cssi/SciSciGPT-SciSciNet huggingface dataset:
A bed of thorns: Female leaders and the self-reinforcing cycle of illegitimacy

Abstract In an attempt to explain why the gender gap in leadership positions persists, we propose a model centered on legitimacy. When women hold powerful positions, they have a harder time than men eliciting respect and admiration (i.e., status) from subordinates. As a result, female power-holders are seen as less legitimate than male power-holders. Unless they are able to legitimize their role, relative illegitimacy will prompt a variety of consequences such as more negative subordinate behavior and reduced cooperation when the leader is a woman. Subordinate rejection will likely put female leaders in a precarious mindset, and trigger negative responses toward subordinates; such behavior can confirm negative expectations of female leaders and further undermine female authority in a self-reinforcing cycle of illegitimacy. Leader or organizational features that enhance status attributions and/or lower subordinates' perceptions of power differentials may increase legitimacy for women in leadership roles.
Emerging Roles of PCSK9: More Than a One-Trick Pony.

Rare human genetic variations at the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus revealed the role of this protein in regulating plasma levels of low-density lipoprotein-cholesterol (LDL-C), and its promise as a therapeutic target.1,2 PCSK9 promotes the internalization and degradation of the hepatic LDL receptor, thereby reducing the liver’s ability to clear LDL from the circulation and causing LDL-C levels to rise.3,4 Monoclonal antibodies against PCSK9 that disrupt the interaction of this protein with the LDL receptor have been studied in numerous clinical trials, and these agents have been shown to safely reduce LDL-C by 50% to 60%.5 Although large cardiovascular outcomes trials are still being conducted, 2 of these agents were recently approved by regulatory authorities on the basis of their LDL-C reductions alone, for the treatment of patients with familial hypercholesterolemia or those with established cardiovascular disease who require additional lipid-lowering therapy despite maximally tolerated doses of statins. See accompanying article on page 2517 of the December 2015 issue The rapid development of a novel therapeutic can often outpace our understanding of the underlying biology, and this is becoming apparent in the case of PCSK9 function. Although most intensely studied for its interaction with the LDL receptor, it is now evident that PCSK9 can promote the degradation of other cell surface receptors, including close structural homologues of the LDL receptor (eg, the very low-density lipoprotein …
A General Model for Fault Covering Problems in Reconfigurable Arrays

An increase in chip density leads to a reduction in the yield of chip production. [Schu78] showed that in most cases, only a small number of elements in defective chips are actually defective. Thus the idea of repairing a chip after fabrication becomes very appealing. Reconfigurable chips are often used for this purpose. These chips contain redundant elements that can be used to repair the defective elements. There are many different ways to reconfigure a chip using redundant elements. The fault covering problem is to assign redundant elements to replace the defective elements such that the chip will function properly. In this paper we introduce a general model to represent the relationships between redundant elements and defective elements in a uniform way. This model generalizes the models discussed in previous approaches. We also give a complete characterization of the complexity of the fault covering problems for all the subcases of our model, most of which have not been studied before.
Reconstruction of basal properties in ice sheets using iterative inverse methods

Inverse problems are used to estimate model parameters from observations. Many inverse problems are ill-posed because they lack stability, meaning it is not possible to find solutions that are stable with respect to small changes in input data. Regularization techniques are necessary to stabilize the problem. For nonlinear inverse problems, iterative inverse methods can be used as a regularization method. These methods start with an initial estimate of the model parameters, update the parameters to match observation in an iterative process that adjusts large-scale spatial features first, and use a stopping criterion to prevent the overfitting of data. This criterion determines the smoothness of the solution and thus the degree of regularization. Here, iterative inverse methods are implemented for the specific problem of reconstructing basal stickiness of an ice sheet by using the shallow-shelf approximation as a forward model and synthetically derived surface velocities as input data. The incomplete Gauss-Newton (IGN) method is introduced and compared to the commonly used steepest descent and nonlinear conjugate gradient methods. Two different stopping criteria, the discrepancy principle and a recent- improvement threshold, are compared. The IGN method is favored because it is rapidly converging, and it incorporates the discrepancy principle, which leads to optimally resolved solutions.
Accelerating the convergence of the LMS adaptive algorithm

Adaptive filters have over the years found many applications in the field of digital signal processing. One of the most common adaptive algorithms is the Least Mean Square (LMS) algorithm, an online method that utilizes a noisy estimate of the mean square error (MSE) performance surface gradient for iteratively computing the weight vector which yields the minimum MSE solution. LMS is a simple and robust algorithm, and thus enjoys great popularity. However, its transient performance may suffer when the input autocorrelation matrix has large eigenvalue spread. In this thesis, we first establish the LMS/Newton algorithm as the optimal theoretical benchmark for reducing eigenvalue spread. We then define the excess error energy of an adaptive algorithm as the area between the transient learning curve and its steady-state asymptotic value and demonstrate that the LMS and LMS/Newton algorithms are equivalent in terms of their average excess error energies. This new result further explains the popularity of the LMS algorithm. We then examine utilizing fixed orthogonal transforms for reducing the input eigenvalue spread and explain the appropriate transform choice based on the input power spectral density. We show that both Discrete Hartley Transform LMS (DHT-LMS) and Discrete Fourier Transform LMS (DFT-LMS) attain the same asymptotic eigenvalue spread for first-order Markov inputs. Since the fastest DHT implementations are a factor of two more computationally efficient than corresponding DFT implementations, we thus show that DHT-LMS is preferred over DFT-LMS for first-order Markov inputs. However, orthogonal transform-based algorithms may perform poorly with certain narrowband inputs. We thus introduce the variable leaky LMS (VL-LMS) algorithm that performs well across a broad range of inputs. We show that the VL-LMS algorithm can reduce the eigenvalue spread without a large increase in the steady-state asymptotic MSE that plagues fixed leaky algorithms. We derive bounds on the convergence of VL-LMS and its steady-state asymptotic MSE in a simple nonstationary system identification model. Finally, we introduce the colored variable leaky LMS (CVL-LMS) algorithm that can utilize additional spectral information about the input to intelligently color the leak. Simulation results demonstrate that VL-LMS and CVL-LMS can significantly outperform LMS.
Source Contributions to Wintertime Elemental and Organic Carbon in the Western Arctic Based on Radiocarbon and Tracer Apportionment.

To quantify the contributions of fossil and biomass sources to the wintertime Arctic aerosol burden source apportionment is reported for elemental (EC) and organic carbon (OC) fractions of six PM10 samples collected during a wintertime (2012–2013) campaign in Barrow, AK. Radiocarbon apportionment of EC indicates that fossil sources contribute an average of 68 ± 9% (0.01–0.07 μg m–3) in midwinter decreasing to 49 ± 6% (0.02 μg m–3) in late winter. The mean contribution of fossil sources to OC for the campaign was stable at 38 ± 8% (0.04–0.32 μg m–3). Samples were also analyzed for organic tracers, including levoglucosan, for use in a chemical mass balance (CMB) source apportionment model. The CMB model was able to apportion 24–53% and 99% of the OC and EC burdens, respectively, during the campaign, with fossil OC contributions ranging from 25 to 74% (0.02–0.09 μg m–3) and fossil EC contributions ranging from 73 to 94% (0.03–0.07 μg m–3). Back trajectories identified two major wintertime source regions to B...
The Role of Human and Social Capital in the Geographic Mobility and Annual Earnings among Mexican Immigrants

The Mexican-origin population continues to be concentrated predominantly in the Southwest, a pattern found among both native- and foreign-born persons. This analysis draws from the human capital and social capital perspectives to examine the impact of human capital and social capital on the outmigration of Mexican immigrants from the Southwest to other regions of the country between 1985 and 1990, the period associated with the initial migration of Mexicans to new-destination areas. In addition, insights from these two perspectives are also used to assess their influence on the earnings of persons who left the Southwest during this period. The analysis is based on data from the 1990 Public Use Microdata Sample (PUMS) and includes 46, 120 foreign-born persons of Mexican-origin who lived in the Southwest in 1985. The results suggest that both human capital and social capital have an impact on the outmigration of Mexican immigrants, with the former varying by length of residence in the United States. Further...
Development of elasto-plastic model with revised plastic work function as hardening function based on plane strain tests

An improved plane strain test apparatus was first developed with some solutions for friction problem between load plate and specimen,control precision of e2 and elimination of influence of confinement of both ends on volumetric strain measurement.A series of plane strain tests for sand were carried out together with triaxial compression tests and an elasto-plastic model was derived according to the test results.The elastic property,failure criteria,hardening parameter and hardening rule,and plastic potential function were all derived directly from the test results.It was shown again that the non-associated flow rule should be used for sand.Test results were simulated by the model using parameters derived from the tests,and the calculated stress-strain relation agreed well with the test results.
Recent Progress in the Welding of Rapidly Solidified Heat-resistant Aluminum Alloy

Heat-resistant aluminum alloy produced by rapidly solidified progress is a kind of promising aluminum al- loy.This kind of alloy has a widespread availability in aviation,space flight,ship and weapons etc.owing to its excellent me- chanical properties at elevate temperatures and low density.In this aticle,the recent year's development and latest progress in the welding of rapidly solidified heat-resistant aluminum alloy are presented,its weldabilities are analysised and the prohlems on the joining of rapidly solidified heat-resistant aluminum alloy by using GTAW,CDW,EBW,LBW,FW and braze welding are discussed.High energy density,low energy input processes such as electron beam welding and laser welding and friction weld- ing are suitable for the welding of rapidly solidified heat-resistant aluminum alloy.
A Randomized Controlled Trial of a Mobile Medical App for Kidney Transplant Recipients: Effect on Use of Sun Protection.

BACKGROUND Perception of skin cancer risk, belief that sun protection prevents skin cancer, and having sun protection choices enhance sun protection behaviors by kidney transplant recipients, who are at greater risk of developing skin cancer than the general population. METHODS A randomized controlled trial used stratified recruitment of non-Hispanic White, non-Hispanic Black, and Hispanic/Latino kidney transplant recipients, who received a transplant 2-24 months prior to the study. The same culturally sensitive SunProtect™ program was delivered to all recipients with tablet personal computers in two urban ambulatory offices. Text messages reminders were provided at two week intervals. Self-reported surveys and skin pigmentation measured prior to the intervention and six weeks later were analyzed. RESULTS Among 552 eligible participants, 170 participated (62 non-Hispanic Whites, 60Blacks, and 48 Hispanics). Among participants receiving the intervention with skin that burns after sun exposure and becomes tan or becomes irritated and gets darker, there was a statistically significant increase in self-reported knowledge, recognition of personal skin cancer risk, confidence in sun protection preventing skin cancer, and sun protection behaviors in participants compared to those receiving usual education (p<0.05). At the six week follow-up, participants in the intervention group with skin that burns or becomes irritated, had significantly less darkening of the sun-exposed forearm than control participants (p<0.05). CONCLUSIONS Providing sun protection education with SunProtect™ in the springwith reminders during the summer facilitated adoption of sun protection behaviors among kidney transplant recipients with skin that burns or becomes irritated.
Changing the trajectory of ischemic heart disease in women: Role of imaging

Mortality from coronary artery disease in women declined from nearly 500,000 deaths in 2000 to 398,096 deaths in 2013. Despite these significant gains, cardiovascular disease mortality in women remains unacceptably high. Much additional progress in awareness, evaluation, and management of cardiovascular diseases is needed. Progress in cardiovascular imaging, over the past four decades, has substantially improved the evaluation and management of ischemic heart disease. Ischemic heart disease is now diagnosed early and with greater accuracy, leading to improved risk assessment and timely therapies. The next gains in ischemic heart disease mortality in women will probably be due to application of these imaging advances in a personalized fashion. Thoughtful leaders provide their viewpoints on the use of imaging in the evaluation and management of ischemic heart disease in women.
HYPERTENSION, ADRENAL CATECHOLAMINE RELEASE, PULMONARY EDEMA AND BEHAVIORAL EXCITEMENT ELICITED FROM THE ANTERIOR HYPOTHALAMUS IN RAT

Publisher Summary The reflex release of adrenomedullary catecholamines (CA) is an important component of the physiological response to stress. It remains to be established if the representation of the adrenal medulla within the brain is distinct from that controlling the activation of the sympathetic vasomotor nerves. The present study demonstrates that bilateral electrolytic lesions of the anterior hypothalamus (AH) in rat result in the development of acute arterial hypertension, leading to pulmonary edema and death as a consequence of ventricular overload. The arterial hypertension as well as some of the peripheral effects of sympathetic activity depend upon a neurally-mediated release of catecholamines from the adrenal gland and can be blocked by adrenal surgery. The release of catecholamines appears to be a direct result of the AH lesion and not secondary to associated components of the syndrome. It is not a consequence of muscular activity, because hypertension was produced by AH lesions in paralyzed rats.
Amplitude convergence in children's conversational speech with animated personas

During interpersonal conversation, both children and adults adapt the basic acoustic-prosodic features of their speech to converge with those of their conversational partner. In this study, 7-to-10year-old children interacted with a conversational interface in which animated characters used text-to-speech output (TTS) to answer questions about marine biology. Analysis of children’s speech to different animated characters revealed a 29% average change in energy when they spoke to an extroverted loud software partner (E), compared with an introverted soft-spoken one (I). The majority, or 77% of children, adapted their amplitude toward their partner’s TTS voice. These adaptations were bi-directional, with increases in amplitude observed during I to E condition shifts, and decreases during E to I shifts. Finally, these results generalized across different user groups and TTS voices. Implications are discussed for guiding children’s speech to remain within system processing bounds, and for the future development of robust and adaptive conversational interfaces.
Continuous production of ethanol-based biodiesel under subcritical conditions employing trace amount of homogeneous catalysts

Abstract Syntheses of ethanol based biodiesel fuel fatty acid ethyl esters (FAEEs) from corn oil were conducted at subcritical ethanol conditions (T: 175–225 °C, P: 80–200 bar) with the presence of trace amount of catalysts (0.1 wt% sulfuric acid, 0.05 and 0.1 wt% potassium ethoxide, based on oil mass). Experiments were conducted in a continuous tubular 316SS reactor. Potassium ethoxide showed a stronger catalytic ability than sulfuric acid at the same temperature of 225 °C, as the reaction yield reached 95% in five minutes with potassium ethoxide while only 25% yield was achieved for sulfuric acid. A three-step partially reversible model was determined to best fit the kinetic data for both catalytic reactions. To investigate the effect of water and free fatty acids (FFA) impurities on reaction yield under subcritical conditions, 10 vol% water (based on ethanol volume) and 30 wt% oleic acid (based on oil mass) were added to the reaction systems. For sulfuric acid, the reaction yield benefitted from the presence of these impurities. On the contrary, for reactions catalyzed by potassium ethoxide, the yield decreased from 96.8% to 15.3% and 2.6% when adding 10 vol% water and 30 wt% oleic acid, respectively. A pressure range of 80–200 bar at 225 °C was investigated to study the pressure effect on reaction yield. The reactions at these pressures were observed to occur in the homogeneous phase, and the yields at all pressures were in the range of 94–96%, which implies that when the reactions are performed in the homogeneous state, pressure will have little effect on the yield.
Cost relationships and globalization in the Australian clothing industry

ABSTRACTAustralia developed a substantial clothing industry with protectionist international trade policies, including prohibitively high tariffs, quotas, and subsidies. The industry became an important source of jobs, with over 6.5 per cent of total manufacturing employment at the close of the 1960s. As Australia has moved towards freer trade, employment in clothing production has fallen substantially. The question of whether the clothing industry can remain viable in its new environment became an important issue. Here, we examine two crucial economic considerations relating to that question: economies of scale and relations (substitute/complementary) between the various inputs, both domestic and outsourced foreign. The findings strongly indicate the presence of economies of scale and that the industry has reduced its unit costs over the period of study. The results also suggest that most of the inputs are substitutes for one another, although only the estimated cross price elasticities between capital a...
Stability of ferrous-iron-rich bridgmanite under reducing midmantle conditions

Our current understanding of the electronic state of iron in lower-mantle minerals leads to a considerable disagreement in bulk sound speed with seismic measurements if the lower mantle has the same composition as the upper mantle (pyrolite). In the modeling studies, the content and oxidation state of Fe in the minerals have been assumed to be constant throughout the lower mantle. Here, we report high-pressure experimental results in which Fe becomes dominantly Fe2+ in bridgmanite synthesized at 40-70 GPa and 2,000 K, while it is in mixed oxidation state (Fe3+/∑Fe = 60%) in the samples synthesized below and above the pressure range. Little Fe3+ in bridgmanite combined with the strong partitioning of Fe2+ into ferropericlase will alter the Fe content for these minerals at 1,100- to 1,700-km depths. Our calculations show that the change in iron content harmonizes the bulk sound speed of pyrolite with the seismic values in this region. Our experiments support no significant changes in bulk composition for most of the mantle, but possible changes in physical properties and processes (such as viscosity and mantle flow patterns) in the midmantle.
Avoiding consistency exceptions under strong memory models

Shared-memory languages and systems generally provide weak or undefined semantics for executions with data races. Prior work has proposed memory consistency models that ensure well-defined, easy-to-understand semantics based on region serializability (RS), but the resulting system may throw a consistency exception in the presence of a data race. Consistency exceptions can occur unexpectedly even in well-tested programs, hurting availability and thus limiting the practicality of RS-based memory models. To our knowledge, this paper is the first to consider the problem of availability for memory consistency models that throw consistency exceptions. We first extend existing approaches that enforce RSx, a memory model based on serializability of synchronization-free regions (SFRs), to avoid region conflicts and thus consistency exceptions. These new approaches demonstrate both the potential for and limitations of avoiding consistency exceptions under RSx. To improve availability further, we introduce (1) a new memory model called RIx based on isolation of SFRs and (2) a new approach called Avalon that provides RIx. We demonstrate two variants of Avalon that offer different performance-availability tradeoffs for RIx. An evaluation on real Java programs shows that this work's novel approaches are able to reduce consistency exceptions, thereby improving the applicability of strong memory consistency models. Furthermore, the approaches provide compelling points in the performance-availability tradeoff space for memory consistency enforcement. RIx and Avalon thus represent a promising direction for tackling the challenge of availability under strong consistency models that throw consistency exceptions.
Theories for Influencer Identification in Complex Networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks, and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation, and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks, and socioeconomic systems.
PREDICTING NON-CODING VARIANT IMPACT ON THE HUMAN BRAIN USING MULTI-OMICS DATA INTEGRATION

Background Recent studies show evidence that non-coding variants may play an important role in disease etiology, including psychiatric disorders. However, prioritizing these less-understood variants and selecting the right candidates for further investigation remains a central challenge in the field. Current tools for annotating non-coding genetic variations provide a general indicator of their deleteriousness, but lack, for example, tissue-specific context that could better illuminate their role in a particular disease. Methods In this work, we propose a new machine learning-based approach that relies on tissue-specific data to estimate variant impact on brain tissues. By integrating information from several genome-scale databases, including GTEx and RoadMap Epigenomics, we derive tissue-related features. Using this data representation, we train a predictive random forest model to discriminate variants with prior evidence for brain relevance from variants unlikely to affect the brain. The resulting model predictions, which we call the Brain Relevance Score (BRS), are an estimate of how related a genome position is to the brain. Results After computing BRS for every nucleotide position in the human genome, we validate it on genomic regions known to be related to psychiatric disorders, such as the 16p11.2 region. In this region, we identify a short list of candidate variants, close from known genes involved in brain disease and mental disorders. We then use BRS as a filter and combine it with state of the art deleteriousness score (e.g., CADD) and report higher sensitivity in detecting brain-related damaging variants in the Simons Simplex Collection data for autism spectrum disorder, compared to 1000Genomes control data set. Discussion Even if we reported high performance in detecting both coding and non-coding variants related to the human brain, ongoing work in our lab involves benchmarking more competitive learning approaches and integrating additional brain databases in the model. The learning framework we demonstrate here could be easily applied to other psychiatric disorders.
Cartilage Restoration: Microfracture and Osteochondral Autograft Transplantation

The treatment of patellofemoral cartilage defects presents several distinct challenges when compared with cartilage restoration techniques used for other compartments of the knee due to the unique anatomy and distribution of forces. The etiologies of patellofemoral articular cartilage lesions include acute traumatic instability injuries, such as dislocation and subluxation, osteochondritis dissecans, and chronic degenerative changes. Regardless of the etiology, untreated patellofemoral cartilage lesions can contribute to activity-limiting anterior knee pain. The goal of patellofemoral cartilage restoration procedures is to impart symptomatic relief and improve quality of life by repairing the articular cartilage surface and any comorbid malalignment or maltracking. Microfracture and osteochondral autograft transplantation (OAT) are two cartilage restoration procedures to consider when treating full-thickness patellofemoral chondral defects. Considered by some experts to be the gold standard therapy, microfracture is one of the most common procedures used for cartilage restoration. The technique involves the perforation of the subchondral bone plate for the release of marrow elements, filling the defect with a fibrocartilage clot repair. Though less commonly used, OAT allows defect replacement with native hyaline cartilage via autologous transplantation from a non-weight bearing area. The purpose of this article is to discuss the indication, technical considerations, and outcomes of microfracture and OAT when used for treating chondral lesions of the patellofemoral joint.
Adaptive management of ecological systems under partial observability

Abstract Adaptive management has a long history in ecology and conservation. Uncertainty in both the state of a system and the model defining its dynamics are fundamental challenges in adaptive management of complex ecological systems. Traditional approaches in conservation biology often ignore one or both sources of uncertainty due to the computational complexity involved. Here, we show that underestimating the role of uncertainty in both model estimation and decision-making results in aggressive decision rules which can potentially lead to the dramatic decline and possible collapse of a population, species, or ecosystem. We propose an approximate solution to adaptive management of ecological systems under both model and state uncertainties that is computationally feasible and applicable to complex management problems and provide a software for detailed implementation of our method, http://doi.org/10.5281/zenodo.1161521 . We apply the proposed method in a marine ecosystem management context and show that by learning from historical data and arrival of new observations, decision makers can adapt their policies to avoid decline in the population and reach a sustainable population stability.
Seasonal and inter-annual variability in sea surface temperature and chlorophyll-a concentration along the West Florida Shelf: analyzing 5 years of satellite data

As the Gulf of Mexico has experienced major environmental hazards in the recent past, e.g. the BP oil spill in 2010, landfall of major hurricanes, and the frequent outbreak of red tide (Karenia brevis), it is required to evaluate possible alterations in the water quality and biogeochemical balance of this partially enclosed waterbody. Chlorophyll concentrations (Chl-a) and sea surface temperature (SST) Level-2 data from five satellites during the period from 2009 to 2013 were analyzed for their spatial, temporal, and inter-annual variability. Based on the evaluation of data from 24 transects from the West Florida Shelf (WFS), highest Chl-a was observed for the sector from St. Petersburg to Sanibel Island. Additionally, high Chl-a was observed for the Big Bend region, particularly during the spring and early summer. SST distribution also closely followed Chl-a distribution, even though occasional uptick in SST values were noticed from the inner continental shelf even during high primary productivity. Furthermore, between 2010 and 2011, monthly Chl-a and SST varied across the shelf significantly and can be due to the incursion of the Loop Current towards the WFS, as suggested by Weisberg et al. (2014).
OXYGEN ACTIVATION AND LIPOPEROXIDATIVE MECHANISMS OF TOXICITY OF PESTICIDES AND OTHER XENOBIOTICS

ABSTRACT The metabolism of certain classes of xenobiotics results in the generation of reactive species of oxygen including superoxide anion (O2−), hydrogen peroxide (H2C2) and hydroxyl radical (OH.). Formation of activated oxygen species can have extremely detrimental consequences on cell function and survival due to their potential reactivity with important cellular macromolecules such as nucleic acids, proteins, polysaccharides and lipids. The reaction of activated oxygen with polyunsaturated lipids is a particularly toxic event since it initiates the membrane-damaging chain reaction process of lipid peroxidation. Lipid peroxidation may also be initiated by other mechanisms, however, including metabolism of xenobiotics to reactive organic radicals or interference by xenobiotics with endogenous defense mechanisms controlling peroxidation reactions. An important aspect of lipid peroxidation is that it is moderated by several tiers of cellular defense mechanisms. The enzymes superoxide dismutase and catalase respectively detoxify O2− and H2O2 and thereby prevent initiation of lipid peroxidation reactions by activated oxygen. Glutathione peroxidase enzymatically detoxifies radical-forming lipid hydroperoxides formed as a result of activated oxygen or organic radical reaction with membrane polyunsaturated lipids. The lipid soluble antioxidant vitamin E scavenges toxic lipid radicals causing termination of the lipid peroxidation reactions. Although the defense mechanisms are adequate to prevent toxicity from normal endogenous oxidative metabolism, fluxes of activated oxygen or organic radicals generated from xenobiotic metabolism may be sufficient to overwhelm the defense mechanisms and cause toxicity. The bipyridylium herbicide paraquat produces pulmonary toxicity which has been attributed to a one-electron redox cycling of the parent molecule with resultant formation of O2−. The redox cycling is thought to be catalyzed by the microsomal enzyme NADPH cytochrome P450 reductase, with NADPH serving as the source of electrons. The microsomal metabolism of carbon tetrachloride to the trichloromethyl radical is an example of organic radical formation capable of initiating lipid peroxidation reactions. Lipid peroxidation may also be stimulated by agents which interfere with defense systems such as reduced glutathione (GSH). Methyl chloride, which severely depresses tissue GSH and thus removes this important defense mechanism, also causes increased tissue lipid peroxidation. Such examples illustrate the wide diversity of compounds whose toxicity may be mediated in part by the common mechanism of lipid peroxidation.
Effects of H2O2 on Insulin Signaling the Glucose Transport System in Mammalian Skeletal Muscle

Abstract Hydrogen peroxide (H 2 O 2 ) is an important regulator of cellular events leading to glucose transport activation in mammalian skeletal muscle. In the absence of insulin, H 2 O 2 in the low micromolar range engages the canonical IRS-1/PI3K/Akt-dependent insulin signaling pathway, as well as other signaling elements (AMPK and p38 MAPK), to increase basal glucose transport activity. In contrast, in the presence of insulin, H 2 O 2 antagonizes insulin signaling by recruitment of various deleterious serine/threonine kinases, producing a state of insulin resistance. Here, we describe the H 2 O 2 enzymatic-generating system, utilizing glucose oxidase, that has been used to investigate the impact of H 2 O 2 on cellular signaling mechanisms related to glucose transport activity in isolated rat skeletal muscle preparations, such as the soleus. By varying the glucose oxidase concentration in the medium, target ranges of steady-state H 2 O 2 concentrations (30–90 μ M ) can be attained for up to 6 h, with subsequent assessment of cellular signaling and glucose transport activity.
A Smart System to Detect Volatile Organic Compounds Produced by Hydrocarbons on Seawater

Hydrocarbons are considered one of the most important and dangerous pollutants for environment, in general, and for marine environment in particular. Their detection can be performed in several ways, employing different kinds of systems, such as fixed gas analyzers or gas chromatographs, to be mainly used in laboratory, or portable analyzers, having good performances but a considerably high cost.
Meditation and the scope of mental action

While philosophers of mind have devoted abundant time and attention to questions of content and consciousness, philosophical questions about the nature and scope of mental action have been relative...
Implementing a surgeon-reported categorization of pediatric appendicitis severity

The purpose of this study was to implement a novel surgeon-reported categorization (SRC) for pediatric appendicitis severity and determine if SRC was associated with outcomes. We conducted a retrospective review of appendectomies by 15 surgeons within a single center from January to December 2016. The SRC was defined as: simple (category 1), gangrenous or adherent (category 2A), perforation with localized abscess (category 2B), and perforation with gross contamination (category 2C). Logistic regression modeled the surgical site infections (SSI) and returns to the system. Cox proportional hazards analyses modeled the length of stay (LOS). The cohort included 697 patients (mean age 10.7 years). Compliance with SRC documentation increased from 33.5 to 85.9%. Review of operative findings revealed 100% concordance with SRC. The combined morbidity (SSI and revisits) rate was 9.8%. Category 2C patients had the highest odds of SSI (odds ratio 3.37 95% confidence interval 1.07–10.59). Median LOS increased with each category (category 1 = 1d, category 2A = 2d, category 2B = 4d, category 2C = 6d). When modeling intra-abdominal abscess, SRC displayed an improved model calibration and discrimination compared to wound class. SRC implementation is feasible and provides a granular assessment of appendicitis severity and outcomes. SRC may guide future quality improvement through development of grade-specific care pathways.
The impact of resection margin on overall survival for patients with colon cancer liver metastasis varied according to the primary cancer location

Introduction Investigation into right and left-sided primary colon liver metastasis (CLM) has revealed differences in the tumor biology and prognosis. This indicates that preoperative and operative factors may affect outcomes of right-sided primary CLM differently than left. This retrospective analysis investigated the effects of resection margin stratified by left and right-sided primary CLM on overall survival (OS) for patients undergoing hepatectomy. Methods A total of 732 patients undergoing hepatic resection for CLM at the Cleveland Clinic and Johns Hopkins were identified between 2002 and 2016. Clinically significant variables were analyzed using Cox proportional hazard regression. The cohort was then divided into patients with right and left-sided CLM and analyzed separately using Kaplan Meier analysis and Cox proportional hazard regression. Results Cox proportional hazard regression showed that left-sided CLM with an R0 margin was a statistically significant predictor of OS even after controlling for other important factors (HR = 0.629, P = 0.024) but right-sided CLM with R0 margin was not (HR = 0.788, P = 0.245). Kaplan–Meier analysis demonstrated that patients with a left-sided CLM and R0 margin had the best prognosis (P = 0.037). Conclusion Surgical margin is an important prognostic factor for left-sided primary CLM but tumor biology may override surgical technique for right-sided CLM.
Book Review of The Growing Out-of-School Time Field: Past, Present, and Future

This first book in the new Current Issues in Out-of-School Time series offers a foundational field perspective on out-of-school time. This volume is designed to inspire thoughtful reflections and critical conversations to further grow, sustain and improve the field by looking at the past and present in order to move forward in innovative ways.
Deciphering Predictive Schedulers for Heterogeneous-ISA Multicore Architectures

Heterogeneous architectures have become increasingly common. From co-packaging small and large cores, to GPUs alongside CPUs, to general-purpose heterogeneous-ISA architectures with cores implementing different ISAs. As diversity of execution cores grows, predictive models become of paramount importance for scheduling and resource allocation. In this paper, we investigate the capabilities of performance predictors in a heterogeneous-ISA setting, as well as the predictors' effects on scheduler quality. We follow an unbiased feature selection methodology to identify the optimal set of features for this task, instead of pre-selecting features before training. We propose metrics that bridge the gap between traditional prediction accuracy metrics and a scheduler's performance. We further present our evaluation methodology, which was meticulously designed with this study in mind, and finally, we incorporate our findings in ML-based schedulers and evaluate their sensitivity to the underlying system's level of heterogeneity.
ASYMPTOTIC PROPERTIES OF SOME ESTIMATORS IN STRUCTURAL MODELS

Publisher Summary This chapter discusses asymptotic properties of some estimators in structural models. Under normality, the k-class estimators are asymptotically efficient and the members with a = 1 are equivalent to the class of bias-adjusted maximum likelihood estimators. The bias-adjusted maximum likelihood estimators constitute an essentially complete class of second-order optimal estimators. Although the k-class estimators are not asymptotically efficient in the absence of normality, they have identical skewness and kurtosis coefficients to order T-1. Under symmetry, the bias-adjusted least variance ratio estimators, although no longer maximum-likelihood based, dominate the other k-class estimators. The effect of skewness and kurtosis of the error distribution on the sampling properties of the alternative estimators is counterintuitive.
Regularity for Shape Optimizers: The Nondegenerate Case

We consider minimizers of F(λ1(Ω),…,λN(Ω))+| Ω |,(1) where F is a function strictly increasing in each parameter, and λk(Ω) is the kth Dirichlet eigenvalue of Ω. Our main result is that the reduced boundary of the minimizer is composed of C1,α graphs and exhausts the topological boundary except for a set of Hausdorff dimension at most n – 3. We also obtain a new regularity result for vector-valued Bernoulli-type free boundary problems.© 2018 Wiley Periodicals, Inc.
α-Synuclein real-time quaking-induced conversion in the submandibular glands of Parkinson's disease patients

Background Identification of a peripheral biomarker is a major roadblock in the diagnosis of PD. Immunohistological identification of p-serine 129 α-synuclein in the submandibular gland tissues of PD patients has been recently reported. Objective We report on a proof-of-principle study for using an ultra-sensitive and specific, real-time quaking-induced conversion assay to detect pathological α-synuclein in the submandibular gland tissues of PD patients. Methods The α-synuclein real-time quaking-induced conversion assay was used to detect and quantify pathological α-synuclein levels in PD, incidental Lewy body disease, and control submandibular gland tissues as well as in formalin-fixed paraffin-embedded sections. Results We determined the quantitative seeding kinetics of pathological α-synuclein present in submandibular gland tissues from autopsied subjects using the α-synuclein real-time quaking-induced conversion assay. A total of 32 cases comprising 13 PD, 3 incidental Lewy body disease, and 16 controls showed 100% sensitivity and 94% specificity. Interestingly, both PD and incidental Lewy body disease tissues showed 100% concordance for elevated levels of pathological α-synuclein seeding activity compared to control tissues. End-point dilution kinetic analyses revealed that the submandibular gland had a wide dynamic range of pathological α-synuclein seeding activity. Conclusions Our results are the first to demonstrate the utility of using the real-time quaking-induced conversion assay on peripherally accessible submandibular gland tissues and formalin-fixed paraffin-embedded tissue sections to detect PD-related pathological changes with high sensitivity and specificity. Additionally, the detection of seeding activity from incidental Lewy body disease cases containing immunohistochemically undetected pathological α-synuclein demonstrates the α-synuclein real-time quaking-induced conversion assay's potential utility for identifying prodromal PD in submandibular gland tissues. © 2019 International Parkinson and Movement Disorder Society.
Use of Contact Lenses to Optimize OCT Scans of the Optic Nerve in Glaucoma Suspects or Patients with Glaucoma with High Myopia

Purpose Patients with myopia are at increased risk for the development of glaucoma. The inability to correct for axial length on spectral-domain (SD) OCT translates into lower signal strength and scan reliability in patients with high axial myopia. We evaluated the effectiveness of a contact lens to increase the signal strength and to assess optic nerve dimensions and nerve fiber layer (NFL) thickness using SD OCT in patients with glaucoma or who are glaucoma suspects with high axial myopia. Design Single-center, prospective, interventional study. Participants Patients with axial lengths of more than 25.5 mm with a diagnosis of glaucoma or glaucoma suspect. Methods The optic nerve cube 200×200 scan using the Cirrus SD OCT 400 (Carl Zeiss Meditec, Inc., Dublin, CA) was carried out first without the use of a contact lens and then repeated with placement of the contact lens to correct for the spherical equivalent of the refractive error. Main Outcome Measures The primary outcome measure was the change in the average NFL thickness before and after use of the contact lens. Secondary outcome measures included the changes in cup volume, disc area, and rim area on OCT. Results Twelve patients were recruited (20 eyes); the average axial length was 27.06 mm, and the average signal strength interval increased by 1.73 (P = 0.001). With the use of a contact lens, the average NFL thickness was significantly thicker. None of the changes in the secondary outcome measures were significant: rim area, cup volume, or disc area. Conclusions Based on our data, the use of a contact lens statistically improved the signal strength and average NFL thickness of the SD OCT scan. The ability to capture the perimeter of the optic disc accurately can be limited in the setting of peripapillary atrophy, which was present in all but 2 participants. Future studies with a larger number of participants and a wider range of axial myopia to discern if contact lens correction has a greater effect on the highest axial lengths are needed.
Chapter 4 – Drug Antagonism: Orthosteric Drug Effects

This chapter deals with the quantification of the effects of antagonists to yield empirical measures of antagonist potency. Beginning with the premise that there are two possible modes of action of antagonism; orthosteric blockade (occlusion of the agonist binding site) and allosteric modulation, this chapter focuses on orthosteric antagonism. Estimates of antagonist potency can be obtained for all modes of antagonism through a pA2 value and/or a pIC50 of antagonism of a fixed agonist effect. Patterns of antagonism are then discussed from the standpoint of using these to identify the mechanism of antagonist action (eg, orthosteric antagonists producing steric hindrance of agonists). The chapter then discusses how these mechanisms can be used to identify the appropriate mathematical analysis to yield estimates of true system-independent antagonist potency that transcend cell type and measuring system.