cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of eprosartan versus hydrochlorothiazide on markers of vascular oxidation and inflammation and blood pressure (renin-angiotensin system antagonists, oxidation, and inflammation)

Antagonists of the renin-angiotensin system, such as angiotensin type 1 (AT(1)) receptor inhibitors and angiotensin-converting enzyme inhibitors, are becoming increasingly popular agents in treating patients with systemic hypertension and minimizing organ damage. In the present study, we compared the effects of eprosartan, an AT(1) receptor inhibitor, with the diuretic hydrochlorothiazide in a group of newly diagnosed hypertensive patients with multiple risk factors for atherosclerosis. The subjects were monitored and tested at 0 and 4 weeks to determine their individual effects on vascular and inflammatory markers. Although blood pressure reduction was comparable between the 2 agents, there were notable differences in their effects on markers of inflammation and oxidation. We observed a 28% reduction in neutrophil superoxide anion generating capacity, a 34% reduction in soluble monocyte chemotactic protein-1, and a 35% reduction in soluble vascular cell adhesion molecule with eprosartan therapy (all p <0.05 from the start of therapy). In addition, eprosartan showed further benefit in its ability to increase low-density lipoprotein oxidation lag time, suggesting an increased resistance to oxidation and/or modification of low-density lipoprotein. Although hydrochlorothiazide was effective in blood pressure reduction, there were no significant changes in any of the above parameters after 4 weeks of treatment. These findings suggest that eprosartan, an AT(1) receptor inhibitor, effectively reduces systemic blood pressure and, compared with hydrochlorothiazide, suggests additional benefits in the vasculature by inhibiting mechanisms of inflammation and oxidation.
The Mixture of Bernoulli Experts: a theory to quantify reliance on cues in dichotomous perceptual decisions.

The appearances of perceptually bistable stimuli can by definition be reported with confidence, so these stimuli may be useful to investigate how visual cues are learned and combined to construct visual appearance. However, interpreting experimental data (percent of trials seen one way or the other) requires a theoretically motivated measure of cue effectiveness. Here we describe a simple Bayesian theory for dichotomous perceptual decisions: the Mixture of Bernoulli Experts or MBE. In this theory, a cue’s subjective reliability is the product of a weight and an estimate of the cue’s ecological validity. The theory (1) justifies the use of probit analysis to measure the system’s reliance on a cue and (2) enables hypothesis testing. To illustrate, we used apparent 3D rotation direction in perceptually ambiguous Necker cube movies to test whether the visual system relied on a newly recruited cue (position of the stimulus within the visual field) to the same extent when a long-trusted cue (binocular disparity) was present or not present in the display. For six trainees, reliance on the newly recruited cue was similar whether or not the long-trusted cue was present, suggesting that the visual system assumed the new cue to be conditionally independent.
Defect characterization in magnetic field coupled arrays

Magnetic Cellular Automata (MCA) utilizes mutual exchange energies of neighboring magnetic cells to order the single-domain magnetic cell which in turn performs computational tasks. In this paper, we study three dominant type of geometric defects (missing, spacing, merging) in array (used as interconnects) based on our fabrication experiments. We study effect of these defects in three segments of the array (near-input, center and near-output) and we have observed that location of these defects play an important role in masking of the errors. The observed simulation results indicate that most of the defects occurring around center and near-output would be masked generating correct behavior while defects in the near-input segment would mostly cause erroneous output. We also observe that MCA is extremely robust towards space irregularities, one of the most common form of defect we observed through our fabrication techniques.
Sensitivity of Model-Based Epidemiological Parameter Estimation to Model Assumptions

Estimation of epidemiological parameters from disease outbreak data often proceeds by fitting a mathematical model to the data set. The resulting parameter estimates are subject to uncertainty that arises from errors (noise) in the data; standard statistical techniques can be used to estimate the magnitude of this uncertainty. The estimates are also dependent on the structure of the model used in the fitting process and so any uncertainty regarding this structure leads to additional uncertainty in the parameter estimates. We argue that if we lack detailed knowledge of the biology of the transmission process, parameter estimation should be accompanied by a structural sensitivity analysis, in addition to the standard statistical uncertainty analysis. Here we focus on the estimation of the basic reproductive number from the initial growth rate of an outbreak as this is a setting in which parameter estimation can be surprisingly sensitive to details of the time course of infection.
Distinct roles for ANG II and ANG-(1-7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes.

Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE that preferentially forms angiotensin-(1–7) [ANG-(1–7)] from angiotensin II (ANG II). Incubation of neonatal rat cerebellar or medullary a...
Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients.

Background: We report on two allogeneic stem cell transplant recipients who developed cytomegalovirus disease associated with new viral mutations that conferred antiviral drug resistance. Methods: Blood specimens obtained during symptomatic disease were analyzed for mutations in the CMV UL97 and DNA polymerase genes and new mutations were assessed by recombinant phenotyping. Results: Rising cytomegalovirus (CMV) antigenemia occurred after 4–5 months of preemptive valganciclovir therapy, followed by symptomatic CMV disease including fatal pneumonia in one case. In one case, a new viral UL97 mutation (deletion of codons 601–603) was found which conferred 15-fold increased ganciclovir resistance. In the other case, a known UL97 resistance mutation M460V and a new DNA polymerase (pol) mutation D413A were found. D413A conferred ganciclovir and cidofovir resistance. Conclusions: Known and newly discovered drug resistance mutations arising during preemptive therapy may complicate post-transplant CMV disease in stem cell recipients. Improved recombinant phenotyping methods enable the rapid quantitation of the resistance conferred by newly identified UL97 and pol mutations.
Horseshoe Vortex Control with Leading Edge Endwall Boundary Layer Removal

Endwall boundary layer removal was applied at the leading edge of a faired cylinder protruding normal from a flat plate. Flow visualization was used to qualitatively understand the impact of boundary layer removal on the formation of the leading edge endwall horseshoe vortex (HV). Total pressure and velocity data were measured using a Kiel probe and particle image velocimetry (PIV). Total pressure losses were measured for five suction rates (0, 6, 11, 15, and 23%). Suction rate is defined as the fraction of the total boundary layer mass flow removed through the suction slot. The total boundary layer mass flow is the boundary layer mass flow that would pass through the cylinder region in an undisturbed flow (without the cylinder). The losses decreased by ~30% with a suction rate of 11.0%. Vorticity contours from the PIV data compared the horseshoe vortex structure with and without endwall suction. Suction effectively removed the adverse pressure gradient responsible for the formation of the horseshoe vortex. Consequently, when suction is applied the vortex system does not form. Boundary layer velocity profiles extracted from the PIV data confirmed that boundary layer separation did not occur when suction was applied. In fact, the near wall boundary layer accelerated due to the suction. This acceleration resulted in the formation of a vortex pair in the region of the suction slot. This vortex pair increased in size and magnitude with increasing suction rates above 11.0%. It also migrated away from the suction slot. It was hypothesized that this vortex pair is responsible for the decreasing effectiveness of suction on the total pressure losses for suction rates greater than 11.0%. PIV results also showed that suction reduced the corner vortex responsible for elevated heat transfer in the corner region. The knowledge gained from this study will be used in future studies to eliminate the HV system in a turbine cascade.
Is climate an important driver of post‐European vegetation change in the Eastern United States?

Many ecological phenomena combine to direct vegetation trends over time, with climate and disturbance playing prominent roles. To help decipher their relative importance during Euro-American times, we employed a unique approach whereby tree species/genera were partitioned into temperature, shade tolerance, and pyrogenicity classes and applied to comparative tree-census data. Our megadata analysis of 190 datasets determined the relative impacts of climate vs. altered disturbance regimes for various biomes across the eastern United States. As the Euro-American period (ca. 1500 to today) spans two major climatic periods, from Little Ice Age to the Anthropocene, vegetation changes consistent with warming were expected. In most cases, however, European disturbance overrode regional climate, but in a manner that varied across the Tension Zone Line. To the north, intensive and expansive early European disturbance resulted in the ubiquitous loss of conifers and large increases of Acer, Populus, and Quercus in northern hardwoods, whereas to the south, these disturbances perpetuated the dominance of Quercus in central hardwoods. Acer increases and associated mesophication in Quercus-Pinus systems were delayed until mid 20th century fire suppression. This led to significant warm to cool shifts in temperature class where cool-adapted Acer saccharum increased and temperature neutral changes where warm-adapted Acer rubrum increased. In both cases, these shifts were attributed to fire suppression rather than climate change. Because mesophication is ongoing, eastern US forests formed during the catastrophic disturbance era followed by fire suppression will remain in climate disequilibrium into the foreseeable future. Overall, the results of our study suggest that altered disturbance regimes rather than climate had the greatest influence on vegetation composition and dynamics in the eastern United States over multiple centuries. Land-use change often trumped or negated the impacts of warming climate, and needs greater recognition in climate change discussions, scenarios, and model interpretations.
Competition and regeneration in quaking aspen-white fir (Populus tremuloides-Abies concolor) forests in the Northern Sierra Nevada, USA.

Question: How does competition between quaking aspen (Populus tremuloides) and white fir (Abies concolor) affect growth and spatial pattern of each species? Location: The northern Sierra Nevada, California, USA. Methods: In paired plots in mixed aspen- (n 5 3) or white fir-dominated (n 5 2) stands, we mapped trees and saplings and recorded DBH, height, species, and condition and took increment cores. We tallied seedlings by species. Tree ring widths were used as a measure of basal area change over the last decade, and canopy openness was identified using hemispherical photographs. Linear mixed models were used to relate neighborhood indices of competition, stand, and tree-level variables to diameter increment. Spatial patterns of stems were identified using the Neighborhood Density Function. Results: White fir radial growth was higher in aspenthan white fir-dominated plots. Individual-level variables were more important for white fir than for aspen growth, while variables representing competitive neighborhood were important only for aspen. The forest canopy was more open in aspen- than white fir-dominated stands, but ample aspen seedlings were observed in all stands. Canopy stems of aspen and white fir were randomly distributed, but saplings and small trees were clumped. Aspen saplings were repelled by canopy aspen stems. Conclusions: Variation in canopy openness explained more stand–stand variation in white fir than aspen growth, but high light levels were correlated with recruitment of aspen seedlings to the sapling class. Radial growth of aspen was predicted by indices of neighborhood competition but not radial growth of white fir, indicating that spacing and stem arrangement was more important for aspen than white fir growth. Fire suppression has removed a major disturbance mechanism that promoted aspen persistence and reduced competition from encroaching conifers, and current forests favor species that regenerate best by advance regeneration (white fir).
COMPARISON OF DENDRITIC GROWTH IN PIVALIC ACID AND SUCCINONITRILE UNDER MICROGRAVITY AND TERRESTRIAL GRAVITY CONDITIONS

The Isothermal Dendritic Growth Experiment (IDGE) is a series of orbital space flight experiments designed to obtain data for a critical test of dendritic growth theory. The first two experiments, flown in 1994 and 1996, were conducted as part of the United States Microgravity Payload Shuttle missions, USMP-2 and USMP-3. These flights provided dendritic growth speeds and tip radii of pure succinonitrile (SCN)—a test material solidifying as body– centered cubic dendritic crystals, as do ferrous metals. These experiments showed that the dendritic speed and radii measured in microgravity were substantially different from those observed in terrestrial experiments. In addition, the results obtained under microgravity conditions differ from theoretical predictions of diffusion–limited dendritic growth. The most recent flight of the IDGE, flown on the fourth, and final, USMP flight, in November, 1997, yielded dendritic growth data on high–purity pivalic acid (PVA). PVA, a test material forming face–centered cubic dendritic crystals like aluminum and copper. Preliminary results from the latest IDGE flight are consistent with diffusion–limited heat transport, indicating that PVA dendrites also grow in a diffusion-limited mode, not significantly affected by molecular processes occurring at the solid-melt interface.
Scholarly activity points: a new tool to evaluate resident scholarly productivity

Abstract Background Scholarly activity is an important aspect of a resident's educational experience; however, evaluation methods have remained underdeveloped despite the increased focus over the last decade. A new scoring system is proposed as a comprehensive evaluation tool. Methods In this scoring system, each scholarly activity (i.e. abstracts, manuscripts, book chapters, research protocols, and research grants) are converted into a numerical score, Scholarly Activity Points (SAPs), which reflects the complexity of the project and the degree of resident's involvement. First, a relative weight value is given to each scholarly category based on its complexity (i.e. 50 points to an abstract, 150 to a manuscript). Then SAPs are calculated with modifiers specific to each scholarly activity (i.e. for an abstract, meeting venue, repeated presentation, authorship, abstract category, and awards). To demonstrate how the system works, a list of scholarly activities by anaesthesia residents graduating from a university programme between 2003 and 2010 was obtained. SAP scores of graduating classes were analysed. Results During the 2003–2010 academic years, a total of 106 residents (the mean of 13 per class, ranging from 9 to 19) graduated from the full 3 yr residency programme. The SAP system allowed statistical comparison among the graduated classes of overall scholarly productivity; significant increases were noted in the average SAPs per resident among the classes of 2009 {154 (204), [mean ( sd )]} and 2010 [524 (471)] compared with those by the classes of 2003–2006 [90 (188), 45 (73), 126 (349), 83 (205), respectively]. Conclusions A new scoring system enabled a comprehensive statistical evaluation of residents’ scholarly productivity.
SEXUAL, FECUNDITY, AND VIABILITY SELECTION ON FLOWER SIZE AND NUMBER IN A SEXUALLY DIMORPHIC PLANT

The evolution of sexual dimorphism will depend on how sexual, fecundity and viability selection act within each sex, with the different forms of selection potentially operating in opposing directions. We examined selection in the dioecious plant Silene latifolia using planted arrays of selection lines that differed in flower size (small vs. large). In this species, a flower size/number trade-off exists within each sex, and males produce smaller and more numerous flowers than females. Moreover, floral traits are genetically correlated with leaf physiology. Sexual selection favoring males in the small-flower line occurred via greater overlap in the timing of flower output between males from this line and females. Fecundity selection favored males with high flower production, as siring success was proportionate to pollen production. Viability selection opposed sexual selection, favoring males from the large-flower line. In females, fecundity and viability selection operated in the same direction, favoring those from the large-flower line via greater seed production and survival. These results concur with the pattern of floral sexual dimorphism. Together with previous results they suggest that the outcome of the different forms of selection will be environmentally dependent, and therefore help to explain variation among populations in sexually dimorphic traits.
High Speed Particle Beam Generation: A Dynamic Focusing Mechanism for Selecting Ultrafine Particles

RSMS-II is a unique characterization technique for analyzing the chemical content of individual airborne ultrafine particles in real time. Although based on earlier versions, the newest implementation offers crucial enhancements including a smart data acquisition system and a completely redesigned particle inlet. The particle inlet is based on a dynamic focusing mechanism that selectively transmits a narrow particle size range in the form of a high speed particle beam. The mean particle size that is optimally transmitted is dynamically altered by changing the nozzle source pressure, thus particles over a wide size range may be selected. Inherent in the design of dynamic focusing mechanisms is the ability to size-select particles based on their aerodynamic characteristics, thus obviating the need for additional sizing components. The principle, design, and calibration of a variable pressure inlet is presented in the current work. Characteristics are estimated employing a theoretical approach based on the S...
Application of Metabolic PET Imaging in Radiation Oncology

Positron emission tomography (PET) is a noninvasive imaging technique that provides functional or metabolic assessment of normal tissue or disease conditions and is playing an increasing role in cancer radiotherapy planning. 18F-Fluorodeoxyglucose PET imaging (FDG-PET) is widely used in the clinic for tumor imaging due to increased glucose metabolism in most types of tumors; its role in radiotherapy management of various cancers is reviewed. In addition, other metabolic PET imaging agents at various stages of preclinical and clinical development are reviewed. These agents include radiolabeled amino acids such as methionine for detecting increased protein synthesis, radiolabeled choline for detecting increased membrane lipid synthesis, and radiolabeled acetate for detecting increased cytoplasmic lipid synthesis. The amino acid analogs choline and acetate are often more specific to tumor cells than FDG, so they may play an important role in differentiating cancers from benign conditions and in the diagnosis...
Hybrid electric sport utility vehicles

Drive-train hybridization improves the fuel economy and emissions of vehicles. This is the concept of hybrid electric vehicles (HEVs). Application of this concept in sport utility vehicles (SUVs), which consume more fuel as compared to passenger cars, will positively have a great impact. However, dynamic performances such as acceleration and gradeability also are of great importance in SUVs. Therefore, the optimum choice of the system hybridization level includes complex tradeoffs between the engine and electric propulsion motor on the one hand and fuel economy, performance, and cost on the other. In this paper, we classify SUVs as small, medium, and large vehicles. Effects of hybridization on the fuel economy and dynamic performances of each class of SUVs are investigated. Different hybridization levels, from mild to full hybrid electric traction systems, are examined.
Protracted Recruitment in the Bay Scallop Argopecten irradians in a West Florida Estuary

Many studies have indicated that annual spawning of bay scallops (Argopecten irradians) peaks during discrete and limited periods each year. Spawning in most Florida bay scallop subpopulations has been shown to occur in fall, whereas more northerly U.S. populations typically spawn in late spring or summer. In this article we describe our efforts to expand our understanding of the seasonality of bay scallop recruitment dynamics in Florida. Visual surveys were conducted by divers each spring from1994 to 2009 to estimate adult scallop abundance. Adult abundance was low (6.1 scallops/600 m 2 ) during the first 3 y of the study (1994 to 1996), prompting a 7-y restoration effort intended to enhance the number of spawning adults and thereby enhance the local production of larval scallops. Adult abundances increased to an average of 21.9 scallops/600 m 2 in 1997 to 2006, and then rose dramatically to an average density of 154.8 scallops/600 m 2 in the most recent years (2007 to 2009). Artificial recruit collectors (n ¼ 12) were deployed monthly near the Anclote River estuary beginning in 1997 and were allowed to soak for 2 mo at a time. Each collector's deployment period overlapped with the preceding and following trap's deployment period by 1 mo. The project is ongoing, but only data collected through December 2009 is included here (bay scallops recruited to the collectors during 163 of the 185 deployment periods). For the entire study period, the average recruitment rate was 0.3 scallops/collector/day, the maximum average for a single deployment period was 5.5 scallops/collector/day during November 2001 to January 2002, and the highest rate for a single collector was 19.6 scallops/collector/day during November 2001 to January 2002. In most years, the collectors retrieved in late fall and early winter had the highest settlement rate; a secondary recruitment peak was observed in the spring. A period of protracted recruitment (December 2005 to December 2009) occurred, during which scallops recruited to at least 1 of the 12 deployed collectors deployed during 53 consecutive deployment periods. The average recruitment rate for this protracted period was 0.4 scallops/collector/day; the maximum recruitment rate for a single deployment period (3.5 scallops/ collector/day) and individual collector (17.7 scallops/day) occurred during December 2008 to February 2009. Early in our study, scallops were detected in a majority of our recruit collectors, and a protracted period of recruitment (October 2001 to February 2004) coincided with the multiyear restoration effort. However, the recent high adult densities and protracted period of recruitment occurred in the absence of any active restoration in this subpopulation, suggesting that, at least within the Anclote River estuary, the population has stabilized for the short term.
Primary and secondary goals in the production of interpersonal influence messages

In this paper we argue that an individual's activities, prior to and during an interpersonal influence attempt, may be explained by his or her goals. Two classes of goals are posited: (1) primary or influence goals which instigate the influence process, and (2) secondary goals which shape it. Three studies are reported whose purpose was to illuminate the substance of each of these goals, to examine their relationships to one another, and finally, to show how the goals shape the interpersonal influence process (for the source) in terms of planning, effort, directness, positivity, and logic. The results suggest the existence of five secondary goals: identity goals, interaction goals, personal resource goals, relational resource goals, and arousal management goals. With the exception of personal goals, each of the goals makes a unique contribution to shaping the source's actions.
Where's All the Teamwork Gone? A Qualitative Analysis of Cooperation between Members of Two Interdisciplinary Teams.

This study explored cooperation between members of two interdisciplinary teams of educators within the agricultural field in a northeastern state. A researcherdeveloped instrument was used to explore individual perceptions regarding interdisciplinary cooperation. Using qualitative methods, the researchers intended to bring to light the thoughts, feelings and perceptions of educators regarding both the benefits and successes they had encountered, as well as the barriers they had come across during their cooperative experiences. Results indicated several areas of overlap for the disciplines. Recognized advantages included programmatic improvement, time saved, workload reduction and an increase in available resources. Barriers mentioned include time constraints, lack of awareness combined with perceived programmatic differences, and the lack of relationships and networks across disciplines. Suggestions include further research on the subject of cooperation, as well as possible combined in-service training sessions, encouraging the development of relationships through pre-service means (i.e., a combined undergraduate course) and administrator education.
Nine Perspectives on Living Orignalism

This Article responds to the nine contributions to a symposium on Living Originalism (Harvard University Press 2011). It considers nine different aspects of the argument in the book: (1) why constitutions around the world contain vague and abstract language, and how a constitution’s choice of language connects to the purposes of a constitution; (2) the book’s theory of democratic legitimacy; (3) how the book’s argument applies to constitutional cultures outside the United States, and the relationship between original and implied meanings; (4) the differences between the book’s theory of constitutional interpretation and that of Ronald Dworkin; (5) whether the book’s account of legal principles is consistent with legal positivism; (6) the book’s account of the U.S. Constitution as both “fallen” and as “higher law;” (7) whether a “protestant” constitutional culture — in which citizens feel authorized to state what the Constitution means for themselves — benefits or harms democratic legitimacy; (8) the book’s account of the original meaning of “commerce” as “intercourse,” and Congress’s power to regulate interstate networks of transportation and communication; and (9) the book’s message for living constitutionalists and constitutional originalists.
Mechanisms of very fast oscillations in networks of axons coupled by gap junctions

Because electrical coupling among the neurons of the brain is much faster than chemical synaptic coupling, it is natural to hypothesize that gap junctions may play a crucial role in mechanisms underlying very fast oscillations (VFOs), i.e., oscillations at more than 80 Hz. There is now a substantial body of experimental and modeling literature supporting this hypothesis. A series of modeling papers, starting with work by Roger Traub and collaborators, have suggested that VFOs may arise from expanding waves propagating through an “axonal plexus”, a large random network of electrically coupled axons. Traub et al. also proposed a cellular automaton (CA) model to study the mechanisms of VFOs in the axonal plexus. In this model, the expanding waves take the appearance of topologically circular “target patterns”. Random external stimuli initiate each wave. We therefore call this kind of VFO “externally driven”. Using a computational model, we show that an axonal plexus can also exhibit a second, distinctly different kind of VFO in a wide parameter range. These VFOs arise from activity propagating around cycles in the network. Once triggered, they persist without any source of excitation. With idealized, regular connectivity, they take the appearance of spiral waves. We call these VFOs “re-entrant”. The behavior of the axonal plexus depends on the reliability with which action potentials propagate from one axon to the next, which, in turn, depends on the somatic membrane potential Vs and the gap junction conductance ggj. To study these dependencies, we impose a fixed value of Vs, then study the effects of varying Vs and ggj. Not surprisingly, propagation becomes more reliable with rising Vs and ggj. Externally driven VFOs occur when Vs and ggj are so high that propagation never fails. For lower Vs or ggj, propagation is nearly reliable, but fails in rare circumstances. Surprisingly, the parameter regime where this occurs is fairly large. Even a single propagation failure can trigger re-entrant VFOs in this regime. Lowering Vs and ggj further, one finds a third parameter regime in which propagation is unreliable, and no VFOs arise. We analyze these three parameter regimes by means of computations using model networks adapted from Traub et al., as well as much smaller model networks.
Financial Statement Analysis And The Harmonization Of Foreign Current Translation

The harmonization of foreign currency translation accounting has lead to global acceptance of the temporal and current or closing rate methods. These methods have the potential to alter financial statement analysis from that done on untranslated information. This paper demonstrates the differences in financial results from these models and calls for revisiting the issue of foreign currency translation to develop a single method for comparability in financial statement analysis.
Lactone Modulation of the γ-Aminobutyric Acid A Receptor: Evidence for a Positive Modulatory Site

The gamma-aminobutyric acid-A (GABA(A)) receptor complex is allosterically modulated by a variety of substances, some of clinical importance. Barbiturates and neurosteroids augment GABA-currents and also directly gate the channel. A variety of gamma-butyrolactone analogues also modulate GABA-induced currents, with some potentiating and others inhibiting. Because several gamma-thiobutyrolactone analogues have biphasic effects on GABA currents, experiments with wild-type and picrotoxinin-insensitive GABA(A) receptors were performed to analyze whether some gamma-thiobutyrolactones interact with two distinguishable sites on the GABA(A) receptor. beta-Ethyl-beta-methyl-gamma-thiobutyrolactone inhibited GABA-induced currents at low concentrations (0.001-1 mM), but potentiated GABA-induced currents at higher concentrations (3-10 mM) in wild-type alpha1beta2gamma2-subunit containing ionophores. The related alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone potentiated submaximal GABA currents in wild-type receptors at both low and high concentrations (0.1-10 mM). Mutations in the second transmembrane domain of alpha1, beta2, or gamma2 conferred picrotoxinin-insensitivity onto GABA(A) receptor complexes. When these mutated alpha1, beta2, or gamma2 subunits were incorporated into the receptor complex, beta-ethyl-beta-methyl-gamma-thiobutyrolactone potentiated GABA currents over the entire concentration range (0.1-10 mM). Neither the potentiating activity nor the EC50 of alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone changed in the mutant receptors. Further studies demonstrated that the mutations did not affect the EC50 of chlordiazepoxide or phenobarbital. These and our earlier results identify a modulatory site on the GABA(A) receptor distinct from that interacting with barbiturates, benzodiazepines, and steroids. Additionally, they show that the gamma-butyrolactones probably interact at two different sites on the ionophore to produce opposite effects on GABA-mediated current.
Arteriotomy closure devices-the FDA perspective.

In this issue of the Journal , Dangas et al. [(1)][1]assessed the incidence of vascular complications at the Washington Hospital Center following percutaneous coronary interventions (PCI) when arteriotomy closure devices (ACD) were used to achieve hemostasis of the femoral artery versus when manual
Linear Immigration-Death Models

Consider first modeling a single population of sizeX(t)with the linear death rate $$ \mu x = aX $$ (4.1) and immigration rate I. This very simple case of the general rates in (3.40) extends the illustration in Chapter 3 by relaxing the assumption of an initial population size zero. The model, as previously noted, is called the linear immigration-death (LID) model, and it is widely used as the standard stochastic one-compartmental model. This model is developed thoroughly in [28] in a compartmental context. A simple application developed subsequently is modeling the bioaccumulation of mercury, described in Section 2.4. We have also used the model extensively to describe the passage of digesta in ruminant animals, see e.g. [15, 16, 59].
Sibling Rivalry in Myxococcus xanthus Is Mediated by Kin Recognition and a Polyploid Prophage

Myxobacteria form complex social communities that elicit multicellular behaviors. One such behavior is kin recognition, in which cells identify siblings via their polymorphic TraA cell surface receptor, to transiently fuse outer membranes and exchange their contents. In addition, outer membrane exchange (OME) regulates behaviors, such as inhibition of wild-type Myxococcus xanthus (DK1622) from swarming. Here we monitored the fate of motile cells and surprisingly found they were killed by nonmotile siblings. The kill phenotype required OME (i.e., was TraA dependent). The genetic basis of killing was traced to ancestral strains used to construct DK1622. Specifically, the kill phenotype mapped to a large "polyploid prophage," Mx alpha. Sensitive strains contained a 200-kb deletion that removed two of three Mx alpha units. To explain these results, we suggest that Mx alpha expresses a toxin-antitoxin cassette that uses the OME machinery of M. xanthus to transfer a toxin that makes the population "addicted" to Mx alpha. Thus, siblings that lost Mx alpha units (no immunity) are killed by cells that harbor the element. To test this, an Mx alpha-harboring laboratory strain was engineered (by traA allele swap) to recognize a closely related species, Myxococcus fulvus. As a result, M. fulvus, which lacks Mx alpha, was killed. These TraA-mediated antagonisms provide an explanation for how kin recognition specificity might have evolved in myxobacteria. That is, recognition specificity is determined by polymorphisms in traA, which we hypothesize were selected for because OME with non-kin leads to lethal outcomes.The transition from single cell to multicellular life is considered a major evolutionary event. Myxobacteria have successfully made this transition. For example, in response to starvation, individual cells aggregate into multicellular fruiting bodies wherein cells differentiate into spores. To build fruits, cells need to recognize their siblings, and in part, this is mediated by the TraA cell surface receptor. Surprisingly, we report that TraA recognition can also involve sibling killing. We show that killing originates from a prophage-like element that has apparently hijacked the TraA system to deliver a toxin to kin. We hypothesize that this killing system has imposed selective pressures on kin recognition, which in turn has resulted in TraA polymorphisms and hence many different recognition groups.
The Realists and Saint Augustine: Skepticism, Psychology, and Moral Action in International Relations Thought

The political thought of Saint Augustine contributed, primarily through the writings of Reinhold Niebuhr, to the development of political realism in the twentieth century. Augustine and the realist share a fundamental skepticism regarding the prospects of moral and political progress. It is this skepticism that is the characteristic and even definitional attribute of realist thought. But Augustine's realism is more radical than that of the modern. Modern realism assumes a certain stylized psychology that allows the realist to portray world politics as an arena of strategic interaction. Augustine's more radical skepticism doubts the possibility of rational strategic action. Yet, building on this more radical skepticism, Augustine demonstrates the possibility and the need for moral action in a realist world. Augustine challenges the modern realist to explore more systematically the skeptical foundations of realist thought.
Holistic Analysis, Discerning Meaning from Narrative and Numeric Data

This chapter reviews the fifth theme-based strategy of a rights research approach, holistic data analysis, discerning meaning from narrative and numeric data. It describes how the interpretation of quantitative numeric and qualitative data can be used and applied to human rights issues. The use of a common factors rights research qualitative data analysis (QDA) method was presented for identifying common patterns and themes in the lived experiences of individuals, families, or communities affected by a human rights condition, such as persons living in poverty and/or who are incarcerated. Content analysis methods also are reviewed as an example of a strategy that can use deductive and inductive analysis strategies. Examples of aging people in prison are presented. In order to apply policy and practice decision-making that impacts the lives of the most vulnerable in society, it is an imperative to understand a human rights issue in its entirety to develop lasting solutions.
A Model of MOSFET’s Second Breakdown Action in Circuit-Level

A method to exact the electrical parameters and model the second breakdown action of MOSFET’s under ESD (Electro-Static Discharge) on circuit-level, using TCAD simulation, is presented. MOSFET is one of the most important ESD protection devices, and is widely used as I/O protection device in integrated circuits. We present an accurate macro model of the MOSFET based on deep analyzing of the physical mechanism of the second breakdown, using TCAD simulation. This macro model owns fine convergency and accuracy which are of importance to the simulation of the ESD protection ability of the ESD protection network on circuit and system level.
A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context.

Overview:Since 1996, the cornerstone of chemotherapy for advanced pancreatic cancer has been gemcitabine, which has a genuine, but modest effect on survival and quality of life. It has been remarka...
Microfluidic Multistage Integration for Analysis of Circulating Exosomes

The study of circulating exosomes has received growing interest in fields of biology and medicine. Exosomes, small (50–150 nm) membrane vesicles of endocytic origin, have emerged as new mechanisms for regulation of a wide range of biological processes, including intercellular communications, immune response, and cancer metastasis. Molecular analysis of exosomes is an emerging paradigm for noninvasive cancer diagnosis and monitoring of disease treatment; however, exosome analysis is challenging due to current low-efficient isolation and molecular measurement approaches. In this chapter, a novel microfluidic strategy is described for rapid, quantitative isolation and analysis of exosomes, as well as intravesicular markers directly from human blood. This microfluidic platform enables multistage integration of immunomagnetic isolation and enrichment, chemical lysis, and immune-sandwich chemifluorescence probing in one sequential process. The developed microfluidic exosome profiling platform has been employed to measure expression levels of total and phosphorylated IGF-1R in non-small-cell lung cancer patient plasma-derived exosomes, thereby opening a new avenue for monitoring IGF-1R and its activation status in a noninvasive manner (i.e., liquid biopsy). This developed microfluidic exosome profiling platform shows great potential for forming the basis of a critically needed infrastructure to advance the biological and clinical utilization of exosomes.
Exploring security metrics for electric grid infrastructures leveraging attack graphs

The electric grid is a critical cyber-physical infrastructure that serves as lifeline for modern society. With the increasing trend of cyber-attacks, electric grid security has become a significant concern. System operators have the difficult task of reducing the risk exposure and maintaining operational reliability under the constant threat of cyber-attacks. Good security metrics for assessing and monitoring the risk to the cyber-physical power grid infrastructure would be very valuable for grid operators. However, security metrics to assess the security posture and risk to even traditional enterprise cyber infrastructure have been a long standing challenge. Cyber-physical systems (CPS) that have interconnected cyber and physical infrastructure add an additional layer of complexity. In this work, we explore security metrics that can be used to monitor the security posture and risk exposure of the electric grid infrastructure. These metrics take both the cyber security posture and physical impact of an attack into account. We consider both individual and coordinated attacks that can cause cascading outages. To illustrate the usefulness of the proposed metrics, we use cyber-physical models for 9-bus and 39-bus test systems. Our metrics provide a novel way to identify and prioritize assets critical to the system and help operators take steps to improve the overall security posture of the system.
Environmental Service and Outdoor Adventure as a Context for Positive Youth Development: An Evaluation of the Crow River Trail Guards Program

Trail Guards, a community-based organization in Minnesota, offers youth the opportunity to participate in park/trail maintenance and enhancement projects. Through these environmental service projects, Trail Guards seeks to foster the following developmental outcomes in youth participants: self-awareness of skills and strengths; self-worth; personal and social self-efficacy; sense of belonging and acceptance; team work and cooperation skills; and a sense of community responsibility. Trail Guards ultimately aims for youth to transfer these skills and socially appropriate behaviors to settings and activities beyond Trail Guards and to participate in the community in other positive ways. A program evaluation indicated Trail Guards seems to be achieving these youth development outcomes, and that the success of the program may be attributed to the program leader serving as a positive adult role model and providing a safe and caring environment, as well as to community involvement. Implications are discussed.
Evolution of Sex Differences in Trait- and Age-Specific Vulnerabilities.

Traits that facilitate competition for reproductive resources or that influence mate choice generally have a heightened sensitivity to stressors. They have evolved to signal resilience to infectious disease and nutritional and social stressors, and they are compromised by exposure to man-made toxins. Although these traits can differ from one species or sex to the next, an understanding of the dynamics of competition and choice can in theory be used to generate a priori predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species. I provide a review of these dynamics and illustrate associated vulnerabilities in nonhuman species. The age- and sex-specific vulnerability of such traits is then illustrated for stressor-related disruptions of boys’ and girls’ physical growth and play behavior, as well as for aspects of boys’ and girls’ and men’s and women’s personality, language, and spatial abilities. There is much that remains to be determined, but enough is now known ...
Does peritoneal flap closure technique following transabdominal preperitoneal (TAPP) inguinal hernia repair make a difference in postoperative pain? A long-term quality of life comparison.

Transabdominal, preperitoneal (TAPP), laparoscopic inguinal hernia repair (IHR) requires the creation of a peritoneal flap (PF) that must be closed after mesh placement. Our previous study indicated that sutured PF closure resulted in less short-term postoperative pain at 2 and 4 weeks compared to tacks and staples. Therefore, the aim of this follow-up study was to compare short-term QOL with a greater sample size and long-term QOL at 2 years by method of PF closure. A prospective institutional hernia-specific database was assessed for all adult TAPP IHRs from July 2012 to May 2015. QOL outcomes were compared by PF closure method at 2 and 4 weeks and 6, 12, and 24 months as measured by the Carolinas Comfort Scale. Standard statistical tests were used for the whole population and then the Bonferroni Correction was used to compare groups (p 0.05). After controlling for confounding variables on multivariate analysis, there was no difference in QOL by PF closure method at any time point (p > 0.05). Tacked, sutured, and stapled techniques for peritoneal flap closure following TAPP have no significant differences in operative outcomes, postoperative quality of life, or resolution of symptoms.
Prior knowledge guided eQTL mapping for identifying candidate genes

Expression quantitative trait loci (eQTL) mapping is often used to identify genetic loci and candidate genes correlated with traits. Although usually a group of genes affect complex traits, genes in most eQTL mapping methods are considered as independent. Recently, some eQTL mapping methods have accounted for correlated genes, used biological prior knowledge and applied these in model species such as yeast or mouse. However, biological prior knowledge might be very limited for most species. We proposed a data-driven prior knowledge guided eQTL mapping for identifying candidate genes. At first, quantitative trait loci (QTL) analysis was used to identify single nucleotide polymorphisms (SNP) markers that are associated with traits. Then co-expressed gene modules were generated and gene modules significantly associated with traits were selected. Prior knowledge from QTL mapping was used for eQTL mapping on the selected modules. We tested and compared prior knowledge guided eQTL mapping to the eQTL mapping with no prior knowledge in a simulation study and two barley stem rust resistance case studies. The results in simulation study and real barley case studies show that models using prior knowledge outperform models without prior knowledge. In the first case study, three gene modules were selected and one of the gene modules was enriched with defense response Gene Ontology (GO) terms. Also, one probe in the gene module is mapped to Rpg1, previously identified as resistance gene to stem rust. In the second case study, four gene modules are identified, one gene module is significantly enriched with defense response to fungus and bacterium. Prior knowledge guided eQTL mapping is an effective method for identifying candidate genes. The case studies in stem rust show that this approach is robust, and outperforms methods with no prior knowledge in identifying candidate genes.