and distribution of alpha-synuclein (α-synuclein), tau and ubiquitin in human derived cultured glial cells. Exposure paradigms mimicked acute (2 h), intermediate (18 h) and prolonged time frames (96 h); consisting of single or repeated low doses (10 ng/ml) or high doses (50 ng/ml), consistent with either mild or serious systemic infectious/inflammatory responses. Images of intracellular protein content and distribution were reconstructed from emission patterns generated by fluorescence deconvolution microscopy. Minor alterations were seen in protein content with IFN; Il-1β decreased α-synuclein and tau at 18 and 96 h; TNFα inversely reduced α-synuclein and increased ubiquitin content. Combinations of Il-1β and IFN produced a robust increase of α-synuclein and tau at 2 h. Consecutive low doses of Il-6 produced only minor increases in α-synuclein and ubiquitin after 4 h, whereas a single high dose resulted in major increases for all three proteins over the first 18 h. Protein localization patterns were distinctly different and were altered dependent upon cytokine treatment. A high dose exposure (2 × 50 ng/ml) with Il-6 and IFN demonstrated that protein increases and dispersals could be sustained and that the normal perinuclear tau and peripheral α-synuclein patterns were disrupted. These results support the postulate that specific cytokines affect temporal protein changes with concomitant pattern disruptions, possibly reflecting a mechanism of cell dysfunction in Parkinson's degeneration.
Single-crystal growth and characterization of Zn- and Ni-substituted YBa2Cu4O8

Abstract Single crystals of Zn- and Ni-substituted YBa 2 Cu 4 O 8 with T c =80–20 K for Zn and T c =80–0 K for Ni have been grown from a BaO–CuO flux at 1090°C under 600 bar of O 2 . Crystals grown in yttrium stabilized ZrO 2 crucibles do not show contamination from the crucible material. The effective distribution coefficients for Zn and Ni are 0.3 and 1, respectively. The solubility limits are around 2% for Zn and above 6.5% for Ni. Single-crystal X-ray diffraction is used to characterize the crystal quality but it lacks the sensitivity to conclusively differentiate the site preference for small amounts of substituted ions. All crystals show sharp superconducting transitions with Δ T c gradually increasing with decreasing T c .
Smooth muscle-targeted overexpression of insulin-like growth factor I results in enhanced vascular contractility.

Insulin-like growth factor I (IGF-I) has been postulated to function as a vasodilator. We explored the vasoactive effects of chronic elevations of arterial IGF-I levels in SMP8-IGF-I mice, in which IGF-I is overexpressed in smooth muscle (SM) by means of a SM α-actin promoter. Denuded aortas from SMP8-IGF-I mice generated increased force in response to KCl or phenylephrine and had greater sensitivity to KCl depolarization. This is not due to desensitization of a SM NO pathway, as pretreatment with n-ω-nitro-l-arginine affected both wild-type and SMP8-IGF-I aortas to a similar degree. The increased contractility ex vivo is not associated with changes in heart rate or blood pressure. Total smooth muscle myosin heavy chain (SMHC) messenger RNA (mRNA) was greater in SMP8-IGF-I aortas, with preferential expression of SMHC-A. Reciprocal effects on contractility and SMHC mRNA were observed in SMP8-IGFBP-4 animals, in which IGF-binding protein-4 was overexpressed through the same promoter. Also, SM α-actin mRNA w...
Light-dependent subcellular movement of photoreceptor proteins.

The intracellular localization of photoreceptor-specific proteins 33 kd, beta-transducin, and 48 kd, as determined by immunocytochemistry, is transient and dependent on the lighting environment to which the retina is exposed. Western analysis of the proteins in isolated rod outer segments from mouse retina demonstrates that beta-transducin actually moves from the outer segment to the inner segement in response to light and that 48 kd moves simultaneously in the opposite direction. The light-induced movements appear to be initiated by the absorption of light by rhodopsin because red light, which does not bleach rhodopsin, does not produce this redistribution of phototoreceptor proteins. Time course analysis of these movements suggests that the light-induced shift is detectable at the earliest time examined (30 seconds). The bidirectional movement suggests that the photoreceptor cells have at least two distinct dyneinlike or kinesin-like translocator molecules that act as microtubule-based motors. This movement appears to be a basic mechanism by which photoreceptor cells rapidly and radically alter the subcellular concentrations of photoreceptor-specific proteins, which in turn may affect the rapid changes in membrane potential that occur during phototransduction.
Efficient and flexible methods for transient versioning of records to avoid locking by read-only transactions

We present efficient and flexible methods which permit read-only transactions that do not mind reading a possibly slightly old, but still consistent, version of the data base to execute without acquiring locks. This approach avoids the undesirable interferences between such queries and the typically shorter update transactions that cause unnecessary and costly delays. Indexed access by such queries is also supported, unlike by the earlier methods. Old versions of records are maintained only in a transient fashion. Our methods are characterized by their flexibility (number of versions maintained and the timing of version switches, supporting partial rollbacks, and different recovery and buffering methods) and their efficiency (logging, garbage collection, version selection, and incremental, record-level versioning). Distributed data base environments are also supported, including commit protocols with the read-only optimization. We also describe efficient methods for garbage collecting unneeded older versions.
Purification and postsynthetic modifications of friend erythroleukemic cell high mobility group protein HMG-I

We have previously detected and purified a Friend erythroleukemic mouse cell nonhistone chromatin protein having extraction and acid-solubility properties like the low molecular weight “high mobility group” (HMG) nuclear proteins. We show here that the electrophoretic properties and the amino acid composition of this mouse cell “HMG-like” protein is comparable to those of the HMG-I proteins isolated from human HeLa S3 cells, African green monkey cells, Ehrlich ascites mouse cells, and rat fibroblast cells. Therefore, we have also designated the Friend erythroleukemic mouse cell protein as HMG-I. In common with the other HMG proteins the Friend cell HMG-I protein can undergo a variety of post-translational biochemical modifications including acetylation, ADP-ribosylation, glycosylation, and phosphorylation. Surprisingly, in the course of these studies we found that in vivo radiolabeling experiments revealed that only two minor HMG-14 subspecies (and/or possibly a minor HMG-I subspecies) are phosphorylated whereas HMG-1, -2, -17, and the major HMG-14 are not heavily phosphorylated.
Cationic-Initiated Ring-Opening Polymerization of Cyclopropenone Ketals. I. Monomer Synthesis and Polymer Structure

3,3-Dimethoxycyclopropene, the first of a series of cyclopropenone ketals, was initially reported from these laboratories in 1972. Polymerization of this compound, which is functionally capable of ...
An Experimental Study in Nucleate Boiling Heat Transfer From a Sphere

The purpose of this work is to report experimental measurements of boiling fluxes in both pool and forced convection from a 3.84-cm copper sphere instrumented with 16 copper-constantan thermocouples. The experiments were conducted in Freon-113 using a quenching technique. The sphere, with surfaces of every orientation, allowed the authors to investigate the effect of surface orientation on the boiling process. Their findings for the sphere are compared with those of Nishikawa for flat plates and those of Van Stralen for wires.
The Effects of Media Context Experiences On Advertising Effectiveness

This study presents a quantitative examination of the qualitative impact of magazines on advertising effectiveness. The research identifies 39 distinct experiences involved in reading magazines. We propose that these experiences are a way of describing the media context for ads that appear in magazines. We show that the large majority of these experiences are related to advertising effectiveness. The more readers experience a magazine as "making them smarter," for instance, the more effective an ad in the magazine is. A context-free control group is included in the analysis. Heterogeneity across magazines is also examined, and it is further shown that these effects hold over the 100 largest magazines in the United States.
Thirty-day hospital re-admissions: a metric that matters.

Health expenditures in the United States are forecasted to be $2.9 trillion in 2013, consuming nearly 18% of the gross domestic product (1). In response to explosive growth in medical expenses, the Affordable Care Act was passed in 2010 with the primary goal of curtailing health care expenses while elevating the overall quality of health care in the United States. The U.S. Centers for Medicare and Medicaid Services (CMS) has identified re-admission of patients within 30 days of discharge as a targeted quality metric and has instituted financial penalties to encourage hospitals to reduce re-admissions (2). This change could affect all physicians, and interventional radiologists must be aware of these efforts. The burden of hospital re-admissions is real, involving 20% of Medicare beneficiaries and costing $17 billion in 2003–2004 (3). Under the Affordable Care Act, hospitals that demonstrate above-average re-admission rates with respect to their peers will be subject to a maximum 1% penalty on all Medicare payments in 2013—a penalty that will eventually increase to 3% in 2015 (4). This penalty can have a severe impact on the financial state of hospital systems. For example, Barnes-Jewish Hospital in St. Louis, Missouri, lost $2 million in Medicare payments in 2012 (5). Nationwide, total Medicare reimbursements declined $300 million, with the maximum penalty being applied to 307 hospitals and lesser penalties to an additional 1,910 hospitals (5). There is no incentive payment for hospitals with low re-admission rates or hospitals that demonstrate improvements in reducing re-admission rates.
Two topics in quantum chromodynamics

Quantum chromodynamics (QCD) has reached a level of credibility and maturity which deserves textbook status. Indeed, textbooks exist1 and others are on the way.2 Nevertheless, to my mind a textbook treatment of QCD is made much more difficult than that of quantum electrodynamics (QED) because of the confinement problem. Even perturbative QCD—which is all that will really be discussed here—suffers this problem. There is no S-matrix theory of quarks and gluons as there is for QED, as given in the LSZ formalism.3 The concept of “on-mass-shell” or “asymptotic” quark and/or gluon is highly suspect. And the typical “Feynman diagram” used in perturbative QCD contains internal quark and gluon lines and external hadron lines. What does that really mean? How does one derive and justify Feynman-rules for such amplitudes in the absence of good control over the confinement question?
Evaluating the Phylogenetic Utility of Genes: A Search for Genes Informative About Deep Divergences among Vertebrates

Genes widely used in systematic studies have proven valuable for the resolution of relatively shallow ( 300 MYA) divergences, but genes useful for moderately deep divergences have been lacking. Computerized data bases of gene sequences are growing at a rapid pace and provide a rich resource of genes likely to contain phylogenetic information about many levels of divergence. Despite the fact that the chosen gene must be appropriately matched to the phylogenetic divergence(s) of interest, little attention has been given to the estimation and/or evaluation of the likely phylogenetic utility of genes. Knowledge of the phylogenetic relationships and divergence times among organisms for which gene sequences are commonly available provides a powerful tool for estimating this utility
Update on Oxalate Crystal Disease

Oxalate arthropathy is a rare cause of arthritis characterized by deposition of calcium oxalate crystals within synovial fluid. This condition typically occurs in patients with underlying primary or secondary hyperoxaluria. Primary hyperoxaluria constitutes a group of genetic disorders resulting in endogenous overproduction of oxalate, whereas secondary hyperoxaluria results from gastrointestinal disorders associated with fat malabsorption and increased absorption of dietary oxalate. In both conditions, oxalate crystals can deposit in the kidney leading to renal failure. Since oxalate is primarily renally eliminated, it accumulates throughout the body in renal failure, a state termed oxalosis. Affected organs can include bones, joints, heart, eyes, and skin. Since patients can present with renal failure and oxalosis before the underlying diagnosis of hyperoxaluria has been made, it is important to consider hyperoxaluria in patients who present with unexplained soft tissue crystal deposition. The best treatment of oxalosis is prevention. If patients present with advanced disease, treatment of oxalate arthritis consists of symptom management and control of the underlying disease process.
Acid secretion, Na+ absorption, and the origin of the potential difference across isolated mammalian stomachs.

The stomach wall of several species will function in isolation for several hours. A normal transmural potential difference is generated, and H+ secretion proceeds at a modest rate. In contrast to the isolated frog gastric mucosa, the isolated mammalian stomach, to a significant but varying degree, actively absorbs Na+. To some extent, the prandial state determines Na+ absorption. Acidification of the solution bathing the mucosal surface of the isolated stomach depresses Na+ absorption and favors Cl− secretion.
The mechanism of hydrogen sulfide adsorption on fine rubber particle media (FRPM).

Abstract A commercial rubber waste product, fine rubber particle media (FRPM), was found to adsorb hydrogen sulfide (H2S) at 0.12 mg H2S/g FRPM of adsorption capacity. Since FRPM seems to be an attractive alternative to treat H2S owing to its economic advantages as well as its physicochemical characteristics, several analyses were conducted to investigate fundamental information, surface properties, and breakthrough characteristics of FRPM as adsorbent. The physical properties of FRPM including composition and surface chemistry were investigated to compare its performance with commonly available commercial H2S adsorbents such as activated carbon and assess the possible adsorption mechanism. The specific surface area of FRPM was less than 1% of activated carbon. FRPM does not have enough surface area supporting a pure physical adsorption of H2S because it is particulate in nature with limited porosity. The adsorption of FRPM to remove H2S was complex mechanism and involved a combination of zinc compounds and carbon black.
Proximity to Alcohol-Serving Establishments and Crime Probabilities in Savannah, Georgia: A Statistical and GIS Analysis

Social science literature links alcohol consumption and human violence and/or crime. Most of the literature in this field only addresses sociological and demographic issues. Crimes occurrences, however, are also location dependent and can be analyzed using GIS methods. Only a handful of studies have analyzed spatial dimensions of crime incidences and their controlling factors. In this paper, we present an in-depth analysis ofcrime probabilities and their proximity to alcohol-serving establishments based on the locations of 12,458 reported crimes and 247 alcohol-serving establish- ments in Savannah, Georgia, for the year 2000. Logistic regression and other GIS methods are employed to determine crime density and crime probability in different distance zones from alco- hol-serving establishments. The results of our analysis confirm that density and probability of all types of crimes declines exponentially with increasing distance from alcohol services. Current research cannot control for myriad of confounding variables for criminal behavior. Although our findings are consistent with research on alcohol consumption as a causal agent in violent criminal activity, our method ofestimating crime probability in space is unique. The crime probability maps produced using this method can be valuable for police resource allocation and patrolling in many other cities.
Time-dependent Conformational Changes in Adsorbed Albumin and its Effect on Platelet Adhesion

Abstract Recent studies have shown that platelets can adhere to adsorbed albumin (Alb) through a receptor-mediated mechanism, but only if the Alb undergoes more than a critical degree of adsorption-induced unfolding. The objectives of this research were to investigate whether Alb that wasinitially adsorbed in a manner that induced unfolding that was less than this critical level wouldundergo further unfolding with time; and if so, whether this would induce the onset of plateletadhesion once this critical level was exceeded. To address these questions, CD spectropolarimetrywas used to monitor the structure of Alb on OH- and CH 3 -functionalized alkanethiol self-assembled monolayer surfaces, with the Alb initially adsorbed under conditions resulting indegrees of unfolding that were below this critical level, and then the adsorbed Alb layers wereaged over a six-month period of time in sterile physiological saline at 37°C. Platelet adhesion toAlb was quantified at selected time points via a lactate dehydrogenase (LDH) assay. The resultsindicate that an adsorbed Alb layer does undergo further structural changes with increasingresidence time and supports platelet adhesion once it unfolds beyond the previously determinedcritical level. These results may be relevant to the clinically observed problem of the onset of late-thrombosis, which occurs on cardiovascular implants such as drug-eluting stents.
The SP-C promoter facilitates alveolar type II epithelial cell-specific plasmid nuclear import and gene expression

Although nonviral gene therapy has great potential for use in the lung, the relative lack of cell-specific targeting has limited its applications. We have developed a new approach for cell-specific targeting based on selective nuclear import of plasmids in nondividing cells. Using a microinjection and in situ hybridization approach, we tested several potential DNA sequences for the ability to mediate plasmid nuclear import in alveolar type II epithelial (ATII) cells. Of these, only a sequence within the human surfactant protein C (SP-C) promoter was able to mediate nuclear localization of plasmid DNA specifically in ATII cells but not in other cell types. We have mapped the minimal import sequence to the proximal 318 nucleotides of the promoter, and demonstrate that binding sites for nuclear factor I, thyroid transcriptional factor 1, and GATA-binding protein 6 and the proteins themselves are required for import activity. Using intratracheal delivery of DNA followed by electroporation, we demonstrate that the SP-C promoter sequence will enhance gene expression specifically in ATII cells in mouse lung. This represents a new activity for the SP-C promoter, and thus ATII cell-specific nuclear import of DNA may prove to be a safe and effective method for targeted and enhanced gene expression in ATII cells.
Effects of Oxygen and Sulfur on Alloying Element Vaporization Rates during Laser Welding

Inadequate control of weld metal composition due to vaporization of volatile alloying elements is a serious problem in the welding of many important engineering alloys. Effectiveness of surface active elements such as oxygen or sulfur in blocking vaporization sites on the weld pool surface was investigated. Several iron samples doped with oxygen or sulfur were exposed to a carbon dioxide laser beam in pulsed mode. The time average metal vaporization rates and the emission spectra were compared with those obtained from ultra pure iron samples. Since the weld pool surface area and temperature distribution are affected by oxygen and sulfur, the true effects of these elements on metal vaporization rates cannot be easily evaluated from welding data. Therefore, rates of isothermal vaporization of iron and copper drops doped with oxygen or sulfur were determined both in the presence and the absence of low pressure argon plasma. These rates were compared with the rates of vaporization of ultrapure metal drops. Presence of sulfur or oxygen in metals always resulted in increased metal vaporization rates. The results are analyzed on the basis of interfacial phenomena.
Variations in histamine, IgE and interferon concentrations in nasal secretions and seraof children with asthma associated with viral or mycoplasma infection

Histamine and virus-specific IgE appear to play some role in the pathogenesis of wheezing which occurs during viral infection. Respiratory viruses can enhance IgE-mediated histamine release in vitro partly by inducing interleron (IFN). To investigate the role of histamine, IgE, and IFN in the pathogenesis of asthma associated with infection, we prospectively studied hospitalized infants and children (8 months to 17 years of age) with acute episodes of asthma. Patients were enrolled and acute samples were collected within 2 days of admission; convalescent samples were obtained 1 to 4 weeks later. Patients were separated into virus/mycoplasma-assoeiated and noninfectious asthma groups by comprehensive virologic and serologic techniques. One third of acute asthma episodes proved to be virus/mycoplasma-associated. In both asthma groups, nasal wash histamine values were significantly higher during acute attack, compared to convalescence. However, during acute attack, there was a trend for more detectable histamine and in higher concentrations from patients with infectious asthma, compared to the noninfectious group. Histamine was correlated with nasal wash and serum IgE during acute episodes of only infectious asthma. Nasal wash or serum IFN levels did not differ between the 2 patient groups. However, high IFN titers were detected in sera of all 3 patients with asthma associated with RSV infection, although RSV is known to be a poor IFN inducer. Our findings suggest an agreement with the hypothesis that histamine and IgE may play a role in attacks of asthma which arc associated with viral or mycoplasma infection. Further studies are required to confirm our obsmution and to evaluate the role of other inflammatory mediators in the mechanism of infectious asthma.
Mortality awareness and risk-taking in late adolescence.

Abstract The relationship of mortality awareness to sexual, drug, and athletic risk-taking by male and female college students was rneasured using two questionnaires. Regression analyses of Study 1 data revealed: (a) significantly greater sexual risk-taking among males (n = 68) than among jirmales (n = 119) β = -.20, p < .01; (b) a significant negative relationship of mortality awareness to sexual risk-taking in males, β = -.36, p < .01; and (c) no relationship of mortality awareness to reported drug use or athletic risk-taking. Regression analyses of data from Study 2, which included only male subjects (n = 40), revealed that initial mortality awareness was significantly related to sexual risk-taking (β = - -33, p < .05), but that manipulated awareness of death did not affect willingness to take sexual risks. It was suggested that mortality awareness may reduce the taking of rish that present nonsalient consequences, and that the consequences of risky sexual behavior my be less salient for males than for...
An empirical study of reported bugs in server software with implications for automated bug diagnosis

Reproducing bug symptoms is a prerequisite for performing automatic bug diagnosis. Do bugs have characteristics that ease or hinder automatic bug diagnosis? In this paper, we conduct a thorough empirical study of several key characteristics of bugs that affect reproducibility at the production site. We examine randomly selected bug reports of six server applications and consider their implications on automatic bug diagnosis tools. Our results are promising. From the study, we find that nearly 82% of bug symptoms can be reproduced deterministically by re-running with the same set of inputs at the production site. We further find that very few input requests are needed to reproduce most failures; in fact, just one input request after session establishment suffices to reproduce the failure in nearly 77% of the cases. We describe the implications of the results on reproducing software failures and designing automated diagnosis tools for production runs.
Diabetes, the metabolic syndrome, and ischemic stroke: epidemiology and possible mechanisms.

Stroke affects more than 700,000 individuals each year; it is the third largest cause of death and the largest cause of adult disability in the U.S. Diabetes is a major risk factor for the development of stroke, yet this risk is not realized or understood by patients with diabetes. This likely reflects a lack of understanding within the medical community of how diabetes confers this risk. We will explore the potential underlying mechanisms that lead to increased incidence of stroke among diabetic patients. Beyond diabetes itself, the metabolic syndrome and its components will also be discussed. The impact of diabetes and hyperglycemia on stroke outcomes and a discussion of current approaches to reduce stroke in this high-risk population are included. Because type 2 diabetes affects the vast majority of those diagnosed with diabetes, it will be the primary focus of this discussion. It has been well documented that diabetes confers a significantly increased risk of stroke, as well as increased mortality following stroke (1–7). Stroke is a preventable disease with high personal and societal cost. While great progress has been made in understanding the link between diabetes and coronary heart disease (CHD), the literature on diabetes and stroke has been less enlightening. CHD is a larger problem that accounts for 40–50% of mortality in diabetes. Because of the overwhelming impact of CHD, the impact of stroke has been relatively underappreciated. Thus, physicians, diabetes educators, and nurses are less equipped to educate patients. We therefore review the relationship between diabetes and stroke. Given that more than one million people are diagnosed with diabetes yearly, a figure that is expected to rise, the impact of diabetes on the incidence of stroke is of increasing importance. Diabetic patients compose roughly 6.3% of the U.S. population but account for 15–27% of all …
Effect of Water Vapor Content in H2–H2O–CO–CO2 Mixtures on the Equilibrium Distribution of Manganese between CaO–MgOsat–SiO2–Al2O3–FeO–P2O5 Slag and Molten Iron

The equilibrium distribution of manganese between slag and molten iron has been investigated under three different gas environments. MgO-saturated CaO–FeO–Al2O3–SiO2–MnO (0.2–0.8 wt%)–P2O5 (0.1–0.9 wt%) slags were studied in the temperature range 1550–1600°C under CO/CO2/H2/H2O (natural/coal gas, NG/CG), H2/H2O (H2 reductant), and CO/CO2 with pO2 = 10−10 to 10−9 atm. The first two gas mixtures represented the case of using natural or coal gas and hydrogen in the novel flash ironmaking technology. The average LMn (manganese distribution ratio) was found to be 4, 5, and 6 under CO/CO2/H2/H2O (natural/coal gas), H2/H2O (H2 reductant), and CO/CO2, respectively. In other words, LMn under H2 and natural/coal gas conditions was 29% and 43% less than under the CO/CO2 atmosphere. Therefore, water in the gas atmosphere depresses LMn. When an ore with Mn content of 0.2 wt% is fed into three routes in addition to coke with 0.07 wt% Mn, which was added at the ratio of 0.4 coke-to-hot metal in the case of the CO/CO2 gas mixture, the hot metal reduced under the CO/CO2, NG/CG, and H2 conditions, is expected to contain 0.13, 0.14, and 0.15 wt% Mn, respectively. That is H2 and NG/CG are expected to produce hot metal with 17% and 25% more Mn than in the CO/CO2 conditions. This work has for the first time determined the effect of water vapor on the distribution of Mn between slag and molten iron.
A two-step adaptive controller for a two-body system

A reduced-order adaptive control scheme using a direct state-feedback control law and an indirect feedforward compensation design is presented for a two-body system with joint flexibility and damping. A detailed stability analysis is given for such a two-step adaptive control design, which ensures closed-loop signal boundedness and asymptotic output tracking.
A Programmable Analog Neural Computer and Simulator

This report describes the design of a programmable general purpose analog neural computer and simulator. It is intended primarily for real-world real-time computations such as analysis of visual or acoustical patterns, robotics and the development of special purpose neural nets. The machine is scalable and composed of interconnected modules containing arrays of neurons, modifiable synapses and switches. It runs entirely in analog mode but connection architecture, synaptic gains and time constants as well as neuron parameters are set digitally. Each neuron has a limited number of inputs and can be connected to any but not all other neurons. For the determination of synaptic gains and the implementation of learning algorithms the neuron outputs are multiplexed, A/D converted and stored in digital memory. Even at moderate size of 103 to 105 neurons computational speed is expected to exceed that of any current digital computer.
Antipsychotics for behavioral and psychiatric symptoms of dementia: a reaudit in a specialist inpatient service.

The use of antipsychotics for the management of behavioral and psychiatric symptoms of dementia (BPSD) remains highly controversial. These drugs are well known to be associated with increased mortality from cerebrovascular events, as well as with falls, cognitive impairment, and other serious side effects. In 2009, a UK target was set to reduce their use in dementia patients by two-thirds over a three-year period (Banerjee, 2009 ).
Interaction of Lung Surfactant Protein A with Phosphatidylcholine Vesicles

Surfactant protein A (SP-A) , a member of the collectin family found in the lung, binds to dipalmitoylphosphatidylcholine (DPPC), and plays roles in the formation of tubular myelin and the regulation of uptake and secretion of surfactant lipids by alveolar type II cells. The calcium dependent binding of SP-A to both small (SUV) and large (LUV) unilamellar vesicles of phosphatidylcholines (PC) has a dramatic effect on the PC dynamics as measured by 1H linewidths of the acyl chains. For fluid bilayers (dipalmitoyl-PC at 42°C, dimyristoyl-PC and 1-palmitoyl-2-oleoyl-PC at 37°C), ω-CH3 as well as bulk (CH2)n and N(CH3)3 resonances are broadened with the addition of SP-A above a molar ratio of 0.02 SP-A/PC. This binding does not cause SUV or LUV fusion as monitored by negative staining TEM. However, the SP-A binding to PC vesicles exhibits two phases, one where the chain resonances are constrained and a second, requiring increased Ca2+ or the presence of 10 mol% cholesterol, characterized by a new downfield (CH2)n resonance. The addition of EDTA can partially reverse the second phase of SP-A binding. The changes in PC acyl chain behavior provide insight into how SP-A interacts with multilamellar bodies and how it may aid in insertion of dipalmitoyl-PC into the air-water interface of the lung.
A Primitive Endogenous Lentivirus in a Colugo: Insights into the Early Evolution of Lentiviruses

Lentiviruses infect a wide range of mammal species. Much remains unknown about their deep history and host distribution. Here, we report the discovery of an endogenous lentivirus within the genome of the Sunda flying lemur (Galeopterus variegatus) (which we designate "Galeopterus variegatus endogenous lentivirus" [GvaELV]). We estimate the GvaELV genome invasion to have occurred more than 14 Ma, supporting an ancient origin of the lentivirus clade and an ancient lentiviral infection in colugo. Phylogenetic analyses show that GvaELV is a sister group of all previously known lentiviruses. The GvaELV genome appears to possess some primitive genomic features of a lentivirus, encoding not only a trans-activator of transcription (tat) gene but also two additional putative accessory genes that share no discernible similarity with other lentiviral accessory genes. The discovery of GvaELV provides novel insights into the prehistory and host distribution of lentivirus.
Thyroxine is a potential endogenous antagonist of macrophage migration inhibitory factor (MIF) activity

Abnormally low plasma concentrations of thyroid hormones during sepsis often occur in the absence of thyroidal illness; however, the mechanisms involved in the “euthyroid sick syndrome” remain poorly understood. Here, we describe a previously unrecognized interaction between the thyroid hormone thyroxine (T4) and the proinflammatory cytokine macrophage migration inhibitory factor (MIF), together with its clinical relevance in sepsis. We found that in both patients with severe sepsis, and our rodent model, low plasma T4 concentrations were inversely correlated with plasma MIF concentrations. The MIF molecule contains a hydrophobic pocket that is important for many of its proinflammatory activities. Binding of L-T4 (or its hormonally inert isomer D-T4) significantly, and dose-dependently, inhibited the catalytic activity of this pocket. Moreover, administration of exogenous D-T4 significantly improved survival in mice with severe sepsis. To examine the specificity of the MIF∶T4 interaction, wild-type and MIF knockout mice were subjected to the carrageenan-air pouch model of inflammation and then treated with D-T4 or vehicle. D-T4 significantly inhibited leukocyte infiltration in wild-type mice but not in MIF knockout mice, providing evidence that in vivo T4 may influence MIF-mediated inflammatory responses via inhibition of its hydrophobic proinflammatory pocket. These findings demonstrate a new physiological role for T4 as a natural inhibitor of MIF proinflammatory activity. The data may also, in part, explain the low plasma T4 concentrations in critically ill, euthyroid patients and suggest that targeting the imbalance between MIF and T4 may be beneficial in improving outcome from sepsis.
On combining multiple clusterings

Many problems can be reduced to the problem of combining multiple clusterings. In this paper, we first summarize different application scenarios of combining multiple clusterings and provide a new perspective of viewing the problem as a categorical clustering problem. We then show the connections between various consensus and clustering criteria and discuss the complexity results of the problem. Finally we propose a new method to determine the final clustering. Experiments on kinship terms and clustering popular music from heterogeneous feature sets show the effectiveness of combining multiple clusterings.
Significant improvements in marine gravity from ongoing satellite missions

Incorporating new altimeter data from CryoSat-2 (30 months), Envisat (18 months), and Jason-1 (7 months) satellites into an updated marine gravity field yields significant reduction in noise and improved resolution. Compared to an older gravity field that did not include the new altimeter data, incoherent power is reduced globally by approximately 2.9 dB at 15 km, 1.6 dB at 20 km, and 1.0 dB at 25 km wavelengths. Coherence analyses between the updated gravity and recent multibeam surveys distributed throughout the world’s oceans shows an average increase of ~0.023 in mean coherence in the 20–160 km waveband, with the biggest increase (>0.08) over fast spreading ridges and smallest ( 3.5 km) over fast spreading ridges and smallest (<1.5 km) over slow spreading ridges and continental shelves. In the Clipperton fracture zone area these improvements result in seamounts that are more accurately located, the detection of smaller seamounts, and the expression of north–south trending abyssal hill fabric. As more altimeter data from the ongoing satellite missions are incorporated into future gravity field updates, finer-scale details of the seafloor will continue to emerge.
Statistical Issues in the Design and Analysis of Clinical Trials in Alzheimer's Disease*:

The nature and symptoms of Alzheimer's disease present unique issues and problems related to the design and analysis of clinical trials for assessing the efficacy of potential therapies. Based on the author's involvement with two multicenter studies in Alzheimer's patients, issues related to the design and analysis of such trials are discussed. Due to the progressive nature of the disease and the potential for carryover and withdrawal effects, crossover and enriched population designs are not recommended. Instead, parallel group comparisons are preferable. Since Alzheimer's disease has both cognitive and behavioral symptoms, both an objective cognitive test and a global assessment are recommended primary outcome variables. Other important design issues are specification of efficacy criteria, length of the double-blind treatment period, dose escalation, and follow-up of dropouts. With respect to statistical analysis, it is important to include all randomized patients in the analysis and to make every possi...
Expression of the breast cancer resistance protein (Bcrp1/Abcg2) in tissues from pregnant mice: effects of pregnancy and correlations with nuclear receptors

The breastcancer resistance protein (BCRP) plays an important role in drug disposition, including limiting drug penetration across the placental barrier. Our goal was to investigate the effects of ...
β-Amyloid Accumulation Impairs Multivesicular Body Sorting by Inhibiting the Ubiquitin-Proteasome System

Increasing evidence links intraneuronal β-amyloid (Aβ42) accumulation with the pathogenesis of Alzheimer’s disease (AD). In Aβ precursor protein (APP) mutant transgenic mice and in human AD brain, progressive intraneuronal accumulation of Aβ42 occurs especially in multivesicular bodies (MVBs). We hypothesized that this impairs the MVB sorting pathway. We used the trafficking of the epidermal growth factor receptor (EGFR) and TrkB receptor to investigate the MVB sorting pathway in cultured neurons. We report that, during EGF stimulation, APP mutant neurons demonstrated impaired inactivation, degradation, and ubiquitination of EGFR. EGFR degradation is dependent on translocation from MVB outer to inner membranes, which is regulated by the ubiquitin-proteasome system (UPS). We provide evidence that Aβ accumulation in APP mutant neurons inhibits the activities of the proteasome and deubiquitinating enzymes. These data suggest a mechanism whereby Aβ accumulation in neurons impairs the MVB sorting pathway via the UPS in AD.
State Failure and Challenges to Democratization in Africa

When Things Fell Apart manages to be wonderfully concise but still compelling. The thing Robert Bates seeks to explain is the secular trend in sub-Saharan Africa toward civil war, although he often characterizes this in broader terms, as a trend toward “political conflict” or “political disorder.” He explains the trend as follows: Public revenues fell in the 1970s and 1980s as a result of commodity price declines, effects of the second oil shock, and bad economic policy choices that overtaxed farmers so that politicians could dispense patronage to smaller, politically more important urban constituencies. The decline in public revenues led elites to become more predatory, which caused an increase in political conflict by mobilizing opposition. Popular demands for political reform, along with increased international pressure for the same at the end of the Cold War, heightened elite insecurity and led to more predation. This had the effect of “provoking their citizens to take up arms” (p. 109). Further, state decline and national-level conflicts exacerbated simmering subnational conflicts, typically in the form of land disputes between locals and migrants from other tribes.
Heart rate variability in premature infants during feeding.

Early mother-infant interaction, a potentially major contributor to the development of a premature infant's behavioral and physiologic regulation, has received very little research attention. This ...
Two distinct mechanisms of nitric oxide-mediated neuronal cell death show thiol dependency.

To better understand the mechanism(s) underlying nitric oxide (⋅ NO)-mediated toxicity, in the presence and absence of concomitant oxidant exposure, postmitotic terminally differentiated NT2N cells...
Effect of Joint Scale and Processing on the Fractureof Sn-3Ag-0.5Cu Solder Joints: Application to Micro-bumpsin 3D Packages

In 3-dimensional (3D) packages, a stack of dies is vertically connected to each other using through-silicon vias and very thin solder micro-bumps. The thinness of the micro-bumps results in joints with a very high volumetric proportion of intermetallic compounds (IMCs), rendering them much more brittle compared to conventional joints. Because of this, the reliability of micro-bumps, and the dependence thereof on the proportion of IMC in the joint, is of substantial concern. In this paper, the growth kinetics of IMCs in thin Sn-3Ag-0.5Cu joints attached to Cu substrates were analyzed, and empirical kinetic laws for the growth of Cu6Sn5 and Cu3Sn in thin joints were obtained. Modified compact mixed mode fracture mechanics samples, with adhesive solder joints between massive Cu substrates, having similar thickness and IMC content as actual micro-bumps, were produced. The effects of IMC proportion and strain rate on fracture toughness and mechanisms were investigated. It was found that the fracture toughness G C decreased with decreasing joint thickness (h Joint). In addition, the fracture toughness decreased with increasing strain rate. Aging also promoted alternation of the crack path between the two joint–substrate interfaces, possibly proffering a mechanism to enhance fracture toughness.
Human Resource Outsourcing: Long Term Operating Performance Effects From The Providers Perspective

Human resource (HR) outsourcing research has primarily focused on the client with little attention paid to the service provider. As an initial step in understanding this important stakeholder in the HR outsourcing relationship, this study focuses on the financial performance of HR service firms that publicly announce outsourcing contracts. From the provider’s perspective, we investigate firm performance changes subsequent to outsourcing contract announcements, using a sample of 94 publicly available press releases. Our tests show that in the long term, small HR service providers contracted by large client firms experience improvements in operating profitability and margins.
Solid Photonic Band-Gap Fiber with 400 nm Bandwidth and Loss below 4 dB/km at 1520 nm

We demonstrate a wide-band and low-loss (< 4 dB/km at 1520 nm) solid photonic band-gap fiber (PBGF). The fiber is practically single-mode in a long length regime and has a large anomalous dispersion over a wide wavelength range.
Microstructure and Property of Novel Heat-resistance Steel Super304H After Being Aged at High Temperature

The microstructure and property of novel austenitic heat-resistance steel Super304H after being aged at 750-1350℃ were investigated by the means of optical microscope,scanning electron microscopy(SEM),X-ray diffraction(XRD),as well as hardness testing and impact test.The experimental results indicated that the microstructure of super304H after being aged included γ-phase and precipitated phase.With the variation of aging temperature,the grain size of matrix and the type of precipitated phase will be changed.When the sample was aged at 750℃,the hardness reached the maximum value due to the precipitation strengthening and fine microstructure.With increasing the aging temperature beyond 750℃,the microhardness rapidly decreased at first and then decreased slowly because of the variation of precipitated phase,grain size and solid solution elements.The impact energy value of aged sample increased before being aged at 850℃,and reached minimum when aged at 850℃ due to M23C6 precipitated along grain boundary and caused embrittlement.The impact energy increased again with increasing aging temperature,because the precipitated phase redissolved and eliminating the grain boundary embrittlement.
Choosing a Mode of Political Marketing Strategy: Voter or Brand Identity Orientation

No entity has as much impact on as many lives as a government. Through social programs, taxes, military use, and many others, every life is affected every day by public sector entities. This power, influence, and relevance to public life is acquired through the means of marketing, with candidates, parties, and interest groups spending billions of dollars each cycle in hopes of “winning” the democratic process, allowing them ultimately to exert their policies upon the public, changing the political and policy landscape of their country, city, state, or nation. Despite the enormous importance, utilization, and impact of marketing on politics, very little thought within marketing research literature has been given to understanding how political marketing strategy is developed, functions, or the antecedents for its success. This paper aims to be a starting point in changing this. It proposes a testable conceptual framework of political marketing strategy modes, using extant research and examples from political campaigns to develop a parsimonious model for what types of campaign modes exist, and how campaign strategies are chosen. Further, this paper lays out an agenda for future research, aiming to help marketing researchers move forward in researching and understanding political campaign strategy.
Stimulated On-Axis Photon Echo Modulation in Ruby

Four wave interaction of optical fields in solids is a subject of extensive investigations in nonlinear optics, being a valuable spectroscopic tool as well as offering applications1 in dynamic optical memories and devices transforming optical wavefronts. Stimulated echoes (SE) may be considered as a delayed four wave interaction. In this paper we present studies of optical SE modulation in ruby. Such modulation has been recently observed 2,3 in solids and, in the case of ruby, only for the magnetic field at an angle with the crystal axis. We describe here, for the first time, studies of the 4A2(−3/2)→Ē(−1/2) (or −3/2→−1/2) transition using a tunable single frequency dye laser. This transition has not been observed before because of the tuning limitations of the CW ruby lasers used thus far 3,4.
New abolition, criminology and a critical carceral studies:

Criminology has been slow to open up a conversation about decarceration and abolition in comparison with other disciplines, including history, geography, and gender, race, and critical ethnic studi...
Malignant Brenner tumor associated with a germline BRCA2 mutation

•The first woman with a Malignant Brenner tumor and a BRCA2 mutation is described.•Not all women with epithelial ovarian cancers are referred for genetic counseling.•Women should be referred for genetics regardless of how rare the histology.