cssi/SciSciGPT-SciSciNet huggingface dataset:
Coordinated Regulation of Murine Cardiomyocyte Contractility by Nanomolar (-)-epigallocatechin-3-gallate, the Major Green Tea Catechin

Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (−)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance. Here, we report that nanomolar concentrations of EGCG significantly enhance contractility of intact murine myocytes by increasing electrically evoked Ca2+ transients, sarcoplasmic reticulum (SR) Ca2+ content, and ryanodine receptor type 2 (RyR2) channel open probability. Voltage-clamp experiments demonstrate that 10 nM EGCG significantly inhibits the Na+-Ca2+ exchanger. Of importance, other Na+ and Ca2+ handling proteins such as Ca2+-ATPase, Na+-H+ exchanger, and Na+-K+-ATPase were not affected by EGCG ≤1 μM. Thus, nanomolar EGCG increases contractility in intact myocytes by coordinately modulating SR Ca2+ loading, RyR2-mediated Ca2+ release, and Na+-Ca2+ exchange. Inhibition of Na+-K+-ATPase activity probably contributes to the positive inotropic effects observed at EGCG concentrations >1 μM. These newly recognized actions of nanomolar and micromolar EGCG should be considered when the therapeutic and toxicological potential of green tea supplementation is evaluated and may provide a novel therapeutic strategy for improving contractile function in heart failure.
Base-invariant symmetric dynamics of free-flying manipulators

The freedom of choice in designating a base-body for free-flying manipulators gives these manipulators a base-invariance symmetry that is not encountered in fixed-base manipulators. This paper analyzes the relationship between this natural symmetry and the dynamical equations for free-flying manipulators. The base-invariance symmetry is used to develop a new formulation of the manipulator dynamics in which two independent O(N) recursions proceeding in opposite directions are summed together to obtain the complete free-flying manipulator dynamics. Computation of the operational space inertia for the links in the manipulator is also discussed. >
Control Strategies for Transport Systems with Nonlinear Waiting Costs

The interaction between a transport company and its passengers is modeled as a cooperative game in which the company, subject to an economic constraint, uses the vehicle dispatch strategy under which a time-related cast function for passengers is minimized. A rudimentary transport system is studied in detail, and the joint optimal strategy for passengers and the transport company is obtained.
Partitioning Nominal Attributes in Decision Trees

To find the optimal branching of a nominal attribute at a node in an L-ary decision tree, one is often forced to search over all possible L-ary partitions for the one that yields the minimum impurity measure. For binary trees (L e 2) when there are just two classes a short-cut search is possible that is linear in n, the number of distinct values of the attribute. For the general case in which the number of classes, k, may be greater than two, Burshtein et al. have shown that the optimal partition satisfies a condition that involves the existence of({L\atop 2}) hyperplanes in the class probability space. We derive a property of the optimal partition for concave impurity measures (including in particular the Gini and entropy impurity measures) in terms of the existence ofL vectors in the dual of the class probability space, which implies the earlier condition. Unfortunately, these insights still do not offer a practical search method when n and k are large, even for binary trees. We therefore present a new heuristic search algorithm to find a good partition. It is based on ordering the attribute‘s values according to their principal component scores in the class probability space, and is linear in n. We demonstrate the effectiveness of the new method through Monte Carlo simulation experiments and compare its performance against other heuristic methods.
Dedicator of Cytokinesis 8 Interacts with Talin and Wiskott-Aldrich Syndrome Protein To Regulate NK Cell Cytotoxicity

Recently, patients with mutations in DOCK8 have been reported to have a combined immunodeficiency characterized by cutaneous viral infections and allergies. NK cells represent a first-line defense against viral infections, suggesting that DOCK8 might participate in NK cell function. In this study, we demonstrate that DOCK8-suppressed human NK cells showed defects in natural cytotoxicity as well as specific activating receptor-mediated NK cytotoxicity. Additionally, compared with control NK cells, NK cells depleted of DOCK8 showed defective conjugate formation, along with decreased polarization of LFA-1, F-actin, and cytolytic granules toward the cytotoxic synapse. Using a proteomic approach, we found that DOCK8 exists in a macromolecular complex with the Wiskott-Aldrich syndrome protein, an actin nucleation-promoting factor activated by CDC42, as well as talin, which is required for integrin-mediated adhesion. Taken together, our results demonstrate an important role for DOCK8 in NK cell effector function and provide important new mechanistic insight into how DOCK8 regulates F-actin and integrin-mediated adhesion in immune cells.
LORES: Low resolution shape program for the calculation of small angle scattering profiles for biological macromolecules in solution

A program for determining the low resolution shape of biological macromolecules, based on the optimization of a small angle neutron scattering profile to experimental data, is presented. This program, termed LORES, relies on a Monte Carlo optimization procedure and will allow for multiple scattering length densities of complex structures. It is therefore more versatile than utilizing a form factor approach to produce low resolution structural models. LORES is easy to compile and use, and allows for structural modeling of biological samples in real time. To illustrate the effectiveness and versatility of the program, we present four specific biological examples, Apoferritin (shell model), Ribonuclease S (ellipsoidal model), a 10-mer dsDNA (duplex helix) and a construct of a 10-mer DNA/PNA duplex helix (heterogeneous structure). These examples are taken from protein and nucleic acid SANS studies, of both large and small scale structures. We find, in general, that our program will accurately reproduce the geometric shape of a given macromolecule, when compared with the known crystallographic structures. We also present results to illustrate the lower limit of the experimental resolution which the LORES program is capable of modeling.
The many meanings of Anti‐Fascism

(1999). The many meanings of Anti‐Fascism. Journal of Modern Italian Studies: Vol. 4, No. 1, pp. 54-59.
Fatal myocardial infarction associated with intravenous N-acetylcysteine error

N-acetylcysteine is used to treat acetaminophen toxicity and is available in both intravenous and oral formulations. Our report describes a patient treated with intravenous N-acetylcysteine for acetaminophen toxicity who died after an anaphylactoid reaction following initiation of the infusion. Clinicians should be aware of potential complications when deciding on which formulation of N-acetylcysteine to administer. A 53-year-old male presented with altered mental status after an overdose of acetaminophen/hydrocodone and carisoprodol. He had an acetaminophen level of 49 mcg/ml with an unknown time of ingestion. The patient was admitted to the intensive care unit (ICU) on a naloxone drip and was started on intravenous N-acetylcysteine (NAC) at the presumed dose of 150 mg/kg. Shortly after initiating the NAC infusion, the patient developed periorbital edema, skin rash, and hypotension. The infusion of N-acetylcysteine was immediately stopped and the patient required emergent intubation. Resuscitation was begun with intravenous fluids followed by the initiation of phenylephrine. He developed ST elevation in the inferior leads on his ECG. This evolved into an inferior myocardial infarction by ECG and cardiac enzymes. Echocardiogram showed global, severe hypokinesis with an ejection fraction of less than 20% in a patient with no pre-existing cardiac history. Despite aggressive support, he died approximately 17 hours after the initiation of intravenous NAC. Further investigation found a 10-fold formulation error in his NAC loading dose. The intravenous formulation of NAC has a higher probability of significant adverse effects and complications not described with the oral formulation. Clinicians should be aware of these potential complications when deciding on which formulation to administer.
Potential Effects of Hemoglobin Concentration on Red Cell Metabolism Together with Observations on Red Cell Metabolic Differences Between Men and Women

One of our major interests has been the glycolytic control mechanisms in the red cell which determine DPG levels normally and during hypoxic stress. We have increasingly utilized the method of assaying the measurable intermediates throughout the glycolytic pathway, along the lines suggested by Yoshikawa and Minakami (1968), in order to determine the key enzymatic step or steps which bring about changes in DPG. Through these studies we have begun to discern a rather consistent pattern, suggesting that the activity of hexokinase, already known to be one of the key regulators of erythrocyte glycolysis (Rapoport, 1968; Yoshikawa and Minakami, 1968), may be a very important factor in regulating DPG levels, in a number of circumstances. This pattern is illustrated in papers on anemia (Oelshlegel, et al. 1972) and altitude adaptation (Moore, et al. 1972) in this volume, but we would also like to illustrate it in the first part of this paper in differences between normal men and women.
The Electoral Fortunes of Gubernatorial Incumbents: 1947–1981

I break down gubernatorial electoral outcomes into expected vote and short-term changes, using an intrastate baseline measure. Employing these measures, I find evidence of period effects in the role played by incumbency, including the growth in its importance in the last decade. Incumbents' gains are most notable in first reelection contest, but tail off in subsequent races. Moreover, these advantages are more pronounced after a two-year term than after a four-year term. Other factors influencing incumbents' success are less clear in their impact: Sabato's measure of reputation is associated with electoral gains, but increasing state bureaucratization appears more weakly linked.
Some results on the L p stability of linear time-varying systems

This paper considers the L p stability of systems with a convolution operator in the forward loop and a time-varying gain in the feedback loop. A frequency-domain condition involving the frequency response of the forward loop and the Fourier coefficients of the time-varying gain of the feedback loop is presented. The paper also contains a somewhat more involved time-domain condition in terms of the open-loop weighting pattern.
Model reduction for reduced order estimation in traffic models

This paper is concerned with model reduction for a complex Markov chain using state aggregation. The work is motivated in part by the need for reduced order estimation of occupancy in a building during evacuation. We propose and compare two distinct model reduction techniques, each of which is based on the potential matrix for the Markov semigroup. The first method is based on spectral graph partitioning where the weights are defined by the entries of the potential matrix. The second approach is based on aggregating states with similar long term uncertainty, where uncertainty is captured using conditional entropy. It is shown that entropy can be conveniently expressed in terms of the potential matrix. In application to the building model, the entries of the potential matrix correspond to the mean time an individual occupies a given cell. Numerical results are described, including a simulation study of the reduced order estimator.
What Do Economics Majors Do and What Do They Earn When They Do it

This paper uses a recent and rich data set to examine the effect of economics major on individual earnings controlling for personal, occupation, and industry characteristics. We found a pronounced positive earnings gain for economics major relative to other majors; this advantage increases as the major’s level of education increases. We document that roughly half of the earnings advantage can be attributed to access to higher paying occupations and half of the advantage reflects higher pay for economics majors within occupations. Overall, these findings concur with Black et al. (2003).
Survival benefits of remote ischemic conditioning in sepsis.

Abstract Background Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Materials and methods Eight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan–Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. Results We performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan–Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS ( P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours ( P Conclusions RIC improves survival in sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an immune-modulatory role in sepsis. Further studies are necessary to refine understanding of the observed survival benefits and its implications in sepsis management.
Pathogenesis of Urothelial Carcinoma

Currently, we recognize two major separate molecular pathways in urothelial carcinogenesis, each leading to neoplasms with distinct morphology and biologic behavior. The more common pathway, the hyperplasia pathway is characterized by FGFR3 mutations, low-grade papillary morphology, relatively high recurrence rate, but very low incidence of progression to invasive disease. The less common pathway, the dysplasia pathway, results in high-grade flat or papillary tumors that have a high potential for muscle invasion and metastases. The main goal of urinary tract cytology is the detection of urothelial neoplasms that have a high risk for invasion and metastasis; therefore, the main focus of The Paris System for Reporting Urinary Cytology is the detection of clinically significant urothelial neoplasia, namely high-grade urothelial carcinoma (HGUC).
Controlled Self-Assembly of Functionalized Carbon Nanotubes on Silicon Substrates

Self-assembly of carbon nanotubes (CNTs) on silicon substrates has myriad applications including nanotube based electrochemical energy conversion and storage devices, such as batteries and super-capacitors. Patterned assembly of CNTs is required in order to control the effective electrical conductivity and mechanical properties of these devices and achieve substantial improvement in their performance. Solution-based self-assembly of CNTs provides a cost-effective means to synthesize uniform vertically or horizontally aligned nanostructures on top of substrates. However, self-assembly of CNTs is a complex dynamical process that involves intermolecular interaction between the CNTs and that between the nanotubes and the substrate as well as solvent molecules. The transport properties of CNTs and solvents also play an important role. The scientific literature lacks detailed study of understanding the mechanism of self-assembly of CNTs on substrates during synthesis process. Often times, nanotubes are functionalized in an effort to make them more soluble and induce partial charges to control the self-assembly. Some of the key factors that govern the transportation and self-assembly of functionalized CNTs are surface charge density on substrate and electrostatic interaction of the functionalized CNTs with the substrate. In an effort to mimic the conditions during the synthesis of carbon nanomaterials on silicon substrate, we have employed molecular dynamics simulations to simulate both pure and functionalized CNTs sandwiched between silicon substrates in presence of commonly used solvent, water. Our simulations indicate that both pure and functionalized CNTs are not significantly soluble in water and form agglomerates. Our results also illustrate that neither pure nor functionalized CNTs tend to deposit on silicon substrates in water. Results presented in this study provide fundamental insight that can help to understand the agglomeration and orientation of CNTs in water.© 2013 ASME
Barriers to and Facilitators of Health for Latina Undergraduate Students

Latina undergraduate students’ barriers and facilitators of health are examined: Barriers to psychological health—separating from family, pressure to succeed, and racism; Barriers to physical healt...
Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1-/- mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1-/- mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1-/- mice is also significantly decreased relative to that from wild-type mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1-/- mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1.
Lateral release for recurrent dislocation of the patella

We reviewed 41 knees after arthroscopic lateral release for recurrent dislocation of the patella at a mean follow-up of four years, and graded the results according to the criteria of Crosby and Insall (1976). There were no dislocations after operation in 28 knees (68%); the less satisfactory results were in patients with subluxation of the patella on extension of the knee and those with generalised ligamentous laxity. There were no complications. A characteristic and previously unreported lesion of the patellar surface was seen in eight of the 41 knees. The results of lateral release are better than those reported for other techniques. This treatment, by either open or arthroscopic methods, is recommended.
The Operation and monitoring of ZaoZhuang Measles Laboratory

Objective Achieve the purpose of eliminating measles in 2012 and Evaluatin the operating condition of the measles laboratory.Methods Analyzing the monitoring results and data of ZaoZhuangmeasles laboratory from 2005-2009.Results In 1684 case of suspected measles,1506 sera specimens were detected.Laboratory diagnosis rate was 89.43%,the case of measles IgM antibody positive was 986,The positive rate was 65.47%.the case of rubella IgM antibody positive was 61,The positive rate was 4.05%.The rate of qualified collection specimens was 83.73%,The rate of submission rate in time was 98.40%,the result agreed with the review of Shandong CDC.Normal population measles IgG positive rate was 90.17%,GMRT WAS 596.74.Conclusion Measles laboratory run well,provided technical support about laboratory diagnosis of suspected measles cases and monitoring of measles epidemic.
Immune response to postsurgical adjuvant active immunotherapy with Canvaxin polyvalent cancer vaccine: correlations with clinical course of patients with metastatic melanoma.

The efficacy of cytoreductive surgery for metastatic melanoma depends in part on the patient's immune response, which can be modulated by post-operative active immunotherapy with Canvaxin therapeutic polyvalent cancer vaccine (CancerVax Corp., Carlsbad, CA). Canvaxin vaccine induces polyvalent humoral and cell-mediated immune responses to a wide variety of protein and ganglioside melanoma antigens; these responses correlate with subsequent prognosis in immunized patients. Matched-pair analyses of data from extensive phase II trials have demonstrated a consistent overall survival (OS) benefit for Canvaxin therapy in stage IV melanoma (five-year OS of 39% for 107 vaccine patients versus 20% for 107 non-vaccine patients; P =.0009) and stage III melanoma (five-year OS of 49% for 739 vaccine patients versus 37% for 739 non-vaccine patients; P =.0001). Vaccine-induced immune responses have been correlated with survival after resection of local, regional, and distant melanoma. In 77 patients who received Canvaxin vaccine after resection of stage IV melanoma five-year OS rate was 75% for patients with an elevated level of IgM antibodies against a 90-kD glycoprotein antigen (TA90) expressed by the vaccine, and a strong delayed-type hypersensitivity (DTH) response to the vaccine; by contrast, survival was 36% for patients who had either an elevated IgM response or a strong DTH response, and only 8% if neither response was strong (P<.001). In 59 patients with resected stage III melanoma, both cellular (DTH) and humoral (anti-TA90 IgG and IgM antibodies) immune responses impacted survival (P = 0.046, 0.0005, and 0.0053, respectively). In stage II melanoma, five-year OS and disease-free survival rates were 94% and 89%, respectively, when maximal anti-TA90 IgM titre was at least 1:800, compared to only 52% and 17%, respectively, for lower titres (P =.0001). Cumulatively, these data represent the largest phase II experience for any cancer vaccine and indicate the clinical efficacy of stimulating a patient's endogenous immune response to melanoma.
Biochemical and Cellular Characterization and Inhibitor Discovery of Pseudomonas aeruginosa 15-Lipoxygenase

Pseudomonas aeruginosa is an opportunistic pathogen that can cause nosocomial and chronic infections in immunocompromised patients. P. aeruginosa secretes a lipoxygenase, LoxA, but the biological role of this enzyme is currently unknown. LoxA is poorly similar in sequence to both soybean LOX-1 (s15-LOX-1) and human 15-LOX-1 (37 and 39%, respectively) yet has kinetics comparably fast versus those of s15-LOX-1 (at pH 6.5, Kcat = 181 ± 6 s(-1) and Kcat/KM = 16 ± 2 μM(-1) s(-1)). LoxA is capable of efficiently catalyzing the peroxidation of a broad range of free fatty acid (FA) substrates (e.g., AA and LA) with high positional specificity, indicating a 15-LOX. Its mechanism includes hydrogen atom abstraction [a kinetic isotope effect (KIE) of >30], yet LoxA is a poor catalyst against phosphoester FAs, suggesting that LoxA is not involved in membrane decomposition. LoxA also does not react with 5- or 15-HETEs, indicating poor involvement in lipoxin production. A LOX high-throughput screen of the LOPAC library yielded a variety of low-micromolar inhibitors; however, none selectively targeted LoxA over the human LOX isozymes. With respect to cellular activity, the level of LoxA expression is increased when P. aeruginosa undergoes the transition to a biofilm mode of growth, but LoxA is not required for biofilm growth on abiotic surfaces. However, LoxA does appear to be required for biofilm growth in association with the host airway epithelium, suggesting a role for LoxA in mediating bacterium-host interactions during colonization.
Practical Steady-State Enzyme Kinetics

Enzymes are key components of most biological processes. Characterization of enzymes is therefore frequently required during the study of biological systems. Steady-state kinetics provides a simple and rapid means of assessing the substrate specificity of an enzyme. When combined with site-directed mutagenesis (see Site-Directed Mutagenesis), it can be used to probe the roles of particular amino acids in the enzyme in substrate recognition and catalysis. Effects of interaction partners and posttranslational modifications can also be assessed using steady-state kinetics. This overview explains the general principles of steady-state enzyme kinetics experiments in a practical, rather than theoretical, way. Any biochemistry textbook will have a section on the theory of Michaelis-Menten kinetics, including derivations of the relevant equations. No specific enzymatic assay is described here, although a method for monitoring product formation or substrate consumption over time (an assay) is required to perform the experiments described.
The Theorems of Asgeirsson and Howard

For the derivation of the theorems in this chapter it is convenient to introduce the integrals of a function f(x) in n-space over a general ellipsoid $$F(x) = \sum\limits_{i,k = 1}^n {{a_{ik}}} {X_i}{X_k} = {r^2}$$ (5.1) .
Trends and racial and ethnic disparities in the prevalence of pregestational type 1 and type 2 diabetes in Northern California: 1996–2014

Background Despite concern for adverse perinatal outcomes in women with diabetes mellitus before pregnancy, recent data on the prevalence of pregestational type 1 and type 2 diabetes mellitus in the United States are lacking. Objective The purpose of this study was to estimate changes in the prevalence of overall pregestational diabetes mellitus (all types) and pregestational type 1 and type 2 diabetes mellitus and to estimate whether changes varied by race-ethnicity from 1996–2014. Study Design We conducted a cohort study among 655,428 pregnancies at a Northern California integrated health delivery system from 1996–2014. Logistic regression analyses provided estimates of prevalence and trends. Results The age-adjusted prevalence (per 100 deliveries) of overall pregestational diabetes mellitus increased from 1996–1999 to 2012–2014 (from 0.58 [95% confidence interval, 0.54–0.63] to 1.06 [95% confidence interval, 1.00–1.12]; P trend P trend P trend Conclusions The prevalence of overall pregestational diabetes mellitus and pregestational type 1 and type 2 diabetes mellitus increased from 1996–1999 to 2012–2014 and racial-ethnic disparities were observed, possibly because of differing prevalence of maternal obesity. Targeted prevention efforts, preconception care, and disease management strategies are needed to reduce the burden of diabetes mellitus and its sequelae.
Clinical Diagnosis of Electrical Versus Anatomic Left Ventricular Hypertrophy: Prognostic and Therapeutic Implications.

Left ventricular hypertrophy (LVH) can develop in association with chronic arterial hypertension and other cardiovascular disorders and is a well-established risk factor for cardiac arrhythmias, cardiovascular events, and mortality.1 Over 4 decades ago the Framingham Heart Study reported that electrocardiographic evidence of LVH (ECG LVH) was associated with 3- to 4-fold increase in cardiovascular and all-cause mortality, with a disproportionately high risk of sudden cardiac death (SCD).2,3 Subsequently, multiple studies in different population samples have confirmed these associations.4,5 In early studies, the 12-lead ECG was the only available method to diagnose LVH in living subjects. In subsequent years, anatomic LVH diagnosed by echocardiography (echo LVH) became the gold standard.6,7 Despite the development of fairly detailed diagnostic ECG criteria for LVH,8 echocardiographic measurements have virtually replaced the ECG diagnosis of LVH. This shift in clinical practice was driven by the low reported sensitivity (usually <25%), albeit high specificity (up to 95%) of ECG criteria for diagnosis of LVH with echocardiography, magnetic resonance imaging (MRI), or during autopsy.9,10 More recently, however, we are learning that ECG LVH and echo LVH may be clinically distinct entities. In fact, there are now data to suggest that although these 2 entities can often overlap, each may provide distinct prognostic and potentially, mechanistic information, especially in the context of cardiac arrhythmias. This review will attempt to put these findings into perspective for the clinical electrophysiologist, by discussing the significance of electrical versus anatomic LVH for occurrence of atrial fibrillation (AF) and SCD. To diagnose increased left ventricular (LV) mass from the 12-lead ECG, over 30 different ECG criteria have been developed. Most of the commonly used LVH criteria, such as Sokolow and Lyon, and Cornell voltage, rely solely on measuring QRS voltage. …
Transgressing the Gendered Norms in Childhood: Understanding Transgender Children and Their Families

ABSTRACTThis qualitative study utilized case-study research methodology and ethnographic techniques to highlight the lived experiences of four prepubescent (female affirmed) transgender children and their families. This article presents the exploratory and descriptive findings from a micro perspective of the children, siblings, and their parents, as the prepubescent children transitioned gender and developed their gender identity over time. Through an in-depth portrait of their lives, this article details the strengths and challenges that these families experienced at the micro level, while sharing the limitations, challenges, and areas for future research with trans children and their families.
A research and experimentation framework for exploiting voI-based methods within analyst workflows in tactical operation centers

In today’s battlefield environments, analysts are inundated with real-time data received from the tactical edge that must be evaluated and used for managing and modifying current missions as well as planning for future missions. This paper describes a framework that facilitates a Value of Information (VoI) based data analytics tool for information object (IO) analysis in a tactical and command and control (C2) environment, which reduces analyst work load by providing automated or analyst assisted applications. It allows the analyst to adjust parameters for data matching of the IOs that will be received and provides agents for further filtering or fusing of the incoming data. It allows for analyst enhancement and markup to be made to and/or comments to be attached to the incoming IOs, which can then be re-disseminated utilizing the VoI based dissemination service. The analyst may also adjust the underlying parameters before re-dissemination of an IO, which will subsequently adjust the value of the IO based on this new/additional information that has been added, possibly increasing the value from the original. The framework is flexible and extendable, providing an easy to use, dynamically changing Command and Control decision aid that focuses and enhances the analyst workflow.
Interactions Among the Soybean Looper (Lepidoptera: Noctuidae), Threecornered Alfalfa Hopper (Homoptera Membracidae), Stem Canker, and Red Crown Rot in Soybean

Field experiments in 1988–1990 determined the (1) effects of defoliation by Pseudoplusia includens (Walker) (soybean looper) or basal stem girdling by Spissistilus festinus (Say) (threecornered alfalfa hopper) on soybean stem canker severity and (2) effects of the soybean looper defoliation on red crown rot incidence. Compared to ungirdled plants, stem canker severity was increased while stem length, stem diameter, and yield were reduced for girdled plants. Stem canker severity, number of perithecia, yield, stem length, and stem diameter were reduced on defoliated soybean, compared to undefoliated soybean. Red crown rot incidence, perithecial production, and yields were reduced on defoliated soybean compared to undefoliated soybean. This suggests different types of insect injury may either increase or decrease the severity of soybean diseases.
Current Practices and Attitudes Toward Cholesterol Management in Patients With Recent Acute Myocardial Infarction: A Survey of Community Physicians

P41 Background: Recurrent coronary events and mortality are associated with elevated serum cholesterol levels in patients with acute myocardial infarction (AMI). It’s unclear what physicians’ current attitudes and practices are toward the management of high cholesterol levels in patients with recent AMI. We carried out a survey of practicing physicians to examine factors that influence physicians prescription of lipid-lowering and dietary therapy in patients with recent AMI and threshold levels of cholesterol for intervention. Methods: Mailed questionnaire survey of general internists, cardiologists, and family physicians practicing and/or having admitting privileges to all Worcester (MA) metropolitan hospitals. Results: Among the 257 responding physicians, lipid lowering therapy was more likely to be initiated in younger patients at lower total and LDL-cholesterol levels than in older patients. Younger physicians were more likely to initiate dietary and lipid lowering drug therapy at lower total and LDL-cholesterol levels. General practice physicians were more likely to initiate dietary therapy at lower total cholesterol levels, but more likely to initiate lipid lowering drug therapy at higher total and LDL-cholesterol levels, than internists and cardiologists. The most important factors reported by physicians which interfered with patient’s use of lipid lowering drug therapy were their concerns about medication costs, issues related to polypharmacy, and failure to recognize the importance of lipid lowering drugs. Several physician associated factors including provider responsibility and importance of other cardiac drugs were associated with the more widespread use of these medications. Conclusions: Results of this survey in a representative sample of community physicians suggest that older physicians are less likely to implement recommended treatment guidelines in patients with recent AMI and high cholesterol. Additional efforts are needed to modify potential barriers to the implementation of effective long-term cholesterol management in patients with recent AMI.
Redox Potential and ROS-Mediated Nanomedicines for Improving Cancer Therapy.

Abstract Significance: The overabundance of reactive oxygen species (ROS) and antioxidants in cancer cells represents a challenge for therapeutic intervention, while also providing an opportunity for the development of new strategies to improve clinical therapeutic outcomes. Recent Advances: Nanotechnology has advanced tremendously in recent decades and now offers many potential opportunities to leverage altered redox status to improve conventional therapies. Highly tunable nanoparticle delivery systems have shown great promise for improving the following: (i) chemotherapy via selective redox-sensitive drug release in tumor cells and limited systemic toxicity; (ii) photodynamic therapy via enhancing photoactivation and/or ROS production; and (iii) radiation therapy via enhancing ROS production. Great progress has also been made regarding novel nanoparticle-mediated therapies to enhance tumor cell death via ROS generation and angiogenic inhibition. Critical Issues: Current anticancer therapies are limited ...
The Electronic Home Note Program: An Internet-Based Intervention to Improve On-Task Behavior, Academic Performance, and Parental Review

The authors examined the effectiveness of the electronic home note program (EHNP). The program features an emailed version of the traditional home note intervention. In addition, the program uses m...
Outlook and Challenges of Perovskite Solar Cells toward Terawatt-Scale Photovoltaic Module Technology

Rapid development of perovskite solar cells (PSCs) during the past several years has made this photovoltaic (PV) technology a serious contender for potential large-scale deployment on the terawatt scale in the PV market. To successfully transition PSC technology from the laboratory to industry scale, substantial efforts need to focus on scalable fabrication of high-performance perovskite modules with minimum negative environmental impact. Here, we provide an overview of the current research and our perspective regarding PSC technology toward future large-scale manufacturing and deployment. Several key challenges discussed are (1) a scalable process for large-area perovskite module fabrication; (2) less hazardous chemical routes for PSC fabrication; and (3) suitable perovskite module designs for different applications.
Model of Tertiary Phosphorites on the World’s Continental Margins

Shallow subsurface Tertiary sediments of mid-latitude, modern continental margins of the world contain a tremendously extensive and poorly known Neogene sediment sequence that has a high theoretical potential for containing major deposits of unconsolidated phosphate sediments. Reworked phosphates occurring in thin, Holocene surface sediments are important tracers for these shelf deposits which may crop out or more commonly occur in the shallow subsurface. This hypothesis should be tested by combining techniques of high-resolution seismics with detailed networks of vibracores on continental shelf areas with anomalous phosphate concentrations in the surface sediments. Ultimately, deeper core drilling is required to adequately understand the third dimension. Future mining and production will undoubtedly combine existing technology from the offshore petroleum industry with new technology being developed within the mineral industry such as hydraulic slurry mining.
DETERMINISTIC AND STOCHASTIC GENETIC AND ECOLOGICAL PROCESSES

One of the principal areas of apphcation of probabihstic ideas is in the study of genetic systems. We begin with a description of the essential quahtative ideas imderlying the genetic mechanism and focus our attention in the next two sections on some classical deterministic models. Some stochastic models of genetic systems and their connections with branching processes will be developed in Section 4. The following presentation should be regarded as merely an introduction to the rich and exciting area of population genetics and its intrinsic probabihstic and stochastic structure.
Application of A-Mode Ultrasound to Characterize Intramuscular Fat Content

Intramuscular fat content and distribution (marbling) are important attributes for beef quality grading. The USDA (United States Department of Agriculture) certified inspectors determine the beef quality grades, based on marbling, by visually inspecting the cross sections of longissimus dorsi (ribeye) muscle at the 12th rib location on chilled beef carcass. This subjective method of grading, however, will not meet the meat industry’s demand for a value based marketing system. One important step towards this goal is an objective method of characterizing intramuscular fat or marbling. B-mode ultrasound has been shown to have the potential for predicting intramuscular percentage fat (%-fat) in live animals [1] as well as carcasses [2]. This paper presents the potential of A-mode ultrasound for characterizing intramuscular fat.
Alexithymia, Irrational Beliefs, and the Rational-Emotive Explanation of Emotional Disturbance

In recent discussions of Rational-Emotive Behavior Therapy (REBT), Ellis has argued that unconscious processes supplement irrational beliefs in explaining psychopathology. The hypothesis of this investigation was that these unconscious processes reflect alexithymia. University students responded to the three factors from the Toronto Alexithymia Scale, the Malouff and Schutte Belief Scale (MSBS), 5 subscales from the Survey of Personal Beliefs, and instruments recording depression, anxiety, and neuroticism. As hypothesized, alexithymia and irrational beliefs predicted greater emotional disturbance while also displaying some small positive correlations with each other. In multiple regressions, both types of variables combined to predict emotional disturbance, with alexithymia explaining the greater amount of variance. Alexithymic difficulties in identifying emotions had uniquely negative mental health implications. The MSBS and the Low Frustration Tolerance subscale were the most noteworthy measures of a pathogenic irrationality. These data supported the claim that the unconscious processes of REBT could be conceptualized in terms of alexithymia.
Inhibition of endoplasmic-reticulum-stress-mediated autophagy enhances the effectiveness of chemotherapeutics on pancreatic cancer

Endoplasmic reticulum (ER) stress and its consequent unfolded protein response (UPR) are believed to be associated with progression, survival and chemoresistance of a variety of tumor cells through multiple cellular processes, including autophagy. Therefore, the ER stress-autophagy pathway presents a potential molecular target for therapeutic intervention. The objective of this study was to evaluate the therapeutic efficacy of ER stress and autophagy modulators in the context of pancreatic ductal adenocarcinoma (PDAC). We first targeted IRE1α, an important regulator of the UPR, through STF-083010 treatment in PDAC cell lines in vitro. Chloroquine was then used to target autophagy and an optimal combination treatment was developed using chloroquine, sunitinib and gemcitabine. Apoptosis was analyzed using TUNEL assay, autophagy was estimated using lysotracker staining and electron microscopy, and UPR was analyzed using anti-GRP78 immunostaining and XBP1 splicing. Transplantation of PDAC derived KPCP1 and Panc02 cells in mouse pancreas were performed to study treatment efficacy in vivo. Suppression of the IRE1α by STF-083010 alone resulted in increased lysosomes and reduced viability of PDAC cells. Chloroquine treatment alone inhibited downstream autophagy but was insufficient in reducing PDAC cell growth. However, combining STF-083010 and chloroquine had additive anti-tumor efficacy when used with gemcitabine. Sunitinib alone caused abnormal maturation of the autolysosomes with increased intracellular multivesicular bodies and increased apoptosis evident in PDAC cells. Sunitinib showed a synergistic effect with chloroquine in reducing in vitro PDAC cell viability and significantly increased the efficacy of gemcitabine in human and murine PDAC cell lines. The anti-proliferative effect of gemcitabine was significantly increased when used in combination with sunitinib and/or chloroquine in both in vitro and in vivo PDAC models. The addition of sunitinib and/or chloroquine to gemcitabine, resulted in a significantly increased survival of the animals without noticeably increased toxicity. Sunitinib, gemcitabine and chloroquine treated mice showed a significant reduction of GRP78 expression, reduced cell proliferation and increased apoptosis in pancreas, compatible with a tumor response. Sunitinib combined with chloroquine reduces tumor growth through suppression of autophagy and increased apoptosis. Co-administration of modulators of ER stress-mediated autophagy with chemotherapy presents a novel therapeutic approach in PDAC.
Development and use of a staffing model for clinical research teams at an NCI Comprehensive Cancer Center.

e18267Background: As the cost and complexity of clinical cancer research increases, the determination of staffing needs based on individual protocol characteristics is critical. There are few strai...
Rapid uncertainty quantification for non-linear and stochastic wind excited structures: a metamodeling approach

The application of performance-based design (PBD) requires the modeling of the dynamic response of the system beyond the elastic limit. If probabilistic PBD is considered, this implies the need to propagate uncertainties through non-linear dynamic systems. This paper investigates the possibility of using advanced metamodeling techniques in order to define a computationally tractable approach for propagating uncertainty through a class of multi-degree-of-freedom non-linear dynamic systems subject to multivariate stochastic wind excitation. To this end, a scheme is introduced that is based on combining model order reduction with a recently introduced metamodeling approach that has been seen to be particularly effective in describing the dynamic response of uncertain non-linear systems of low dimensions. A case study consisting in a 40-story moment resisting frame subject to multivariate stochastic wind excitation and an array of non-linear viscous dampers is presented to illustrate the potential of the scheme.
Assessing the Value of Scholarly Book Reviews among Geographers

According to the latest data available, in 2013 a staggering 68,000 scholarly books reached print in North America alone. Book reviews have long served as an important tool to keep tabs on the cont...
MMP9 inhibition increases erythropoiesis in RPS14-deficient del(5q) MDS models through suppression of TGF-β pathways.

The del(5q) myelodysplastic syndrome (MDS) is a distinct subtype of MDS, associated with deletion of the ribosomal protein S14 (RPS14) gene that results in macrocytic anemia. This study sought to identify novel targets for the treatment of patients with del(5q) MDS by performing an in vivo drug screen using an rps14-deficient zebrafish model. From this, we identified the secreted gelatinase matrix metalloproteinase 9 (MMP9). MMP9 inhibitors significantly improved the erythroid defect in rps14-deficient zebrafish. Similarly, treatment with MMP9 inhibitors increased the number of colony forming unit-erythroid colonies and the CD71+ erythroid population from RPS14 knockdown human BMCD34+ cells. Importantly, we found that MMP9 expression is upregulated in RPS14-deficient cells by monocyte chemoattractant protein 1. Double knockdown of MMP9 and RPS14 increased the CD71+ population compared with RPS14 single knockdown, suggesting that increased expression of MMP9 contributes to the erythroid defect observed in RPS14-deficient cells. In addition, transforming growth factor β (TGF-β) signaling is activated in RPS14 knockdown cells, and treatment with SB431542, a TGF-β inhibitor, improved the defective erythroid development of RPS14-deficient models. We found that recombinant MMP9 treatment decreases the CD71+ population through increased SMAD2/3 phosphorylation, suggesting that MMP9 directly activates TGF-β signaling in RPS14-deficient cells. Finally, we confirmed that MMP9 inhibitors reduce SMAD2/3 phosphorylation in RPS14-deficient cells to rescue the erythroid defect. In summary, these study results support a novel role for MMP9 in the pathogenesis of del(5q) MDS and the potential for the clinical use of MMP9 inhibitors in the treatment of patients with del(5q) MDS.