cssi/SciSciGPT-SciSciNet huggingface dataset:
Intact calcium signaling in adrenergic-deficient embryonic mouse hearts.

Abstract Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh−/-) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10.5 (E10.5). To test this hypothesis, we used ratiometric fluorescent calcium imaging techniques to measure cytosolic calcium transients, [Ca2+]i in isolated E10.5 mouse hearts. Our results show that spontaneous [Ca2+]i oscillations were intact and robustly responded to a variety of stimuli including extracellular calcium (5 mM), caffeine (5 mM), and NE (100 nM) in a manner that was indistinguishable from controls. Further, we show similar patterns of distribution (via immunofluorescent histochemical staining) and activity (via patch-clamp recording techniques) for the major voltage-gated plasma membrane calcium channel responsible for the L-type calcium current, ICa,L, in adrenergic-deficient and control embryonic cardiac cells. These results demonstrate that despite the absence of vital adrenergic hormones that consistently leads to embryonic lethality in vivo, intracellular and extracellular calcium signaling remain essentially intact and functional in embryonic mouse hearts through E10.5. These findings suggest that adrenergic stimulation is not required for the development of intracellular calcium oscillations or extracellular calcium signaling through ICa,L and that aberrant calcium signaling does not likely contribute to the onset of heart failure in this model.
Family Psychiatry and the Medical Student: The Marital and Family Assessment Seminar

This paper addresses itself to the importance of the family as it affects individual patients seen by the medical student in a psychiatric clerkship. The clerkship and the seminar in marital and family assessment are geared to sensitize the student to the stresses upon the family, the nature of family systems as well as his role in his own family. A brief review of the literature pertaining to the importance of family systems in understanding the individual is presented as is a model for medical student training in marital and family systems. A follow-up with the first 80 student-participants is presented. The seminar attempts to integrate theory, application, and self understanding in providing the physician-to-be with a grounding in assessment skills which will be necessary in his future practice.
Optimal timing of initiation of thromboprophylaxis in spine trauma managed operatively: A nationwide propensity-matched analysis of trauma quality improvement program.

BACKGROUNDPatients with spinal trauma are at high risk for venous thromboembolic events (VTE). Guidelines recommend prophylactic anticoagulation but they are unclear on timing of initiation of thromboprophylaxis. The aim of our study was to assess the impact of early versus late initiation of venous
Quasi-static and dynamic mechanical behavior of transparent graft-interpenetrating polymer networks (graft-IPNs)

Abstract Mechanical characterization of transparent graft Interpenetrating Polymer Networks or graft-IPNs based on polyurethane and acrylic copolymer are reported under both quasi-static and dynamic loading conditions. This study builds on an earlier work detailing the synthesis of the graft-IPNs [1]. Optically transparent graft-IPNs were synthesized using elastomeric polyurethane (PU) phase and stiff acrylate-base copolymer (CoP) phase. The ratios of CoP:PU were varied from 90:10 up to 60:40 by weight. Two grades of graft-IPNs were synthesized by using 650 g mol−1 and 1400 g mol−1 poly (tetramethylene ether) glycol (PTMG) during synthesis to study the molecular weight effect. Quasi-static tensile and fracture tests as well as dynamic fracture tests were performed. The dynamic fracture tests were carried out at high strain rate using a modified-Hopkinson pressure bar in conjunction with an optical technique called Digital Gradient Sensing (DGS) and ultrahigh-speed photography. Quasi-static tests indicate significant enhancements in crack initiation toughness and change in failure mode (brittle to ductile) when the constituents were varied. Enhancements in crack inititation toughness were also observed under dynamic loading. These results were further compared with those for commercial poly (methyl methacrylate) (PMMA) and polycarbonate (PC) sheet stock. Further improvement in fracture properties were observed under quasi-static loading conditions with increase in molecular weight of PTMG. The relatively high values of fracture toughness obtained for graft-IPNs is attributed to the crosslinks generated between the CoP and PU networks.
Los olmecas. Los primeros petroleros

La exploracion, extraccion y refinacion del petroleo son algunas de las actividades economicas mas relevantes del Mexico actual; sus raices se remontan a los olmecas, quienes fueron “los primeros petroleros”. Se sabe que utlizaron el chapopote para sellar acueductos y embarcaciones, como decoracion de figurillas y en mangos de cuchillos, y como material de construccion. Los olmecas fueron los primeros mesoamericanos en recoger y procesar el petroleo que brotaba de los yacimientos naturales (comunmente llamado chapopote, asfalto o betun), asi como en utilizarlo para la ornamentacion y sellado, como pegamento y en otros usos aun desconocidos. Entre los olmecas, el chapopote era usado para sellar acueductos de basalto y las embarcaciones; como decoracion de figurillas y en mangos de cuchillos; y como material de construccion, pues se utilizaba como recubrimiento de pisos, y tal vez de muros y techos
Simulating expert judgment: Actuarial models and applications

INTRODUCTION I f uncertainty is the essence of decision, then the modeling of human decision making, at i ts core, must model uncertainty. Given h is tor ica l perspective, the uncertainty can be translated into probabi l i ty distr ibut ions that can form the basis for future predictions. On the other hand, a lack of exp l i c i t data leads to a si tuat ion where the expert decision maker is l i k e l y to exercise i n tu i t i ve judgment. This decision environment can be modeled by simulating the expert decision maker's judgment. And such models fa l l within the domain of a body of knowledge called behavioral decision theory that has developed in the last two dozen years.
Emotion, Social Action, and Agency: A Case Study of an Intercultural, Technical Communication Intern

This article reviews literature on emotions within communication settings and proposes that emotions serve as motivations to accomplish social action; these motivations also serve as opportunities ...
Preclinical safety and efficacy of cannabidivarin for early life seizures.

Abstract A significant proportion of neonatal and childhood seizures are poorly controlled by existing anti-seizure drugs (ASDs), likely due to prominent differences in ionic homeostasis and network connectivity between the immature and mature brain. In addition to the poor efficacy of current ASDs, many induce apoptosis, impair synaptic development, and produce behavioral deficits when given during early postnatal development. There is growing interest in new targets, such as cannabidiol (CBD) and its propyl analog cannabidivarin (CBDV) for early life indications. While CBD was recently approved for treatment of refractory childhood epilepsies, little is known about the efficacy or safety of CBDV. Here, we addressed this gap through a systematic evaluation of CBDV against multiple seizure models in postnatal day (P) 10 and 20 animals. We also evaluated the impact of CBDV on acute neurotoxicity in immature rats. CBDV (50–200 mg/kg) displayed an age and model-specific profile of anticonvulsant action. In P10 rats, CBDV suppressed seizures only in the pentylenetetrazole model. In P20 rats, CBDV suppressed seizures in the pentylenetetrazole, DMCM, and maximal electroshock models. Between P10 and P20, we identified significant increases in mRNA expression of TRPV1 in multiple brain regions; when CBDV was tested in P20 TRPV1 knockout mice, anticonvulsant effects were attenuated. Finally, CBDV treatment generally avoided induction of neuronal degeneration in immature rats. Together, the efficacy and safety profile of CBDV suggest it may have therapeutic value for early life seizures.
The Binding Problem after an eye movement

Spatial attention is thought to be the "glue" that binds features together (e.g., Treisman & Gelade, 1980, Psychology, 12[1], 97-136)-but attention is dynamic, constantly moving across multiple goals and locations. For example, when a person moves her eyes, visual inputs that are coded relative to the eyes (retinotopic) must be rapidly updated to maintain stable world-centered (spatiotopic) representations. Here, we examined how dynamic updating of spatial attention after a saccadic eye movement affects object-feature binding. Immediately after a saccade, participants were simultaneously presented with four colored and oriented bars (one at a precued spatiotopic target location) and instructed to reproduce both the color and orientation of the target item. Object-feature binding was assessed by applying probabilistic mixture models to the joint distribution of feature errors: feature reports for the target item could be correlated (and thus bound together) or independent. We found that compared with holding attention without an eye movement, attentional updating after an eye movement produced more independent errors, including illusory conjunctions, in which one feature of the item at the spatiotopic target location was misbound with the other feature of the item at the initial retinotopic location. These findings suggest that even when only one spatiotopic location is task relevant, spatial attention-and thus object-feature binding-is malleable across and after eye movements, heightening the challenge that eye movements pose for the binding problem and for visual stability.
Using Media Coverage to Teach Advocacy in PETE

This article discusses advocacy in physical education, specifically a response by the University of New Mexico pre service teachers to an article published by The Atlantic (2019).
Are we preaching to the choir? Where should studies on frequent users of EDs be published?

After more than 30 years of publications in the emergency medicine literature on frequent ED use, what have we learnt? We know that patients are coming to our EDs because we offer a good service, and because they are unable to find the service they need when they need it. We know that those who tend to come more frequently have more chronic medical problems than less frequent users; that they have mental health, substance abuse and social issues that contribute to their illnesses and prevent them from them from getting care in the ‘usual way’. We know that their frequent visits are not because they enjoy the companionship of an overflowing waiting room, or find us ‘a more convenient’ and enjoyable experience than an appointment in a doctor’s office. We know they come because they need to, when they need to. So why publish yet another study of frequent use. For one thing, the report by Greenfield et al on frequent use of EDs in the UK1 is the largest data set to be produced on this issue in the UK, although there have been a number of similar studies from other countries. More importantly, the fact that it draws similar conclusions to large studies in many other countries is important; regardless of …
Popular Will against Democracy: Populist Autocratization in Turkey

In this article, I study the relationship of the Justice and Development Party’s (Adalet ve Kalkinma Partisi, AKP) populism-in-power and democracy, from a comparative and historical perspective, and based on a critical engagement with the populism literature. I begin by highlighting the political institutional expression of the populist political vision (to reflect the popular will in power), which prioritizes competitive elections among a variety of modern democratic institutions and mechanisms. Based on this perspective, I outline a particular populist route to competitive (or electoral) authoritarianism: when in power, because populists exalt elections and undermine existing liberal democratic mechanisms that bridge people to power, they deprive citizens of the power to hold rulers accountable. I then trace the lineage of the populist political imagination in Turkey, demonstrating the continuities and discontinuities between the Democrat Party’s (Demokrat Parti, DP) and the AKP’s conceptions of the people and democracy. I argue that despite these parties’ differences on the level of the politicization of cultural divisions, there is a crucial continuity: the equalization of democracy with an exalted elected executive branch. Finally, I concentrate on the impact of the AKP’s populism-in-power on the Turkish political regime. I argue that because the AKP came to power in a defective democracy (with extra-democratic checks on the elected rulers and prone to the concentration of power), by 2011, the party managed to reframe Turkish political institutions according to their right-wing populist vision of democracy, an authoritarian regime with competitive elections.
Anti-reflux mucosectomy (ARMS) results in improved recovery and similar reflux quality of life outcomes compared to laparoscopic Nissen fundoplication.

Anti-reflux mucosectomy (ARMS) is a new endoscopic procedure involving a hemi-circumferential endoscopic mucosal resection (EMR) around the gastroesophageal junction. We aim to compare perioperative and quality of life outcomes of patients with reflux who underwent ARMS to a comparable group who underwent laparoscopic Nissen fundoplication (NF). A retrospective review of a prospectively maintained quality database was performed. All patients who underwent ARMS (n = 33) were matched with patients who underwent NF (n = 67). Clinical and quality of life (QOL) outcomes were collected preoperatively and up to two years postoperatively, measured by the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL), and Dysphagia Score. Outcomes were compared using the Wilcoxon rank-sum and Fisher’s exact test. While 10 patients (30.3%) who underwent ARMS required additional laparoscopic anti-reflux operations, the ARMS group had shorter OR time (p<0.001), less estimated blood loss (p<0.001), shorter hospital stay (p<0.001), less pain at discharge (p = 0.007), earlier narcotic discontinuation (p<0.001), and earlier return to activities of daily living (p<0.001) compared to the NF group. There was no difference in 30-day complication rates, emergency room visits, or readmission rates between the groups. There was no difference between ARMS and NF groups in terms of GERD-HRQL, RSI, or Dysphagia scores at 3 weeks, 6 months, 1 year, or 2 years postoperatively. However, the ARMS group reported less symptoms of gas and bloating postoperatively at all time points (all p<0.05). Both groups reported increased dysphagia at 3 weeks postoperatively (p<0.01) but this did not persist at 6 months, 1 year, or 2 years. While ARMS had better perioperative outcomes compared to NF, reflux quality of life outcomes were comparable. ARMS can be an effective endoscopic intervention for GERD when performed on appropriately selected patients without limiting future laparoscopic anti-reflux interventions.
Comparative Effect of Endotoxin and Reticuloendothelial “Blocking” Colloids on Selected Inducible Liver Enzymes

The LD50 of endotoxin lowers the activity of the hormonally inducible mouse liver enzyme tryptophan pyrrolase to less than one-half the control value and keeps it at a depressed level for about 24 hr. Endotoxin, by contrast, increases the activity of a similarly inducible liver enzyme, tyrosine-α-ketoglutarate transaminase. Endotoxin also prevents the induction of tryptophan pyrrolase by cortisone but does not prevent the induction of the transaminase. Either zymosan or glucan exerts an effect similar to endotoxin on both enzymes, except that the colloids do not prevent induction by cortisone. Both enzymes in mice made tolerant to endotoxin are less subject to change by endotoxin or zymosan than in normal mice. In animals given a series of injections of zymosan or saccharated iron oxide this does not occur.
“No Difference Between African American,Immigrant, or White Children! They Are All the Same.”: Working Toward Developing Teachers’ Raciolinguistic Attitudes Towards ELs

This study explored Midwestern US teachers’ raciolinguistic attitudes toward English learners. Two research questions guided the study: “How did teachers perceive racism and linguicism” and “How did a professional training influence teachers’ awareness of them?” Critical race theory was used to examine how racism evolved into racialized linguicism. Data analysis demonstrated that teachers tended to conflate the experiences of African American students and English learners, even though they are linguistically and culturally distinct. They also tended to understand the racism and linguicism encountered by the two groups in Black/White and Standard-English/Nonstandard-English binaries. Implications consider the future direction of TESOL teacher education.
Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols

ABSTRACT The yeast Saccharomyces cerevisiae is a powerful tool for studying G protein-coupled receptors (GPCRs) as they can be functionally coupled to its pheromone response pathway. However, some exogenous GPCRs, including the mu opioid receptor, are non-functional in yeast, which may be due to the presence of the fungal sterol ergosterol instead of the animal sterol cholesterol. We engineered yeast to produce cholesterol and introduced the human mu opioid receptor, creating an opioid biosensor capable of detecting the peptide DAMGO at an EC50 of 62 nM and the opiate morphine at an EC50 of 882 nM. Furthermore, introducing mu, delta, and kappa opioid receptors from diverse vertebrates consistently yielded active opioid biosensors that both recapitulated expected agonist binding profiles with EC50s as low as 2.5 nM and were inhibited by the antagonist naltrexone. Additionally, clinically relevant human mu opioid receptor alleles, or variants with terminal mutations, resulted in biosensors that largely displayed the expected changes in activity. We also tested mu opioid receptor-based biosensors with systematically adjusted biosynthetic intermediates of cholesterol, enabling us to relate sterol profiles with biosensor sensitivity. Finally our cholesterol-producing biosensor background was applied to other human GPCRs, resulting in SSTR5, 5-HTR4, FPR1 and NPY1R signaling with varying degrees of cholesterol dependence. Our sterol-optimized platform will be a valuable tool in generating human GPCR-based biosensors, aiding in ongoing receptor deorphanization efforts, and providing a framework for high-throughput screening of receptors and effectors.
Phylogenetic organization in the assimilation of chemically distinct substrates by soil bacteria

Soils are among the most biodiverse habitats on earth and while the species composition of microbial communities can influence decomposition rates and pathways, the functional significance of many microbial species and phylogenetic groups remains unknown. If bacteria exhibit phylogenetic organization in their function, this could enable ecologically meaningful classification of bacterial clades. Here, we show non-random phylogenetic organization in the rates of relative carbon assimilation for both rapidly mineralized substrates (amino acids and glucose) assimilated by many microbial taxa and slowly mineralized substrates (lipids and cellulose) assimilated by relatively few microbial taxa. When mapped onto bacterial phylogeny using ancestral character estimation this phylogenetic organization enabled the identification of clades involved in the decomposition of specific soil organic matter substrates. Phylogenetic organization in substrate assimilation could provide a basis for predicting the functional attributes of uncharacterized microbial taxa and understanding the significance of microbial community composition for soil organic matter decomposition.
Temporal Control of Lux Gene Expression in the Symbiosis between Vibrio Fischeri and Its Squid Host

A long-standing question in the study of luminous bacterial symbionts has been: What is the importance of light-emission to the bacteria? We have used the symbiosis between Vibrio fischeri and the Hawaiian sepiolid squid Euprymna scolopes as a model system (McFall-Ngai & Ruby, 1991; Ruby, 1996) with which to discover the answer to this question. Within hours of hatching, juvenile squids become inoculated by a few cells of V. fischeri present in the ambient seawater (Ruby & Asato, 1993). These bacteria rapidly colonize the epithelium-lined crypts of the nascent light-emitting organ, attaining a population size of about one million cells. Their light emission is used by the host in its nocturnal behavior (McFall-Ngai, 1997), and evidence is accumulating that suggests that the host regulates the bacterial luminescence on multiple levels (Boetttcher & Ruby, 1995; Boettcher et al., 1996).
5 – HYPOTHESIS TESTING

This chapter deals with hypothesis testing. The goal of statistical hypothesis testing is to find a decision rule about whether the null hypothesis is true or should be ruled out. This descision is based on observations. When the null hypothesis is rejected, this means that the corresponding alternative hypothesis is accepted. Alternative way of describing hypothesis testing, which is frequently employed, is based on what is called the significance level or p-value, an idea that appears to have been proposed first by Deming in 1943. The idea behind the p-value or significance level is that it provides more information about α level at which the null hypothesis would be rejected. An argument for testing hypotheses based on the mean is that under normality, the sample mean has a smaller standard error than any other measure of location. This means that no other hypothesis-testing method has more power than the method based on Student's T. However, this argument is not very compelling, because arbitrarily small departures from normality can result in extremely low power relative to other methods and of course there is the concern about getting accurate confidence intervals and good control over the probability of a Type I error.
Evaluating Specification Search in Cross-country Growth Regressions: Extreme Bounds vs. General-to-Specific Methodologies

This paper is a substantially revised version of our earlier working paper, "Truth and Robustness in Cross-country Growth Regressions." The most important revisions concern the handling of missing observations in the cross-country data set. In the earlier paper, these had been handled through case-wise deletion-the method common to all previous studies. In this version, they are handled through multiple imputation-a method that retains substantially more of the information content of the data set. Two variants of Leamer's (1983) extreme-bounds analysis are evaluated for their ability to recover the true specification and compared to a cross-sectional version of the general-to-specific search methodology associated with the LSE approach to econometrics. Evaluations are based on a realistic Monte Carlo experiment in which the universe of potential determinants is drawn from those in Levine and Renelt's (1992) study. Levine and Renelt's method is shown to have low size and extremely low power: nothing is robust. Sala-i-Martin's (1997a, b) method is shown to have high size and high power: it is undiscriminating. The general-to-specific methodology is shown to have size near nominal size and high power. Sala-i-Martin's method and the general-to-specific method are then applied to the actual data from Sala-i-Martin's original study. The results are consistent with the Monte Carlo results and suggest that only a few of the 61 potential determinants of growth matter.
Abstract 19788: SIRT1 as a Novel Regulator of Cardiac Na+ Channels: A Potential Therapeutic Target for Arrhythmia

Introduction: Ion channel disorders are responsible for inherited and acquired forms of heart disease. Mutations in the cardiac voltage-gated Na+ channel (Nav1.5) cause inherited long QT and Brugada syndromes, and changes in Nav1.5 expression and function can promote arrhythmia susceptibility. In spite of the critical role of Nav1.5 in cardiac excitation-contraction coupling, the identity and role(s) of Nav1.5 modifying genes in both inherited and acquired arrhythmias are less well established. Aim of studies: We previously showed in both heterologous expression systems and in rat neonatal cardiac myocytes that SIRTUIN1 (SIRT1), an NAD+-dependent lysine deacetylase, increases Na+ current (INa) by binding to, deacetylating, and promoting membrane localization of Nav1.5. Here, we tested the hypothesis that SIRT1 increases INa in vivo by modifying Nav1.5 acetylation. Methods: We engineered cardiac-specific Sirt1-knockout mice (cSirt1-/-: Sirt1flox/flox x αMHC-Cre), recorded INa from isolated ventricular myocytes by whole cell patch clamp, detected Nav1.5 acetylation by Western blot and immunostaining, and recorded electrocardiograms (ECGs) in anesthetized and telemetry in ambulatory mice. Results: INa in cSirt1-/- ventricular myocytes was decreased by 39 ± 6 % compared to the littermate controls (n=8 each, p=0.02; Figure). Nav1.5-acetylation was increased in cSirt1-/- mice by Western blot and immunostaining. ECG recordings from 6 month-old cSirt1-/- mice showed QRS prolongation, and ambulatory telemetry showed high degree heart block and runs of ventricular tachycardia. Sudden death was prominent in cSirt1-/- mice despite only mild depression of left ventricular function. Conclusion: Cardiac-specific disruption of Sirt1 in mice leads to arrhythmias in vivo by decreasing INa, most likely through changes in Nav1.5 trafficking. Increasing SIRT1 expression and/or activity may provide a mechanism for preventing and/or treating arrhythmias. ![][1] [1]: /embed/graphic-1.gif
Reinforcement learning approach to individualization of chronic pharmacotherapy

Effective pharmacological therapy in chronic treatments poses many challenges to physicians. Individual response to treatment varies across patient populations. Furthermore, due to the prolonged character of the therapy, the response may change over time. A reinforcement learning-based framework is proposed for treatment individualization in the management of renal anemia. The approach is based on numerical simulation of the patient performed by Takagi-Sugeno fuzzy model and a radial basis function network implementation of an on-policy Q-learning critic. Simulation results demonstrate the potential of the proposed method to yield policies that achieve the therapeutic goal in individuals with different response characteristics.
Use of genetic analysis to test the potential role of serotonin in alcohol preference.

Abstract The hypothesis that alcohol preference in mice is influenced by brain serotonin levels was tested using genetic analysis. Alcohol preference and static serotonin content were assessed in C57BL/Ibg (alcohol-preferring) and DBA/2 (alcohol-avoiding) mice, as well as in Fl and F2 generations obtained by crossbreeding. The two parental strains showed dissimilar alcohol preferences but identical concentrations of brain serotonin. Serotonin concentration segregated independently of alcohol preference in the F1 and F2 generations. These data provides strong evidence against the hypothesis that brain serotonin content influences alcohol preference. However, they do not preclude the possibility that differential alcohol influences on serotonin metabolism or turnover rate may result in differing preference for a alcohol.
Abstract 20527: Nrf2 Signaling Modulates Human Endothelial Cell Barrier Regulation by S1P

Endothelial cell (EC) barrier dysfunction results in increased vascular permeability observed in inflammation, tumor angiogenesis, and atherosclerosis. The platelet-derived phospholipid, sphingosine-1-phosphate (S1P), decreases EC permeability in vitro and in vivo, features of obvious therapeutic potential. Oxidative stress is a common primary or secondary cause of vascular hyperpermeability in multiple pathological conditions, including inflammation, and exposure to excessive mechanical stress. Thus it is important to understand the relationship between S1P-mediated vascular protection and oxidative stress-induced barrier disruption. We examined the interaction of S1P and human pulmonary artery EC signaling and barrier regulation by the oxidative stress signaling mediator, Nrf2. Human pulmonary ECs pre-treated with either tBHQ (Nrf2 inducer) or Brusatol (Nrf2 inhibitor), were evaluated by transendothelial electric resistance (TER) in response to S1P or thrombin. tBHQ clearly augmented S1P-mediated endothelial barrier enhancement. In parallel, brusatol reduced the S1P-mediated endothelial barrier enhancement. In addition, neither tBHQ or brusatol modified the peak effects of thrombin-induced endothelial barrier disruption. However, tBHQ accelerated the recovery of endothelial barrier disruption induced by thrombin, whereas brusatol retarded EC recovery process. Furthermore, we demonstrated that tBHQ enhanced S1P mediated cortical actin polymerization and barrier enhancement, whereas Brusotal enhanced stress fiber formation in endothelial cells and inhibited S1P-mediated cortical actin formation confirming the active role of Nrf2 signaling in S1P-mediated endothelial barrier regulation. The effect of Brusatol on endothelial barrier function was confirmed by Nrf2 siRNA. These functional analyses confirm the importance of Nrf2 signaling in EC barrier restoration, a highly relevant response in acute lung inflammation resolution and lung fluid balance and further define a novel role of Nrf2-dependent signaling in vascular barrier regulation and cytoskeleton rearrangements
Late-life depression is not associated with dementia-related pathology.

OBJECTIVE: To test the hypothesis that late-life depression is associated with dementia-related pathology. METHOD: Older participants (n = 1,965) in 3 longitudinal clinical-pathologic cohort studies who had no cognitive impairment at baseline underwent annual clinical evaluations for a mean of 8.0 years (SD = 5.0). The authors defined depression diagnostically, as major depression during the study period, and psychometrically, as elevated depressive symptoms during the study period, and established their relation to cognitive outcomes (incident dementia, rate of cognitive decline). A total of 657 participants died and underwent a uniform neuropathologic examination. The authors estimated the association of depression with 6 dementia-related markers (tau tangles, beta-amyloid plaques, Lewy bodies, hippocampal sclerosis, gross and microscopic infarcts) in logistic regression models. RESULTS: In the full cohort, 9.4% were diagnosed with major depression and 8.6% had chronically elevated depressive symptoms, both of which were related to adverse cognitive outcomes. In the 657 persons who died and had a neuropathologic examination, higher beta-amyloid plaque burden was associated with higher likelihood of major depression (present in 11.0%; OR = 1.392, 95% CI = 1.088, 1.780) but not with elevated depressive symptoms (present in 11.3%; OR = 0.919, 95% CI = 0.726, 1.165). None of the other pathologic markers was related to either of the depression measures. Neither dementia nor antidepressant medication modified the relation of pathology to depression. CONCLUSION: The results do not support the hypothesis that major depression is associated with dementia-related pathology. (PsycINFO Database Record Language: en
A Review Of: “An Eye for Hitchcock”: by Murray Pomerance (Rutgers: University Press, 2004)

An Eye for Hitchcock is, according to Murray Pomerance, “a series of meditations upon six very great symphonic works of a very great composer” (3). The six “symphonic” works are in order of their p...
Compelled by the Diagram: Thinking through C. H. Waddington’s Epigenetic Landscape

Between 1940 and about 1960, Conrad Hal Waddington produced several illustrations to explain a concept central to his theories of developmental biology. The concept Waddington explained, the epigenetic landscape, was not based on settled science, and its implications were not easy to grasp. Unlike proponents of the most successful contemporary biological theory, Waddington was committed to including all biological phenomena–no matter how complex or unusual–in a single theoretical system. His intellectual style and use of images matched his ambition. Waddington used compelling images to get his readers to engage with and work through his theories. His images used a shifting, even contradictory, set of metaphors and analogical models, from train yards to crafted topological surfaces. Through an analysis of Waddington’s images and theories, I show that taking a close look at what scientific images show and how they show it is important for the historiography of science. Images can be effective at drawing viewers in, confounding them, and prodding them to ask questions; this is one reason images are necessary for science.
Dihydroergotamine in idiopathic orthostatic hypotension: short-term intramuscular and long-term oral therapy.

The efficacy of dihydroergotamine (DHE-45) in the treatment of orthostatic hypotension due to deficient circulatory reflexes was investigated in 10 patients. Over the short term, intramuscular DHE-45 induced an increase (P less than 0.005) in supine blood pressure (137 +/- 8.9 to 158 +/- 8.1 mm Hg 15 min after DHE-45 and 142 +/- 9.9 to 183 +/- 7.5 mm Hg 60 min after DHE-45) associated with an increase in total peripheral resistance (TPR) (37 +/- 1.9 to 41 +/- 2.8 U . m2 and 34 +/- 2.2 to 41 +/- 2.3) and no change in cardiac output (CO), plasma renin activity (PRA), or plasma norepinephrine. Eight patients tolerated head-up tilt to a higher angle--the drop of mean arterial pressure at equivalent angles of tilt (pre- and post-DHE-45) was less. The other two patients did not improve. On the other hand, oral DHE-45 (1-mo therapy) did not induce a change in mean arterial pressure, heart rate, CO, or TPR; the only significant hemodynamic change was an increase in the ratio cardiopulmonary volume/total blood volume (12 +/- 1.9% to 16 +/- 0.7%, P less than 0.025). Changes in PRA, plasma aldosterone, and plasma catecholamines were not significant. Response to head-up tilt was variable after the first week of therapy. Blood level 2 hr after an oral dose was one order of magnitude lower (0.1 to 0.2 ng/ml) than after intramuscular injection (1.2 to 3.2 ng/ml). The discrepancy between the effects of intramuscular and oral DHE-45 for treatment of idiopathic orthostatic hypotension in this group of patients might be related to the nature of the disease (autonomic insufficiency) or to low bioavailability, suggesting that either another formulation of the drug or methods to improve absorption are needed for long-term therapy.
The postnatal maternal environment affects autoimmune disease susceptibility in A/J mice.

The postnatal maternal environment is known to increase susceptibility to a number of autoimmune diseases. Here we asked whether the postnatal maternal environment could influence autoimmune disease development to day 3 thymectomy (d3tx)-induced autoimmune ovarian disease (AOD) and experimental allergic encephalomyelitis (EAE) in cross-fostered A/J and B6 mice. A/J pups foster-nursed by B6 mothers exhibit an increase in autoimmune disease development while cross-fostering B6 pups on A/J mothers did not alter their susceptibility. The increase in AOD incidence seen in foster-nursed d3tx A/J mice correlated with a decrease in the total number of CD4+ T cells in the lymph nodes of these animals. Analysis of the cellular composition in the milk revealed that B6 mice shed significantly more maternally derived lymphocytes into their milk compared to A/J mothers. These data suggest that there are maternally derived postnatal factors that influence the development of autoimmune disease in A/J mice.
Axilog: language support for approximate hardware design

Relaxing the traditional abstraction of "near-perfect" accuracy in hardware design can lead to significant gains in energy efficiency, area, and performance. To exploit this opportunity, there is a need for design abstractions that can systematically incorporate approximation in hardware design. We introduce Axilog, a set of language annotations, that provides the necessary syntax and semantics for approximate hardware design and reuse in Verilog. Axilog enables the designer to relax the accuracy requirements in certain parts of the design, while keeping the critical parts strictly precise. Axilog is coupled with a Relaxability Inference Analysis that automatically infers the relaxable gates and connections from the designer's annotations. The analysis provides formal safety guarantees that approximation will only affect the parts that the designer intended to approximate, referred to as relaxable elements. Finally, the paper describes a synthesis flow that approximates only the relaxable elements. Axilog enables applying approximation in the synthesis process while abstracting away the details of approximate synthesis from the designer. We evaluate Axilog, its analysis, and the synthesis flow using a diverse set of benchmark designs. The results show that the intuitive nature of the language extensions coupled with the automated analysis enables safe approximation of designs even with thousands of lines of code. Applying our approximate synthesis flow to these designs yields, on average, 54% energy savings and 1.9X area reduction with 10% output quality loss.
Use of the laryngeal mask airway in oral and maxillofacial surgery

Abstract Purpose: General anesthesia for the nonintubated oral and maxillofacial surgical patient presents unique anesthetic conditions. The primary concern is the maintenance of an unobstructed airway and protection against aspiration, while minimizing both interference and interruption of the surgical procedure. The laryngeal mask airway is an alternative to the nasal hood for such airway management. The purpose of this article is to inform the oral and maxillofacial surgeon of the clinical relevant information pertaining to the use of the laryngeal mask airway in oral and maxillofacial surgery. Experience with clinical use is discussed.
Application of sparse dictionaries to SAR speckle reduction

Synthetic Aperture Radar (SAR) provides day/night all weather imagery, and as such is being increasingly utilized for overhead reconnaissance. Additionally, the active, coherent nature of the system provides for analysis not readily achievable with electro-optical imagery. However, like all coherent systems, SAR imagery suffers degradation from speckle (a random interference pattern) which hinders interpretation. Herein, we investigate SAR denoising with a new method based on sparse reconstruction over learned dictionaries and show this approach performs better than the current state of the art speckle filters.
Trauma and Substance Abuse Among Women in Prostitution: Implications for a Specialized Diversion Program

This study was undertaken to inform the implementation of a specialized prostitution diversion program to help women quit prostitution and avoid criminal prosecution. Data on 17 women's experience of trauma and substance abuse and their views on how these experiences affected their involvement in prostitution were gathered in focus groups and face-to-face interviews (including measures of substance abuse, trauma, and PTSD) conducted at a drop-in program in Baltimore, Maryland. The results indicate that the women experienced high levels of trauma and substance abuse interwoven with prostitution. Trauma-informed services and integrated substance abuse and trauma-specific treatment are needed.
Excimer laser ablation of aluminum nitride

Excimer laser wavelengths ablate aluminum nitride at rates up to 0.2 μm/pulse where the rate increases with decreasing background pressure and increasing fluence. The ablation threshold for AlN at 248 nm is approximately 2 J/cm2. Blind vias are produced with flat bottoms, straight walls, and a decomposed metallic layer remaining on the surface. Ablation rate dependence on fluence saturates at high fluences due to absorption by the ablation plume. The influence of processing variables on ablation rate and ablation mechanisms are discussed. Statistical design of experiments is used to compare data sets.
Anatomic and physiologic heterogeneity in patients with syndrome X: An intravascular ultrasound study

Objectives. We used intravascular ultrasound imaging of the epicardial vessels to assess coronary morphology, vasomotor response to exercise and exercise-vasomotion after betaadrenoceptor blockade in patients with syndrome X. Background. Syndrome X is defined as chest pain, abnormal exercise test results and normal coronary angiographic findings. Because of the limitations of coronary angiography, intravascular ultrasound was used to define coronary pathophysiology. Methods. Thirty patients with syndrome X were studied with intravascular ultrasound imaging (30 MHz, 4.3F catheter) of all three major epicardial vessels. Supine arm exercise was performed during coronary imaging. Lumen area was assessed at rest and during peak exercise. The exercise-imaging protocol was repeated after loading with 0.1 mg/kg body weight of intravenous propranolol. Results. Three morphologic groups were identified using intravascular ultrasound: normal coronary arteries (no plaque, intimal thickness Conclusions. Most patients with syndrome X have abnormal coronary arteries by intravascular ultrasound. Intravascular ultrasound identifies three distinct morphologic groups: normal coronary arteries, atheromatous plaque and intimal thickening. Exercise-vasomotion is normal in patients with syndrome X who have normal coronary arteries by ultrasound; patients with abnormal arteries (plaque or intimal thickening) have an abnormal (constrictive) response to exercise. Propranolol loading attenuates vasoreactivity in all subgroups, suggesting divergent therapeutic utility.
The complexity of G-protein coupled receptor-ligand interactions

The G-protein coupled receptors (GPCRs) play fundamental roles in the human biololgy and drug discovery. GPCRs function as signalling molecules that transduce extracellular signals into cells. The signalling transduction is generally triggered by interacting with ligands, including photons, ions, small organic compounds, peptides, proteins and lipids. In this review, we focus on interactions with diffusible ligands such as hormones and neurotransmitters. We discuss three aspects of the complexity of the GPCR-ligand interactions: functional selectivity of ligands, receptor subtype selectivity of ligands and orphan GPCRs.
A Demographic Profile of Obesity in the Adult and Veteran US Populations in 2008

Obesity is increasing in the US population and seems to be disproportionately burdening disadvantaged groups. Veterans using the Veterans Healthcare System (VHS) tend to be more disadvantaged socioeconomically than the general population and in poorer health. It is important to understand how the veteran population differs from or is similar to the general population and whether the VHS is able to mediate obesity risk among veterans. This research assesses the sociodemographic, behavioral, and health risk factors for obesity in the US adult and veteran populations in 2008. We use data from the 2008 Behavioral Risk Factor Surveillance System (BRFSS) to empirically assess predictors of obesity risk. We find that women have lower odds of obesity than men once controls for sociodemographic, behavioral, and health conditions are included in our models. We also observe a veteran obesity disadvantage in the full adult sample when conducting bivariate tests, but no significant association with the odds of obesity in the logistic regression models among veterans and non-veterans. Gender specific models indicate that male veterans have increased odds of obesity compared to non-veterans, but no difference in obesity risks among veterans and non-veterans are noted for women, controlling for all variables. Further, we find no significant differences in the odds of obesity of veterans using VHS for all, some, or none of their health care needs; further no significant gender differences in obesity risk were observed among VHS usages and non-users. Based on the strong, positive association between the number of chronic health conditions and the odds of obesity, we suggest that health policy should focus efforts on weight management counseling for obese patients that have obesity related co-morbidities, and more targeted attention to male veterans would help to address the high level of obesity in this vulnerable population group.
The ’manipulative response memory system’in the white rat

Adult albino rats, previously trained on a series of three latch box problems, sustained bilateral cortical or subcortical lesions and were subsequently tested for retention. Those animals showing defective retention of all three problems suffered damage to either the sensorimotor cortex, corpus striatum, posterior thalamus, subthalamus, red nucleus, or brainstem reticular formation. Excellent retention of at least two of the three problems was found in animals suffering extensive occipital, cingulate, pyriform, hippocampal, septal, amygdaloid, pretectal, or tectal damage. These findings provide additional evidence for a localized cortico-subcortical system mediating learned responses in the rodent.
Screening procedures for eye irritation.

Abstract Screens aid in identifying some severe irritants or corrosives and eliminating them from consideration for in vivo eye irritation testing. Products may be evaluated for ocular irritation potential in a stepwise progression as follows: (1) products at pH extremes of 2 or below or of 11.5 or above may be considered to be ocular irritants; (2) based on chemical structure—activity considerations, some products may be judged to have ocular irritation potential; (3) validated and accepted in vitro systems may possibly be used as a screen in the future; (4) when a test material demonstrates severe acute dermal toxicity (lethality at ⩽200 mg/kg body weight), further testing for either dermal or ocular irritation may not need to be undertaken; (5) if a substance shows a primary dermal irritation index of 5 or above, it may be considered to be an ocular irritant; (6) materials that are not removed from consideration based on these proposed screens may then be considered for testing for ocular irritation in rabbits under accepted procedures. In a survey given to participants in the workshop, a high percentage believed that screens should be used. However, opinions on the use of the individual screens varied between the different interested groups attending, with the possible future use of in vitro screens for specific product lines having the highest percentage of agreement (57–100%).