cssi/SciSciGPT-SciSciNet huggingface dataset:
Efficient Farm Organization for Livestock Production in the South-Eastern States

In developing an organization for livestock production, it is necessary to evolve a system to meet all the conditions brought about by the environment or by the economic situation. This at once establishes the fact that the farm organization cannot be hard-and-fast, but even within a limited area, will have to be exceedingly elastic. Consequently, an exact knowledge of conditions, not generally available, is required. It is true, that such knowledge has been gained by many farmers through experience, but it is generally of value only to themselves. However, if a permanent business is to be established, this knowledge must be utilized. It is desirable that the farm organization for livestock production should take into consideration a cash crop. As this crop would be variable, even in the limited area under discussion, the organization would vary somewhat. The general rule should be that the cash crop should contribute something to the livestock production; as, for example, the straw from small grain for either feed or bedding, or, cottonseed meal for feed, in the case of the cotton crop. One of the profits usually attributed to the livestock business is that coming from the manure. An advantage of having a cash crop connected with the livestock business is that the manure can be cashed through this crop and some estimate can be made of its value. As a matter of raising the crop producing power of the farm, no better place can be found than on a leguminous green manure crop. The area under consideration is exceedingly variable. The soils range from the sands and sandy loams of the Coastal Plain region to the rather heavy clays of the limestone sections. This variation in itself will change the organization, since it is not conceivable that the same methods could be used in the blue-grass sections of the limestone region and in the Coastal Plain. In elevation the variation is from sea level to 4,000 feet or more. The topography ranges from level plains to rugged mountains. The natural growth varies with these different conditions. The general type is that afforded by
EXPERIMENTAL EVIDENCE FOR GENETIC VARIATION IN COMPATIBILITY BETWEEN THE FUNGUS ATKINSONELLA HYPOXYLON AND ITS THREE HOST GRASSES.

Variation in compatibility has been documented within and among several natural plant populations infected by fungal pathogens. In this study, seeds and isolates of the fungus Atkinsonella hypoxylon (Ascomycetes, Clavicipitaceae) were collected from three populations of the grass Danthonia spicata, two populations of D. compressa, and four populations of Stipa leucotricha. Each fungal strain was reciprocally inoculated into seedlings grown in aseptic culture from its original host population, into seedlings from other conspecific host populations, and into seedlings from the other two host species. There were three distinct patterns of compatibility, as evidenced by the ability of the fungus to grow on the seedling and to colonize new tillers. Fungal strains from one host genus were incompatible with seedlings from the other host genus. Strains from the two Danthonia species were broadly compatible among Danthonia populations and had very high rates of infection, while strains from Stipa also were broadly compatible among Stipa populations but had relatively low rates of infection. Literature surveys indicate that, in contrast to pathogenic microorganisms, mutualistic microorganisms typically exhibit broad patterns of compatibility among hosts, which lack resistance to infection. The effect of A. hypoxylon on host fitness is most detrimental in Stipa, where the fewest seedlings became infected, and most beneficial in Danthonia, where most seedlings became infected.
Association of genetic variations of selenoprotein genes, plasma selenium levels, and prostate cancer aggressiveness at diagnosis.

BACKGROUND Genetic variations in some of the selenoprotein genes, alone or together with an individual's selenium status, may influence risk or progression of prostate cancer. We investigated the impact of genetic variants of selenoproteins on plasma selenium levels and cancer aggressiveness at diagnosis in men with localized prostate cancer (PCa). METHODS The study cohort comprised 722 patients seen at Dana-Farber Cancer Institute who had localized/locally advanced PCa (i.e., stage T3 or less, N0, and M0) from 1994 to 2001. Fifty-five tagging single nucleotide polymorphisms (SNPs) from six selenoprotein genes (TXNRD1, TXNRD2, SEP15, GPX3, SELENBP1, and SEPP1) were analyzed. Logistic regression is used to examine associations of genotypes and plasma selenium levels with risk of aggressive disease, defined as D'Amico intermediate/high risk categories. Step down permutation was applied to adjust for multiple comparisons. RESULTS Three hundred and forty-eight patients (48%) had aggressive disease at diagnosis. Two SNPs were associated with cancer aggressiveness at diagnosis (unadjusted P = 0.017 and 0.018, respectively). The odds ratio for aggressive disease in patients carrying TXNRD2 rs1005873-AG/GG genotypes or SELENBP1 rs10788804-AG/AA genotypes was 1.54 (95%CI = 1.08, 2.20) and 1.45 (95%CI = 1.07, 1.98), respectively, compared to TXNRD2 rs1005873-AA or SELENBP1 rs10788804-GG carriers. Four SNPs in TXNRD2 (rs1005873, rs13054371, rs3788310, and rs9606174) and the rs230820 in SEPP1 were associated with plasma selenium levels (unadjusted P < 0.05). Permutation adjusted P-values were not statistically significant for all these comparisons at the cut-off point of 0.05. CONCLUSION We identified polymorphisms in selenoproteins that may influence the plasma selenium levels and may be associated with the risk of presenting with aggressive PCa in men with localized or locally advanced PCa. These results should be validated in other independent datasets. Prostate 76:691–699, 2016. © 2016 Wiley Periodicals, Inc.
Emergency Preparedness Plan

Although some disasters can be predicted, others may occur without much warning. The occupational and environmental health nurse should be involved in all aspects of an emergency response plan.
Caught Yellow-Handed

This case discusses both pharmacokinetic and pharmacodynamics interactions between turmeric and warfarin.
Predictors of local support for a seawater desalination plant in a small coastal community

Abstract Seawater desalination is increasingly being pursued to address freshwater shortages. In California, multiple coastal seawater desalination facilities have been proposed to diversify water portfolios and to increase reliability of water supply. This paper explores local residents support for a newly constructed desalination plant in Carlsbad, a small coastal community in Southern California. The plant is the first high-capacity desalination facility in California and started operation in December 2015. We found strong support for the desalination plant as 71.9% of residents reported support for the plant. Only 15.5% of respondents were undecided indicating that residents had a clear opinion on the plant. Perceptions about local water resources were significant predictors of support. Attitudes may change over time if the state of water resources and perceptions thereof change. Expected outcomes of the plant also predicted support. An increase in available drinking water was a positive predictor, while environmental and social impacts were negative predictors. Economic impacts in terms of an increase in the price of water did not influence local support. Ethnicity and age were the only socio-demographic variables that had an effect on support suggesting that the socio-demographic profile of a community may not be a good predictor of community support or rejection of this water supply technology.
Characterization of Bond-Loss Failures in Pretensioned Concrete Girders

AbstractFailures of strand–concrete bonds have been widely observed in load tests of precast-pretensioned concrete I girders. Through a review of 22 test programs, 15 terminologies were identified to describe failures associated with bond loss. In many cases, previous researchers used different terms to describe the same failure behavior. In response to the wide-ranging and sometimes inconsistent terminologies used in the literature, this technical note makes two contributions. First, the different types of failure that involve strand–concrete bond loss are characterized, and a consistent labeling scheme is proposed. The 15 labels given in the referenced test programs are condensed into four primary behaviors. Second, a flowchart is presented for assisting future researchers in characterizing and labeling bond-loss failures. Decision points in the flowchart are based on a synthesis of the reviewed test programs, which included 120 unique load tests having some type of bond-loss failure.
Comprehensive Sustainability Indicators: The Houston Sustainability Indicators Program

The goal of the Houston Sustainability Indicators (HSI) program is to develop a system of indicators best suited to monitor development in the City of Houston. Considered as a process model, HSI was developed to cover the following four objectives: (1) Prioritizing issues (2) Examining interrelatedness in urban development (3) Conducting spatial analysis through the use of Geographic Information Systems (GIS) and (4) Public education, stakeholder participation and public policy development.
Epilogue: An Essay About Adaptability, Employability, and Resilience in an Age of Uncertainty

This epilogue explores the major themes of this book by embedding these important contributions on adaptability, employability, and resilience into an explicitly contextual framework. Beginning with a discussion of the major political shifts in recent years, the epilogue then discusses how both distal and proximal contexts can be more supportive of individuals who face an increasingly daunting world of work.
The Role of Protein Loss and Denaturation in Determining Outcomes of Heating, Cryotherapy, and Irreversible Electroporation on Cardiomyocytes

Atrial fibrillation affects millions of people in the US. Focal therapy is an attractive treatment for atrial fibrillation that avoids the debilitating effects of drugs for disease control. Perhaps the most widely used focal therapy for atrial fibrillation (AF) is heat-based radiofrequency (heating), although cryotherapy (cryo) is rapidly replacing it due to a reduction in side effects and positive clinical outcomes. A third focal therapy, irreversible electroporation (IRE), is also being considered. This study was designed to help guide treatment thresholds and compare mechanism of action across heating, cryo, and IRE. Testing was undertaken on HL-1 cells, a well-established cardiomyocyte cell line, to assess injury thresholds for each treatment method. Cell viability, as assessed by Hoechst and PI staining, was found to be minimal after exposure to temperatures =-40 °C (cryo), =60 °C (heating), and when field strengths =1500 V/cm (IRE) were used. Viability was then correlated to protein denaturation fraction (PDF) as assessed by Fourier Transform Infrared (FTIR) spectroscopy, and protein loss fraction (PLF) as assessed by Bicinchoninic Acid (BCA) assay after the three treatments. These protein changes were assessed both in the supernatant and the pellet of cell suspensions post treatment. We found that dramatic viability loss (=50%) correlated strongly with =12% protein change (PLF, PDF or a combination of the two) in every focal treatment. These studies help in defining both cellular thresholds and protein-based mechanisms of action that can be used to improve focal therapy application for atrial fibrillation.
Living donor liver transplantation: post-operative imaging follow-up of right lobe liver donors

To identify long-term post-operative imaging findings resulting from right lobe liver donation. This retrospective imaging review consisted of 42 adults (20 males, 22 females, mean age 36.6 years, range 18.7–55.9 years) who underwent right lobe liver donation with pre- and post-operative imaging between 1999 and 2006. The mean follow-up period was 30.2 months (range 12.3–69.6 months). Follow-up imaging evaluation included assessment of the biliary tree, particularly isolated bile ducts draining to and terminating at the cut surface (orphan ducts). Three-dimensional volumetry of the liver remnant was also assessed. After liver donation, 29/42 (69%) participants demonstrated orphan ducts on follow-up imaging (95% confidence interval 52.9% to 82.4%). In those patients with orphan ducts, the main draining ducts were normal in 70% and dilated in 69%. Nearly all right lobe liver donors with orphan ducts had no clinical symptoms on follow-up (28/29); the only liver donor with clinical symptoms on follow-up was subsequently diagnosed with primary biliary cirrhosis. Mean regenerated liver volume was approximately 93%, with mean pre-operative total liver volume of 1552 ml (median 1504 ml, range 1040–2520 ml) and mean post-operative total liver volume of 1446 ml (median 1455 ml, range 964–2090 ml). Orphan ducts are changes that may be seen after liver donation. The presence of these findings in the absence of clinical symptoms or abnormal hepatic chemistries does not require further work-up and should not be considered pathologic.
Cognitive Sequelae of Unruptured and Ruptured Intracranial Aneurysms and their Treatment: Modalities for Neuropsychological Assessment.

Background Cognitive sequelae frequently follow subarachnoid hemorrhage (SAH) and include deficits across multiple domains of executive function. This factor affects overall functional outcomes negatively, especially in younger patients. Several clinical correlates predict development and severity of cognitive dysfunction after SAH. Hypothetical mechanisms of cognitive dysfunction in the absence of radiographic lesion include cerebral hypoperfusion and blood breakdown products, resulting in perturbed interneuronal communication and network synchrony, excitotoxicity, and altered microRNA expression. Methods The PubMed database was searched for articles discussing cognitive outcomes in patients with unruptured and ruptured intracranial aneurysmal disease, sequelae of treatment, and modalities for neuropsychologic testing. Results Treatment of unruptured intracranial aneurysms, although capable of preventing SAH, comes with its own set of complications and may also affect cognitive function. Neuropsychological tests such as the Montreal Cognitive Assessment, Mini-Mental Status Examination, and others have proved useful in evaluating cognitive decline. Studies using functional neurologic imaging modalities have identified regions with altered activation patterns during various cognitive tasks. The sum of research efforts in this field has provided useful insights and an initial understanding of cognitive dysfunction after aneurysm treatment and SAH that should prove useful in guiding and rendering future investigations more fruitful. Conclusions Development of finer and more sensitive neuropsychological tests in evaluating the different domains of cognitive function after aneurysm treatment and SAH in general will be useful in accurately determining outcomes after ictus and comparing efficacy of different therapeutic strategies.
Methods for Measuring Spatial Cognition

Measures of spatial cognition include a diverse array of methodologies and reflect a major dimension in the study of individual differences. Several spatial abilities assessment methods are reviewed that could be incorporated into the development of geographic informations systems. A new experimental procedure, using pointing behaviors, digital video technology and fractal geometry, to estimate the dimensionality of imagined environments is described. It is suggested that the fractal dimension (D) represents a useful measure for the study of spatial cognition.
Multi-way semi-blind AF relaying networks over Rayleigh fading channels

Abstract In this paper, we investigate multi-way semi-blind amplify-and-forward (MWSB-AF) relaying networks over Rayleigh fading channels. We provide closed-form expressions for bounds of some metrics such as average symbol error probability (SEP) and outage probability. The global outage event occurs when at least one channel goes into outage. The main requirement of the proposed (MWSB-AF) relaying is the availability of statistical channel state information (CSI) which leads to a low treatment complexity at the intermediate node. However, multi-way CSI-assisted AF (MWCSIA-AF) relaying leads to a highly complex processing at the cooperative node by requiring instantaneous CSI of the first link and provides a relatively identical performance as MWSB-AF relaying. In order to justify the exactness of our proposed analysis, numerical and simulation results are presented and a comparison with MWCSIA-AF relaying networks is introduced.
Using WinBUGS for Bayesian Estimation

Historically, an important roadblock to using Bayesian inference has been the difficulty of computing posterior distributions of parameters. Thus, a major focus of this book is to show how such computations can be done using modern hardware and software.
Differential forms and dynamical systems

One of the modern geometric views of dynamical systems is as vector fields on a manifold, with or without boundary. The starting point of this paper is the observation that, since one-forms are the natural expression of linear functionals on the space of vector fields, the interaction between the two makes some aspects of the study of equilibria and periodic orbits more tractable, at least in certain cases.
Recombinant vaccinia viruses as vectors for studying T lymphocyte specificity and function.

Over the past 20 years, a steadily increasing portion of immunological research has been directed towards understanding the specificity and function of T lymphocytes. Vaccinia virus (VV) has proven to be the preferred vector for determining the specificity of T lymphocytes for individual gene products derived from a variety of organisms, including viruses, protozoa, and mammalian cells (we refer to these genes as “extrinsic genes”, their products as “extrinsic antigens” and their origin as “source organisms”) and for studying the processing and presentation of antigens to T lymphocytes by antigen presenting cells (APCs). The popularity of VV recombinants has two sources. First, the technology of producing VV recombinants is relatively straightforward and VV recombinants consistently provide high levels of expression of extrinsic antigens. Second, studies of T lymphocytes require the expression of antigens in histocompatible cells. The ability of VV to infect mice and a broad variety of mouse and human cell lines of diverse lineages that can function as APCs make them ideal vectors for studies of T lymphocytes.
Methotrexate, cyclosporine, or both to prevent graft-versus-host disease after HLA-identical sibling bone marrow transplants for early leukemia?

Optimal prophylaxis of graft-versus-host disease (GVHD) is controversial. We compared efficacy of three posttransplant immune suppressive regimens in 2,286 recipients of HLA-identical sibling bone marrow transplants for acute lymphoblastic leukemia (ALL) in first remission, acute myelogenous leukemia (AML) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase. Six hundred forty received methotrexate, 977 received cyclosporine, and 669 received combined cyclosporine and methotrexate. In children, the three regimens resulted in similar outcomes. In adults, cyclosporine and methotrexate had comparable risks of acute and chronic GVHD. Compared with methotrexate, cyclosporine was associated with less interstitial pneumonia (relative risk [RR] = 0.6; P
Effect of Racial Inequities in Pre-exposure Prophylaxis Use on Racial Disparities in HIV Incidence Among Men Who Have Sex With Men: A Modeling Study

Background Pre-exposure prophylaxis (PrEP) uptake has been slow among African American men who have sex with men (AAMSM) in the United States. We used an agent-based model (ABM) to simulate race-specific PrEP coverage to estimate their impact on racial disparities in HIV incidence among MSM in Atlanta, GA. Methods An ABM was constructed to simulate HIV transmission in a dynamic network of 10,000 MSM over 10 years, beginning in 2015. We modeled a base scenario with estimated PrEP coverage of 2.5% among AAMSM and 5.0% among white MSM (WMSM). We then compared HIV incidence over 10 years and calculated a disparity ratio of AAMSM to WMSM incidence rates across varying PrEP scale-up scenarios, with equal and unequal coverage among AAMSM and WMSM. Results Assuming current coverage remains constant, the model predicts HIV incidence rates of 2.95 and 1.76 per 100 person-years among AAMSM and WMSM, respectively, with a disparity ratio of 1.68. If PrEP coverage was to increase 6-fold without addressing inequities in PrEP uptake, the model predicts incidences of 2.65 and 1.34, corresponding to a mean decrease of 10.4% and 24.0% in HIV incidence, respectively. This stronger benefit for WMSM increased the disparity ratio to 1.98. Equal PrEP coverage among AAMSM and WMSM resulted in lower incidence rates overall with lower disparity ratios. Conclusions Lower uptake among AAMSM relative to WMSM may limit the population-level impact of PrEP use among AAMSM, which may ultimately culminate in wider racial disparities in HIV incidence among MSM.
Subcortical brain volumes and neurocognitive function in survivors of childhood acute lymphoblastic leukemia (ALL) treated with chemotherapy-only.

10517Background: Brain deep grey nuclei and glucocorticoid receptor rich hippocampal subregions may be sensitive to neurotoxic effects of chemotherapy-only protocols for childhood ALL and associate...
Identification of somatic mutations to predict development of autoimmune adverse events to immune therapy in melanoma.

3041Background: Immunotherapy has quickly altered the treatment paradigm for advanced melanoma. Prior studies in melanoma using whole exome sequencing (WES) in patient tumor samples who have receiv...
Occupational burnout among PTSD specialty clinic providers in the Veterans Health Administration: Perceptions of bureaucratic and political oversight

Abstract Background and objectives Prior research suggests a link between occupational burnout and perceived vulnerability to organizational oversight. The purpose of this exploratory study was to examine the relationship between perceptions of political and bureaucratic oversight (e.g., by Congress, media, or policies, rules, and performance metrics) and occupational burnout among mental health providers working in Veterans Health Administration (VHA) PTSD specialty clinical teams (PCTs). Design This cross-sectional study included 481 prescribing and non-prescribing PCT providers throughout the VHA system. The sample was mostly female (70%), Caucasian (84%), and psychologists (48%). Method Participants completed an online survey that assessed demographics, perceptions of political and bureaucratic oversight, and burnout. Burnout was evaluated using the Maslach Burnout Inventory-General Survey. Results High levels of emotional exhaustion (55%), cynicism (55%), and professional efficacy (53%) were found. Results indicate that burnout in PCT providers was associated with: feeling vulnerable to complaints to media, Congress, and VHA leadership; reporting “political influence” on PTSD diagnoses or treatment offerings; and feeling care delivery is hindered by the large volume of VHA policies, rules, and performance metrics. Conclusion Results suggest increasing providers’ sense of psychological safety and reducing metric overload may support burnout prevention in VHA's complex environment of care.
Culturing and Manipulation of O9-1 Neural Crest Cells

Neural crest cells (NCCs) are migrating multipotent stem cells that can differentiate into different cell types and give rise to multiple tissues and organs. The O9-1 cell line is derived from the endogenous mouse embryonic NCCs and maintains its multipotency. However, under specific culture conditions, O9-1 cells can differentiate into different cell types and be utilized in a wide range of research applications. Recently, with the combination of mouse studies and O9-1 cell studies, we have shown that the Hippo signaling pathway effectors Yap and Taz play important roles in neural crest-derived craniofacial development. Although the culturing process for O9-1 cells is more complicated than that used for other cell lines, the O9-1 cell line is a powerful model for investigating NCCs in vitro. Here, we present a protocol for culturing the O9-1 cell line to maintain its stemness, as well as protocols for differentiating O9-1 cells into different cell types, such as smooth muscle cells and osteoblasts. In addition, protocols are described for performing gene loss-of-function studies in O9-1 cells by using CRISPR-Cas9 deletion and small interfering RNA-mediated knockdown.
Cyberincivility in the Massive Open Online Course Learning Environment: Data-Mining Study

Background: Cyberincivility is a pervasive issue that demands upfront thinking and can negatively impact one’s personal, professional, social, and educational well-being. Although massive open online courses (MOOCs) environments could be vulnerable to undesirable acts of incivility among students, no study has explored the phenomena of cyberincivility in this learning environment, particularly in a health-related course in which mostly current or eventual health professions students enroll. Objective: This study aimed to analyze the characteristics of text entries posted by students enrolled in a medicine and health care MOOC. The objectives were to (1) examine the prevalence of posts deemed disrespectful, insensitive or disruptive, and inconducive to learning; (2) describe the patterns and types of uncivil posts; and (3) highlight aspects that could be useful for MOOC designers and educators to build a culture of cybercivility in the MOOC environment. Methods: We obtained data from postings in the discussion forums from the MOOC Medical Neuroscience created by a large private university in the southeast region of the United States. After cleaning the dataset, 8705 posts were analyzed, which contained (1) 667 questions that received no responses; (2) 756 questions that received at least one answer; (3) 6921 responses that applied to 756 posts; and (4) 361 responses where the initiating post was unknown. An iterative process of coding, discussion, and revision was conducted to develop a series of a priori codes. Data management and analysis were performed with NVivo 12. Results: Overall, 19 a priori codes were retained from 25 initially developed, and 3 themes emerged from the data—Annoyance, Disruption, and Aggression. Of 8705 posts included in the analysis, 7333 (84.24%) were considered as the absence of uncivil posts and 1043 (11.98%) as the presence of uncivil posts, while 329 (3.78%) were uncodable. Of 1043 uncivil posts analyzed, 466 were coded to >1 a priori codes, which resulted in 1509 instances. Of those 1509 instances, 826 (54.74%) fell into “annoyance”, 648 (42.94%) into “disruption”, and 35 (2.32%) into “aggression”. Of 466 posts that related to >1 a priori codes, 380 were attributed to 2 or 3 themes. Of those 380 posts, 352 (92.6%) overlapped both “annoyance” and “disruption,” 13 (3.4%) overlapped both “disruption” and “aggression,” and 9 (2.4%) overlapped “annoyance” and “aggression,” while 6 (1.6%) intersected all 3 themes. Conclusions: This study reports on the phenomena of cyberincivility in health-related MOOCs toward the education of future health care professionals. Despite the general view that discussion forums are a staple of the MOOC delivery system, students cite discussion forums as a source of frustration for their potential to contain uncivil posts. Therefore, MOOC developers and instructors should consider ways to maintain a civil discourse within discussion forums.
Nature Abhors a Vacuum: Highly Diverse Mechanisms Enable Spoilage Fungi to Disperse, Survive, and Propagate in Commercially Processed and Preserved Foods.

Fungal spoilage in processed foods remains a challenge for food manufacturers despite the increasing availability of diverse processing and formulation strategies used to control foodborne microorganisms. Physiological features of yeasts and molds contribute to their tolerance to thermal processing, acidity, desiccation, and oxygen and nutrient limitations. These features variably include growth form, cell wall structure, cytoplasmic composition, cell membrane-bound proteins, and secretion of secondary metabolites. Collectively, these mechanisms contribute to the ability of fungi to disperse, survive, and propagate in highly restrictive food environments. The diversity of fungal growth and survival mechanisms has resulted in organisms adapted to nearly all food environments; although, only a small subset of fungi are particularly suited for spoilage of a given product. The relationship between the individual physiology and metabolic capabilities of a yeast or mold and the product's specific physicochemical attributes and processing history determines spoilage potential. Explicit characterization of the fungal features responsible for this extremotolerance contributes to more targeted and effective control strategies.
Space-based relative orbit estimation using information sharing and the consensus Kalman filter

The consensus extended Kalman filter is employed for the problem of multiple chief spacecraft cooperatively estimating the orbit of one deputy spacecraft in a connected communication network. The i...
Comparison between cuff-based and radial tonometry exercise-induced central blood pressure

Non-invasive central blood pressure assessed during exercise may provide better cardiovascular prognostic than measurements taken at rest. Radial tonometry is the only technique validated to perform this type of assessment; however, it relies on the experience of the tester. Cuff-based devices have been developed to avoid operator dependency, although these systems have yet to be validated during exercise. The purpose of this study was to compare exercise-induced central blood pressure estimations between a cuff-based device and radial tonometry. Twenty young healthy subjects were recruited to perform a three-workload steady-state exercise test at blood lactate levels of 4 mmol/L, respectively. Central systolic and diastolic blood pressure (cSBP and cDBP, respectively), central pulse pressure (cPP), and augmentation index (AIx) were assessed at rest and during each workload with a cuff-based device and radial tonometry. Statistical analysis included Bland–Altman analysis for agreement between techniques. Agreement was considered when 95% of the data set for each central blood pressure parameter was within 1.96 standard deviations from the mean difference. Significance was considered at α = 0.05. Central blood pressure measurements with the cuff device were obtained only at rest and during low-intensity exercise. During low-intensity exercise, all measurements showed agreement between both devices (cSBP 95% CI [− 6.0 to 10.7], cDBP 95% CI [− 4.5 to 6.3], cPP 95% CI [− 4.7 to 8.3], and AIx (95% CI [− 20.1 to 22.2]). A cuff-based device can estimate central blood pressure at low-intensity exercise, without operator dependency, and showing agreement to radial tonometry.
ER stress sensor, glucose regulatory protein 78 (GRP78) regulates redox status in pancreatic cancer thereby maintaining "stemness".

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) signaling have been shown to be dysregulated in multiple cancer types. Glucose regulatory protein 78 (GRP78), the master regulator of the UPR, plays a role in proliferation, invasion, and metastasis in cancer. Cancer stem cells (CSCs) make up a crucial component of the tumor heterogeneity in pancreatic cancer, as well as other cancers. “Stemness” in pancreatic cancer defines a population of cells within the tumor that have increased therapeutic resistance as well as survival advantage. In the current study, we investigated how GRP78 was responsible for maintaining “stemness” in pancreatic cancer thereby contributing to its aggressive biology. We determined that GRP78 downregulation decreased clonogenicity and self-renewal properties in pancreatic cancer cell lines in vitro. In vivo studies resulted in delayed tumor initiation frequency, as well as smaller tumor volume in the shGRP78 groups. Additionally, downregulation of GRP78 resulted in dysregulated fatty acid metabolism in pancreatic tumors as well as the cells. Further, our results showed that shGRP78 dysregulates multiple transcriptomic and proteomic pathways that involve DNA damage, oxidative stress, and cell death, that were reversed upon treatment with a ROS inhibitor, N-acetylcysteine. This study thus demonstrates for the first time that the heightened UPR in pancreatic cancer may be responsible for maintenance of the “stemness” properties in these cells that are attributed to aggressive properties like chemoresistance and metastasis.
Comparing methods for clinical investigator site inspection selection: a comparison of site selection methods of investigators in clinical trials

Background During the past two decades, the number and complexity of clinical trials have risen dramatically increasing the difficulty of choosing sites for inspection. FDA's resources are limited and so sites should be chosen with care. Purpose To determine if data mining techniques and/or unsupervised statistical monitoring can assist with the process of identifying potential clinical sites for inspection. Methods Five summary-level clinical site datasets from four new drug applications (NDA) and one biologics license application (BLA), where the FDA had performed or had planned site inspections, were used. The number of sites inspected and the results of the inspections were blinded to the researchers. Five supervised learning models from the previous two years (2016-2017) of an on-going research project were used to predict site inspections results, i.e., No Action Indicated (NAI), Voluntary Action Indicated (VAI), or Official Action Indicated (OAI). Statistical Monitoring Applied to Research Trials (SMARTTM) software for unsupervised statistical monitoring software developed by CluePoints (Mont-Saint-Guibert, Belgium) was utilized to identify atypical centers (via a p-value approach) within a study.Finally, Clinical Investigator Site Selection Tool (CISST), developed by the Center for Drug Evaluation and Research (CDER), was used to calculate the total risk of each site thereby providing a framework for site selection. The agreement between the predictions of these methods was compared. The overall accuracy and sensitivity of the methods were graphically compared. Results Spearman's rank order correlation was used to examine the agreement between the SMARTTM analysis (CluePoints' software) and the CISST analysis. The average aggregated correlation between the p-values (SMARTTM) and total risk scores (CISST) for all five studies was 0.21, and range from -0.41 to 0.50. The Random Forest models for 2016 and 2017 showed the highest aggregated mean agreement (65.1%) amongst outcomes (NAI, VAI, OAI) for the three available studies. While there does not appear to be a single most accurate approach, the performance of methods under certain circumstances is discussed later in this paper. Limitations Classifier models based on data mining techniques require historical data (i.e., training data) to develop the model. There is a possibility that sites in the five-summary level datasets were included in the training datasets for the models from the previous year's research which could result in spurious confirmation of predictive ability. Additionally, the CISST was utilized in three of the five site selection processes, possibly biasing the data. Conclusion The agreement between methods was lower than expected and no single method emerged as the most accurate.
Identification of a Kinase-Active CheA Conformation in Escherichia coli Chemoreceptor Signaling Complexes

Escherichia coli chemotaxis relies on control of the autophosphorylation activity of the histidine kinase CheA by transmembrane chemoreceptors. Core signaling units contain two receptor trimers of dimers, one CheA homodimer, and two monomeric CheW proteins that couple CheA activity to receptor control. Core signaling units appear to operate as two-state devices, with distinct kinase-on and kinase-off CheA output states whose structural nature is poorly understood. A recent all-atom molecular dynamic simulation of a receptor core unit revealed two alternative conformations, "dipped" and "undipped," for the ATP-binding CheA.P4 domain that could be related to kinase activity states. To explore possible signaling roles for the dipped CheA.P4 conformation, we created CheA mutants with amino acid replacements at residues (R265, E368, and D372) implicated in promoting the dipped conformation and examined their signaling consequences with in vivo Forster resonance energy transfer (FRET)-based kinase assays. We used cysteine-directed in vivo cross-linking reporters for the dipped and undipped conformations to assess mutant proteins for these distinct CheA.P4 domain configurations. Phenotypic suppression analyses revealed functional interactions among the conformation-controlling residues. We found that structural interactions between R265, located at the N terminus of the CheA.P3 dimerization domain, and E368/D372 in the CheA.P4 domain played a critical role in stabilizing the dipped conformation and in producing kinase-on output. Charge reversal replacements at any of these residues abrogated the dipped cross-linking signal, CheA kinase activity, and chemotactic ability. We conclude that the dipped conformation of the CheA.P4 domain is critical to the kinase-active state in core signaling units.IMPORTANCE Regulation of CheA kinase in chemoreceptor arrays is critical for Escherichia coli chemotaxis. However, to date, little is known about the CheA conformations that lead to the kinase-on or kinase-off states. Here, we explore the signaling roles of a distinct conformation of the ATP-binding CheA.P4 domain identified by all-atom molecular dynamics simulation. Amino acid replacements at residues predicted to stabilize the so-called "dipped" CheA.P4 conformation abolished the kinase activity of CheA and its ability to support chemotaxis. Our findings indicate that the dipped conformation of the CheA.P4 domain is critical for reaching the kinase-active state in chemoreceptor signaling arrays.
Health Care Expenditure Burden of Cancer Care in the United States.

Using nationwide data, this study estimated and compared annual health care expenditures per person between noncancer and cancer patients, and among patients with the 4 most common cancers. Two-par...
The Holocaust and Slavery? Working Towards A Comparative History of Genocide and Mass Violence

Exactly twenty-five years after the first volume of his global comparative history of the Holocaust, Steven T. Katz has now published the second volume on New World slavery. 1 This comparison intri...
3D Nanowire Arrays by Nanoimprint lithography and Mechanical Buckling

Metallic nanowires (NWs) are widely utilized in microelectronics, optics, biosensors and wearables. In many of these applications, there is a need for 3D curved and folded arrays. However, cost-effective nanomanufacturing of such arrays is challenging. Here, we describe a fabrication methodology that leverages high throughput nanoimprint lithography (NIL), photolithography, selective bonding and transfer printing on flexible elastomers. We demonstrate large area fabrication of uniformly and periodically buckled arrays composed of 60 x 350 nm NWs. We anticipate that this methodology could be utilized to create complex 3D NW arrays of broad relevance to wearables, nanoengineering, and nanomedicine.
Basic principles of tissue oxygen determination from mitochondrial signals.

The importance of measuring intracellular oxygen concentrations in tissues has, over the years, emerged as a basic parameter in the physiology and biochemistry of living tissues. The credibility of oxyhemoglobin determinations, even as refined A/V differences, is taxed especially in cases where inhomogeneous tissues with variable oxygen demands and oxygen supply are served. The formation of lactic acid in the venous blood is often used as a criterion of anoxia, but it also lacks credibility where inhomogeneous circulatory pathways are served and in addition, is questionable from the standpoint of whether the appearance of excess lactate is an unequivocal criterion of oxygen insufficiency. To indicate my empathy with polarographic techniques as they have been developed at the Johnson Foundation, I wish to recall the pioneering works of Bronk(1) Brink (2), Davies and Remond (3) that stand as landmarks in the exploration of tissue oxygen tension by microelectrode methods. I served my apprenticeship with them.
Abstract 14312: Hexokinase 1 Cellular Localization Regulates the Metabolic Fate of Glucose

Introduction: The product of hexokinase (HK) enzymes, glucose-6-phosphate (G6P), can be metabolized through glycolysis or directed to alternative pathways, such as the pentose-phosphate-pathway (PP...
Chapter II: The United Provinces of the Río de la Plata, Paraguay and the Republic of Uruguay

This chapter presents the situation of Uruguay and Paraguay vis-a-vis Buenos Aires and proposes that the solution to the region’s problems should be entrusted neither to Rosas nor to the Buenos Aires province. Rather, Sarmiento suggests that the interests of every Argentine province, as well as those of Uruguay and Paraguay, need to be taken into account by gathering their representatives in a Congress, with the goal of joining together in a federation called the United States of South America. Said gathering would also result in the ending of the Commission of Foreign Affairs.
Optical coherence tomography demonstrates occult optic neuropathy in neurosarcoidosis (1701)

Objective: To evaluate whether retinal layer thicknesses differ in a large cohort of patients with neurosarcoidosis (NS) as compared to healthy controls (HCs), and examine retinal layer thickness abnormalities according to NS phenotypes and global disability levels. Background: Clinically-evident optic neuropathy is a known manifestation in NS and can be characterized using optical coherence tomography (OCT). However, the presence and clinical significance of occult optic neuropathy in patients with NS – a disorder with diverse clinical phenotypes - remains largely unexplored. Design/Methods: In this cross-sectional study, 88 patients with NS (176 eyes; 38 with history of clinically-evident optic neuropathy [NS-ON] and 144 without [NS-NON]) and 83 age-,race- and sex-matched HCs underwent spectral-domain OCT assessment. Patients with a history of other ophthalmological disorders, including intraocular sarcoidosis, were excluded. Statistical analyses were performed using mixed-effects linear regression models, accounting for within-subject inter-eye correlations. Results: Mean ganglion cell + inner plexiform layer (GCIPL) thickness was reduced in both NS-ON eyes (64.6±11.4μm) and NS-NON eyes (73.2±6.5μm) as compared to HC eyes (75.3±8.8μm; p Conclusions: Patients with NS exhibit lower GCIPL and pRNFL thicknesses as compared to HCs. Furthermore, GCIPL thickness – a sensitive marker of retinal neuro-axonal loss – is reduced even in NS eyes without a history of clinically-evident optic neuropathy. Our findings suggest that occult optic neuropathy occurs in NS and may act as a marker of widespread central nervous system degeneration. Disclosure: Dr. Salazar Camelo has nothing to disclose. Dr. Murphy has nothing to disclose. Dr. Lambe has nothing to disclose. Dr. Filippatou has nothing to disclose. Dr. Calabresi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Disarm Therapeutics. Dr. Calabresi has received personal compensation in an editorial capacity for JCI Editorial Board. Dr. Calabresi has received research support from Biogen. Dr. Saidha has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has served on scientific advisory boards forBiogen-Idec, Genzyme, Genentech Corporation, EMD Serono a Novartis. He is the PI of investigator-initiated studies funded by Genentech Corporation and Biogen Idec, and the site investigator of a trial sponso. Dr. Saidha has received research support from Biogen, Genentech. Dr. Pardo-Villamizar has received research support from McLean’s foundation.
Quadratically Constrained Problems

In this chapter, we discuss nonconvex quadratically constrained test problems. These include problems with separable quadratic constraints, complementarity type constraints, and integer type constraints. Notice that every simple binary constraint of the form: $$ x \in \left\{ {0,1} \right\} $$ can be written as: $$ - {x^2} + x \leqslant 0 $$ or $$ {x^2} - x = 0 $$
Evaluation of colorimetric assays for analyzing reductively methylated proteins: Biases and mechanistic insights.

Colorimetric protein assays, such as the Coomassie blue G-250 dye-binding (Bradford) and bicinchoninic acid (BCA) assays, are commonly used to quantify protein concentration. The accuracy of these assays depends on the amino acid composition. Because of the extensive use of reductive methylation in the study of proteins and the importance of biological methylation, it is necessary to evaluate the impact of lysyl methylation on the Bradford and BCA assays. Unmodified and reductively methylated proteins were analyzed using the absorbance at 280 nm to standardize the concentrations. Using model compounds, we demonstrate that the dimethylation of lysyl e-amines does not affect the proteins' molar extinction coefficients at 280 nm. For the Bradford assay, the responses (absorbance per unit concentration) of the unmodified and reductively methylated proteins were similar, with a slight decrease in the response upon methylation. For the BCA assay, the responses of the reductively methylated proteins were consistently higher, overestimating the concentrations of the methylated proteins. The enhanced color formation in the BCA assay may be due to the lower acid dissociation constants of the lysyl e-dimethylamines compared with the unmodified e-amine, favoring Cu(II) binding in biuret-like complexes. The implications for the analysis of biologically methylated samples are discussed.
Metastatic mesothelioma of the oral cavity: Report of two cases

Malignant mesothelioma is an aggressive neoplasm originating from the serosal surfaces of the pleural or peritoneal cavity. The following article describes two cases of metastatic mesothelioma to the oral cavity; one involves the tongue, the other involves the mandible. The diagnostic criteria for differentiating metastatic mesothelioma from adenocarcinoma are also discussed.
High performance InAs/InP C-band quantum dot coherence frequency comb lasers

We have experimentally demonstrated several InAs/InP quantum dot C-band coherence frequency comb lasers with the frequency spacing from 10 GHz to 100 GHz with the total output power of up to 50 mW.