cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of TCDD on the fate of naive dendritic cells

The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), causes immune suppression via activation of the aryl hydrocarbon receptor. Dendritic cells (DCs), the professional antigen-presenting cells in the immune system, are adversely affected by TCDD. We hypothesized that TCDD alters DC homeostasis, resulting in a loss of DCs in naive mice. To test this hypothesis, C57Bl/6 mice were gavaged with either vehicle or an immunosuppressive dose of TCDD (15 mg/kg). TCDD exposure decreased the frequency and number of splenic CD11c high DCs on day 7 when compared with vehicle-treated controls. TCDD increased the expression of CD86 and CD54, while decreasing the frequency of splenic CD11c high DCs expressing CD11a and major histocompatibility complex (MHC) class II. Moreover, TCDD selectively decreased the CD11c high CD8a 2 33D1 1 splenic DCs specialized at activating CD4 1 T cells but did not affect the regulatory CD11c high CD8a 1 DEC205 1 splenic DCs. TCDD did not alter the number or frequency of CD11c low splenic DCs but decreased their MHC class II and CD11a expression. Loss of splenic CD11c high DCs was independent of Fas-mediated apoptosis and was not due to alterations in the numbers of common DC precursors in the bone marrow or their ability to generate steady-state DCs in vitro. Instead, increased CCR7 expression on CD11c high DCs suggested involvement of a migratory event. Popliteal and brachial lymph node CD11c 1 cells showed elevated levels of MHC class II and CD40 following TCDD exposure. Collectively, this study shows the presence of a TCDD-sensitive splenic DC subpopulation in naive mice, suggesting that TCDD may induce suppression of T-cell-mediated immunity by disrupting DC homeostasis.
The reaction 14C(3He, n)16O and the coexistence model of 16O

Abstract The reaction 14 C( 3 He, n) 16 O has been measured at a 3 He bombarding energy of 25.4 MeV. The zero-degree differential cross section for the excitation of the three low lying 0 + T = 0 states, at energies 0.0, 6.05 and 12.05 MeV are, respectively, 1.33 ± 0.10, 0.49 ± 0.10, and 0.50 ± 0.10 mb/sr These measured cross sections are in rough agreement with single-step zero-range DWBA calculations using an empirically determined 14 C ground state wave function and in which the Brown and Green coexistence-model wave functions are used to describe the 16 O 0 + states. The angular distribution of the transition to the ground state is measured between 0° and 32°.
New classification criteria for gout: a framework for progress

The definitive classification or diagnosis of gout normally relies upon the identification of MSU crystals in SF or from tophi. Where microscopic examination of SF is not available or is impractical, the best approach may differ depending upon the context. For many types of research, clinical classification criteria are necessary. The increasing prevalence of gout, advances in therapeutics and the development of international research collaborations to understand the impact, mechanisms and optimal treatment of this condition emphasize the need for accurate and uniform classification criteria for gout. Five clinical classification criteria for gout currently exist. However, none of the currently available criteria has been adequately validated. An international project is currently under way to develop new validated gout classification criteria. These criteria will be an essential step forward to advance the research agenda in the modern era of gout management.
Corn and soil response to biochar application and stover harvest.

Abstract Soil biochar amendments are hypothesized to help mitigate potential negative soil quality effects of harvesting crop residues for bioenergy production. This study quantified effects of a onetime biochar application on crop yields and changes in soil properties at a Midwestern U.S.A. site where corn (Zea mays) stover is being harvested. The long-term experiment was established in Boone County, Iowa by application of 0, 9.8, and 18.4 Mg ha −1 of −1 , averaged across all biochar treatments. When analyzed on an annual basis, biochar had no significant effect on grain yield, but when averaged across years, the 18.4 Mg ha −1 biochar application rate significantly increased yields by 0.49 Mg ha −1 for the zero residue removal treatment but not for the 50% and 90% residue removal treatments. Residue removal increased yield to a greater extent during years of stress due to either excess moisture (2008 and 2010) or drought (2012). There was no yield effect in 2011, a year with favorable climatic conditions. The results suggest that during the first five years of study, residue removal in general had positive effect on yield of continues corn. Application of biochar at the high rate increased yield in the plots with 0% residue removal.
Intravenous Fluid Therapy of Calves

Dehydration in neonatal calves with diarrhea is a common cause of death. Severely dehydrated calves that are unable to suckle need intravenous fluids for effective resuscitation. This article gives an overview of the principles of intravenous fluid therapy for dehydrated calves including the types of fluids commonly used and methods of fluid administration. Practical on-farm options for simple clinical assessment and treatment of dehydration and acidosis in calves are also discussed in this article.
Easily missed fracture: distal radius and concomitant proximal ulna.

An 8-year-old girl presented to the emergency department following a fall from a climbing frame onto her outstretched left hand. On examination, the left wrist was swollen and tender. The skin was intact with no neurovascular compromise. The patient also reported pain in the left elbow, which was tender on palpation. Anteroposterior and lateral radiographs of the left forearm showed a fracture of the distal radius and proximal ulna (figures 1 and 2). …
Multiaxis unsteady aerodynamic characteristics of an aircraft

The multiaxis unsteady aerodynamic characteristics of en F-18 aircraft are presented and analyzed in this paper. The wind-tunnel tests using the Dynamic Plunge Pitch-Roll model mount at Virginia Tech Stability Wind Tunnel are first described, and the data reduction techniques are briefly discussed. The typical experimental results for harmonic oscillatory maneuvers in roll are illustrated, and the resulting hysteresis loops analyzed. On the basis of data obtained, a state-space formulation is proposed to describe the unsteady aerodynamic characteristics of the aircraft in multiple axes. This formulation consists of a number of basic statespace models each of which is used to characterize the unsteady aerodynamics of a single lifting surface. The unsteady aerodynamic characteristics of the whole aircraft along and about each axis are then obtained by the contributions of these lifting surfaces about the corresponding axis. The performance of this aerodynamic formulation is also shown based on the current windtunnel data.
Relation between Geochemical Characteristics of Natural Gas and Hydrocarbon Accumulation in Yuanba and Tongnanba Areas

Based on the gas geochemistry characteristics of drilled wells and analysis of gas origin in Yuanba and Tongnanba Areas,and in combination with regional geological background,study results showed that two work areas were the same of high thermal evolution of methane,dry gas content was low heavy hydrocarbon,and the content of non-hydrocarbon was high.Gas parent material was typeⅡorganic matter that is the product from high thermal evolution stage.And at the same time,the gas origin was chaotic.The distribution range of ln(C1/C2) and ln(C2/C3) in gas obviously indicated that the gases in Changxing Formation and Feixianguan Formation were the products of secondary cracking of oil in Yuanba Area.And the gases in the Upper Permian and Lower Triassic were the result of first cracking of kerogen.It is considered that the thermochemical sulfate reduction(TSR)happens in native reservoirs in Yuanba Area,which causes high hydrogen sulfide content in Changxing Formation and Feixianguan Formation.The native reservoir in Tongnanba Area has no TSR,which is the reason the gas in Upper Permian and Lower Triassic excludes hydrogen sulfide.
What has been learned from mouse models of the Fragile X Premutation and Fragile X-associated tremor/ataxia syndrome?

AbstractObjective: To describe in this review how research using mouse models developed to study the Fragile X premutation (PM) and Fragile X-associated tremor/ataxia syndrome (FXTAS) have contributed to understanding these disorders. PM carriers bear an expanded CGG trinucleotide repeat on the Fragile X Mental Retardation 1 (FMR1) gene, and are at risk for developing the late onset neurodegenerative disorder FXTAS. Conclusions: Much has been learned about these genetic disorders from the development and study of mouse models. This includes new insights into the early cellular and molecular events that occur in PM carriers and in FXTAS, the presence of multiorgan pathology beyond the CNS, immunological dysregulation, unexpected synthesis of a potentially toxic peptide in FXTAS (i.e., FMRpolyG), and evidence that the disease process may be halted or reversed by appropriate molecular therapies given early in the course of disease.
Microaggressions and Intersectionality in the Experiences of Black Women Studying Abroad through Community Colleges: Implications for Practice

Community colleges have a unique opportunity to both increase access to and improve the quality of education abroad for underrepresented students. Their use of faculty-led programs (Raby 2008; Amani 2011) can be capitalized upon to reach students of color as well as first-generation and low-income students and to provide them with supportive environments that help maximize their learning experiences. However, despite the relative diversity of many community colleges, underrepresented minority students can still be marginalized on their home campuses, and by extension, when they study abroad.
Measures for use in asthma clinical research. Overview of the NIH workshop.

Asthma is a major health problem in the United States; both mortality and morbidity are increasing. Approximately 12million Americans, including 4 million under the age of 18 years, are affected. People with asthma experience more than 100 days of restricted activity annually, and costs for asthma care exceed $4.6 billion a year (1). The National Asthma Education Program (NAEP) was established by the National Heart, Lung, and Blood Institute (NHLBI) in 1989 in recognition of the impact of asthma on individuals, their families, the medical care system, and society. The goals of the program are to educate patients, health professionals, and the public about asthma. Effective control of asthma is promoted through modern, science-based treatment and education programs and by encouraging a partnership among patients, physicians, and other health professionals (2). The first major task of the NAEP was to develop and disseminate Guidelines for the Diagnosis and Management of Asthma (3). Rather than just relieving acute exacerbations of respiratory distress with bronchodilator therapy, first-line therapy now aims to control inflammation by use of cromolyn and inhaled corticosteroids. That report, which is changing clinical management of the disease, was followed in 1992 by Management of Asthma During Pregnancy (4). Another report in preparation focuses on management of asthma in the elderly.
Radiology Reports: What YOU Think You're Saying and What THEY Think You're Saying.

Abstract Background Image interpretation and translation into written language is an imperfect process. Yet, the radiology report represents the link between radiologist's opinion and patient's images. Increased access to images through remote viewing stations has made direct communication between radiologists and clinicians less commonplace. We are interested in how accurately the descriptive contents within radiology reports convey the feelings of the radiologist to the referring clinician. We hypothesize that certain words and phrases hold different connotations for radiologists and clinicians. Materials and Methods A two part survey was designed. Medical specialty, level of training, and number of radiology reports read/week was contained in part I. Part II concerned the quantification of radiologists' diagnostic confidence in range percentages based on specific words and phrases. These voluntary surveys were emailed to all faculty at a single university medical center. Additional paper surveys were randomly distributed to medical students, residents, and physicians. A total of 100 completed surveys were collected (33 radiologists and 67 non-radiologists). Data was exported to EXCEL for statistical analysis. Direct comparisons were made between the survey answers from radiologists and nonradiologists. Discussion Percentile ranges for most radiologists and non-radiologists were in agreement in 25/36 questions. However, the absolute percentage value was somewhat variable. 11/36 questions generated discrepancy between radiologists and non-radiologists. The following words and phrases were in disagreement: “diagnostic of”, “consistent with”, “compatible with”, “evidence of”, “may represent”, “normal”, “degraded by artifact”, “obscured detail”, “mildly limited”, “moderately limited”, and “nondiagnostic”. Conclusion Sound physician communication is a critical component of quality healthcare delivery. Certain words and phrases carry different meanings for radiologists and clinicians. With structured reporting becoming more prevalent, the radiology lexicon should be defined in a more concrete manner. Ambiguous terms should be eliminated all together.
Pricing in linear-quadratic dynamic games

We investigate the use of pricing mechanisms as a means to achieve a desired feedback control strategy among selfish agents. We study a hierarchical linear-quadratic game with many dynamically coupled Nash followers and an uncoupled leader. The leader influences the game by choosing the quadratic dependence on control actions for each follower's cost function. We show that determining whether the leader can establish the desired feedback control as a Nash equilibrium among the followers is a convex feasibility problem for the continuous-time infinite horizon, discrete-time infinite horizon, and discrete-time finite horizon settings, and we present several extensions to this main result. In particular, we discuss methods for ensuring that the total cost incurred due to the leader's pricing is as close as possible to a specified nominal cost, as well as methods for minimizing the explicit dependence of a player's cost on other players' control inputs. Finally, we apply the proposed method to the problem of ensuring the security of a multi-network and to the problem of pricing for controlled diffusion in a general network.
An approach to big data inspired by statistical mechanics

A family of techniques in physics known as statistical mechanics is useful for describing the macroscopic properties of materials composed of a large (Avogadro's # ≈ 1024) number of atoms. This talk applies the same approach to the analysis of big data problems. The initial problem examined is that of classification, specifically binary hypothesis testing, in the big data, high dimensional scenario. The lessons learned from the binary hypothesis testing problem are extended to other signal processing paradigms.
Discrimination of alkyl and aromatic amine vapors using TTF–TCNQ based chemiresistive sensors

We report a chemiresistive sensor approach based on a TTF–TCNQ charge transfer material, which can real-time detect and distinguish the vapors of alkyl amine and aromatic amine species under ambient conditions, based on the dramatic difference in the kinetics of the electric current recovery processes after the exposure of the two amine species.
Improving predictive state representations via gradient descent

Predictive state representations (PSRs) model dynamical systems using appropriately chosen predictions about future observations as a representation of the current state. In contrast to the hidden states posited by HMMs or RNNs, PSR states are directly observable in the training data; this gives rise to a moment-matching spectral algorithm for learning PSRs that is computationally efficient and statistically consistent when the model complexity matches that of the true system generating the data. In practice, however, model mismatch is inevitable and while spectral learning remains appealingly fast and simple it may fail to find optimal models. To address this problem, we investigate the use of gradient methods for improving spectrally-learned PSRs. We show that only a small amount of additional gradient optimization can lead to significant performance gains, and moreover that initializing gradient methods with the spectral learning solution yields better models in significantly less time than starting from scratch.
Testimony Before the U.S. House of Representatives Task Force on Executive Overreach

This testimony discusses the non-delegation doctrine. It also discusses the tendency of executive agencies to eschew rule-making (which is subject to notice and comment) in favor of issuing guidances and why that tendency is often an abuse. It also gives two examples of guidances issued by the Department of Education's Office for Civil Rights that go beyond what the statute they purport to interpret allow. The first such example is its Dear Colleague Letter issued on April 4, 2011 (often called “the Sexual Violence Guidance”). The second example is its Colleague Letter dated May 13, 2016, jointly issued with the Civil Rights Division of the Department of Justice (often called the “Transgender Guidance”).
Computer science, biology and biomedical informatics academy: outcomes from 5 years of immersing high-school students into informatics research

The University of Pittsburgh's Department of Biomedical Informatics and Division of Pathology Informatics created a Science, Technology, Engineering, and Mathematics (STEM) pipeline in 2011 dedicated to providing cutting-edge informatics research and career preparatory experiences to a diverse group of highly motivated high-school students. In this third editorial installment describing the program, we provide a brief overview of the pipeline, report on achievements of the past scholars, and present results from self-reported assessments by the 2015 cohort of scholars. The pipeline continues to expand with the 2015 addition of the innovation internship, and the introduction of a program in 2016 aimed at offering first-time research experiences to undergraduates who are underrepresented in pathology and biomedical informatics. Achievements of program scholars include authorship of journal articles, symposium and summit presentations, and attendance at top 25 universities. All of our alumni matriculated into higher education and 90% remain in STEM majors. The 2015 high-school program had ten participating scholars who self-reported gains in confidence in their research abilities and understanding of what it means to be a scientist.
Methodological moralism in political philosophy

AbstractAn important strand in the school of thought known as ‘political realism’ is a distancing from, if not a rejection of ‘political moralism,’ the application of moral standards to political phenomena. This initial formulation of realism’s opposition to moralism suggests several distinct theses. One is that moral thinking, as a social phenomenon, is causally subsidiary to political structure. Another is that moral convictions are mere rationalizations of preferences and interests. A third is that proper political thought takes the moral defects of humans as given. Another thesis yet would be that political standards are not ‘applied ethics,’ applications of moral principles applicable to individual behavior. I argue that none of these positions, even if they were correct, would raise any difficulty for the thesis that political arrangements are subject to moral standards of what is right or just.
Direct Benefits and the Evolution of Female Mating Preferences: Conceptual Problems, Potential Solutions, and a Field Cricket

Abstract Of the many hypotheses for the evolution of female mating preferences, the direct benefits hypothesis is one of the most widely accepted and, paradoxically, one of the least understood. This chapter begins with an overview of the hypothesis and discusses some of the challenges in testing it. While commonly thought to be a simple hypothesis to test, a strong test of the hypothesis is just as difficult as for other major explanations for the evolution of mating preferences. The chapter then discusses some of the conceptual problems with the hypothesis, including potential solutions to these problems. For example, it is not clear why some types of direct benefits evolve, why male signals provide reliable information to females about benefit quality, or how females can consistently select males that provide above average benefits when environmental conditions are variable. It concludes by illustrating some of the challenges and conceptual problems with work by the author on a North American field cricket.
Characterization of platelet-releasable forms of beta-amyloid precursor proteins: the effect of thrombin

Activated platelets release a potent inhibitor of factor XIa previously identified as a Kunitz proteinase inhibitor domain-containing form of the beta-amyloid precursor proteins (beta APP). Two carboxy-terminal truncated forms of the beta APP, beta APP-751 and beta APP-770, are shown to be the predominant isoforms secreted by platelets. The release of beta APP from platelets is responsible for the higher concentration of beta APP in serum compared with plasma, and thrombin dose-response data show that release of beta APP is most consistent with alpha granule localization within the platelet. Thrombin induces a limited and specific proteolysis of platelet-secreted beta APP, resulting in loss of a carboxy-terminal fragment. This phenomena is dependent on both thrombin concentration and duration of incubation and is inhibited by the thrombin-specific inhibitor hirudin, characteristics that can be duplicated in a mixture of purified recombinant beta APP-751 and thrombin. A similar effect of thrombin on full-length transmembrane forms of beta APP would result in a membrane-bound remnant containing the intact beta-amyloid protein.
Dinuclear nitrido-bridged ruthenium complexes bearing diimine ligands.

Reactions of K3[Ru2NCl8(H2O)2] with 2,2′-bipyridine (bpy), 4,4′-dimethyl-2,2′-bipyridine (dmbpy), and 4,4′-dimethoxy-2,2′-bipyridine (dmobpy) yielded the nitrido-bridged dinuclear complexes [Ru2N(L)2Cl5(DMF)] where L = bpy (1), dmbpy (2), and dmobpy (3). The crystal structures of these complexes reveal a linear Ru–N–Ru moiety with each ruthenium center bearing a bidentate diimine ligand. The complexes were further characterized by NMR, IR, and UV-vis spectroscopic methods and cyclic voltammetry. Because the compounds bear some structural similarities with the mitochondrial calcium uptake inhibitor Ru360, the ability of these complexes to act in this capacity was evaluated. The results demonstrate that 1–3 all fail to block mitochondrial calcium uptake, revealing new facets of the structure–activity relationships for ruthenium-based mitochondrial calcium uptake inhibitors.
Decreased inappropriate shocks with new generation ICDs in children and patients with congenital heart disease.

Objective Inappropriate implantable cardioverter defibrillator (ICD) shocks in children and patients with congenital heart disease (CHD) remain a major complication of device therapy, occurring in as many as 50% of children with ICDs. New generation devices include algorithms designed to minimize inappropriate shocks. This study aimed to evaluate the effect of new generation ICDs on the incidence of inappropriate shocks in the pediatric and CHD population. Design Retrospective study of patients with CHD or under age 25 receiving ICDs between 2000 and 2015. New generation ICDs were defined as those with Medtronic “SmartShock” algorithms. Results Two hundred eight devices were implanted in 146 patients. Rates of inappropriate shocks were similar between diagnoses (P = .71). The rate of inappropriate shock was 15% over median 5.8 years follow-up. In the 36 patients (25%) with new generation ICDs, the rate of inappropriate shock was 6.3% over 4 years. Comparing old to new generation ICDs, freedom from first inappropriate shock was 90.6% versus 97.1% at 1 year and 80.4% versus 97.1% at 3 years (P = .01). Lead fracture was associated with having inappropriate shock (hazard ratio 8.5, P < .0001), and there was no significant difference between the device groups when lead fractures were excluded. Clinical actions were taken in 69% of patients after initial inappropriate shock (such as medication or program change, system revision, or explant). When an action was taken, subsequent inappropriate shock was reduced (5.3% vs 49.2% at 1 year; P = .002). Conclusions Pediatric and CHD patients are experiencing reduced inappropriate shocks with new generation ICD systems, though reduced lead fracture may account for this improvement. Clinical interventions after inappropriate shock favorably impact the subsequent rate of shocks once an inappropriate shock occurs.
Only the instantaneous global warming potential is consistent withhonest and responsible greenhouse gas accounting

Abstract. This paper presents a simple model to describe the impact on global warming of methane (natural gas) when used for energy production. The model is used to estimate the near-term effect of energy policies based on natural gas as a bridge fuel. The results make it clear that the commonly employed global warming potential of methane with a 100-year time horizon has the following problems: 1: it produces misleading results; 2: is inconsistent with meaningful tracking of greenhouse gas emissions; and 3: is incompatible with the precautionary principle.
Individual differences in combat experiences and error-related brain activity in OEF/OIF/OND veterans.

Abstract Increased error-related negativity (ERN) has been implicated in the pathophysiology of multiple forms of psychopathology. Although there is increasing evidence that the ERN can be shaped by environment and experience, no studies to date have examined this question in a clinical sample. In the current study, we examined the influence of combat exposure on the ERN using electroencephalogram (EEG) in a sample of military veterans with a high prevalence of psychopathology. Participants included sixty-seven U.S. military veterans from Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). The degree of combat exposure was assessed using the Deployment Risk and Resilience Inventory-2 (DRRI-2) and Combat Exposure Scale (CES). A well-validated flanker task was used to elicit the ERN during continuous EEG recording. Results revealed that veterans who reported experiencing greater combat exposure exhibited a more enhanced ERN, even when adjusting for broad anxiety and posttraumatic stress disorder (PTSD) symptoms. The association between combat exposure and ERN was not moderated by PTSD symptom severity. The current study demonstrates that greater combat exposure is associated with a more enhanced ERN among OEF/OIF/OND veterans. This enhanced ERN may be one mechanism that places veterans at greater risk for developing psychiatric disorders following exposure to combat. Future longitudinal studies are needed to directly test whether the ERN mediates the relation between level of combat exposure and the development of internalizing disorders.
Formal Specification of Button-Related Fault-Tolerance Micropatterns

Fault tolerance has been a major concern in the design of computing platforms. However, currently, fault tolerance has been done mostly with just heuristics, high level probabilistic analysis and extensive testing. In this work, we explore how we can use formal patterns to achieve fault-tolerance designs and methods. In particular, we look at faults that occur in mechanical button interfaces such as button bounce, button stuck, and phantom button faults. Our primary goal is the safety of such interfaces for medical devices [7], but the methods are more widely applicable. We formally describe corresponding patterns to address these faults including button debouncing, button stuck detection, and phantom press filtering. We prove stuttering-bisimulation results for some patterns showing their fault-masking capabilities. Furthermore, for patterns where fault-masking is not possible, we prove fault-detection properties. We also instantiate these patterns to a simple instance of a button-press counter and perform execution and model checking as further validation.
Overview of Constipation

Constipation is one of the most frequently encountered digestive complaints in both primary care and gastroenterology subspecialty settings. A symptomatically defined disorder, constipation is commonly characterized by infrequent and/or difficult evacuation of stool. Conventionally, constipation was defined as having fewer than or equal to three bowel movements per week; however, it is now understood that reports of stool frequency alone are inconsistent and that number of stools does not necessarily correlate with complaints or pathology. Constipated patients may experience a variety of other symptoms, including straining during defecation, passage of hard or lumpy stools, feelings of incomplete rectal evacuation, prolonged stooling time, and need for manual maneuvers to pass stool. Thus, constipation is now commonly defined by the Rome criteria, an evidence-based consensus opinion that embraces the inherent heterogeneity of this condition. Prevalence estimates of constipation are high with a median range of 12–19 % in the United States alone. The economic burden and health-care costs associated with diagnosing and treating constipation are significant, and patients experiencing the condition report diminished quality of life. Various factors can lead to constipation including systemic processes and medications. Once these factors are ruled out, patients can be diagnosed with primary constipation. This clinical classification can be further divided into normal- or slow-transit constipation, pelvic floor disorders, or constipation-predominant irritable bowel syndrome (IBS-C). Significant overlap exists among these subcategories. Therefore, a thorough history and physical examination are essential in guiding diagnostic testing and tailoring management strategies.
HDAC Inhibitors and Other Histone Modifying Natural Products as Emerging Anticancer Agents

Histone deacetylase (HDAC) inhibitors represent a new class of anticancer agents that target dysregulated acetylation of histone lysines, an epigenetic rather than a genetic event. Certain HDACs are overexpressed and hyperactive in cancer cells, and suppression of these enzymes’ activities provides superior selectivity over more traditional anticancer agents. To date, two HDAC inhibitors—vorinostat and romidepsin—have reached the market, with romidepsin being an actual natural product and vorinostat closely related to the natural product HDAC inhibitor trichostatin A. Over the past 15 years, several secondary metabolites with high structural diversity from microorganisms, marine sponges, and cyanobacteria have been discovered to possess HDAC inhibitory activity and are currently at the clinical and preclinical stages. In this chapter, we recapitulate the discovery of natural product HDAC inhibitors, enumerate the challenges in their development and provide insights in the continuing role of natural products in the discovery of HDAC inhibitors as well as new modulators for other clinically-relevant epigenetic events, including histone methylation.
Taxonomical Diversity of Extremophiles in the Deep Biosphere

Abstract In the past few years, surface drillings have expanded our perspective of the Earth’s deep biosphere from the terrestrial and oceanic realms to include deep dark subterranean and subseafloor environments. Conditions in the deep biosphere approach the limits for life, but scientific expeditions undertaken for deep subsurface life suggest that these biospheres are hosting a large fraction of microorganisms; living in water, occupying pore space, or colonizing mineral and rock surfaces. Microbes in the deep biosphere are phylogenetically different from most cultured taxa and represent novel microbial assemblages with novel metabolic capabilities. Thus, investigating these subsurface terrains, which are the deepest and potentially the largest accessible ecosystem on Earth, provides a unique opportunity for obtaining direct insights into the deep microscopic world. The insights obtained from deep biosphere expeditions are also likely to facilitate and inform exobiological exploration. This chapter describes current understanding of the subsurface depth and environmental limits of our planet’s life processes and factors that potentially define diversity/distribution of life in the deep terrestrial crustal system. The chapter also highlights the microbiological studies from the selected deep terrestrial biospheres such as hydrothermal vents, oil reservoirs, caves, and subsurface mines.
Diameter quality control of Nb3Sn wires for MQXF cables in the USA

Author(s): Pong, I; Cooley, LD; Lin, A; Higley, HC; Sanabria, C | Abstract: The 0.850 ± 0.003 mm Nb3Sn wires for the low-beta quadrupole magnets 'MQXFA' procured for the U.S. LHC Accelerator RaD Program (LARP) and the U.S. High Luminosity LHC Accelerator Upgrade Project (US HL-LHC AUP, or simply AUP) are received at Lawrence Berkeley National Laboratory (LBNL). There, the wires are respooled and then fabricated into Rutherford cables for winding coils. As part of the quality control program, AUP obtains from the wire manufacturer values of the maximum, average, minimum, and standard deviation of the two orthogonal axes, which are assessed prior to shipment approval. At LBNL, a dual-axis optical micrometer is used to measure the wire diameter of each spool every ∼30 cm prior to cabling. This helps decide whether wire pieces with abnormal diameters should be distributed across the cable cross section, in order to improve cable parameter quality and mechanical stability consistency. This paper presents: 1) diameter data of LARP cables and of the first AUP cables made using wires acquired under LARP; 2) our deviation acceptance/rejection justification; and 3) the impact of wire diameter statistics on cable fabrication.
Passive Stiffness and Maximal and Explosive Strength Responses After an Acute Bout of Constant-Tension Stretching.

Context Constant-tension (CT) stretching has been used to reduce hamstrings passive stiffness; however, the time course of hamstrings stiffness responses during a short bout of this type of stretch...
Climate change exacerbates hurricane flood hazards along US Atlantic and Gulf Coasts in spatially varying patterns

One of the most destructive natural hazards, tropical cyclone (TC)–induced coastal flooding, will worsen under climate change. Here we conduct climatology–hydrodynamic modeling to quantify the effects of sea level rise (SLR) and TC climatology change (under RCP 8.5) on late 21st century flood hazards at the county level along the US Atlantic and Gulf Coasts. We find that, under the compound effects of SLR and TC climatology change, the historical 100-year flood level would occur annually in New England and mid-Atlantic regions and every 1–30 years in southeast Atlantic and Gulf of Mexico regions in the late 21st century. The relative effect of TC climatology change increases continuously from New England, mid-Atlantic, southeast Atlantic, to the Gulf of Mexico, and the effect of TC climatology change is likely to be larger than the effect of SLR for over 40% of coastal counties in the Gulf of Mexico. Tropical cyclone-induced coastal flooding will increase under climate change. Here the authors estimate the effects of sea level rise and tropical cyclone climatology change on late–21st–century flood hazards along the US Atlantic and Gulf Coasts and find that the effect of tropical cyclone change could surpass the effect of sea level rise at some areas in the Gulf of Mexico.
Exponent for the power-law relation between activation energy for dislocation nucleation and applied stress

The strength of defect-free crystalline materials is known to be close to the theoretical strength of the material and is typically governed by the nucleation of dislocations. Dislocation nucleation is controlled by the energy barrier associated with the nucleation process, which is a function of both the temperature and stress. Previous work has suggested that the energy barrier decreases with stress towards zero as a power-law relationship and that there may be an exponent with universal value for nucleation. In this paper, we analyze atomistic simulations and continuum models to determine if such a universal exponent exists. Fitting of all available atomistic data to the power-law expression does not yield evidence of a universal power-law behavior. The examination of continuum models, however, provides particular interesting insight. Sufficiently far away from the athermal limit, the energy barrier decays with an effective exponent greater than one such that both the energy barrier and activation volume decrease. However, very close to the athermal limit, the activation volume diverges, due to a divergent activation area of the dislocation loop, resulting in a limiting exponent around 0.5. The divergent activation volume is a result of including the generalized stacking fault energy and allowing the Burgers vector to go to zero during nucleation. These results further provide insight into strategies for empirically modeling the activation energy and activation volume, because they contradict the idea that the activation volume goes to zero, which is currently assumed in most empirical forms of the activation energy.
Making Our Information Ecosystem Explicit

For librarians working in research, reference, and instruction, information literacy (IL) is foundational to their work. Since the advent of the Association of College and Research Libraries' Framework for Information Literacy for Higher Education, IL has been substantially reimagined both theoretically and in professional practice. While much attention and scholarship has focused on broad-based, undergraduate education, there has been less work on information literacy for specific disciplines, such as theological and religious studies, or in library settings with unique curricular and professional needs.Information Literacy and Theological Librarianship: Theory & Praxis gathers together reflective practices and theoretical explorations from librarians across a range of theological libraries, including research universities with divinity schools, seminaries, religious universities, and small liberal arts colleges. This volume engages key concepts and concerns in information literacy pedagogy for theological libraries, and furnishes applied examples drawn from instructional experience. Placing the Framework in conversation with the study of religion and theological education, Information Literacy and Theological Librarianship provides theological and religious studies librarians working in different academic environments with concrete and practical ways to extend their own work on information literacy that is grounded in pedagogy and applicable to the unique features of theological librarianship.
Phase I dose-escalation trial of trifluridine/tipiracil (TAS-102) and temozolomide in the treatment of advanced neuroendocrine tumors.

615Background: Systemic chemotherapy plays a role in treating neuroendocrine tumors. Trifluridine/tipiracil (FTD/TPI), known as TAS-102, is an antineoplastic agent that is non-cross resistant with ...
Beyond survival: the broader consequences of prehospital transport by police for penetrating trauma.

Background Time to definitive hemorrhage control is a primary driver of survival after penetrating injury. For these injuries, mortality outcomes after prehospital transport by police and emergency medical service (EMS) providers are comparable. In this study we identify patient and geographic predictors of police transport relative to EMS transport and describe perceptions of police transport elicited from key stakeholders. Methods This mixed methods study was conducted in Philadelphia, Pennsylvania, which has the highest rate of police transport nationally. Patient data were drawn from Pennsylvania’s trauma registry and geographic data from the US Census and American Community Survey. For all 7500 adults who presented to Philadelphia trauma centers with penetrating injuries, 2006–2015, we compared how individual and geospatial characteristics predicted the odds of police versus EMS transport. Concurrently, we conducted qualitative interviews with patients, police officers and trauma clinicians to describe their perceptions of police transport in practice. Results Patients who were Black (OR 1.50; 1.20–1.88) and Hispanic (OR 1.38; 1.05–1.82), injured by a firearm (OR 1.58; 1.19–2.10) and at night (OR 1.48; 1.30–1.69) and who presented with decreased levels of consciousness (OR 1.18; 1.02–1.37) had higher odds of police transport. Neighborhood characteristics predicting police transport included: percent of Black population (OR 1.18; 1.05–1.32), vacant housing (OR 1.40; 1.20–1.64) and fire stations (OR 1.32; 1.20–1.44). All stakeholders perceived speed as police transport’s primary advantage. For patients, disadvantages included pain and insecurity while in transport. Police identified occupational health risks. Clinicians identified occupational safety risks and the potential for police transport to complicate the workflow. Conclusions Police transport may improve prompt access to trauma care but should be implemented with consideration of the equity of access and broad stakeholder perspectives in efforts to improve outcomes, safety, and efficiency. Level of evidence Epidemiological study, level III.
Online daily coupons: Understanding how prepayment impacts spending at redemption

Abstract Online daily coupons (ODCs) (e.g., Groupon) differ from conventional coupons, in that they require customers to make a prepayment for a product or service to receive a substantive discount at a later point in time. Drawing from escalation of commitment literature, this article examines how ODCs’ unique prepayment structure might affect customers’ spending upon redemption. The results reveal that a high prepayment enhances redemption spending, but only if the temporal distance between the prepayment and the redemption is small. A high prepayment also can enhance redemption spending if the consumer purchases the ODC (versus receives it as a gift). In combination, this evidence reveals a joint impact of the prepayment amount and redemption spending on the revenue generated for the ODC provider.
Measurement of vertebral endplate bone marrow lesion (Modic change) composition with water-fat MRI and relationship to patient-reported outcome measures.

Vertebral endplate bone marrow lesions (“Modic changes”, MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water–fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics. In this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression. Twenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference −22.3%; p < 0.001); in MC 2, BMF was higher (absolute difference 21.0%; p < 0.001). Absolute BMF differences between affected and unaffected marrow were larger in patients with greater disability (p = 0.029–0.032) and were not associated with pain (p = 0.49–0.83). BMF is significantly altered in MC. Water–fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression.
Non-Invasive Office Screening Methods

Small intestinal bleeding accounts for 5–10% of patients who present with gastrointestinal bleeding and remains a relatively uncommon cause. Unfortunately there are no guidelines or recommendations on screening this population. The office based screening of patients with occult gastrointestinal bleeding includes history and physical. Other strategies are based on screening guidelines for other conditions such as iron deficiency anemia and colorectal cancer screening. In addition patients with incidental findings of fecal occult blood test, or iron deficiency anemia with or without a positive fecal occult blood test may require further work up.
Buying Out Coaches: The Secret Billion Dollar Public Industry

In most states, the highest paid public employee is a head coach at a public university in either football or men’s and women’s basketball. With such large salaries, a coach will have large buyouts when he or she is terminated without cause. If a university can find a way to terminate a coach for cause, it can, based on the coach’s contract, skirt its buyout and pay the coach a significantly lesser amount or nothing at all. Terminating a coach for cause can be extremely difficult and the NCAA has been proven to show a large amount of inconsistency when ruling whether a coach should or should not be terminated for cause. Universities need to adjust the structure of these large buyouts and favor a coach who does well, rather than a coach who does poorly.
Audacity of huge: overcoming challenges of data scarcity and data quality for machine learning in computational materials discovery.

Machine learning (ML)-accelerated discovery requires large amounts of high-fidelity data to reveal predictive structure-property relationships. For many properties of interest in materials discovery, the challenging nature and high cost of data generation has resulted in a data landscape that is both scarcely populated and of dubious quality. Data-driven techniques starting to overcome these limitations include the use of consensus across functionals in density functional theory, the development of new functionals or accelerated electronic structure theories, and the detection of where computationally demanding methods are most necessary. When properties cannot be reliably simulated, large experimental data sets can be used to train ML models. In the absence of manual curation, increasingly sophisticated natural language processing and automated image analysis are making it possible to learn structure-property relationships from the literature. Models trained on these data sets will improve as they incorporate community feedback.