cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of aminophospholipid asymmetry in murine fibroblast plasma membranes by choline and ethanolamine analogues.

Abstract The regulation of the asymmetric distribution of aminophospholipids in mammalian cell plasma membranes is not understood at this time. One approach to determine the nature of such regulatory mechanisms is to attempt alteration of the plasma membrane phospholipid composition. Choline analogues such as N,N′- dimethylethanolamine and N- monomethylethanolamine lowered the quantity of phosphatidylethanolamine in the plasma membrane of LM fibroblasts grown in defined medium without serum. Ethanolamine supplementation increased the phosphatidylethanolamine content while ethanolamine analogues such as 2-amino-2-methyl-1-propanol, 2-amino-1-butanol, 1-aminopropanol, and 3-aminopropanol did not alter the aminophospholipid content significantly. The transverse distribution of aminophospholipids in the plasma membrane was determined by use of a chemical labelling reagent trinitrobenzenesulfonic acid. The percent phosphatidylethanolamine trinitrophenylated by trinitrobenzenesulfonate in the outer plasma membrane monolayer of LM cells supplemented with choline analogues was not altered. In contrast, ethanolamine analogue supplementation increased the percentage of aminophospholipid in the outer monolayer 2–3-fold. Ethanolamine analogue-containing phospholipids were distributed asymmetrically across the plasma membrane with 85 to 91% being located in the inner monolayer of the plasma membrane, a distribution similar to that of phosphatidylethanolamine. The fatty acyl composition of aminophospholipids in the outer monolayer was in all cases more saturated than in the corresponding phospholipids of the inner monolayer. However, choline analogues and especially the ethanolamine analogues reduced this difference. Thus, base analogues of choline and ethanolamine may alter the aminophospholipid asymmetry, the surface charge, and the acyl chain asymmetry of LM cell plasma membranes
Transcending organizational boundaries: virtual team approach in UI guideline development

This paper covers the experience of creating the IBM Web Application User Interface Design guidelines. The guidelines represent the integration of five other guideline sets that were in use at IBM. This paper discusses how the guidelines were developed, problems encountered, and lessons learned in that process. Some of the problems included difficulty in finding realistic examples of guideline topics, too much time spent on low-level detail with not enough on developing design patterns, and the time constraints of the virtual team. Recommendations for overcoming these issues are given.
Assessing the cost of transfer inconvenience in public transport systems: A case study of the London Underground

Abstract Few studies have adequately assessed the cost of transfers 2 in public transport systems, or provided useful guidance on transfer improvements, such as where to invest (which facility), how to invest (which aspect), and how much to invest (quantitative justification of the investment). This paper proposes a new method based on path choice, 3 taking into account both the operator’s service supply and the customers’ subjective perceptions to assess transfer cost and to identify ways to reduce it. This method evaluates different transfer components (e.g., transfer walking, waiting, and penalty) with distinct policy solutions and differentiates between transfer stations and movements. The method is applied to one of the largest and most complex public transport systems in the world, the London Underground (LUL), with a focus on 17 major transfer stations and 303 transfer movements. This study confirms that transfers pose a significant cost to LUL, and that cost is distributed unevenly across stations and across platforms at a station. Transfer stations are perceived very differently by passengers in terms of their overall cost and composition. The case study suggests that a better understanding of transfer behavior and improvements to the transfer experience could significantly benefit public transport systems.
Effect of triiodothyronine and insulin on glucose metabolism in tissue explants and isolated adipocytes from lean and obese Zucker rats

The effect of triiodothyronine ( T 3 ) and insulin treatment on glucose metabolism in isolated adipocytes of 5 week old lean and obese Zucker rats was examined. Insulin had a strong stimulatory effect on glucose metabolism. Insulin stimulated and non-stimulated glucose utilization was greater in the obese than the lean rats. The effect of insulin and phenotype on glucose utilization was pathway specific as fatty acid, COg and glycerol-glyceride formation were stimulated by different magnitudes. Pretreatment of isolated adipocytes with pharmacological conce.itrations of T3 for 1/2 hour prior to measurement of glucose metabolism decreased fatty acid synthesis more in the adipocytes from lean than obese rats. The presence of insulin was required in the T3 pretreated cells to observe any effect of T3. The effect of a 2 hour pretreatment of adipocytes with T3 was dependent upon the phenotype of the cells, insulin status and the specific pathway of glucose utilization. The effect of T3 in the presence of insulin in both lean and obese adipocytes was to decrease lipogenesis. In the absence of insulin, the 2 hour pretreatment effect of T3 in tissue from a euthyroid animal was to increase lipogenesis at physiological concentrations and decrease lipogenesis at pharmacological concentrations. A pharmacological dose of T3 was required to increase lipogenesis in the absence of insulin in hypothyroid tissue. This is suggestive that obese tissue is resistant to thyroid hormones. However, in the presence of insulin, physiological levels of T3 decreased fatty
Alcohol dependence and hospitalization in schizophrenia.

Treatment of schizophrenia is often complicated by substance abuse. We report here findings of a retrospective study evaluating readmission rates of patients meeting DSM IV criteria comorbid for schizophrenia and alcohol or drug dependence treated with depot haloperidol or fluphenazine over a 2-year period. During the study period, 14 of the 26 (54%) male veteran patients were admitted to the VAMC, Charleston; 46% of patients met criteria for alcohol, marijuana or cocaine dependence. Patients with alcohol dependence appeared to be at highest risk for hospital admission (p<0.05). Moreover, patients with alcohol dependence had longer hospital stays (p<0.05) than patients without alcohol dependence. Marijuana or cocaine dependence was slightly, but not statistically more common among admitted patients. Marijuana or cocaine dependence did not predict length of stay or number of admissions. Alcohol dependence may be an important factor in schizophrenic exacerbation, and may be an important target for treatment.
To Cover Their Child, One Couple Navigates A Health Insurance Maze In Pennsylvania

Two graduate students fight the bureaucracy to gain coverage for their son under the Children’s Health Insurance Program—and hope that provisions of the Affordable Care Act will cut the red tape.
Quantification of Isoprostanes as Indices of Oxidant Stress and the Risk of Atherosclerosis in Humans

Enhanced oxidant stress occurring either locally in the vessel wall or systemically is implicated in the pathogenesis of atherosclerosis in humans. Nonetheless, evidence that oxidant stress is increased in vivo in association with this disease and that it can be quantified in living human beings has been lacking because of the unavailability of biomarkers to assess oxidant stress in humans. Recently, the development of methods to quantify the F(2)-isoprostanes (IsoPs), prostaglandin (PG)-like compounds derived from the free radical-catalyzed peroxidation of arachidonic acid, has allowed, for the first time to the author's knowledge, a facile and accurate assessment of oxidant stress in vivo. The purpose of this brief review is to discuss the usefulness of quantifying IsoPs as an index of oxidative injury in association with atherosclerosis. F(2)-IsoPs can be measured in human biological fluids, such as plasma and urine, using highly precise assays. They have been shown to be increased in association in with a number of atherosclerotic risk factors, including cigarette smoking, hypercholesterolemia, diabetes mellitus, and obesity, among others. In addition, recent evidence suggests their quantification may represent an independent marker of atherosclerotic risk. A reduction in cardiovascular risk factors is associated with a decrease in IsoP formation in humans. Despite the fact that the role of oxidant stress in the pathogenesis of atherosclerosis is a hotly debated issue, current evidence suggests that the IsoPs represent a biomarker that has the potential to be of great importance in the assessment of human atherosclerotic cardiovascular disease. Enhanced oxidant stress occurring either locally in the vessel wall or systemically is implicated in the pathogenesis of atherosclerosis in humans. Nonetheless, evidence that oxidant stress is increased in vivo in association with this disease and that it can be quantified in living human beings has been lacking. Recently, the development of methods to quantify the F2-isoprostanes (IsoPs) has allowed a facile and accurate assessment of oxidant stress in vivo. The purpose of this brief review is to discuss the usefulness of quantifying IsoPs as an index of oxidative injury in association with atherosclerosis.
Stereo in the presence of specular reflection

The problem of accurate depth estimation using stereo in the presence of specular reflection is addressed. Specular reflection, a fundamental and ubiquitous reflection mechanism, is viewpoint dependent and can cause large intensity differences at corresponding points, resulting in significant depth errors. We analyze the physics of specular reflection and the geometry of stereopsis which led us to a relationship between stereo vergence, surface roughness, and the likelihood of a correct match. Given a lower bound on surface roughness, an optimal binocular stereo configuration can be determined which maximizes precision in depth estimation despite specular reflection. However, surface roughness is difficult to estimate in unstructured environments. Therefore, trinocular configurations, independent of surface roughness, are determined such that at each scene point visible to all sensors, at least one stereo pair can compute produce depth. We have developed a simple algorithm to reconstruct depth from the multiple stereo pairs. >
Media Use and Children's Perceptions of Societal Threat and Personal Vulnerability

This study examined children's media use (i.e., amount of television and Internet usage) and relationships to children's perceptions of societal threat and personal vulnerability. The sample consisted of 90 community youth aged 7 to 13 years (M = 10.8; 52.2% male) from diverse economic backgrounds. Analyses found children's television use to be associated with elevated perceptions of personal vulnerability to world threats (i.e., crime, terrorism, earthquakes, hurricanes, and floods). An interactive model of television use and child anxiety in accounting for children's personal threat perceptions was supported, in which the strength of television consumption in predicting children's personal threat perceptions was greater for children with greater anxiety. Relationships were found neither between children's Internet use and threat perceptions nor between media use and perceptions of societal threat.
A power MOSFET model based on a lumped-charge approach

The lumped-charge approach offers a compact, physical power MOSFET model which is equivalent in complexity to the SPICE MOSFET model (level 1) used for low voltage devices. The surface charge is assumed to be lumped into nodes calculated using standard delta depletion (body region) or moderate depletion (drain region) approximations. An equivalent circuit for the MOSFET model can be derived from the interaction of the internal lumped-charges with the three external terminal voltages. The model is implemented in the SABER simulator. Simulated results are in good agreement with measured results. >
Review of objective room acoustics measures and future needs

ISO 3382-1 describes a number of objective room acoustics parameters that are generally accepted as useful for rating some specific aspects of concert hall sound fields. They include measures of decay times, energy ratios, measures of sound strength and several quantities related to the spatial aspects of sound fields. In most cases there are details of the measures, or their application, that raise questions. In general, there has not been a lot of practical research to explore how best to develop and use these objective measures to evaluate conditions in concert halls. For some well established measures such as Early Decay Time (EDT), we are not really sure how best to calculate their values. For other measures such as energy ratios, modifications are often proposed but without the support of subjective evaluations of the proposed changes. In other cases, such as measures of spatial impression, two approaches have been suggested, but their relative merits are not well understood. It is easy to propose ever more complex measures, but it is much more difficult to demonstrate their general utility. On the other hand, some commonly described characteristics do not have accepted related objective measures. Many more important and more general problems relate to the need, for design criteria in terms of each quantity, and for an improved understanding of just noticeable differences for each measure. This paper discusses each measure illustrating particular problems with measurements in various halls.
Image-based motion control for the bending section of a colonoscope

An image guidance control system for colonoscopy is investigated with a dynamic model for the bending section. The lumen image is used to orient the colonoscope tip for tracking as the instrument moves through the colon. Simulation results show control system stability. By automating tip orientation it is expected to reduce doctor training times, improve the efficiency of operations, and reduce surgical errors. Relieving the medical professional from controlling tip orientation should enable greater proficiency in inspecting the lining of the colon for diagnostics and operations, such as biopsy.
Using qualitative methods to access the pain experience

Qualitative methods provide us with techniques to access the pain experience of patients in ways that provide explanation for apparent contradictions and idiosyncrasies that are difficult to access. In this article, I review three such strategies and the application of qualitative research to practice: (1) the analysis of the ways participants speak about agonizing pain using narrative inquiry, (2) comparisons of childbirth pain in two cultural groups using ethnography and (3) present a qualitative theory, the Praxis Theory of Suffering. This theory provides a theoretical explanation for behaviours that presently confound the understanding of distress using the Distress Thermometer. An alternative approach, ‘reading’ patients’ behavioural manifestations of distress, is recommended.
Porter's value chain model for assessing the impact of the internet for environmental gains

The revolutionary potential of the internet promises to transform economic and environmental gains. By reducing the amount of energy and materials consumed by business, the internet stands to revolutionise the relation between economic growth and the environment. The internet is improving the capability to understand the science of environmental degradation and communicate that knowledge to public and private decision makers. It also helps decrease resource waste and associated pollution by improving the efficiency of economic activity and provides improved sensors and instantaneous telecommunications links to control pollution spillovers, better manage shared resources and reduce waste. This paper examines the impact and potential of internet-based technologies in the performance of important information and communication functions for resolving the environmental issues using Porter's value chain model. Managerial implications of using the internet for environmental gains for SMEs are also discussed.
In‐state tuition for the undocumented: Education effects on Mexican young adults

This paper examines the effect of tuition subsidy in the form of in-state tuition to undocumented students on the education of noncitizen Mexican young adults. The policy is found to be associated with a 2.5 percentage point increase in college enrollment (base mean = 8%), a 3.7 percentage point increase in the proportion of students with at least some college education (base mean = 10%), and a 1.3 percentage point increase in the proportion with at least an associate degree (base mean = 4%). These results are robust to a variety of specifications. When the analysis is restricted to samples more likely to be affected by the policy, point estimates become larger. The study finds no evidence that in-state tuition policy for the undocumented adversely affects the educational outcomes of natives. © 2008 by the Association for Public Policy Analysis and Management.
Dynamic power management in a mobile multimedia system with guaranteed quality-of-service

In this paper we address the problem of dynamic power management in a distributed multimedia system with a required quality of service (QoS). Using a generalized stochastic Petri net model where the non-exponential inter-arrival time distribution of the incoming requests is captured by the “stage method”, we provide a detailed model of the power-managed multimedia system under general QoS constraints. Based on this mathematical model, the power-optimal policy is obtained by solving a linear programming problem. We compare the new problem formulation and solution technique to previous dynamic power management techniques that can only optimize power under delay constraints. We then demonstrate that these other techniques yield policies with higher power dissipation by over-constraining the delay target in an attempt to indirectly satisfy the QoS constraints. In contrast, our new method correctly formulates the power management problem under QoS constraints and obtains the optimal solution.
Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human

1. UK-224,671 is a sulphamide-containing NK2 antagonist with moderate lipophilicity and basicity. 2. The physicochemical properties of UK-224,671 are reflected in its pharmacokinetics following intravenous (i.v.) administration. The compound partitioned extensively into red blood cells in all species examined and the blood clearance was moderate to low with respect to liver blood flow and distribution into tissues was extensive. 3. UK-224,671 exhibited species differences in oral bioavailability. In dog, the compound exhibited moderate bioavailability (55%), whereas in rat and man oral bioavailability was < 10%. 4. In rat and dog, the major excreted form after i.v. administration was unchanged UK224,671 in both urine and faeces. In addition, of three metabolites observed, the most abundant was the N-descyclopropylmethyl (UK-280,045). 5. The profile of radioactivity in rat following oral administration of [14C]-UK-224,671 was not consistent with a 10% absorbed compound with 40% of the dose present as me...
A Col9a1 enhancer element activated by two interdependent SOX9 dimers

The transcription factor SOX9 plays a critical role in chondrogenesis as well as in sex determination. Previous work has suggested that SOX9 functions as a DNA-dependent dimer when it activates genes involved in chondrogenesis, but functions as a monomer to activate genes involved in sex determination. We present evidence herein for a third binding configuration through which SOX9 can activate transcription. We have identified four separate SOX consensus sequences in a COL9A1 collagen gene enhancer. The sites are arranged as two pairs, and each pair is similar to previously discovered dimeric SOX9 binding sites. Increasing the spacing between the pairs of sites eliminated enhancer activity in chondrocytic cells, as did the mutation of any one of the four sites. The COL9A1 enhancer is ordinarily inactive in 10T1/2 cells, but cotransfection with a SOX9 expression plasmid was sufficient to activate the enhancer, and mutation of any one of the four sites reduced responsiveness to SOX9 overexpression. These results suggest a novel mechanism for transcriptional activation by SOX9, in which two SOX9 dimers that are bound at the two pairs of sites are required to interact with one another, either directly or indirectly, in order to produce a functional transcriptional activation complex.
Differential Effects of Right-Wing Authoritarianism and Social Dominance Orientation on Political Candidate Support: The Moderating Role of Message Framing

Employing a dual process motivational (DPM) model perspective, we found that how political messages are framed influences the differential effects of right-wing authoritarianism (RWA) and social dominance orientation (SDO) on political candidate support in the United States. Study 1 (N = 85) found that RWA and SDO differentially predicted support for right-wing candidates who used cohesion and group status threats to frame same-sex marriage, respectively. Study 2 (N = 89) largely replicated those findings on immigration policy. In Study 3 (N = 128), the hypothesis that RWA and SDO negatively predicted support for left-wing candidates who framed same-sex marriage in terms of individual liberty and social equality, respectively, received partial support. Additional analyses indicated that the effects of RWA on candidate support in these studies were driven by specific theoretically-relevant dimensions of RWA. Together, these results indicate that candidates can enhance their appeal by strategically employing value-based political messages targeting different subsets of their constituency.
Edward Gibbon and Byzantine Ecclesiastical History

It is generally acknowledged that Gibbon's Decline and Fall of the Roman Empire ranks as one of the supreme masterpieces of historical writing. Yet surprisingly enough, more than a third of his entire narrative, that portion dealing with the later Roman or Byzantine Empire, has been badly neglected by historiographers. Now Gibbon as a Byzantinist must needs be an ecclesiastical historian as well, given the nature of Byzantine civilization with its close identification of the religious and the political. But here again, though sharp controversy has for long raged over Gibbon's judgment of early Christianity, especially its responsibility for the fall of the Roman Empire in the West, his treatment of medieval Greek Christianity has been almost ignored by critics, except for sporadic, general remarks by Bury, Dawson, Giarrizzo—remarks which have added little to the traditionally accepted view that Gibbon was contemptuous of Byzantine civilization.
Hepatic Glycine N-Methyltransferase Is Up-Regulated by Excess Dietary Methionine in Rats

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAM) levels and the ratio of SAM:S-adenosylhomocysteine (SAH). In liver, methionine availability, both from the diet and via the folate-dependent one-carbon pool, modulates GNMT activity to maintain an optimal SAM:SAH ratio. The regulation of GNMT activity is accomplished via posttranslational and allosteric mechanisms. We more closely examined GNMT regulation in various tissues as a function of excess dietary methyl groups. Sprague Dawley rats were fed either a control diet (10% casein plus 0.3% L-methionine) or the control diet supplemented with graded levels (0.5-2%) of L-methionine. Pair-fed control groups of rats were included due to the toxicity associated with high methionine consumption. As expected, the hepatic activity of GNMT was significantly elevated in a dose-dependent fashion after 10 d of feeding the diets containing excess methionine. Moreover, the abundance of hepatic GNMT protein was similarly increased. The kidney had a significant increase in GNMT as a function of dietary methionine, but to a much lesser extent than in the liver. For pancreatic tissue, neither the activity of GNMT nor the abundance of the protein was responsive to excess dietary methionine. These data suggest that additional mechanisms contribute to regulation of GNMT such that synthesis of the protein is greater than its degradation. In addition, methionine-induced regulation of GNMT is dose dependent and appears to be tissue specific, the latter suggesting that the role it plays in the kidney and pancreas may in part differ from its hepatic function.
Two-stage over the air (OTA) test method for MIMO device performance evaluation

Conformance tests for SISO OTA were introduced in recent years but so far nothing exists for the newly introduced MIMO devices. Unlike SISO systems where multipath fading is something to be overcome, MIMO takes advantage of fading to identify and use orthogonal communication channels to enable simultaneous transmission of multiple streams of data. A consequence of this is that the fading channel characteristics are an integral part of the test conditions and directly influence the measured MIMO OTA performance. The major test challenge for MIMO OTA is how to create a repeatable scenario which accurately reflects the MIMO antenna radiation performance in a realistic wireless propagation environment. This paper describes a novel cost-effective test method based on antenna pattern measurement.
Thermal conductivity of a metal-organic framework (MOF-5): Part II. Measurement

The thermal conductivity of MOF-5 single crystals is measured over a wide temperature range between 6 K and 300 K, using the longitudinal, steady-state heat flow method. Between 6 K and 20 K, the thermal conductivity increases with the increase in temperature and exhibits a peak near 20 K. This peak results from the crossover between the decreasing mean free path and the increasing phonon specific heat with the increasing temperature. From 20 K to 100 K, the thermal conductivity decreases rapidly with increasing temperature. Above 100 K, the thermal conductivity is nearly temperature independent, and its value at 300 K is 0.32 W/m K, a rather low value for crystals. The mean free path analysis shows that at high temperature, the phonon mean free path is minimized to the cage size due to the porous, flexible structure of MOF-5. 2006 Elsevier Ltd. All rights reserved.
Treatment of rotavirus-associated diarrhea using enteral immunoglobulins for pediatric stem cell transplant patients.

Diarrhea is a common complication associated with allogeneic and autologous stem cell transplant patients. One potential cause of viral diarrhea is rotavirus gastroenteritis. This study represents a single-center experience of using multiple daily doses of enteral immunoglobulins in four pediatric hematopoietic stem cell transplant patients with confirmed rotavirus infections. Four courses of enteral immunoglobulin administration were included for analysis. Clinical characteristics recorded included duration of diarrhea symptoms, frequency of bowel movements, and consistency of stool. Four single courses of enteral immunoglobulins in four patients were included for analysis. Patient age range was from 10 months to 14 years. Three out of four courses observed displayed an improvement in diarrhea frequency and/or stool consistency. Median time from therapy initiation to symptom improvement was three days. At a median 22-month follow-up, one patient was diagnosed with gastrointestinal graft-versus-host disea...
Catalysis Without Tears

A semiclassical model of baryon-monopole interactions is presented. The model, which could serve as the basis for practical calculations of catalysis cross sections, interpolates between a soliton model of baryons at large distances and a radial field theory near the monopole core.
REFLECTIONS ON WATER RESOURCES RESEARCH

“Fortunately, this nation is well endowed with water. We get enough precipitation every year to cover the whole country with water 30 inches deep.”
Analysis of human attractiveness using manifold kernel regression

This paper uses a recently introduced manifold kernel regression technique to explore the relationship between facial shape and attractiveness on a heterogeneous dataset of over three thousand images gathered from the Web. Using the concept of the Frechet mean of images under a diffeomorphic transformation model, we evolve the average face as a function of attractiveness ratings. Examining these averages and associated deformation maps enables us to discern aggregate shape change trends for male and female faces.
Isolating the Arabidopsis thaliana genes for de novo purine synthesis by suppression of Escherichia coli mutants. I. 5'-Phosphoribosyl-5-aminoimidazole synthetase.

We have initiated an investigation of the de novo purine nucleotide biosynthetic pathway in the plant Arabidopsis thaliana. Functional suppression of Escherichia coli auxotrophs allowed the direct isolation of expressed Arabidopsis leaf cDNAs. Using this approach we have successfully suppressed mutants in 4 of the 12 genes in this pathway. One of these cDNA clones, encoding 5[prime]-phosphoribosyl-5-aminoimidazole (AIR) synthetase (PUR5) has been characterized in detail. Analysis of genomic DNA suggests that the Arabidopsis genome contains a single AIR synthetase gene. Analysis of the cDNA sequence and mRNA size suggests that this enzyme activity is encoded by a monofunctional polypeptide, similar to that of bacteria and unlike other eukaryotes. The Arabidopsis AIR synthetase contains a basic hydrophobic transit peptide consistent with transport into chloroplasts. Comparison of both the predicted amino acid and nucleotide sequence from Arabidopsis to those of eight other distant organisms suggests that the plant sequence is more similar to the bacterial sequences than to other eukaryotic sequences. This study provides the groundwork for future investigations into the regulation of de novo purine biosynthesis in plants. Additionally, we have demonstrated that functional suppression of bacterial mutants may provide a useful method for cloning a variety of plant genes.
Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1

Alzheimer9s disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ. SIGNIFICANCE STATEMENT Synaptic changes in Alzheimer9s disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-19s established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression.
Preparation and Hydrogen Pumping Characteristics of BaCe0.8Y0.2O3-δ Thin Film

Thin films of BaCe0.8Y0.2O3−δ (BCY) were prepared by colloidal spray deposition. Dense, crack-free BCY films having a grain size of 2–7 µm were successfully deposited on NiO/BCY substrates. Electrochemical hydrogen pumping with the BCY films showed that the maximum current density increased with temperature. The maximum current density was sensitive to the moisture in the cathode gas; the value obtained with a dry cathode gas was only half that with a wet cathode gas. A very high hydrogen-pumping current density of 3.4 A/cm2 was measured at 700°C with an applied voltage of 1.5 V.
Laser Densification of Micro-Optical Arrays

Optical microlens arrays are important in many optical systems. A new method for producing arrays of negative lenses, geodesic lenses, and planar GRIN lenses is described. The lenses and arrays are produced using CO2 laser densification of near fully densified gel-silica (Type VI) matrices. Critical processing conditions include initial density of the matrix, laser power, laser pulse width, focal length of the laser beam, and ambient atmosphere.
In the Biosimilar Marketplace Will There Be 50 Ways to Leave Your Insulin

The future biosimilar insulin marketplace could be a bane, benefit, or something in between, to patients under our care in the United States. Formulary preferred product status, with or without FDA interchangeability designation, coupled with current and proposed state pharmacy substitution laws may lead to an environment with as many as 50 different substitution guidelines depending on in which state a patient presents his or her prescription to be filled. If online global prescription supply options, often referred to as "Canada Drug," are utilized, other country substitution guidelines come into play, which may yield a recipe for confusion, if not disaster.
Gaining Ground: Merging Cognitive Load Theory with Human Factors Principles

Although considered one of the best in the world, in many ways America's educational system is not living up to its expectations. Taking an interdisciplinary approach to learning and training through integrating human factors (HF) is not a novel idea, yet it seems that further work can still be done to increase outcomes. This paper intends to investigate the similarities and differences of the theory of cognitive load (CLT), which is used extensively in instructional design, with various fundamental human factors constructs (workload, flow state, and transfer appropriate processing.). This may help to increase understanding between the fields. as well as find important similarities and differences between the given theories to increase the benefits of instructional design.
Effect of Normal and Raw Apple Diet on the Flora of the Duodenum, Ileum and Cecum of Monkeys

Many clinical studies have been published concerning the therapeutic effect of a raw apple diet on diarrhea and bacillary dysentery in children. The original purpose of this investigation was to study the bacterial flora at different levels of the intestine in monkeys which are natural hosts to bacillary dysentery. The flora on the normal diet was to be compared with that of an apple diet and subsequently the effect of an apple diet on experimental bacillary dysentery. The first two objects have been accomplished but not the latter, due to our failure to produce experimental dysentery in these animals.
A Computational Method for Task Allocation and Coordination in a Distributed Design Environment

Managing the product realization process is a difficult endeavor in today’s global product development environment. Design project managers are required to form teams from geographically distributed designers as well as effectively manage the collaborative design process. In this paper, a computational method is proposed to aid design managers in allocating design tasks to geographically distributed designers and identify appropriate coordination mechanisms to manage the collaborative design process. The method involves three stages: i) arriving at an initial design task sequence using the design structure matrix through partitioning of design tasks into blocks of dependent, independent and interdependent tasks, ii) allocating of design tasks to design teams and the improvement of the design sequence accounting for the number of designers available and their competencies and iii) determination of design review meeting frequencies as a coordination mechanism for interdependent tasks using agent based modeling simulations.© 2008 ASME
Apparent reversible influence of cosmic-ray-induced showers upon a biological system.

Summary1. Fiddler crabs, of the species Uca pugnax, were studied with respect to their capacity to show a response of their chromatophore system to increase in showers of cosmic-ray origin obtained through the interpolation of lead screens. 2. Increasing the showers by lead screen varying from 0.3 to 2.1 cm in thickness and held 5 inches directly above the animals produced significant differences in the response of the pigmentary effector system of the crabs as compared with appropriate controls. 3. There was a strong suggestion of the existence of a diurnal rhythm in the character of the response to increasing showers. The response was increased pigment concentration or body-lightening during the initiation of transition into the day phase of the endogenous daily cycle and increased pigment-dispersion or body-darkening during at least most of the remaining hours of the day. 4. The lead screens, and distances from screen to animals, which were used were responsible for an increase in degree of darkening d...
An Unusual Iron-Dependent Oxidative Deformylation Reaction Providing Insight into Hydrocarbon Biosynthesis in Nature

The development of new pathways for next-generation biofuel production has spurred recent investigations into the mechanisms of enzymes that biosynthesize hydrocarbons. One widely distributed group of enzymes, aldehyde decarbonylases, catalyze unusual deformylation reactions in which long-chain fatty aldehydes are converted to alkanes. These enzymes are all iron-dependent and in insects are represented by a cytochrome P450 enzyme that releases the aldehyde carbon as CO2. Here we describe a novel nonenzymatic reaction of an α-cyclopropyl-substituted aldehyde that mimics the enzyme reaction. This aldehyde is oxidatively deformylated in the presence of aqueous iron(II) salts and oxygen to yield an alkyl-substituted cyclopropane and CO2, in a reaction that competes with the more conventional oxidation of the aldehyde to the carboxylic acid. Like the enzymatic reaction, the reaction occurs with retention of the aldehyde proton in the alkane product and probably proceeds through an iron–peroxo species. Computat...
Clinical Research on Three Therapeutic Regimens of Common Hand-foot-mouth Disease

Objective To compare the clinical effects of three therapeutic regimens of common hand-foot-mouth disease(HFMD). Methods 200 common HFMD children were assigned to TCM group(n=75),western medicine group(n=75) and integrative medicine group(n=75). The time of deflorescence,and relief time of fever,cough,anorexia,chills and other symptoms of children were observed. Results The time of deflorescence in TCM group,integrative medicine group was shorter respectively than that of western medicine group(P0.05),the relief time of cough,anorexia and chills were also shorter significantly than those of western medicine group(P0.05),but there was not significant difference in relief time of cough between integrative medicine group and western medicine group. Conclusion Chinese medicines have some advantages in improving the clinical symptoms and reducing complications for treating HFMD.
From Adoptive Immunity to CAR Therapy: An Evolutionary Perspective

Adoptive cell transfers have been used in basic immunology for over half a century, enabling detailed functional characterization of immune cells including T lymphocytes. This experimental approach inspired multiple human cell therapies, spanning both allogeneic and autologous T cell transfers. The use of lymphokine-activated killer cells, tumor-infiltrating lymphocytes, donor leukocyte infusions, and virus-specific lines or clones has taught us a great deal about the biological and clinical challenges of developing safe and effective T cell–based therapies to treat cancer. The advent of T cell engineering in the 1990s changed the adoptive cell therapy paradigm from one based on the isolation and expansion of available donor or patient T cells to the design and genetic recomposition of T cells with optimal antitumor properties. The rise of second generation chimeric antigen receptors, in particular those targeting CD19, epitomizes this paradigm shift from classic cellular immunology to synthetic biology.
Gas chromatographic determination of deoxynivalenol in wheat with electron capture detection: collaborative study.

Description et mise en oeuvre d'une technique de dosage de cette mycotoxine du groupe des trichothecenes. La methode est adoptee a l'essai
Economic Aspects of Soviet Policy in the Third World: A Comment

(1986). Economic Aspects of Soviet Policy in the Third World: A Comment. Soviet Economy: Vol. 2, No. 3, pp. 261-268.
Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation.

Background: Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. Methods: Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. Results: Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. Conclusions: In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.
Robustness Quantification and Worst-Case Robust Optimization in Intensity-Modulated Proton Therapy

Intensity-Modulated Proton Therapy (IMPT) is highly sensitive to uncertainties in beam range, patient setup and organ motion. Therefore, it is essential to evaluate the robustness of the IMPT plans against these uncertainties and design robustly optimized plans to improve the plan quality. The root-mean-square-dose volume histograms (RVH) measure the sensitivity of the dose to uncertainties and the areas under the RVH curve (AUCs) can be used to evaluate plan robustness. Results of our research have shown the following. In the worst case and nominal scenarios, robustly optimized plans have better target coverage, improved dose homogeneity, and lower or equivalent dose to organs at risk (OARs). Additionally, robust optimization provides significantly more robust dose distributions to targets and organs than conventional optimization in IMPT. Reduction of PTV and planning directly based on CTV provides better or equivalent OAR sparing. Also 4D robust optimization provides more respiratory-motion-insensitive plans compared to 3D robust optimization.
Establishing Age-Specific Cost-Effective Annual Revision Rates for Unicompartmental Knee Arthroplasty: A Meta-Analysis.

Abstract Background Improved survivorship has contributed to the increased use of unicompartmental knee arthroplasty (UKA) as an alternative to total knee arthroplasty (TKA) for unicompartmental knee osteoarthritis. However, heterogeneity among cost-effectiveness analysis studies comparing UKA to TKA has prevented the derivation of discrete implant survivorship targets. The aim of this meta-analysis was to determine the age-stratified annual revision rate (ARR) threshold for UKA to become consistently cost-effective for unicompartmental knee osteoarthritis. Methods A systematic search was performed for cost-effectiveness analysis studies of UKA vs TKA. Selected publications were rated by evidence level and assessed for methodological quality. Target UKA survivorship values determined by sensitivity analysis were retrieved, converted to ARR, and combined by age category ( Results Four studies met all inclusion criteria. All publications were evidence level I-B, with high methodological quality. Combined data indicated median threshold cost-effective ARR of 1.471% (interquartile range [IQR], 1.415-1.833; age Conclusion The findings indicate that implant survivorship is a limiting factor toward achieving cost-effective UKA in patients aged
Application of pharmacologically induced transcriptomic profiles to interrogate PI3K-Akt-mTOR pathway activity associated with cancer patient prognosis.

// Matthew H. Ung 1 , George L. Wang 1 , Frederick S. Varn 1 , Chao Cheng 1, 2, 3 1 Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, 03755 USA 2 Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, 03755 USA 3 Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, 03766 USA Correspondence to: Chao Cheng, email: chao.cheng@dartmouth.edu Keywords: pharmacogenomics, computational biology, PI3K, drug treatment Received: May 16, 2016 Accepted: August 25, 2016 Published: August 31, 2016 ABSTRACT The PI3K-Akt-mTOR signaling pathway has been identified as a key driver of carcinogenesis in several cancer types. As such, a major area of focus in cancer biology is the development of genomic biomarkers that can measure the activity level of the PI3K-Akt-mTOR pathway. In this study, we systematically estimate PI3K-Akt-mTOR pathway activity in breast primary tumor samples using transcriptomic profiles derived from drug treatment in MCF7 cell lines. We demonstrate that gene expression profiles derived from chemically-induced protein inhibition allows us to measure PI3K-Akt-mTOR pathway activity in patient tumor samples. With this approach, we predict prognosis and response to chemotherapy in cancer patients, and screen for potential pharmacological modulators of PI3K-Akt-mTOR pathway inhibitors.