cssi/SciSciGPT-SciSciNet huggingface dataset:
NEPTUNE: an automatic test pattern generator for finite state machines

The authors present a novel test algorithm for one-hot encoded finite-state machines (FSMs) that are strongly connected, fully specified, and nonredundant. The algorithm generates test vectors in the HILO format. Fault simulation results are presented which show 100% fault coverages. The test vectors are generated by first identifying and then sensitizing a minimal set of paths containing all the edges in the state transition diagram. The state-to-state sequencing information presented in the state transition table is utilized to identify these paths and generate the test vectors. This work builds on previous work (R.Z. Makki, J. Muha, S. Bou-Ghazale, T. Kaylani, 1990) that was restricted to a class of FSMs designed under a controlled environment. The restriction is removed here so as to target a larger class of FSMs. >
"We Will Never Go Back to the Old Way Again": Germany in the African-American Debate on Civil Rights

This special edition of Central European History is concerned with how America viewed Germany, and my contribution focuses on how, beginning with Hitler's rise to power, Germany became a point of reference for the emerging American civil-rights movement. By looking at Crisis, published by the National Association for the Advancement of Colored People (NAACP), and Opportunity, published by the National Urban League, as well as African-American newspapers, such as the Pittsburgh Courier, Chicago Defender, Amsterdam News, Afro-American, Negro Digest, Ebony, and Jet, I will show how the black community discussed developments in Germany, America's struggle against Nazi racism, and the black soldiers' experience in postwar Germany.
Internalizing and externalizing behaviors predict elevated inflammatory markers in childhood.

Summary Background Children with behavior problems, such as internalizing or externalizing disorders, are at increased risk for poorer physical health in adulthood. Inflammation has been posited as a potential biological mediator underlying this association. However, it is unclear how early in development associations between behavior problems and inflammation may be detected, and whether associations are present for both internalizing and externalizing behaviors in pre-pubertal children. Methods Using data from children in the Avon Longitudinal Study of Parents and Children, we examined associations between behavior problems at age 8 (assessed via the parent-report Strengths and Difficulties Questionnaire) and inflammatory markers assessed at age 10. Inflammatory markers included C-reactive protein (CRP; n = 4069) and interleukin-6 (IL-6; n = 4061). We further evaluated whether body mass index (BMI) mediated associations, and tested for potential reverse causality by considering whether age 10 inflammation was associated with changes from initial levels to age 12 behavior problems. Results After adjusting for relevant covariates, age 8 externalizing behaviors were associated with elevated CRP at age 10, and age 8 internalizing and externalizing behaviors were associated with elevated IL-6 at age 10 (p's Conclusions These findings document an association between behavior problems and elevated concentrations of CRP and IL-6 at 10 years. Heightened inflammation in childhood may be a pathway through which early behavior problems increase risk for adult chronic diseases.
Summer food habits and trophic overlap of roundtail chub and creek chub in Muddy Creek, Wyoming

Abstract Native fishes of the Upper Colorado River Basin have experienced substantial declines in abundance and distribution, and are extirpated from most of Wyoming. Muddy Creek, in south-central Wyoming (Little Snake River watershed), contains sympatric populations of native roundtail chub (Gila robusta), bluehead sucker, (Catostomus discobolus), and flannelmouth sucker (C. latipinnis), and represents an area of high conservation concern because it is the only area known to have sympatric populations of all 3 species in Wyoming. However, introduced creek chub (Semotilus atromaculatus) are abundant and might have a negative influence on native fishes. We assessed summer food habits of roundtail chub and creek chub to provide information on the ecology of each species and obtain insight on potential trophic overlap. Roundtail chub and creek chub seemed to be opportunistic generalists that consumed a diverse array of food items. Stomach contents of both species were dominated by plant material, aquatic and...
Förster resonance energy transfer-based imaging at the cell surface of live cells.

Understanding the molecular mechanisms of protein–protein interactions at the cell surface of living cells is fundamental to identifying the nature of cellular processes. Here, we discuss how fluorescence-based approaches have been successfully developed to visualize protein–protein interactions in living cells. Forster resonance energy transfer (FRET) is unique in generating fluorescence signals between proteins that are highly spatially sensitive. Furthermore, total internal reflectance fluorescence (TIRF) microscopy combined with FRET is a robust technique used to assay protein/protein interactions and the functionality of proteins assembled at the cell surface membrane.
Other Optic Nerve Maladies in Cancer Patients

Many optic neuropathies in cancer patients are related to the direct effect of cancer on the optic nerve (e.g., orbital and parasellar skull base compressive lesions or infiltration of the optic nerve with leptomeningeal disease). However, a number of optic neuropathies occur unrelated to those mechanisms. Other mechanisms of optic neuropathy in cancer patients include those caused by raised intracranial pressure (ICP), nutritional deficiencies, drugs, and radiation injury. Optic neuropathy related to elevated ICP does not initially affect vision; therefore, early recognition of the underlying problem is important for visual preservation. In patients with nutritional or drug-related optic neuropathy, symptoms and signs usually present simultaneously and bilaterally with visual loss that is progressive and painless; color vision is affected early on, but pupil examination may remain normal. The nutritional deficiencies may present slowly and symmetrically, and potential deficiencies include vitamins B12, folate, and thiamine B1. Radiation-related optic neuropathy often manifests within about 18 months after radiotherapy and usually after cumulative radiation doses greater than 50 Gy or single doses greater than 10 Gy. Patients often do not have optic disc swelling, and they develop progressive visual loss over weeks to months, with bilateral sequential loss being more common; the end result is vision of 20/200 or worse. Rarely, paraneoplastic syndrome can result in an optic neuropathy.
TRATAMENTO DA HEPATITE C CRÔNICA

Chronic C hepatitis is a worldwide problem, affecting 2% of human population. In this scenario, treating the disease is essential, because it will limit or prevent the development of complications. The approval of new agents that inhibit viral replication has dramatically increased the viral clearance rate, with less adverse events. The availability of these safe curative regimens for hepatitis C virus holds promise for rapid adoption into clinical practice. It is certain that the interferon-free regimens will dominate the therapeutic horizon of chronic hepatitis C in the coming years.
Major bibliographic errors in PubMed: personal experience among 240 publications and proposed remediation process for errors.

Although substantial data exist on errors in bibliographic citations in journal articles [1], literature review reveals no data on errors in bibliographic citations in PubMed. Yet bibliographic errors in PubMed are much more important than errors in individual journals. PubMed is a ubiquitous literature search engine. Errors in PubMed could render articles inaccessible to researchers or clinicians performing computerized literature searches.
A hidden Markov model approach to analyze longitudinal ternary outcomes when some observed states are possibly misclassified

Understanding the dynamic disease process is vital in early detection, diagnosis, and measuring progression. Continuous-time Markov chain (CTMC) methods have been used to estimate state-change intensities but challenges arise when stages are potentially misclassified. We present an analytical likelihood approach where the hidden state is modeled as a three-state CTMC model allowing for some observed states to be possibly misclassified. Covariate effects of the hidden process and misclassification probabilities of the hidden state are estimated without information from a 'gold standard' as comparison. Parameter estimates are obtained using a modified expectation-maximization (EM) algorithm, and identifiability of CTMC estimation is addressed. Simulation studies and an application studying Alzheimer's disease caregiver stress-levels are presented. The method was highly sensitive to detecting true misclassification and did not falsely identify error in the absence of misclassification. In conclusion, we have developed a robust longitudinal method for analyzing categorical outcome data when classification of disease severity stage is uncertain and the purpose is to study the process' transition behavior without a gold standard.
Abstract TP253: Adjuvant Treatment with N-acetyl-seryl-aspartyl-lysyl-proline Extends the Therapeutic Window of Tissue Plasminogen Activator in a Rat Model of Embolic Stroke

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a peptide normally found in human plasma, which has been shown to exert anti-inflammatory and pro-angiogenic activities in the experimental cardiovascular diseases. The present study evaluated the neuroprotective effect of AcSDKP alone and in combination with delayed thrombolytic therapy on focal cerebral ischemia. Rats subjected to embolic middle cerebral artery occlusion were treated with: 1) AcSDKP (2.4mg/kg for 3 days) starting at 1 (n=6), or 4h (n=5) after stroke; 2) combination treatment of tissue plasminogen activator (tPA, 10mg/kg) and AcSDKP (n=12) starting at 4h after stroke; 3) tPA at 4 h after stroke (n=10); 4) saline (n=10). Plasma and cerebrospinal fluid (CSF) samples were taken 24h post stroke to assess the AcSDKP activity by EIA assay. Infarct volume and the incidence of hemorrhage were measured at 7 days after stroke. Monotherapy with AcSDKP starting 1h after stroke onset significantly (p 2 ) compared with monotherapy of tPA (54±5/mm 2 ) or saline (47±4/mm 2 ), and completely blocked tPA-induced increase in the density of nuclear transcription factor-κB (NF-κB) positive vessels (9±1/mm 2 vs 13±2/mm 2 in tPA monotherapy group). Treatment with AcSDKP significantly increased AcSDKP levels in plasma (9±3nM vs 3±1nM in control) and CSF (6±2nM vs 3±1nM in control). Our data indicate that: 1) AcSDKP passes the BBB and reduces ischemic cell damage, 2) Combination treatment with AcSDKP and tPA extends the therapeutic window for thrombolysis, and 3) NF-κB and TGFβ signaling are likely involved in the neuroprotective effect of AcSDKP.
TRAPP Complexes in Secretion and Autophagy

TRAPP is a highly conserved modular multi-subunit protein complex. Originally identified as a “transport protein particle” with a role in endoplasmic reticulum-to-Golgi transport, its multiple subunits and their conservation from yeast to humans were characterized in the late 1990s. TRAPP attracted attention when it was shown to act as a Ypt/Rab GTPase nucleotide exchanger, GEF, in the 2000s. Currently, three TRAPP complexes are known in yeast, I, II, and III, and they regulate two different intracellular trafficking pathways: secretion and autophagy. Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1. Another small subunit, Trs20/Sedlin, is an adaptor required for the association of core TRAPP with larger subunits to form TRAPP II and TRAPP III. Whereas the molecular structure of the core TRAPP complex is resolved, the architecture of the larger TRAPP complexes, including their existence as dimers and multimers, is less clear. In addition to its Ypt/Rab GEF activity, and thereby an indirect role in vesicle tethering through Ypt/Rabs, a direct role for TRAPP as a vesicle tether has been suggested. This idea is based on TRAPP interactions with vesicle coat components. While much of the basic information about TRAPP complexes comes from yeast, mutations in TRAPP subunits were connected to human disease. In this review we will summarize new information about TRAPP complexes, highlight new insights about their function and discuss current controversies and future perspectives.
Prostate-specific Antigen Mass Density--A Measure Predicting Prostate Cancer Volume and Accounting for Overweight and Obesity-related Prostate-specific Antigen Hemodilution.

Objective To test prostate-specific antigen mass density (PSAMD) as a predictor of total tumor volume (TTV) at radical prostatectomy (RP). Methods We conducted a detailed pathologic analysis of 469 RP from men with NCCN low-risk prostate cancer who had Gleason score of 3 + 3 = 6 (grade group 1) at RP. We then compared the ability of PSA, PSA density (PSAD), PSA mass (PSAM-absolute amount of PSA in patient's circulation), and PSAM density (PSAM divided by prostate weight without seminal vesicles) to predict TTV at RP. PSAM was calculated by multiplying plasma volume (estimated body surface [weight, kg 0.425 × height, m 0.72 × 0.007184] × 1.67) by PSA. Performance of the above measures in different BMI categories was assessed. Kruskal-Wallis test was used to compare the means and Spearman's rank correlation coefficient to assess the correlations. Results The 469 men were normal weight (n = 129), overweight (n = 253), and obese (n = 87). Mean age of the patients' was 57.4 years and PSA of 4.53 ng/ml. Increase of prostate weight with body mass index (BMI) was reflected in PSAM (both P r = 0.336; P r = −0.394; Conclusion PSAMD is the biochemical measure with the best correlation with TTV at RP. Unlike other measures, it is not affected by BMI-related hemodilution. Thresholds should be established to use this more objective measure clinically in surveillance algorithms and in planning radical prostatectomy.
Immunoaffinity column coupled with liquid chromatography for determination of fumonisin B1 in canned and frozen sweet corn.

A modified liquid chromatographic (LC) method for determining fumonisin B 1 (Fa 1 ) in corn was applied to canned and frozen sweet corn. The corn is extracted with methanol-water (8 + 2), and the extract is filtered. The filtrate is diluted with water and passed through an immunoaffinity column. After the column is washed with water, FB 1 is eluted with methanol-water (8 + 2). The eluate is evaporated to dryness by using a vacuum concentrator, and the residue is dissolved in acetonitrile-water (1 + 1). FB 1 is derivatized with o-phthaldialdehyde. The derivative is separated on a reversed-phase C 18 LC column using acetonitrile-water-acetic acid (50 + 50 + 1) and quantitated with a fluorescence detector. Recoveries of FB 1 from canned and frozen corn spiked over the range of 50-200 ng/g were 76-88%. The limit of determination was about 25 ng/g, and the limit of detection was about 4 ng/g. The method was applied to 97 commercial canned and frozen sweet corn samples collected from different areas of the United States. Sixty samples contained no FB 1. Low levels (trace-82 ng FB 1 /g corn) were found in 35 samples ; 235 ng FB 1 /g was found in 1 canned corn sample, and 350 ng FB 1 /g was found in 1 frozen corn sample.
The Dynamic Relation between Earnings Management and the Violation of Debt Covenants

This study presents evidence consistent with managers using accounting procedures and discretionary accruals as partial substitutes for low-cost violations. Using a sample of 143 firms reporting violations in annual reports, I estimate sets of simultaneous equations that capturers managers' incentives to violate debt covenants rather than to manipulate earnings. These incentives include the probabilities of waiver, temporary waiver, and renegotiation of debt covenant violations. The results indicate a significant negative association between probabilities of waivers and earnings management from one side, and a significant positive association between earnings management and both the anticipation of temporary waiver and contract renegotiaiton from the other side. Thus, it seems that managers' decision to manipulate earnings or to violate covenants vary considerably across firms depending, in part, on the probability of waiver, its type, and the probability of renegotiation. The findings question the ability of the covenant-based hypothesis in providing explanations for managers accounting choices. In addition, the study has crucial implications on earnings management research and users of financial reports concerned with the quality of earnings.
Joplin relief: nifty asssignment

The Joplin Relief assignment is used to demonstrate input/output, constant values, and simple numerical computation.
Gas-phase complexes formed between amidoxime ligands and vanadium or iron investigated using electrospray ionization mass spectrometry.

Rationale Amidoxime-functionalized sorbents can be used to extract uranium from seawater. Iron(III) and vanadium(V) may compete with uranium for adsorption sites. We use 2,6-dihydroxyiminopiperidine (DHIP) and N(1) ,N(5) -dihydroxypentanediimidamide (DHPD) to model amidoxime functional groups and characterize the vanadium(V) and iron(III) complexes with these ligands. We also examine the effect of iron(III) and vanadium(V) on uranyl(VI) complexation by DHIP and DHPD. Methods The experiments were carried out in positive ion mode using a quadrupole ion trap mass spectrometer equipped with an electrospray ionization source. The effect on the mass spectra of changes in ligand, metal:ligand mole ratio, and pH was examined. Results Iron(III) formed a 1:2 metal:ligand complex with DHIP at all metal:ligand mole ratios and pH values investigated; it formed both 1:2 and 1:3 metal:ligand complexes with DHPD. Vanadium(V) formed 1:1 and 1:2 metal:ligand complexes with DHIP. A 1:2 metal:ligand complex was formed with DHPD at all vanadium(V):DHPD mole ratios investigated. Changes in solution pH did not affect the ions observed. The relative binding affinities of the metal ions towards DHIP followed the order iron(III) > vanadium(V) > uranyl(VI). Conclusions This study presents a first look at the gas-phase vanadium(V)- and iron(III)-DHIP and -DHPD complexes using electrospray ionization mass spectrometry. These metals form stronger complexes with amidoxime ligands than uranyl(VI), and will affect uranyl(VI) adsorption to amidoxime-based sorbents. Copyright © 2016 John Wiley & Sons, Ltd.
Maratha insurgency and Mughal conquest in the Deccan

In the hilly areas of the western Deccan, around Puna, the Maratha leader Shivaji Bhonsla was carving out a self-sufficient state within the enfeebled shell of the Sultanate of Bijapur. The Bhonsla regime offered a new option for ambitious and aggressive men from both the Maratha warrior caste and literate Maratha Brahmin castes. Shivaji's successes shaped a new mode of aggressive political and military action against the Indo-Muslim powers. His insurgent state gained resources and confidence as it challenged imperial might. By the early 1660s the Maratha had adopted a new style of wide-ranging predatory raiding into Mughal and Bijapur lands. With the fall of the two Deccan Sultanates, Aurangzeb then turned his attention to the Marathas. Aurangzeb sent Muqarrab Khan immediately to capture both Shambhaji and his Brahmin chief minister who were hacked to death. Four new provinces were added to Mughal empire: Bijapur and the Bijapur Karnatak, and Hyderabad and the Hyderabad Karnatak.
“The End is Near!”: The Phenomenon of the Declaration of Closure in a Discipline:

L'auteur discute de la notion de fin d'une discipline, et plus precisement de la fin de la science, quand toutes les explications ont ete donnees et quand il ne reste rien a accomplir ... C'est ici une approche philosophique, sociologique et ethnologique de la science qui est donnee.
The world distribution of military spending: is there a convergence?

This paper examines the issue of convergence in military spending among NATO countries. In particular, the paper employs the sequential panel selection method (SPSM) to ascertain whether the military spending of NATO countries has converged relative to that of the USA. The results from the SPSM for both the full- and sub-periods indicate that military spending of NATO countries, with the exception of Hungary, have converged to that of the USA. The results show that the number of NATO countries whose military spending converged relative to that of the USA did not change following the collapse of the Soviet Union. The overall finding of this study contradicts the alliance theory which stipulates that alliances tend to weaken or dissolve following the elimination of the unifying threat.
"Treat Me Like a Normal Person!" A Meta-Ethnography of Adolescents' Expectations of Their Health Care Providers.

Abstract Purpose Preventive health care services provide an important opportunity to assist adolescents to establish and maintain a healthy lifestyle and assume an increasing independent role in their health care. National guidelines emphasize the importance of an annual wellness visit to identify and address risk-behaviors that contribute significantly to the morbidity and mortality in this population. Despite these recommendations, adolescents utilize preventive health care at declining rates throughout adolescence. The purpose of this study was to capture a more holistic view of what adolescents, as consumers of health care services, expect from their primary health care providers (HCPs). Method A metasynthesis of 12 qualitative research studies was conducted using Noblit and Hare's (1988) meta-ethnographic approach. Results Five overarching metaphors, Talk with Me- Not at Me, Accept Me, Respect My Privacy and Confidentiality, Show Me You Are a Professional, and A Trusted Relationship described adolescents' expectations of their HCPs. Conclusions This study provides a more holistic view of adolescents' expectations of their HCPs. Clinical strategies are suggested to assist HCPs to meet adolescents' expectations.
Hybrid schemes for exact conditional inference in discrete exponential families

Exact conditional goodness-of-fit tests for discrete exponential family models can be conducted via Monte Carlo estimation of p values by sampling from the conditional distribution of multiway contingency tables. The two most popular methods for such sampling are Markov chain Monte Carlo (MCMC) and sequential importance sampling (SIS). In this work we consider various ways to hybridize the two schemes and propose one standout strategy as a good general purpose method for conducting inference. The proposed method runs many parallel chains initialized at SIS samples across the fiber. When a Markov basis is unavailable, the proposed scheme uses a lattice basis with intermittent SIS proposals to guarantee irreducibility and asymptotic unbiasedness. The scheme alleviates many of the challenges faced by the MCMC and SIS schemes individually while largely retaining their strengths. It also provides diagnostics that guide and lend credibility to the procedure. Simulations demonstrate the viability of the approach.
Rare sporophyte found in Europe for Herbertus sendtneri with a range expansion to Africa and Malesia

The sporophytes of the genus Herbertus are rare or completely absent in some areas. The first discovery of the sporophyte of Herbertus in Europe, on H. sendtneri from a herbarium specimen collected in Austria in 1851, is reported here. We report that finely papillose spores characterize Herbertus species which have originated in the Northern Hemisphere, whereas the spores of the species which have originated in the Southern Hemisphere are tuberculate or shortly spinulose. Based on morphological studies of over 600 herbarium specimens of Herbertus , supported by previously published molecular phylogenetic studies, H. armitanus and H. circinatus are new synonyms of H. sendtneri . It is distinct from other Northern Hemisphere species by its coarsely toothed leaf base, despite large variation in leaf size and shape, and leaf apex cilia. The range of H. sendtneri is now extended to east Africa (Tanzania) and Malesia (Papua New Guinea and the Solomon Islands).
Endothelial-dependent dilation following chronic hypoxia involves TRPV4-mediated activation of endothelial BK channels

Following chronic hypoxia (CH), the systemic vasculature exhibits blunted vasoconstriction due to endothelial-dependent hyperpolarization (EDH). Previous data demonstrate that subsequent to CH, EDH-mediated vasodilation switches from a reliance on SKca and IKca channels to activation of the endothelial BKca channels (eBK). The mechanism by which endothelial cell stimulation activates eBK channels following CH is not known. We hypothesized that following CH, EDH-dependent vasodilation involves a TRPV4-dependent activation of eBK channels. ACh induced concentration-dependent dilation in pressurized gracilis arteries from both normoxic and CH rats. Inhibition of TRPV4 (RN-1734) attenuated the ACh response in arteries from CH rats but had no effect in normoxic animals. In the presence of L-NNA and indomethacin, TRPV4 blockade attenuated ACh-induced vasodilation in arteries from CH rats. ACh elicited endothelial TRPV4-mediated Ca2+ events in arteries from both groups. GSK1016790A (GSK101, TRPV4 agonist) elicited vasodilation in arteries from normoxic and CH rats. In arteries from normoxic animals, TRAM-34/apamin abolished the dilation to TRPV4 activation, whereas luminal iberiotoxin had no effect. In CH rats, only administration of all three Kca channel inhibitors abolished the dilation to TRPV4 activation. Using Duolink®, we observed co-localization between Cav-1, TRPV4, and BK channels in gracilis arteries and in RAECs. Disruption of endothelial caveolae with methyl-β-cyclodextrin significantly decreased ACh-induced vasodilation in arteries from both groups. In gracilis arteries, endothelial membrane cholesterol was significantly decreased following 48 h of CH. In conclusion, CH results in a functional coupling between muscarinic receptors, TRPV4 and Kca channels in gracilis arteries.
Chromesthetic Responses to the Music of G. F. Handel

This vivid account describes one of the most unusual forms of mental imagery, synesthesia. It is defined as “production, from a sense-impression of one kind, of an associated mental image of a sense-impression of another kind” (Synaesthesia, 1970, P. 373). Synesthesia can theoretically occur among any sense modalities. However, it does occur more frequently between some modalities than others. In this paper, we are concerned with chromesthesia or colored hearing, a particular form of synesthesia in which color images (photisms) are evoked by auditory stimuli.
Exploring Visualization Methods for Complex Variables

Applications of complex variables and related manifolds appear throughout mathematics and science. Here we review a family of basic methods for applying visualization concepts to the study of complex variables and the properties of specific complex manifolds. We begin with an outline of the methods we can employ to directly visualize poles and branch cuts as complex functions of one complex variable. $CP^2$ polynomial methods and their higher analogs can then be exploited to produce visualizations of Calabi-Yau spaces such as those modeling the hypothesized hidden dimensions of string theory. Finally, we show how the study of N-boson scattering in dual model/string theory leads to novel cross-ratio-space methods for the treatment of analysis in two or more complex variables.
TCT-831 Differences in Short-Term Outcomes and Cost between Alcohol Septal Ablation and Septal Myectomy for Hypertrophic Cardiomyopathy in the United States

Choice of septal reduction procedure with either alcohol septal ablation (ASA) or septal myectomy (SM) for hypertrophic cardiomyopathy (HCM) is largely guided by patient age, anatomy, and comorbidity status. Given clinical equipoise in a subset of patients who are candidates for both procedures,
Transcriptomic responses to extreme low salinity among locally adapted populations of Olympia oyster (Ostrea lurida).

The Olympia oyster (Ostrea lurida) is a foundation species inhabiting estuaries along the North American west coast. In California estuaries, O. lurida is adapted to local salinity regimes and populations differ in low salinity tolerance. In this study, oysters from three California populations were reared for two generations in a laboratory common garden and subsequently exposed to low salinity seawater. Comparative transcriptomics was then used to understand species-level responses to hyposmotic stress and population-level mechanisms underlying divergent salinity tolerances. Gene expression patterns indicate Olympia oysters are sensitive to hyposmotic stress: All populations respond to low salinity by up-regulating transcripts indicative of protein unfolding, DNA damage and cell cycle arrest after sub-lethal exposure. Among O. lurida populations, transcriptomic profiles differed constitutively and in response to low salinity. Despite two generations in common-garden conditions, transcripts encoding apoptosis modulators were constitutively expressed at significantly different levels in the most tolerant population. Expression of cell death regulators may facilitate cell fate decisions when salinity declines. Following low salinity exposure, oysters from the more tolerant population expressed a small number of mRNAs at significantly higher levels than less tolerant populations. Proteins encoded by these transcripts regulate ciliary activity within the mantle cavity and may function to prolong valve closure and reduce mortality in low salinity seawater. Collectively, gene expression patterns suggest sub-lethal impacts of hyposmotic stress in Olympia oysters are considerable and that even oysters with greater low salinity tolerance may be vulnerable to future freshwater flooding events.
Voltage Dependence of Dissipation Factor Measurements on High Voltage Instrument Transformers

Dissipation Factor is defined as a routine test in virtually every ANSI/IEEE standard applicable to oil filled High Voltage Instrument Transformers (C57.13, C57.13.5, etc.). These standards, recommend performing Dissipation Factor tests at rated voltage and 10 kV rms, both values at rated frequency. There is a clause which states the 10 kV is optional as the values are useful as a reference for commissioning. For years, the industry has performed the Dissipation Factor at the 10 kV value. This is not a problem when performing the tests at the factory as the test set is a permanent fixture in the test laboratory. Performing the test onsite is a different story. Performing Dissipation Factor tests onsite required bringing the test set, normally a 10 kV power supply and measurement set, to the site and running power to operate the system. Recently various manufactures of high voltage testing equipment have introduced new portable Dissipation Factor test sets which operate at 2.5 kV rms. Most of these sets are battery powered which make them ideal to use for onsite commissioning tests as well as routine yearly evaluation tests. The question which arises from performing Dissipation Factor at 2.5 kV verses 10 kV is, what are the differences in Dissipation Factor values at the different voltage levels? The standards require a maximum Dissipation Factor of 0.5%. To test this, a variety of High Voltage Instrument Transformers from different manufactures were tested at both 10 kV and 2.5 kV. The style of transformers tested included line to line and line to ground voltage transformers, current transformers and station service voltage transformers. Dissipation Factor tests were performed on each transformer using the same 10 kV and 2.5 kV Dissipation Factor test set. This paper presents the procedures and results to provide a comprehensive look at the differences and similarities of performing Dissipation Factor tests on a wide variety of high Voltage Instrument Transformers at both 10 kV and 2.5 kV.
Design and Synthesis of a Novel Pyrrolidinyl Pyrido Pyrimidinone Derivative as a Potent Inhibitor of PI3Kα and mTOR.

Lead optimization efforts that employed structure-based drug design and physicochemical property based refinement lead to the discovery of title compound (XIII) which exhibits potent activity against PI3Kα and mTOR, good kinase selectivity, and robust ADMET properties as well as good oral bioavailability.
Libertarian Paternalism and the Park, Recreation, and Tourism Profession

In this paper we apply the concept of “libertarian paternalism” to the park, recreation, and tourism profession. Libertarian paternalism is a term coined in Nudge: Improving Decisions About Health, Wealth, and Happiness by Thaler and Sunstein (2009). Nudges influence people’s choices without compromising or restricting their ability to choose, and therefore may be particularly appropriate in parks, recreation, and tourism. Nudges are proven ways for leaders, programmers, directors, administrators, planners, and policymakers to encourage recreational conduct that is good for recreationists, and that recreationists would likely choose for themselves if only they were privy to all the information about the consequences of their conduct. We begin by briefly discussing “self-paternalism,” a precursor to libertarian paternalism espoused by Sax (1980) in Mountains without Handrails . Then, after explaining what Thaler and Sunstein mean by libertarian paternalism, we describe park, recreation, and tourism professionals as “choice architects” who are responsible for managing the contexts within which recreational choices are made. Choice architects orchestrate nudges by taking advantage of what is known about human psychology, and, in particular, what is known about human psychological predispositions to behave in certain ways. We offer four examples of how choice architects currently influence human behavior, and then challenge readers to think of their own ways to nudge their constituencies in a manner that contributes to human and environmental health. Finally, we advocate for libertarian paternalism, choice architecture, and nudging as an appropriate orientation to service for the park, recreation, and tourism profession. Subscribe to JPRA
Measurements on scaled models of thrust pads: The theoretical pressures and loads on a thrust pad can be confirmed by means of measurements on scaled models

Reasons for use of scaled models in lubrication are put forward. It is shown how such models of thrust pads having a stepped surface can be used and how pressures, thrust and friction can be measured. In the family of pads chosen for experimentation, the lateral steps make an angle of cot−12 with the free-stream direction, and the position of step which is at right angles to the oil flow and which joins the lateral steps is assumed to be at both optimum and non-optimum conditions with respect to the thrust/friction ratio. The mean experimental results for thrust load lie within +10 percent of the theory when obtained from pressure distribution and within +20 percent when obtained from direct-force measurements. For friction, the appropriate departures when obtained from pressure and direct-force measurements are ±2 percent and +8 percent.
A Cholecystokinin Receptor Antagonist Halts Nonalcoholic Steatohepatitis and Prevents Hepatocellular Carcinoma.

Nonalcoholic steatohepatitis (NASH) is a common inflammatory liver condition that may lead to cirrhosis and hepatocellular carcinoma (HCC). Risk factors for NASH include a saturated fat diet, altered lipid metabolism, and genetic and epigenetic factors, including microRNAs. Serum levels of cholecystokinin (CCK) are elevated in mice and humans that consume a high-saturated fat diet. CCK receptors (CCK-Rs) have been reported on fibroblasts which when activated can induce fibrosis; however, their role in hepatic fibrosis remains unknown. We hypothesized that elevated levels of CCK acting on the CCK-Rs play a role in the development of NASH and in NASH-associated HCC. We performed a NASH Prevention study and Reversal study in mice fed a saturated fat 75% choline-deficient–ethionine-supplemented (CDE) diet for 12 or 18 weeks. In each study, half of the mice received untreated drinking water, while the other half received water supplemented with the CCK-R antagonist proglumide. CCK-R expression was evaluated in mouse liver and murine HCC cells. CCK receptor antagonist treatment not only prevented NASH but also reversed hepatic inflammation, fibrosis, and steatosis and normalized hepatic transaminases after NASH was established. Thirty-five percent of the mice on the CDE diet developed HCC compared with none in the proglumide-treated group. We found that CCK-BR expression was markedly upregulated in mouse CDE liver and HCC cells compared with normal hepatic parenchymal cells, and this expression was epigenetically regulated by microRNA-148a. These results support the novel role of CCK receptors in the pathogenesis of NASH and HCC.
OpiA, a Type Six Secretion System Substrate, Localizes to the Cell Pole and Plays a Role in Bacterial Growth and Viability in Francisella tularensis LVS

ABSTRACT Francisella tularensis is an intracellular pathogen and the causative agent of tularemia. The F. tularensis type six secretion system (T6SS) is required for a number of host-pathogen interactions, including phagolysosomal escape and invasion of erythrocytes. One known effector of the T6SS, OpiA, has recently been shown to be a phosphatidylinositol-3 kinase. To investigate the role of OpiA in erythrocyte invasion, we constructed an opiA-null mutant in the live vaccine strain, F. tularensis LVS. OpiA was not required for erythrocyte invasion; however, deletion of opiA affected growth of F. tularensis LVS in broth cultures in a medium-dependent manner. We also found that opiA influenced cell size, gentamicin sensitivity, bacterial viability, and the lipid content of F. tularensis. A fluorescently tagged OpiA (OpiA–emerald-green fluorescent protein [EmGFP]) accumulated at the cell poles of F. tularensis, which is consistent with the location of the T6SS. However, OpiA-EmGFP also exhibited a highly dynamic localization, and this fusion protein was detected in erythrocytes and THP-1 cells in vitro, further supporting that OpiA is secreted. Similar to previous reports with F. novicida, our data demonstrated that opiA had a minimal effect on intracellular replication of F. tularensis in host immune cells in vitro. However, THP-1 cells infected with the opiA mutant produced modestly (but significantly) higher levels of the proinflammatory cytokine tumor necrosis factor alpha compared to these host cells infected with wild-type bacteria. We conclude that, in addition to its role in host-pathogen interactions, our results reveal that the function of opiA is central to the biology of F. tularensis bacteria. IMPORTANCEF. tularensis is a pathogenic intracellular pathogen that is of importance for public health and strategic defense. This study characterizes the opiA gene of F. tularensis LVS, an attenuated strain that has been used as a live vaccine but that also shares significant genetic similarity to related Francisella strains that cause human disease. The data presented here provide the first evidence of a T6SS effector protein that affects the physiology of F. tularensis, namely, the growth, cell size, viability, and aminoglycoside resistance of F. tularensis LVS. This study also adds insight into our understanding of OpiA as a determinant of virulence. Finally, the fluorescence fusion constructs presented here will be useful tools for dissecting the role of OpiA in infection.
Full characterization of ultrathin 5-nm low- k dielectric bilayers: Influence of dopants and surfaces on the mechanical properties

Author(s): Frazer, TD; Knobloch, JL; Hernandez-Charpak, JN; Hoogeboom-Pot, KM; Nardi, D; Yazdi, S; Chao, W; Anderson, EH; Tripp, MK; King, SW; Kapteyn, HC; Murnane, MM; Abad, B | Abstract: Ultrathin films and multilayers, with controlled thickness down to single atomic layers, are critical for advanced technologies ranging from nanoelectronics to spintronics to quantum devices. However, for thicknesses less than 10 nm, surfaces and dopants contribute significantly to the film properties, which can differ dramatically from that of bulk materials. For amorphous films being developed as low dielectric constant interfaces for nanoelectronics, the presence of surfaces or dopants can soften films and degrade their mechanical performance. Here we use coherent short-wavelength light to fully and nondestructively characterize the mechanical properties of individual films as thin as 5 nm within a bilayer. In general, we find that the mechanical properties depend both on the amount of doping and the presence of surfaces. In very thin (5-nm) silicon carbide bilayers with low hydrogen doping, surface effects induce a substantial softening - by almost an order of magnitude - compared with the same doping in thicker (46-nm) bilayers. These findings are important for informed design of ultrathin films for a host of nano- and quantum technologies, and for improving the switching speed and efficiency of next-generation electronics.
Bayesian estimation of cell-type-specific gene expression per bulk sample with prior derived from single-cell data

Abstract When assessed over a large number of samples, bulk RNA sequencing provides reliable data for gene expression at the tissue level. Single-cell RNA sequencing (scRNA-seq) deepens those analyses by evaluating gene expression at the cellular level. Both data types lend insights into disease etiology. With current technologies, however, scRNA-seq data are known to be noisy. Moreover, constrained by costs, scRNA-seq data are typically generated from a relatively small number of subjects, which limits their utility for some analyses, such as identification of gene expression quantitative trait loci (eQTLs). To address these issues while maintaining the unique advantages of each data type, we develop a Bayesian method (bMIND) to integrate bulk and scRNA-seq data. With a prior derived from scRNA-seq data, we propose to estimate sample-level cell-type-specific (CTS) expression from bulk expression data. The CTS expression enables large-scale sample-level downstream analyses, such as detecting CTS differentially expressed genes (DEGs) and eQTLs. Through simulations, we demonstrate that bMIND improves the accuracy of sample-level CTS expression estimates and power to discover CTS-DEGs when compared to existing methods. To further our understanding of two complex phenotypes, autism spectrum disorder and Alzheimer’s disease, we apply bMIND to gene expression data of relevant brain tissue to identify CTS-DEGs. Our results complement findings for CTS-DEGs obtained from snRNA-seq studies, replicating certain DEGs in specific cell types while nominating other novel genes in those cell types. Finally, we calculate CTS-eQTLs for eleven brain regions by analyzing GTEx V8 data, creating a new resource for biological insights.
Community Context and Family Resilience

Family resilience refers to the ability of families to spring back or recover from a stress or challenge like poverty, unemployment, homelessness, or food insecurity. Humans have lived in communities throughout history because they can address key life sustaining problems like providing food, shelter, and protection better collectively than they can individually. Communities are, in short, human associations for problem solving. This paper argues that many larger social problems manifest themselves in families at the local level and that understanding communities can help promote resilient families.
Measuring Alignments between Galaxies and the Cosmic Web at z ̃ 2-3 Using IGM Tomography

Author(s): Krolewski, A; Lee, KG; Lukic, Z; White, M | Abstract: Many galaxy formation models predict alignments between galaxy spin and the cosmic web (i.e., directions of filaments and sheets), leading to an intrinsic alignment between galaxies that creates a systematic error in weak-lensing measurements. These effects are often predicted to be stronger at high redshifts (z 1) that are inaccessible to massive galaxy surveys on foreseeable instrumentation, but IGM tomography of the Lyα forest from closely spaced quasars and galaxies is starting to measure the z ∼ 2-3 cosmic web with requisite fidelity. Using mock surveys from hydrodynamical simulations, we examine the utility of this technique, in conjunction with coeval galaxy samples, to measure alignment between galaxies and the cosmic web at z ∼ 2.5. We show that IGM tomography surveys with ≲5 h -1 Mpc sightline spacing can accurately recover the eigenvectors of the tidal tensor, which we use to define the directions of the cosmic web. For galaxy spins and shapes, we use a model parameterized by the alignment strength, , with respect to the tidal tensor eigenvectors from the underlying density field, and also consider observational effects such as errors in the galaxy position angle, inclination, and redshift. Measurements using the upcoming ∼1 deg2 CLAMATO tomographic survey and 600 coeval zCOSMOS-Deep galaxies should place 3σ limits on extreme alignment models with , but much larger surveys encompassing g10,000 galaxies, such as Subaru PFS, will be required to constrain models with . These measurements will constrain models of galaxy-cosmic web alignment and test tidal torque theory at z ∼ 2, improving our understanding of the physics of intrinsic alignments.
Charcot-marie-tooth disease and related disorders

Publisher Summary Charcot–Marie–Tooth (CMT) neuropathy (also called Hereditary Motor and Sensory Neuropathy, or HMSN) is a heterogeneous group of inherited diseases of peripheral nerves. Collectively, CMT is a common disorder affecting both children and adults and, in some cases, may lead to significant disability. An estimated 1 in 2500 persons has a form of CMT, establishing it as a major diagnostic category within neurogenetic diseases. Modes of inheritance seen in CMT include autosomal dominant, autosomal recessive, and X-linked forms. The various chromosomal locations, causal genes, and genetic mechanisms underlying forms of CMT and related disorders are described in the chapter. Although both motor and sensory nerves are affected in all forms of CMT, motor function is generally more significantly impaired. The principal clinical features of CMT include distal muscle weakness and atrophy, impaired sensation, and absent or hypoactive deep tendon reflexes. Most often, patients are afflicted with signs and symptoms related to muscle loss and weakness, typically involving the lower legs and feet, then later progressing to affect the hands and distal forearms. Patients may also have complaints related to foot deformity, which results from a loss of intrinsic muscles of the feet. In contrast to muscle weakness related problems, such complaints are usually less common, despite unequivocally impaired sensation on examination. In some patients, a postural tremor affecting the upper limbs is present.