cssi/SciSciGPT-SciSciNet huggingface dataset:
Redistribution of income

P. Nelson Reid, MSW, is Assistant Professor, Department of Social Work, Ohio University, Athens, Ohio. A common observation, derived from De Tocqueville's remarkable vision of the United States and its future, is that the concept of equality is both America's moral and actual founda tion and its potential undoing.1 No concept has so shaped the literature of democracy as has the ideal of equality. Yet, in the sense that most people understand it, no concept of democratic thought has been put into effect so little. The history of America is in good part a history of the strug gle to put this elusive concept into operation, because no ideal has formed the basis of so many enduring social movements.
New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets

Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. The software is provided at https://desairegroup.ku.edu/research.
Abstract 983: Effect of optically active Englerin A on global metabolism of A498 renal cell cancer: Impact on carnitine metabolism

Introduction and Objectives: The Natural Products Branch of the National Cancer Institute examined extracts from a number of plants from South Africa. One extract in particularly, from the Phyllanthus engleri plant exhibited selective toxicity towards renal cancer cells in the NCI panel of 60 cell lines. The active ingredient from the plant extract has been recently isolated and identified as Englerin A (Beutler, J., et al). Renal cancers are notorious for their resistance to various therapies. Therefore, the potential for any agent that has selective anti-tumor activity is attractive. In additions, renal cancers are associated with a variety of metabolic changes, regardless of the tumors VHL status (wild type vs. mutant). Using the synthetic, optically active compound to Englerin A, we have examined its impact on global metabolism in the sensitive human renal carcinoma cell line A498. Methods: Using the synthetic material of Englerin A (Applichem Co., Germany) and A498 renal cancer cell line (ATCC, Baltimore MD), we tested for cytotoxicity and growth inhibition using the CellTiter-Glo ® assay (Promega). Cell Titer-Glo measures the number of viable cells in culture based on quantitation of the ATP present, an indicator of metabolically active cells. Cell cycle was determined with the aid of flow cytometry following propidium iodide staining. Global metabolism was determined by GC and LC/mass SPEC in the A498 cells receiving treatment with Englerin A (30nM and 150nM) at 0, 2, 4, 8 and 24 hour time points (Metabolon, Durham, N.C.). Statistical analysis of the 2,000 standard metabolites (and unknown metabolites) is compared between treated/non-treated cells, at the various time periods, utilizing the commercial package JMP (SAS). Following log transformation and samples in which the metabolite was detected within at least two/thirds of the specimens will be included in the analysis. Results: In the A498 cells, we observed an IC 50 of 3nM, comparable to reported studies for Englerin A. Flow cytometry data revealed a delayed cell cycle progression through S phase. In the metabolic studies, the most sensitive aspect of the Englerin A toxin was the alteration of carnitine metabolism. Conclusion: Englerin A is a newly isolated molecule that has selective toxicity towards renal cancer cell lines, but also inhibits other types of tumor lines and cancers. Renal cell cancers are notorious for their insensitivity to treatment with a variety of therapies. The low dose of Englerin A required producing selective toxicity towards renal cell cancers, suggests that this newly identified toxin is likely to be impacting a novel signaling pathway. Identification of that signaling pathway may provide additional means for targeted tumor therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 983. doi:10.1158/1538-7445.AM2011-983
Epidemiology and detection of acinetobacter using conventional culture and in-house developed PCR based methods

Active surveillance cultures for multidrug-resistant (MDR) gram-negative bacteria is one strategy to control outbreaks. The objectives of the study are to evaluate the prevalence of Acinetobacter colonization and to compare conventional culture and in-house developed PCR based method. Swabs were collected from patients transferred from another organization or were admitted to the intensive care units. Swabs were cultured by conventional method and were tested using in-house LightCycler® 2.0 real-time PCR method. Of 449 tested samples, the majority came from cardiac step down unit (188, 42%), male medical floor (80; 18%), and coronary care unit (66; 13.4%). Of the total specimens, 14 (3%) were positive by PCR and 12 (2.6%) were positive by routine cultures. The positivity rates among wounds, respiratory, perineal, and nasal samples were 3.2%, 9.7%, 4.6% and 0.8% respectively. Two positive samples by PCR were negative by routine culture. The overall concordance rate was 99.5% and the positive concordance rate was 85.7%. The current study revealed a low prevalence of MDR Acinetobacter among the studied population. The LightCycler® 2.0 PCR produced comparable positive results to routine cultures.
Design and implementation of rural information service system based on SSH2 framework

The internet and other modern information technologies were used to provide farmers with efficient and convenient,simple and intuitive,two-way interactive and personalized rural information services.According to user's needs and local characteristics of agriculture,the rural information service system was developed in the Eclipse development environment based on the SSH2 architecture and MySQL database.The system implements the integretion of subsite building,information collection and intelligent push,and safety management,and offers information browsing,query,remote diagnosis,remote education for the farmers.
Contributions of Protease-Activated Receptors PAR1 and PAR4 to Thrombin-Induced GPIIbIIIa Activation in Human Platelets

Human platelets display a unique dual receptor system for responding to its primary endogenous activator, α-thrombin. Because of the lack of efficacious antagonists, the field has relied on synthetic peptides and pepducins to describe protease-activated receptor PAR1 and PAR4 signaling. The precise contributions of each receptor have not been established in the context of thrombin. We took advantage of newly discovered PAR antagonists to contrast the contribution of PAR1 and PAR4 to thrombin-mediated activation of the platelet fibrin receptor (GPIIbIIIa). PAR1 is required for platelet activation at low but not high concentrations of thrombin, and maximal platelet activation at high concentrations of thrombin requires PAR4. As the concentration of thrombin is increased, PAR1 signaling is quickly overcome by PAR4 signaling, leaving a narrow window of low thrombin concentrations that exclusively engage PAR1. PAR4 antagonism reduces the maximum thrombin response by over 50%. Thus, although the PAR1 response still active at higher concentrations of thrombin, this response is superseded by PAR4. Truncation of a known PAR4 antagonist and identification of the minimum pharmacophore converted the mechanism of inhibition from noncompetitive to competitive, such that the antagonist could be outcompeted by increasing doses of the ligand. Fragments retained efficacy against both soluble and tethered ligands with lower cLogP values and an increased free fraction in plasma. These reversible, competitive compounds represent a route toward potentially safer PAR4 antagonists for clinical utility and the development of tools such as radioligands and positron emission tomography tracers that are not currently available to the field for this target.
GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells (APP3P.113)

Central tolerance is critical to prevent autoimmunity, but limits T cell responses to tumor Ag that are self Ag. We have identified that gamma-interferon-inducible lysosomal thiol reductase (GILT) is required for thymic deletion of CD4+ T cells specific for the self and melanoma Ag, tyrosinase-related protein 1 (TRP1). To define GILT’s role in central tolerance, we show that GILT expression is enriched in thymic APC capable of mediating deletion, medullary thymic epithelial cells (mTEC) and dendritic cells. TRP1 expression is restricted to mTEC. GILT facilitates MHC class II-restricted presentation of endogenous TRP1 by pooled thymic APC. Bone marrow (BM) chimeras demonstrate that GILT expression in TEC is necessary and sufficient for efficient deletion of TRP1-specific thymocytes. In chimeras that express GILT in TEC, TRP1-specific T cells undergo deletion, and chimeras are not protected from melanoma challenge. Although an intermediate level of TRP1-specific T cells develop in chimeras with GILT expression limited to BM-derived cells, only chimeras lacking GILT in both populations are protected from melanoma challenge. Chimeras that express GILT in TECs or in which GILT is limited to BM-derived cells have a substantially higher percentage of TRP1-specific regulatory T (Treg) cells and lower effector:Treg cell ratio. These findings suggest that GILT operates in mTEC to facilitate the presentation of tissue-specific self Ag and promote deletion and development of Treg cells.
Early analysis of laparoscopic common bile duct exploration simulation.

Abstract Background We developed a laparoscopic common bile duct exploration (LCBDE) simulation course for resident surgeons (RS) and practicing surgeons (PS). We hypothesized that course completion would provide LCBDE procedural skills and increase procedure utilization. Methods RS and PS were prospectively enrolled. Pre- and post-course ability were assessed with written examinations and LCBDE simulations. PS completed pre-course, post-course, and 1-year follow-up surveys (5-point Likert-type scale). Results 17 RS and 8 PS were enrolled. Median written test scores improved (70.0%–80.0%, p Conclusions The LCBDE course is appropriate for RS and PS. PS also reported increased comfort with LCBDE and procedure utilization.
A cosmic multimessenger gold rush

Direct detection of gravitational waves (GWs) from black hole (BH) mergers began in earnest in 2015, but until this August, astronomers hunting for electromagnetic (EM) counterparts to GW events were left in the dark. Published in Science 's First Release this week, Kasliwal et al. ( 1 ), Evans et al. ( 2 ), Hallinan et al. ( 3 ), and Coulter et al. ( 4 ) detail the exciting search and discovery of a panchromatic transient, dubbed EM170817, which they argue is the first unassailable EM counterpart to a GW event. That event (GW170817) was promptly recognized by the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaboration ( 5 ) as resulting from the merger of two neutron stars (NSs), compact stellar remnants about 40% more massive than the Sun but only a few kilometers in radius. The reported observations, connecting GWs to both gamma-ray bursts (GRBs) and a long-theorized—but hitherto undetected—short-lived EM transient represents a watershed moment in astrophysics.
Analytical procedures in external auditing: A comprehensive literature survey and framework for external audit analytics

Abstract There is an increasing recognition in the public audit profession that the emergence of big data as well as the growing use of business analytics by audit clients has brought new opportunities and challenges. That is, should more complex business analytics beyond the customary analytical procedures be used in the engagement and if so, where? Which techniques appear to be most promising? This paper starts the process of addressing these questions by examining extant external audit research. 301 papers are identified that discuss some use of analytical procedures in the public audit engagement. These papers are then categorized by technique, engagement phase, and other attributes to facilitate understanding. This analysis of the literature is categorized into an External Audit Analytics (EAA) framework, the objective of which is to identify gaps, to provide motivation for new research, and to classify and outline the main topics addressed in this literature. Specifically, this synthesis organizes audit research, thereby offering guidelines regarding possible future research about approaches for more complex and data driven analytics in the engagement.
Acute Hospital Care

Acute hospitalization provides an opportunity to improve chronic disease management. Hospital care ideally starts with a structured, patient-centered approach at admission and ends with successful posthospital planning. When evaluating a chronically ill patient for possible admission, it is important to address the patient’s presenting complaints and gather collateral subjective and objective information regarding both the acute problem and underlying chronic medical conditions. During the hospital course, a team-based approach can promote the prevention of iatrogenic errors and nosocomial infections as well as the acute care management of the presenting problem and the chronic illness. Discharge planning should ideally begin at the time of admission in order to facilitate a timely and effective transition after the acute hospitalization. When hospital care is well executed, there is great potential to improve outcomes, maximize healthcare utilization, and reduce costs.
Reassessing Nietzsche's ‘Great Politics’

Did Friedrich Nietzsche offer a coherent account of politics in his writings? If so, what was it and what potential relevance might it hold for today? These are the central questions that Hugo Droc...
Genetics of the Neutrophilic Dermatoses

Neutrophilic dermatoses are a heterogeneous group of skin disorders linked together by overlapping histopathologic findings, pathophysiology, clinical features, and principles of management. Although many of the neutrophilic dermatoses are idiopathic, they can occur in association with systemic diseases and genetic factors. In-depth knowledge of the genetic basis of some of the neutrophilic dermatoses is important because it explains responsiveness to certain treatments and can help guide management. This chapter will discuss the neutrophilic dermatoses with known and emerging associated genetic alterations, which include Sweet syndrome, pyoderma gangrenosum, and pustular psoriasis, among others.
Elevated levels of adrenomedullin in eutopic endometrium and plasma from women with endometriosis.

Objective To test adrenomedullin (Adm, ADM) as a downstream target of signal transducer and activator of transcription 3 (STAT3) in endometrial cells and to test midregional proadrenomedullin (MR-proADM) as a biomarker of endometriosis. Design Cross-sectional analysis of Adm expression in eutopic endometrium and of MR-proADM in plasma from women with and without endometriosis; and prospective study of MR-proADM levels in women with endometriosis undergoing surgical resection of ectopic lesions. Setting Academic medical centers. Patient(s) Fifteen patients with endometriosis and 11 healthy control subjects who donated eutopic endometrial biopsies; and 28 patients with endometriosis and 19 healthy control subjects who donated plasma for MR-proADM analysis. Intervention(s) None. Main Outcome Measure(s) Adm mRNA levels according to quantitative real-time polymerase chain reaction after activation of STAT3 by interleukin-6 (IL-6) in Ishikawa cells; immunohistochemistry for ADM in eutopic endometrial biopsies from women with endometriosis compared with healthy donors; and MR-proADM levels measured by commercial immunoassay in plasma from healthy women and women with endometriosis who subsequently underwent surgical resection of ectopic lesions. Result(s) Activation of STAT3 by IL-6 up-regulated Adm mRNA expression in Ishikawa cells. ADM protein levels were elevated in the eutopic endometrium of women with endometriosis. MR-proADM concentrations were higher in women with endometriosis but were not correlated with disease stage, corrected by surgery, or predictive of fertility outcome. Conclusion(s) MR-proADM may be able to serve as a biomarker of endometriosis, but it is unknown whether elevated MR-proADM levels are secondary to the estrogenic and inflammatory properties of endometriosis or an inciting pathogenic factor.
Inflamed neutrophils sequestered at entrapped tumor cells via chemotactic confinement promote tumor cell extravasation.

Systemic inflammation occurring around the course of tumor progression and treatment are often correlated with adverse oncological outcomes. As such, it is suspected that neutrophils, the first line of defense against infection, may play important roles in linking inflammation and metastatic seeding. To decipher the dynamic roles of inflamed neutrophils during hematogenous dissemination, we employ a multiplexed microfluidic model of the human microvasculature enabling physiologically relevant transport of circulating cells combined with real-time, high spatial resolution observation of heterotypic cell–cell interactions. LPS-stimulated neutrophils (PMNs) and tumor cells (TCs) form heterotypic aggregates under flow, and arrest due to both mechanical trapping and neutrophil–endothelial adhesions. Surprisingly, PMNs are not static following aggregation, but exhibit a confined migration pattern near TC–PMN clusters. We discover that PMNs are chemotactically confined by self-secreted IL-8 and tumor-derived CXCL-1, which are immobilized by the endothelial glycocalyx. This results in significant neutrophil sequestration with arrested tumor cells, leading to the spatial localization of neutrophil-derived IL-8, which also contributes to increasing the extravasation potential of adjacent tumor cells through modulation of the endothelial barrier. Strikingly similar migration patterns and extravasation behaviors were also observed in an in vivo zebrafish model upon PMN–tumor cell coinjection into the embryo vasculature. These insights into the temporal dynamics of intravascular tumor–PMN interactions elucidate the mechanisms through which inflamed neutrophils can exert proextravasation effects at the distant metastatic site.
Abnormal Cochleovestibular Anatomy and Hearing Outcomes: Pediatric Patients with a Questionable Cochleovestibular Nerve Status May Benefit from Cochlear Implantation and/or Hearing Aids.

Objective: Imaging characteristics and hearing outcomes in children with cochleovestibular or cochleovestibular nerve (CVN) abnormalities. Study Design: Retrospective, critical review. Setting: Tertiary referral academic center. Patients: Twenty-seven children with CVN abnormalities with magnetic resonance (MRI) and/or computed tomography (CT). Study Intervention(s): None. Main Outcome Measure(s): Determine the likely presence or absence of a CNV and auditory stimulation responses. Results: Two of 27 cases had unilateral hearing loss, and all others had bilateral loss. Eleven (46%) were identified with a disability or additional condition. Twenty-two (42%) ears received a cochlear implant (CI) and 9 ears (17%) experienced no apparent benefit from the device. MRI acquisition protocols were suboptimal for identification of the nerve in 22 (42%) ears. A likely CVN absence was associated with a narrow cochlear aperture and internal auditory canal and cochlear malformation. Thirteen (48%) children with an abnormal nerve exhibited normal cochleae on the same side. Hearing data were available for 30 ears, and 25 ears (83%) exhibited hearing with or without an assistive device. One child achieved closed set speech recognition with a hearing aid, another with a CI. One child achieved open set speech recognition with a CI. Conclusions: Current imaging cannot accurately characterize the functional status of the CVN or predict an assistive device benefit. Children who would have otherwise been denied a CI exhibited auditory responses after implantation. A CI should be considered in children with abnormal CVN. Furthermore, imaging acquisition protocols need standardization for clear temporal bone imaging.
The Narrative Construction of Emotional Life

Will Sarah eventually learn one of life’s more important lessons? With further experience, will she no longer “feel sad and disappointed” when others fail to meet her expectations? Traditional students of emotional life might ask: Has William been socialized into suppressing his “true emotions,” thus making him a candidate for a life of tension-ridden inauthenticity?
Real-time optical spectroscopic monitoring of nonirrigated lesion progression within atrial and ventricular tissues

Despite considerable advances in guidance of radiofrequency ablation (RFA) therapy for the treatment of cardiac arrhythmias, success rates have been hampered by a lack of tools for precise intraoperative evaluation of lesion extent. Near-infrared spectroscopic (NIRS) techniques are sensitive to tissue structural and biomolecular properties, characteristics that are directly altered by radiofrequency (RF) treatment. In this work, a combined NIRS-RFA catheter is developed for real-time monitoring of tissue reflectance during RF energy delivery. An algorithm is proposed for processing NIR spectra to approximate nonirrigated lesion depth in both atrial and ventricular tissues. The probe optical geometry was designed to bias measurement influence toward absorption enabling enhanced sensitivity to changes in tissue composition. A set of parameters termed "lesion optical indices" are defined encapsulating spectral differences between ablated and unablated tissue. Utilizing these features, a model for real-time tissue spectra classification and lesion size estimation is presented. Experimental validation conducted within freshly excised porcine cardiac specimens showed strong concordance between algorithm estimates and post-hoc tissue assessment.
Analysis and Design of a Wireless Charger for Underwater Vehicles Fed from a Constant Current Distribution Cable

Existing conductive power supplies for undersea electronic systems are typically fed from constant low-current distribution with a seawater return. In such systems, power converters are connected in series along the distribution cable to supply power to sensor loads and underwater vehicles. Isolated voltage fed resonant converters are often used for the advantages of soft-switching and low component stress. When supplying underwater vehicles, there is further motivation to develop a wireless solution to improve reliability by removing the seawater exposed contacts. This can be accomplished by replacing the isolation transformer of existing resonant converters with series-series compensated coupled coils to create an inductive power transfer (IPT) solution. The introduction of the IPT system changes many factors in the design that need to be considered. This paper presents detailed analysis and design of wireless charger for underwater vehicles fed from a constant current distribution cable. The design is validated with experimental results for a 330 W prototype supplied from a 1 A source operated underwater with a switching frequency of 250 kHz.
Assessment of machine learning approaches for predicting the crystallization propensity of active pharmaceutical ingredients

In the current report, three machine learning approaches were assessed for their ability to predict the crystallization propensities of a set of small organic compounds (<709 Da). The algorithms evaluated included: random forest regression (RFR), support vector machine regression (SVMR) and neural networks (NN). In addition to these algorithms, the influence of different molecular descriptors, the size of the training sets used, and various experimental factors on the predictive ability of the methods were also taken into consideration. For example, factors such as the solvent used, presence of impurities and/or degradants, influence of potential seeded crystallizations and implied supersaturation levels were explicitly investigated. For smaller training set sizes (e.g., ∼50), very little difference in the accuracy of the three algorithms was observed. However, beyond training set sizes of 150, the RFR algorithm typically outperformed the others by up to 20% RMSE. Additionally, as a result of the improved performance with larger training set sizes, the RFR models built with the explicit treatment of solvent typically outperformed models only considering the active pharmaceutical ingredient (API). For example, the best performing API only model had an RMSE of 30% whereas for the API + solvent models the RMSE was found to be 20%. Beyond inclusion of the solvent, it was found that the presence of impurities and/or degradants had the greatest influence on model accuracy. When these experiments were excluded, an additional improvement of up to 10% RMSE was observed in some cases.
COINCIDENT PEAK PREDICTION USING A FEED-FORWARD NEURAL NETWORK

A significant portion of a business’ annual electrical payments can be made up of coincident peak charges: a transmission surcharge for power consumed when the entire system is at peak demand. This charge occurs only a few times annually, but with per-MW prices orders of magnitudes higher than non-peak times. A business is incentivized to reduce its power consumption, but accurately predicting the timing of peak demand charges is nontrivial. In this paper we present a decision framework based on predicting the day-ahead likelihood of peak demand charges. We train a feed-forward neural net-work to estimate the probability of system demand peaks and show it outperforms conventional forecasting methods using historical load. Using ERCOT demand and weather data from 2010-2017, we show the effectiveness of our framework.
Abstract P2044: Renoprotective Effects of Canagliflozin in Db/db Diabetic Mice

Diabetes is one of the major causes of chronic kidney disease which could lead to end-stage renal disease. Previously, we have shown increased urinary angiotensin converting enzyme 2 (ACE2) and nep...
Intramarital Status Differences Across Africa's Educational Expansion

Objective This paper documents how intra-marital differences in educational status vary across Africa's heterogeneous educational expansion, which has encompassed an enormous breadth of educational opportunities over the past 50 years. Background Educational expansion influences intra-marital status differences both by altering the educational composition of men and women and by reconfiguring the social conventions associated with a given educational context. Status differentials between marital partners can influence spousal wellbeing and, in the aggregate, determine the extent to which marriage provides a pathway to upward social mobility. Method Using Demographic and Health Survey data representing 32 sub-Saharan African countries and 5 decades of birth cohorts, the paper examines the prevalence and propensity of educational pairings as a function of educational access (the percentage of a cohort who ever attended school) and wife's education level. Results Educational expansion created gendered changes in educational compositions of married individuals, which led to increased prevalence of hypergamy (wives who married "up") in most countries. Educational expansion has also led hypogamous marriages to become less of a social aberration: in lower-education contexts (but less so in higher-education contexts), conventions lead women to "marry down" at far lower rates than would be expected based on the sex-specific compositions of husbands and wives. Conclusion Educational attainment remains a central determinant of social positioning in African society. However, as schooling expands across the continent, social conventions regarding educational status are playing a weakening role in determining who marries whom.
Intrahost cytomegalovirus population genetics following antibody pretreatment in a monkey model of congenital transmission

Human cytomegalovirus (HCMV) infection is the leading non-genetic cause of congenital birth defects worldwide. While several studies have addressed the genetic composition of viral populations in newborns diagnosed with HCMV, little is known regarding mother-to-child viral transmission dynamics and how therapeutic interventions may impact within-host viral populations. Here, we investigate how preexisting CMV-specific antibodies shape the maternal viral population and intrauterine virus transmission. Specifically, we characterize the genetic composition of CMV populations in a monkey model of congenital CMV infection to examine the effects of passively-infused hyperimmune globulin (HIG) on viral population genetics in both maternal and fetal compartments. In this study, 11 seronegative, pregnant monkeys were challenged with rhesus CMV (RhCMV), including a group pretreated with a standard potency HIG preparation (n = 3), a group pretreated with a high-neutralizing potency HIG preparation (n = 3), and an untreated control group (n = 5). Targeted amplicon deep sequencing of RhCMV glycoprotein B and L genes revealed that one of the three strains present in the viral inoculum (UCD52) dominated maternal and fetal viral populations. We identified minor haplotypes of this strain and characterized their dynamics. Many of the identified haplotypes were consistently detected at multiple timepoints within sampled maternal tissues, as well as across tissue compartments, indicating haplotype persistence over time and transmission between maternal compartments. However, haplotype numbers and diversity levels were not appreciably different between control, standard-potency, and high-potency pretreatment groups. We found that while the presence of maternal antibodies reduced viral load and congenital infection, it had no apparent impact on intrahost viral genetic diversity at the investigated loci. Interestingly, some minor haplotypes present in fetal and maternal-fetal interface tissues were also identified as minor haplotypes in corresponding maternal tissues, providing evidence for a loose RhCMV mother-to-fetus transmission bottleneck even in the presence of preexisting antibodies.
Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer

Introduction Advanced unresectable gastroesophageal cancers continue to confer a dismal patient prognosis. Limited options remain once the cancer is refractory to cytotoxics/biologics (like irinotecan, taxane, and ramucirumab). Recently, anti-programmed death-1 (anti-PD-1) inhibitors have been used with limited efficacy in select patients with adenocarcinoma. Similarly, irinotecan-based therapy has marginal efficacy. We combined irinotecan plus a fluoropyrimidine with an anti-PD-1 antibody, nivolumab, with hopes of having a higher advantage for patients. Objectives Primary objective was to assess safety judged by toxicities, dose delays, or dose reductions. Secondary endpoints included the assessment of response, overall survival (OS), and progression-free survival (PFS). Methods We treated 15 patients with this combination during July 2017 to April 2019. Patients were included if they had follow-up at our institution. Results Median doses given were nivolumab 240 mg + irinotecan 120 mg/m2 + 5-FU 2,000 mg/m2 over 46-48 h (or capecitabine 1,250 mg/m2/day; 7 days on, 7 days off) given every 2 weeks. Median age of the patients was 55 years, and all patients had an ECOG performance status of 0-1. The patients had a median of 1 prior therapy. Slightly over half of the patients had PD-L1 expression. The median number of cycles was 7. Five patients (33%) had a dose delay or dose adjustment. The most common reason for dose delay or adjustment was grade 2 fatigue. Disease control (response or stability) on first scan was 73.3% (n = 11). Median PFS and OS for the entire group was 7 and 13.3 months, respectively. Conclusion In this small cohort of patients, we conclude that this combination is quite feasible and resulted in prolonged stability in some patients. Further development of this regimen is warranted.
Abstract P236: Breastfeeding and Drug Free Moms and Babies Project: Comparing Rates in a Rural Appalachia Project to Project Watch to Support Healthy Baby Outcomes

Breastfeeding is linked to improved cardiovascular health for both child and mother; however, many hospitals do not encourage or provide support for breastfeeding while either in the hospital or af...
Correlation between vitamin D levels and hard-to-heal wounds: a systematic review.

Objective: Hard-to-heal wounds are a major biological, psychological, social and financial burden on both individual patients and the broader health system. They are associated with a variety of co...
gem5-SALAM: A System Architecture for LLVM-based Accelerator Modeling

With the prevalence of hardware accelerators as an integral part of the modern systems on chip (SoCs), the ability to quickly and accurately model accelerators within the system it operates is critical. This paper presents gem5-SALAM as a novel system architecture for LLVM-based modeling and simulation of custom hardware accelerators integrated into the gem5 framework. gem5-SALAM overcomes the inherent limitations of state-of-the-art trace-based pre-register-transfer level (RTL) simulators by offering a truly "execute-in-execute" LLVM-based model. It enables scalable modeling of multiple dynamically interacting accelerators with full-system simulation support. To create sustainable long-term expansion compatible with the gem5 system framework, gem5-SALAM offers a general-purpose and modular communication interface and memory hierarchy integrated into the gem5 ecosystem which streamlines designing and modeling accelerators for new and emerging applications. Validation on the MachSuite [17] benchmarks present a timing estimation error of less than 1% against Vivado High-Level Synthesis (HLS) tool. Results also show less than a 4% area and power estimation error against Synopsys Design Compiler. Additionally, system validation against implementations on a Ultrascale+ ZCU102 shows an average end-to-end timing error of less than 2%. Lastly, this paper presents the capabilities of gem5-SALAM in cycle-level profiling and full system design space exploration of accelerator-rich systems.
Neutrophils From Patients With Invasive Candidiasis Are Inhibited by Candida albicans Biofilms.

Invasive candidiasis frequently involves medical device placement. On the surfaces of these devices, Candida can form biofilms and proliferate in adherent layers of fungal cells surrounded by a protective extracellular matrix. Due in part to this extracellular matrix, biofilms resist host defenses and antifungal drugs. Previous work (using neutrophils from healthy donors) found that one mechanism employed to resist host defenses involves the inhibition of neutrophil extracellular traps (NET) formation. NETs contain nuclear DNA, as well as antimicrobial proteins that can ensnare pathogens too large or aggregated to be effectively killed by phagocytosis. Given that these neutrophil structures are anticipated to have activity against the large aggregates of C. albicans biofilms, understanding the role of this inhibition in patients could provide insight into new treatment strategies. However, prior work has not included patients. Here, we examine NET formation by neutrophils collected from patients with invasive candidiasis. When compared to neutrophils from healthy participants, we show that patient neutrophils exhibit a heightened background level of NET release and respond to a positive stimulus by producing 100% more NETs. However, despite these physiologic differences, patient neutrophil responses to C. albicans were similar to healthy neutrophils. For both groups, planktonic cells induce strong NET release and biofilms inhibit NET formation. These results show that a mechanism of immune evasion for fungal biofilms translates to the clinical setting.
Effects of surface roughness topography in transient channel flows

The dynamical effects of roughness geometry on the response of a half-height turbulent channel flow to an impulse acceleration are investigated using direct numerical simulations. Two rough surface...
Inclusive Online Teaching and Digital Learning: Lessons Learned in the Time of Pandemic and Beyond

When the COVID-19 pandemic swept across the world in 2020 and into 2021, the entire system of education faced the most challenging task to provide education to students using virtual instruction. Within the United States specifically, the pandemic transformed teaching. Teachers were and have continued to be compelled to learn digital technology and integrate varied digital tools into their instruction. As guest editors, Eric and I had the opportunity to reflect on the many instructional challenges and valuable lessons learned about virtual teaching and learning in k-12 and higher education. One of the biggest lessons observed was exposure of huge equity gaps between the tech haves and have nots, regarding access to digital devices and reliable Wi-Fi. It was from this observation that the call for proposals of this special issue was developed. What does inclusion look like in the era of digital and virtual teaching? With this in mind, we were tasked to coedit this special issue of JCSR focusing on the theme “Inclusive Curriculum in the Era of Digital & Virtual Learning.” We had the opportunity to review five exemplary articles responding to the theme.
Intracranial Malignant Peripheral Nerve Sheath Tumors Not Associated with a Cranial Nerve: Systematic Review and Illustrative Case.

Objective Primary intracranial malignant peripheral nerve sheath tumors (MPNSTs) not associated with cranial nerves are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. In addition, we present our own experience managed with resection, radiotherapy, and first use of targeted therapy in a tumor of this type for a BRAF mutation identified during next-generation sequencing. Methods Two databases, PubMed and Embase, and crossed references were queried for intracranial MPNSTs not associated with a cranial nerve. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analysis was performed to identify factors with survival benefit. Results A total of 56 patients (including the present case) were included from 743 literature results. There was a male/female ratio of 1.5:1 and mean diagnosis age of 29.7 ± 21.8 years. Seventy-one percent of cases were sporadic and 23% neurofibromatosis type 1 related. Median survival was 29 ± 22.1 months with 1-year survival of 60%. Factors associated on univariate analysis with reduced survival were subtotal resection (P = 0.05), older age (P = 0.023), triton histology (P Conclusions We present a systematic review of intracranial MPNSTs not associated with a cranial nerve. These tumors have poor prognosis and benefit from aggressive resection, multimodal treatment, and close follow-up. Next-generation sequencing can show molecular alterations for potential targeted therapy.
Crime, credible enforcement, and multiple equilibria

Abstract This paper examines the credibility of threats to punish criminal offenders. The motivation is the sequential nature of crime and punishment, which unfolds as follows: enforcers threaten punishment, offenders commit crimes (or are deterred), and enforcers (possibly comprising different decision makers) enact punishments. The cost of carrying out threatened punishments after the fact is what potentially undermines the credibility of the initial threat. The model shows that, given the sequential nature of the crime and punishment game, multiple equilibria are possible entailing different crime rates. Changes in law enforcement policy over recent decades are discussed in light of the results.
Text Critical Notes on 4QJoba

Several commentaries on the book of Job have appeared since the publication of 4QJoba in 2000. Yet none has taken its readings into consideration in the exegesis of the passages represented therein. It is the purpose of this study, therefore, to reexamine the variants in 4QJoba, assess their value for the textual criticism and exegesis of the book, and consider the relationship of the ms to the mt and other Vrss. This article contends that 4QJoba does not strictly belong to the text tradition represented by the mt and that in several cases it preserves readings that are at least viable if not even superior to what one finds in the mt, including at 31:15; 36:23, 24; 37:1, and 37:2.
Inositol triphosphate generation in cultured rat retinal pigment epithelium.

PURPOSE To evaluate the generation of the second messenger molecule inositol triphosphate (IP3) in response to phagocytic challenge in cultures of retinal pigment epithelium (RPE) prepared from normal Long Evans or dystrophic Royal College of Surgeons (RCS) rats. METHODS RPE cultures were phagocytically challenged with isolated rat rod outer segments (ROS) or polystyrene latex spheres (PSL). Carbachol was added to some cultures as a positive control to stimulate the IP3 pathway. Inositol triphosphate levels in RPE cells were analyzed by high-pressure liquid chromatography and radioreceptor assay. Incorporation of 3H-myoinositol into phosphatidylinositol lipids was analyzed by thin layer chromatography and autoradiography. RESULTS Long Evans RPE phagocytically challenged with ROS or exposed to carbachol showed a significant increase in IP3 levels compared to unchallenged control cultures or cultures phagocytically challenged with PSL. RCS RPE cells did not show an increase in IP3 levels upon phagocytic challenge with ROS or PSL. Carbachol treatment of RCS RPE produced an increase in IP3 levels, demonstrating that the components of the IP3 pathway are present and the pathway can be activated. Phagocytic challenge of Long Evans RPE with ROS was associated with a decrease in the IP3 precursor, phosphatidylinositol bisphosphate (PIP2). No decrease in PIP2 was observed in RCS RPE incubated with ROS. CONCLUSIONS These results show that phagocytic challenge of Long Evans RPE with ROS is associated with PIP2 hydrolysis and subsequent generation of IP3 as a second messenger. In RCS RPE, ROS stimulation of the IP3 pathway is absent.
Generation green: understanding the motivations and mechanisms influencing young adults' environmental volunteering

Environmental issues are particularly salient for today's generation of young adults. Indeed, many have suggested that it will be this generation that will lead the environmental movement forward. Therefore, this study examines the motivations and mechanisms that influence proclivity and intensity of young adults' environmental volunteerism. Using a survey of environmental attitudes and behaviors of college students at a large urban Canadian university (n = 1 372), we assess why today's young adults volunteer for the environment and the factors that motivate their commitment. Our findings suggest that young adults who engage in pro-environmental behaviors in general, as well as those who volunteer for other types of nonprofit organizations, are more likely to volunteer for environmental nonprofit organizations. Moreover, we find that social aspects of volunteering are the strongest positive predictor of the intensity of volunteerism in environmental groups. Copyright © 2011 John Wiley & Sons, Ltd.
Carbohydrate metabolism with three months of low-estrogen contraceptive use.

Abstract Prospective studies of carbohydrate metabolism were performed by means of an oral glucose tolerance test in 29 women. The studies were performed before and after 3 months of treatment with an oral contraceptive that contained 0.035 mg of ethinyl estradiol and 0.4 mg of norethindrone. The 24 women with a “normal” control test had no significant alteration in any of their blood glucose and plasma insulin values, except that the fasting glucose level decreased with treatment. Three of these women (12.5%) had a slight deterioration of their glucose curves into a “borderline abnormal” grouping during treatment. There were five women with “borderline abnormal” control glucose curves, and in four of these (80%) the curves returned to “normal” during treatment, whereas one curve stayed “borderline abnormal.” These data suggest that this low-estrogen oral contraceptive has minimal short-term adverse effects on the carbohydrate metabolism.
108 Aprataxin and the threat of RNA contamination in DNA

The maintenance of eukaryotic genomes is ensured by three-step DNA ligation reactions employed by ATP-dependent DNA ligases. However, when DNA ligases engage DNA or RNA/DNA structures with non-cano...
The reuse and modification of rulebases by predicate substitution

We propose a method for reusing and modifying a deductive database. The need for such techniques occurs when new rulebased applications differ only slightly from existing ones or when an application is to be incrementally updated. Such techniques are particularly important when reprogramming is expensive or unreliable. In order to facilitate reuse we extend deductive database systems by the concept of predicate substitution. In this way, during query evaluation, not only variables, but also predicates can be substituted. Substitution increases the expressive power of Datalog. Not only does data complexity increase from PTIME to EXPTIME, but substitution also allows large sets of Datalog rules to be succinctly expressed. The paper provides a proof and model theory for this language, including a fixpoint semantics.