cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification and characterization of a novel RON/c-Met small molecule inhibitor

A223 RON is a receptor tyrosine kinase closely related, both structurally and functionally, to c-Met. Like c-Met, RON is involved in cell proliferation, migration, invasion and there is evidence that both receptors are deregulated in cancer. Receptor over-expression has been most frequently described, but other mechanisms can lead to the oncogenic activation of RON and c-Met. They include activating mutations or gene amplification for c-Met while constitutively active RON splicing variants have been found in cell lines and in colorectal cancer. Furthermore, RON and c-Met cross-talk in vitro and co-expression in cancer has been documented and may contribute to tumor growth. Thus, targeting both RON and c-Met could represent a useful strategy to treat malignant disease in patients. We identified and characterized the in vitro and in vivo activities of a dual RON/c-Met inhibitor, Compound I, on c-Met-dependent models (U-87 MG and NIH3T3 TPR-Met) and on HT-29 cells which express a constitutively active form of RON. Compound I potently inhibited the kinase activity of RON and c-Met with IC 50 s of 9 nM and 4 nM, respectively, while it had much weaker activity on a large set of other kinases. Compound I inhibited HGF- and MSP-mediated signaling in a dose-dependent manner in several cell lines. We then tested the ability of Compound I to inhibit the constitutively active RONΔ160 splicing variant found naturally in HT-29 cells. HT-29 cells also express the b-Raf V600E mutant and are therefore predicted to be only partially dependent on RON. As expected, Compound I partially inhibited the phosphorylation of ERK1/2 in HT-29 cells. Consistent with its effects on cell signaling, Compound I caused significant, but incomplete tumor growth inhibition in HT-29 xenografts while it completely inhibited the growth of the c-Met-dependent models at doses that were well-tolerated. Compound I had no effect in Colo205 tumor xenografts which express both wild-type RON and c-Met, but are not dependent on either for their growth. Taken together, our results suggest that a small molecule dual inhibitor directed at RON/c-Met has the potential to inhibit tumor growth and could therefore be useful for the treatment of patients with cancers where RON and/or c-Met are activated.
Violence Exposure as a Mediator Between Parenting and Adolescent Mental Health

For youth exposed to community violence, parenting has been found to play a significant role in protecting adolescents from associated mental health symptoms. Yet little is known about the potential of parenting to prevent such exposure in the first place and thereby reduce the likelihood of adolescents’ mental health symptoms. This study examined two parental practices that have often been examined as moderators, but not yet as predictors, of youth exposure to community violence associations with adolescent mental health, namely parental control and parental harshness. Analyses of self-reported data from 908 adolescents (M age = 16.5, SD = 1.71; 52 % girls; 13 % non-Hispanic White) revealed that harsh parenting was indirectly associated with youth mental health symptoms through higher levels of exposure to community violence, whereas links between controlling parenting and mental health symptoms were either non-significant or mediated through lower levels of adolescent violence exposure. These findings highlight the potential positive role parental control may play by preventing adolescents from exposure to potentially dangerous situations. Conversely, our results suggest that harsh parenting appears to pose a risk for adolescents by driving youth away from the home environment and potentially into places where violence may be more prevalent.
Semantic Relations Cause Interference in Spoken Language Comprehension When Using Repeated Definite References, Not Pronouns

The choice and processing of referential expressions depend on the referents’ status within the discourse, such that pronouns are generally preferred over full repetitive references when the referent is salient. Here we report two visual-world experiments showing that: (1) in spoken language comprehension, this preference is reflected in delayed fixations to referents mentioned after repeated definite references compared with after pronouns; (2) repeated references are processed differently than new references; (3) long-term semantic memory representations affect the processing of pronouns and repeated names differently. Overall, these results support the role of semantic discourse representation in referential processing and reveal important details about how pronouns and full repeated references are processed in the context of these representations. The results suggest the need for modifications to current theoretical accounts of reference processing such as Discourse Prominence Theory and the Informational Load Hypothesis.
Bending with the Wind: Revisiting Islamist Parties’ Electoral Dilemma

Islamist parties' electoral performance is a hotly debated question. Two arguments dominate the literature in terms of Islamist parties' performance in democratic elections. The conventional argument has been the “one man, one vote, one time” hypothesis. More recently, Kurzman and Naqvi challenge this argument and show that Islamists tend to lose in free elections rather than win them. We argue that existing arguments fall short. Specifically, we theorize that moderateness of Islamist platform plays a key role in increasing the popularity of these parties and leads to higher levels of electoral support. Using data collected by Kurzman and Naqvi, we test our hypothesis, controlling for political platform and political economic factors in a quantitative analysis. We find that there is empirical support for our theory. Islamist parties' support level is positively associated with moderateness; however, this positive effect of moderation is also conditioned by economic openness.
A New Adulteration Detection Method on Edible Vegetable Oils by Gas Chromatography

The components and contents of fatty acid in common edible vegetable oile were analyzed and determined with newreagents by gas chromatography.The experiment conditions involved were optimized and their normal contents were obtained.By testing the adulterated and imitated common edible vegetable oils,the variational regularity of the fatty acid components andcontents were obtained. The new method for discerming the adulterant from the gemuine by gas chromatography was established,which could idemtify the common kinds of edible vegetable oils,determine the oils adulteration rapidly and analyze the oils bothqualitatively and quantiatively.262 pieces of oil samples sold in the market were spot-tested with thes method,in which 83pieces of adulterated sesame oil,47 pieces of adulterated rape oil,23 pieces of adulterated peanut oil, and 11 pieces of olive oilwere checked out respectively, accounting for 10%～95% totally.It indicated that the method has been feasible and effective.
It's time to start practicing population-based health care.

You don't have to be part of an integrated delivery system to optimize care for populations of patients with common conditions.
Detection of IgE Reactive With Lipopolysaccharide in Plasma of Traumatically Injured Patients

Gram-negative sepsis occurs commonly in patients who have sustained major traumatic injury. The study of the pathogenic mechanisms of gram-negative sepsis has focused on activation of macrophages by lipopolysaccharide and subsequent release of mediators such as interleukin-1 and tumor necrosis factor. These cytokines are believed to initiate processes which then lead to sepsis. The potential for allergic mechanisms participating in the sepsis syndrome has not been well studied. Anaphylaxis produces some manifestations that are similar to those with the sepsis syndrome. IgE-dependent activation of basophils and mast cells could potentially be involved in the sepsis syndrome. Recently, Jacobs and associates (1989) reported that blood histamine concentrations were not elevated in humans with septic shock. However, the presence of IgE reactive with bacterial products (such as lipopolysaccharide) may indicate the involvement of allergic mechanisms in this syndrome. This report presents data on anti-lipopolysaccharide IgE and total IgE in plasma of patients after major traumatic injury.
Diabetes self-management among Arab Americans: patient and provider perspectives

Arab Americans have a high burden of diabetes and poor outcomes compared to the general U.S. population. Diabetes self-management (DSM) requires a partnership between patients and providers that fosters mutual understanding and shared decision-making. Cultural factors influence this process; however, little is known regarding the cultural impact on DSM or if perceptions differ between patients and providers. Qualitative content analysis was used to analyze five focus groups–two groups with Arab American providers (n = 8) and three groups with adult Arab Americans with diabetes (n = 23). Focus groups examined patient and provider perspectives on the meaning of DSM and cultural barriers and facilitators among Arab American patients. Four distinct themes included limited resources for DSM education and support, stigma as a barrier to ongoing support, family support as an opportunity and challenge, and Arab American patient-provider relationships. Findings indicate several domains should be considered for clinical practice including a need to develop linguistically and culturally reliant educational materials and relevant supports for use in the Arab American population. Findings highlight differing views among providers and patients on the familial role in supporting DSM efforts and why some patients feel dissatisfied with clinical encounters.
Thrombin Generation in Children after Acute Venous Thromboembolism

Introduction: Venous thromboembolism (VTE) is a major and growing problem in children. The annual rate of VTE has increased by 70% in the U.S hospitalized children in the past decade. Accompanying this increase in VTE is the attendant increase in chronic, post-thrombotic sequeale of VTE. Strategies to identify children at high risk of developing poor outcomes after initial management of VTE are unclear. We hypothesized that 9global coagulation assessment9 may identify children likely to suffer from poor thrombosis outcomes following an initial event. In this pilot study, we therefore, evaluated thrombin generation (TG) after an acute episode of provoked VTE in children. Methods: Baseline patient, thrombus characteristics and thrombophilia testing were prospectively collected for 50 consecutive children with acute, provoked VTE after informed consent. Subjects with cancer, protein C, protein S and antithrombin deficiency, persistent antiphospholipid positivity and inflammatory disorders were excluded. Thrombin generation, using corn trypsin inhibited treated plasma by calibrated automated thrombogram was measured in the presence and absence of thrombomodulin (TM), 4 weeks after completion of anticoagulation therapy, and compared to 50 healthy controls. All cases were treated according to the 9th edition of American College of Chest Physicians Clinical Practice Guidelines. Results: The mean age of VTE cases was 14 years (range: 6 weeks to 18 years). Two thirds (33/50) of VTE cases consisted of deep venous thrombosis of the limbs and/or pulmonary embolism, and nearly 20% (10/50) were cerebral sinovenous thrombosis. Thrombin generation of subjects showed significantly higher endogenous thrombin potential (ETP) compared to healthy controls (1150 ± 281 vs. 763 ± 274 nM.min; p 150%) at end of therapy and TM induced reduction of ETP ( r =0.297 vs. 0.171; p In conclusion , a novel finding in children with provoked VTE was persistent elevation of TG after successful completion of anticoagulation therapy. A role for FVIII as an important cause of hypercoagulability after anticoagulation therapy is reflected by the reduced inhibitory effect of TM at high FVIII levels. Further studies are ongoing to determine the utility of TG as a biomarker for predicting poor outcomes after VTE in children. Disclosures Journeycake: CSL, Baxalta, NovoNordisk: Consultancy; ATHN: Research Funding; Biogen: Speakers Bureau; ATHN: Membership on an entity9s Board of Directors or advisory committees.
Should Investors Worry About Commodity Shocks

In this paper, I investigate which commodity disturbances are significant in regards to a country’s business cycle. I develop a Small Open New Keynesian model that is estimated for twenty-three countries using nineteen primary commodities within the energy, metal, timber, rubber, cotton and food sectors. The findings show that petroleum shocks are the only commodity shocks that are significant in affecting a country’s output. Also, a country’s openness plays an important role in shaping the output response initiated by a petroleum shock. In addition, disturbances caused by petroleum shocks dissipate within six to ten quarters.
Application of wavelet transformation and vector quantization for power system fault detection and compression waveform

In a power grid the occurrence of a fault causes significant changes in the system variables such as current, voltage, etc. Under this circumstance, detection of the fault location is a challenging task. To deal with this problem this paper proposes a systematic approach using the discrete wavelet transform in the power grid for finding the place of the fault. In addition, optimal vector quantization is used to compress the voltage and current profile in order to transmit them to the control center where the fault location processing is performed. The IEEE 9-bus system is used to prove the effectiveness of the proposed technique.
Motivational processes from expectancy–value theory are associated with variability in the error positivity in young children

Motivational beliefs and values influence how children approach challenging activities. The current study explored motivational processes from an expectancy-value theory framework by studying children's mistakes and their responses to them by focusing on two event-related potential (ERP) components: the error-related negativity (ERN) and the error positivity (Pe). Motivation was assessed using a child-friendly challenge puzzle task and a brief interview measure prior to ERP testing. Data from 50 4- to 6-year-old children revealed that greater perceived competence beliefs were related to a larger Pe, whereas stronger intrinsic task value beliefs were associated with a smaller Pe. Motivation was unrelated to the ERN. Individual differences in early motivational processes may reflect electrophysiological activity related to conscious error awareness.
THE ROLE OF RUMINAL MICROBES IN THE METABOLISM OF TOXIC CONSTITUENTS FROM PLANTS

I. ABSTRACT Ruminal microbes interact with some of the toxic substances from plants and this interaction may be of great importance to the host. Examples are given for microbial degradation of toxic substances, production of toxic substances by the microbes, and toxicity due to induced changes in or inhibitions of the microbial population. Diets may induce a selection or change in the proportions of functional microbes so that rates of interaction with toxic substances are changed. In some cases this “adaptation” may be crucial to the well-being of the ruminant. For many toxic substances the interactions with ruminal microbes have not yet been adequately characterized.
Increasing stability of result organization for session search

Search result clustering (SRC) organizes search results into labeled hierarchical structures as an "information lay-of-land", providing users an overview and helping them quickly locate relevant information from piles of search results. Hierarchies built by this process are usually sensitive to query changes. For search sessions with multiple queries, this could be undesirable since it may leave users a seemly random overview and partly diminish the benefits that SRC intents to offer. We propose to integrate external knowledge from Wikipedia when building concept hierarchies to boost their stability for session queries. Our evaluations on both TREC 2010 and 2011 Session tracks demonstrate that the proposed approaches outperform the state-of-the-art hierarchy construction algorithms in stability of search results organization.
Chest Trauma and Lung Contusions

The combination of major orthopedic injuries and chest trauma is worthy of special attention, as cardiopulmonary dysfunction is expected, and the patient is at risk for serious morbidity. Primary pulmonary injury (particularly lung contusion) and chest wall injury (rib fractures) make meeting the increased respiratory demands of critical injury problematic. Secondary pulmonary injury from adult respiratory distress syndrome or fat emboli syndrome can further complicate the picture. This chapter strives to review the underlying pathophysiology of chest injury relevant to the orthopedic patient and review the current understanding of which patients are at highest risk from operative interventions. Recent studies of multiply injured patients are discussed to inform the reader about which patients may deserve an early damage control approach to fracture care. Specific guidelines are suggested which may be used to assess individual patients at risk.
The Halle Orphanage as Scientific Community: Observation, Eclecticism, and Pietism in the Early Enlightenment. By KellyJoan Whitmer. (Chicago, IL: University of Chicago Press, 2015. Pp. xii, 202. $40.00.) : Book Review

It is rare to find the words “orphanage” and “scientific community” in the same sentence, let alone to encounter a whole book devoted to their relation, yet this is precisely what the author of thi...
Gas permeation and separation properties of large-sheet stacked graphene oxide membranes

Abstract Graphene oxide (GO) membranes offer attractive gas separation properties. However, the gas separation mechanism for GO membranes is unclear due to inconsistent permeation and separation results reported in the literature. In this work, pure gas permeation and separation of equimolar (H2/CO2) mixture experiments were conducted on GO membranes made from large GO sheets of different sizes (33 and 17 µm) to understand the gas permeation and separation characteristics of these membranes. At room temperature the permeation of large molecules (CH4, N2 and CO2,) through GO membranes exhibits Knudsen–like diffusion characteristics, with the permeance for the small sheet GO membrane about twice that for the large sheet GO membrane. The smaller gases (H2 and He) exhibit much higher permeance, showing additional transport in additional pathway. The GO membranes show good H2/CO2 selectivity for both pure and binary gas feeds, without CO2 pore blockage effect for mixture separation found for crystalline microporous membranes. An inter-sheet and inner-sheet two-pathway model is proposed which can explain the results obtained in this work. Gas permeation in GO membranes, more complex than in crystalline microporous membranes, is determined by solubility (surface properties), diffusivity (relative molecular size to pore size), porosity and tortuosity of both the inter-sheet pores and inner-sheet defect pores. These properties are strongly influenced by synthesis method and conditions for GO sheets and membranes.
A Systematic Literature Review on Interaction Flow Modeling Language (IFML)

Design of front-end interfaces in software applications is a complex process. In this context, Interaction Flow Modeling Language (IFML) is an emerging standard introduced in 2013 by Object Management Group (OMG). In this article, a Systematic Literature Review (SLR) is performed to examine the applications of IFML. Particularly, 22 research studies (2014-2017) are identified and analyzed. Consequently, four major areas are recognized where IFML is frequently applied i.e. mobile applications (9 studies), web applications (8 studies), others (4 studies) and desktop applications (1 study). Furthermore, 9 leading IFML tools are presented i.e. Modeling (3) and model transformation (6). It has been concluded that IFML certainly simplifies the design and implementation of front-end interfaces. However, the existing IFML tools are not mature enough to be utilized for complex and large software applications.
Antibodies to DNA Epiphenomena or Pathogens

The study of antibodies directed against DNA began in the 1950s with the discovery of the L.E. cell by Hargraves. Several investigators found that the L.E. cell phenomenon resulted from ingestion of altered nuclear material by circulating phagocytic cells. Close examination of that material showed that it consisted of DNA-protein (predominantly DNA-histone) and IgG. Thus, the existence of antibodies to the supposedly “forbidden” constituents of the human nucleus was recognized.
Clinical Aspects of Neuropeptide Research

Increasing evidence suggests that depression is found in a high percentage of patients with cancer (Petty and Noyes 1981; Buckberg et al. 1984), but depression appears to be both underdiagnosed and inadequately treated in cancer patients. There is also a growing body of evidence suggesting that experimentally induced stress in animals as well as psychiatric illness and stressful life experience in humans are associated with alterations in both neuroendocrine and immune function. Alterations in immune function have been found in patients with major depression (Kronfol et al. 1983; Schliefer et al. 1984,1985), and there is one report suggesting an epidemiologic relationship between depression and cancer (Shekelle et al. 1981). However, it is not known whether the alterations in immune function found in depression are of clinical significance, and there have been no comprehensive studies of both neuroendocrine and immune function in depressed cancer patients.
Competency to Stand Trial on Trial

This Article considers the legal standards for the determination of competency to stand trial, and whether those standards are understood and applied by psychiatrists and psychologists in the forensic evaluations they perform and in the judgments they make - judgments that are routinely accepted by trial courts as their own judgments. The Article traces the historical development of the competency construct and the development of two competency standards. One standard, used today in eight states that contain 25% of the population of the United States, requires that the defendant be able to assist counsel in the conduct of a defense "in a rational manner." The second, adopted by the Supreme Court in Dusky v. United States, 362 U.S. 402 (1960) as the Court's interpretation of the federal competency statute, requires that the defendant have an ability to consult with counsel with a reasonable degree of "rational understanding." The "rational manner" standard seemingly focuses on the defendant's behavior; the "rational understanding" standard seemingly focuses on the defendant's thinking. The Article reports on a survey we conducted of 273 forensic psychiatrists and psychologists who were asked to read two case study vignettes and assess the competency of each criminal defendant using the "rational manner" standard, the "rational understanding" standard, and the federal statutory standard that merely requires that the defendant be able to "assist properly" in his or her defense. In one vignette, the defendant's thinking was irrational but his behavior was rational. In the other, the defendant's thinking was rational, but her behavior was irrational. In responding to both vignettes, more than three-fourths of all respondents either found the defendant competent under all three standards or incompetent under all three standards. Surprisingly, in answering the first vignette, the respondents divided almost equally in deciding whether the defendant was competent. The Article analyzes the results of the study and concludes with specific proposals to improve competency to stand trial assessments. Fairness to the defendant requires that the competency standard be clearly defined and applied by those who assess and determine competency.
Evidence from Tll and Related Phenomena for Local Structure in the Amorphous State of Polymers

We have recently completed what we conceived as a definitive review of T ll and related liquid state transitions (relaxations) in the T>T g region of atactic polymers and the T>T m region of crystalline polymers.1 A table of contents appears on page 233 of that article. In general the subject matter covered definition of terms, history, theories for T ll , experimental techniques, practical significance, and a guide to the literature.
Robust Analysis of RCTs Using Generalized Linear Models

It is typical in RCTs for extensive information to be collected on subjects prior to randomization. For example, age, ethnicity, socioeconomic status, history of disease, and family history of disease may be recorded. Baseline information can be leveraged to obtain more precise estimates of treatment effects than the standard unadjusted estimator. This is often done by carrying out model-based analyses at the end of the trial, where baseline variables predictive of the primary study outcome are included in the model. As shown in Moore and van der Laan (2007), such analyses have potential to improve precision and, if carried out in the appropriate manner, give asymptotically unbiased, locally efficient estimates of the marginal treatment effect even when the model used is arbitrarily misspecified.
Issues in Outpatient Rehabilitation Management of the Stroke Survivor

The postacute rehabilitation of the stroke survivor covers a broad range of patient problems with which the outpatient physiatrist must contend. Issues encompassing the treatment setting, i.e., the community or hospital, and the economic resources necessary for comprehensive outpatient management are presented in this article. Knowledge of the long-term medical and functional sequelae of cerebrovascular disease is outlined as a basis for making appropriate rehabilitation interventions for the stroke survivor. The aggressive pursuit of interventions to enhance function and reduce the social and physical stigmata of stroke is encouraged.
Neurophysiologic measures of target engagement predict response to auditory-based cognitive training in treatment refractory schizophrenia

Cognitive impairment is a core feature of schizophrenia and a strong predictor of psychosocial disability. Auditory-based targeted cognitive training (TCT) aims to enhance verbal learning and other domains of cognitive functioning through “bottom-up” tuning of the neural systems underlying early auditory information processing (EAIP). Although TCT has demonstrated efficacy at the group level, individual response to TCT varies considerably, with nearly half of patients showing little-to-no benefit. EEG measures of EAIP, mismatch negativity (MMN) and P3a, are sensitive to the neural systems engaged by TCT exercises and might therefore predict clinical outcomes after a full course of treatment. This study aimed to determine whether initial malleability of MMN and P3a to 1-h of auditory-based TCT predicts improvements in verbal learning and clinical symptom reduction following a full (30-h) course of TCT. Treatment refractory patients diagnosed with schizophrenia were randomly assigned to receive treatment-as-usual (TAU; n = 22) or TAU augmented with TCT (n = 23). Results indicated that malleability (i.e., change from baseline after the initial 1-h dose of TCT) of MMN and P3a predicted improvements in verbal learning as well as decreases in the severity of positive symptoms. Examination of MMN and P3a malleability in patients after their first dose of TCT can be used to predict clinical response to a full course of treatment and shows promise for future biomarker-informed treatment assignment.
Regression Analysis with Dummy Variables: Innovation and Firm Performance in the Tourism Industry

The chapter demonstrates an application of correlation and regression analysis in tourism research. The chapter provides the concepts of product moment correlation, partial and part correlation, regression, and regression with dummy variables. The chapter provides, in particular, an application of regression analysis with dummy variables to estimate the economic effects of innovation on firm financial performance in the tourism industry of an economy in Asia. The paper examines signs and significance of the relationship between technological innovation and firm financial performance in the tourism industry of Thailand. The study employs multiple regression analysis with dummy variables, correlation analysis (i.e., the Pearson correlation), and chi-square tests (i.e., the Pearson chi-square test), and the associated statistics are explained. The dataset includes a total of 188 data points from 46 listed firms in tourism in the Stock Exchange of Thailand over a period of five fiscal years, 2011–2015.
Marx, Engels and the Democratic Communist Tradition

Marx’s and Engels’ commitment to democracy is often doubted. This article argues that support for democratic political processes was integral to the political tradition with which they identified themselves: broadly speaking, that of support for the French Revolution, and more specifically, for the kind of democratic communism advocated during the Revolution by Gracchus Babeuf and his followers. The Babeuvistes aimed primarily at the reinstitution of the democratic Constitution of 1793, and expected any future communist society to be run on wholly democratic lines; Marx and Engels held similar beliefs.
Knowledge and Power in the Philosophies of Ḥamīd al-Dīn al-Kirmānī and Mullā Ṣadrā Shīrāzī

With the great progress made in the study of Shiʿi Islam over the last few decades, the field is in a better position to devote careful attention to the specificities and nuances in the worldviews ...
Effective error-specification inference via domain-knowledge expansion

Error-handling code responds to the occurrence of runtime errors. Failure to correctly handle errors can lead to security vulnerabilities and data loss. This paper deals with error handling in software written in C that uses the return-code idiom: the presence and type of error is encoded in the return value of a function. This paper describes EESI, a static analysis that infers the set of values that a function can return on error. Such a function error-specification can then be used to identify bugs related to incorrect error handling. The key insight of EESI is to bootstrap the analysis with domain knowledge related to error handling provided by a developer. EESI uses a combination of intraprocedural, flow-sensitive analysis and interprocedural, context-insensitive analysis to ensure precision and scalability. We built a tool ECC to demonstrate how the function error-specifications inferred by EESI can be used to automatically find bugs related to incorrect error handling. ECC detected 246 bugs across 9 programs, of which 110 have been confirmed. ECC detected 220 previously unknown bugs, of which 99 are confirmed. Two patches have already been merged into OpenSSL.
Cardiac and Stress Biomarkers and Chronic Kidney Disease Progression: The CRIC Study.

BACKGROUND: Increases in cardiac and stress biomarkers may be associated with loss of kidney function through shared mechanisms involving cardiac and kidney injury. We evaluated the associations of cardiac and stress biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), soluble ST-2 (sST-2)] with progression of chronic kidney disease (CKD). METHODS: We included 3664 participants with CKD from the Chronic Renal Insufficiency Cohort study. All biomarkers were measured at entry. The primary outcome was CKD progression, defined as progression to end-stage renal disease (ESRD) or 50% decline in estimated glomerular filtration rate (eGFR). Cox models tested the association of each biomarker with CKD progression, adjusting for demographics, site, diabetes, cardiovascular disease, eGFR, urine proteinuria, blood pressure, body mass index, cholesterol, medication use, and mineral metabolism. RESULTS: There were 1221 participants who had CKD progression over a median (interquartile range) follow-up of 5.8 (2.4–8.6) years. GDF-15, but not sST2, was significantly associated with an increased risk of CKD progression [hazard ratios (HRs) are per SD increase in log-transformed biomarker]: GDF-15 (HR, 1.50; 95% CI, 1.35–1.67) and sST2 (HR, 1.07; 95% CI, 0.99–1.14). NT-proBNP and hsTnT were also associated with increased risk of CKD progression, but weaker than GDF-15: NT-proBNP (HR, 1.24; 95% CI, 1.13–1.36) and hsTnT (HR, 1.11; 95% CI, 1.01–1.22). CONCLUSIONS: Increases in GDF-15, NT-proBNP, and hsTnT are associated with greater risk for CKD progression. These biomarkers may inform mechanisms underlying kidney injury.
Effect of Previous Electroconvulsive Therapy on Subsequent Response to Transcranial Magnetic Stimulation for Major Depressive Disorder.

OBJECTIVES Patients with major depressive disorder (MDD) who received electroconvulsive therapy (ECT) often seek transcranial magnetic stimulation (TMS) therapy as a less invasive treatment option. How prior history of ECT and its responsiveness may affect TMS treatment outcomes for MDD is unclear. We aim to contribute evidence to this important clinical question. MATERIALS AND METHODS Retrospective naturalistic TMS treatment data from n = 257 MDD patients. Three sets of analyses were conducted: History of past exposure to ECT (n = 71, "+ECT" vs. n = 186 ECT-naive, "-ECT") was examined as a potential predictor of TMS outcomes (measured by two self-report scales); A subset of n = 38 +ECT patients with adequate ECT trials in current depression episode were compared with -ECT patients blindly matched on clinical variables associated with TMS outcomes; for a subset with available data, TMS outcomes were explored in relation to positive/negative response to prior ECT. RESULTS Compared to -ECT, +ECT patients more likely had past psychiatric hospitalizations (p < 0.01) and were more severely depressed at baseline (p = 0.07). Response (p = 0.07) and remission (p = 0.02) rates were higher in -ECT than +ECT groups on one scale. However, comparison between the subsets (n = 38 each) matched on confounding factors did not find history of ECT to be a significant independent predictor of TMS outcomes. Differential responsiveness to ECT and ECT treatment characteristics did not significantly impact TMS outcomes. CONCLUSIONS Although limited by the retrospective nature of this analysis, the results suggest that history of the past ECT, regardless of responsiveness to ECT, may not independently portend differential TMS treatment outcomes.
Voluntary climate action and credible regulatory threat: evidence from the carbon disclosure project

This paper examines the role that the U.S. Environmental Protection Agency’s introduction of the Clean Power Plan played in voluntary carbon disclosure by the Global 500 firms during 2011–2015. Results from difference-in-difference-in-differences estimators nested in a two-stage endogenous binary-variable model—which accounts for the correlation between a firm’s participation and intensity of participation—show that U.S.-based firms acted preemptively in anticipation of a more stringent regulatory environment. Regardless of country of origin, among firms making voluntary disclosures, the Clean Power Plan was associated with higher levels of carbon disclosure in firms with favorable management structures and practices involving the agency of corporate management, ceteris paribus. Empirical analysis includes controls for firm size, natural gas prices, sector-specific market pressures, and macro-economic and political economy dynamics. Results are robust to alternative specifications, including a trimmed matching sample, the Heckman selection model, and sector-specific regressions.
Beliefs About Emotion Are Tied to Beliefs About Gender: The Case of Men’s Crying in Competitive Sports

Gender and emotion stereotypes suggest that men do not and should not cry, yet men's crying seems to be particularly prominent in contexts such as competitive sports. In two studies, I investigated the possibility that men's crying is more frequent and seen as more acceptable in these settings because such contexts are perceived to be highly masculine, and can buffer men from the negative consequences associated with violating gender stereotypes. Specifically, I tested the hypotheses that (a) observers would perceive men's crying more positively in a masculine-stereotyped than a feminine-stereotyped setting, and following from this, (b) men would report being more likely to shed tears in a stereotypically masculine than a stereotypically feminine setting. To test these predictions, I conducted two between-subjects experiments in which participants (N = 250; N = 192), read a vignette about a man or a woman crying in either a stereotypically masculine (firefighting, weightlifting) or stereotypically feminine (nursing, figure skating) setting, and then rated the target on several emotion-related dependent variables. In line with predictions, results of Study 1 indicated that participants rated crying male firefighters as more emotionally appropriate, emotionally strong, and as higher in workplace status than crying male nurses, and that these effects were mediated by perceptions of the target's masculinity and femininity. Study 2 replicated these effects using sports-related vignettes, and showed that male participants reported being more likely to shed tears after losing a competition in weightlifting than in figure-skating. Taken together, these findings suggest that men who are perceived to embody cultural ideals of masculinity may be given more room to cry than those who are perceived as less stereotypically masculine.
Individualized estimation of the Speech Intelligibility Index for short sentences: Test-retest reliability.

The speech intelligibility index (SII) model was modified to allow individualized parameters. These parameters included the relative weights of speech cues in five octave-frequency bands ranging from 0.25 to 4 kHz, i.e., the band importance function, and the transfer function that allows the SII to generate predictions on speech-recognition scores. A Bayesian adaptive procedure, the quick-band-importance-function (qBIF) procedure, was utilized to enable efficient estimation of the SII parameters from individual listeners. In two experiments, the SII parameters were estimated for 30 normal-hearing adults using Institute of Electrical and Electronics Engineers (IEEE) sentences at speech levels of 55, 65, and 75 dB sound pressure level (in Experiment I) and for 15 hearing-impaired (HI) adult listeners using amplified IEEE or AzBio sentences (in Experiment II). In both experiments, even without prior training, the estimated model parameters showed satisfactory reliability between two runs of the qBIF procedure at least one week apart. For the HI listeners, inter-listener variability in most estimated SII parameters was larger than intra-listener variability of the qBIF procedure.
Organophosphate pesticide exposure: Demographic and dietary predictors in an urban pregnancy cohort.

Abstract Pregnant women are widely exposed to organophosphate (OP) pesticides, which are potentially neurotoxicant for the developing fetus. We aimed to identify principal demographic and dietary predictors of OP pesticide exposure among 450 pregnant women participating in the New York University Children’s Health and Environment Study (enrolled 2016–19). Urinary concentrations of six dialkyl phosphate (DAP) metabolites (3 dimethyl (DM) metabolites and 3 diethyl (DE) metabolites) of OP pesticides were determined at three time points across pregnancy. At mid-gestation, the Diet History Questionnaire II was used to assess women’s dietary intake over the past year. Demographic characteristics were obtained using questionnaires and/or electronic health records. We used linear mixed models to evaluate the associations of demographic and food groups with DAP metabolite levels, and partial-linear single-index (PLSI) models to analyze the contribution proportions of food groups to DAP metabolite concentrations and the dose-response relationships between them. We observed that pregnant women in NYC had lower levels of OP pesticide metabolites than pregnant populations in Europe, Asia, and other regions in the U.S. Having lower pre-pregnancy body mass index and being Asian, employed, and single were associated with higher DAP metabolite concentrations. Fruit and grain intakes were associated with higher ∑DM, ∑DE, and ∑DAP levels. ∑DE concentrations increased 9.0% (95% confidence interval (CI) = 1.2%, 17.4%) per two-fold increase in dairy consumption, whereas ∑DE concentrations decreased 1.8% (95%CI = −3.1%, −0.4%) per two-fold increase in seafood consumption. The PLSI model indicated that among the food mixture, fruit and grains were the main food groups contributed to higher levels of ∑DAP, while meat contributed to lower levels of ∑DAP. The contribution proportions of fruit, grains, and meat were 18.7%, 17.9%, and 39.3%, respectively. Our results suggest that fruit, grains, and meat are major dietary components associated with OP pesticide exposure in urban pregnant women.
Von Hippel–Lindau Syndrome

Von Hippel–Lindau syndrome (VHL) is a heritable neoplastic disease resulting in multisystem carcinoma, benign tumors, and cysts. VHL is inherited in an autosomal dominant manner and could result in benign or malignant tumors, with high penetrance affecting multiple organ systems, including the central nervous system (CNS) and visceral organs [1]. Incidences of VHL are associated with a germline mutation of a tumor suppressor gene, VHL, on the short arm of chromosome 3 (3p25.5) [2].
Screening with Under-Utilization: Tiers, Multi-Part Tariffs, and Welfare Implications

We study a screening model in which agents can under-utilize goods. We characterize implementable and optimal contracts and show that, whenever the principal values usage instrumentally, the optimal menu involves multi-part tariffs with tiers of zero marginal prices. We apply our results to study the pricing of digital goods which naturally feature usage-based revenue and unpunishable under-utilization, such as social media, news, and content streaming. We derive comparative statics that map the structure of usage-based revenues to familiar multi-part pricing schemes (premium plans, free trials, and free products) and study the welfare implications of technological progress in targeted advertising. We show how partial contractibility of usage generates an endogenous separation between "users" and "employees" of digital platforms.
Linear Quadratic Phasor Control of Unbalanced Distribution Networks

This paper investigates the feedback control challenge of tracking a voltage phasor target at a given node on an unbalanced three phase distribution network. We derive a quasi-steady state system model, modeling the progression of phasors as a martingale and describing the input sensitivity with the linearization of the unbalanced three phase power flow manifold for the Thevenin equivalent circuit. We establish the convexity of the stable linear feedback matrix region, and investigate the stability of Single Input Single Output Phasor Control (SISOPC) with gains chosen based on the reactance of the Thevenin equivalent circuit. To improve upon SISOPC, we propose the Linear Quadratic Phasor Controller (LQPC), which generates a multiple input multiple output linear feedback matrix which takes into account both the network resistance and the mutual impedances that couple the unbalanced three phase injections. We demonstrate the performance of the LQPC using OpenDSS simulations on an unbalanced three phase distribution network, demonstrating the effectiveness of the LQPC.
CTS teams: a new model for translational team training and team science intervention.

Introduction Clinical/translational science (CTS) is team-based, requiring effective collaboration and communication across many disciplines involving a variety of stakeholders. We implemented a pre-doctoral team-based training model with didactic and experiential curricular interventions to support the development of CTS research skills in a cross-disciplinary team environment. We assessed the potential impact of this new training model as a team science intervention that can catalyze new cross-disciplinary collaborations across the institution. Methods Between 2016 and 2020, 32 pre-doctoral students and 26 co-mentors participated in the assessment of the CTS Team program over a two-year period of TL1 training grant support. Data collection and analyses followed a program logic model and used a variety of metrics for clinical and translational scientist career success. Results CTS training in the context of CTS Teams supported improved self-efficacy for clinical research skills and resulted in a significant increase in the frequency of participation in cross-disciplinary collaborative activities by both trainees and mentors. Most CTS Team co-mentor pairs had not previously collaborated. Two-thirds of the co-mentors plan to continue collaborating, and most (85%) currently use or plan to use collaboration tools, for example, written collaboration plans, authorship agreements. Conclusions The CTS Team training model provides a unique clinical and translational science team training experience that embeds authentic cross-disciplinary research collaboration into PhD research projects. It establishes trainee cohorts that are diverse in terms of scientific disciplines and translational research phases, and creates a new cross-disciplinary community of practice across faculty members and research groups in multiple colleges.
Current Treatment Options in Patients with Hepatitis C Virus Genotype 6

Approximately 3% of the world's population is chronically infected with hepatitis C virus (HCV). In some southeast Asian countries the prevalence of HCV (∼6%-7%) far exceeds that seen in the United States (1.8%). The lesser known HCV genotype 6 (HCV-6) is also common in patients from southeast Asia and the surrounding regions. Most data on direct-acting antivirals (DAAs) to date have been derived from clinical trials conducted in Western countries, where HCV-6 is rare. The standard of care for patients with HCV-6 is still pegylated interferon and ribavirin. However, data are emerging for several DAA combinations.
Studies on the turnover of plasma membranes in cultured mammalian cells. II. Demonstration of heterogeneous rates of turnover for plasma membrane proteins and glycoproteins.

Abstract The relative rate of turnover of individual membrane proteins and glycoproteins in exponentially growing and contact-inhibited MK2 cells was investigated. Plasma membranes were isolated from cells that had been sequentially labelled with 14C and 3H isotopes of leucine and glucosamine. The membranes were then solubilized in sodium dodecylsulfate and their polypeptides separated by acrylamide gel electrophoresis. The 3H/14C ratios of the individual polypeptides reflected their relative rates of turnover. The proteins and glycoproteins of the exponentially growing cells exhibited markedly heterogeneous rates of turnover. In contrast, polypeptides in membranes of contact-inhibited cells exhibited a lesser degree of heterogeneity of turnover. In both exponential and contacted cell membranes a glycoprotein with a high apparent molecular weight exhibited the fastest rate of turnover.
Alternative Splicing in the Human Genome and its Evolutionary Consequences

Alternative splicing, or the ability of genes to produce multiple messenger ribonucleic acid (mRNA) and protein isoforms by using different combinations of a gene's segments (exons), has recently been regarded as a mechanism that can explain how functional diversity in higher organisms can be achieved from a small number of genes, and thus can ultimately contribute to the increase in organism complexity during evolution. Keywords: alternative splicing; evolution; exons; introns; nonsense-mediated decay