cssi/SciSciGPT-SciSciNet huggingface dataset:
Noncanonical STAT3 Activation Regulates Excess TGF-β1 and Collagen I Expression in Muscle of Stricturing Crohn’s Disease

Increased TGF-β1 and TGF-β1-dependent Collagen I production in intestinal mesenchymal cells result in fibrosis in patients with Montreal B2 fibrostenotic Crohn's disease. Numerous cytokines, including IL-6, are produced by activated mesenchymal cells themselves and activate STAT3. The aim of the current study was to determine the mechanisms by which STAT-3 activation might result in intestinal fibrosis. Cytokine levels were measured by ELISA. STAT3 and suppressor of cytokine signaling 3 protein levels were measured by immunoblot, STAT3-TGFB1 DNA-binding activity by chromatin immunoprecipitation, and TGFB1 transcriptional activity by luciferase reporter assay. TGF-β1 (TGFB1), Collagen1α1, and connective tissue growth factor (CTGF) gene expression was measured by quantitative RT-PCR. The role of STAT3 activation was determined using STAT3 inhibitor, Stattic, and by transfection of STAT3 mutants. Autocrine production of cytokines was increased in muscle cells of B2 phenotype patients from strictures and normal intestine in the same patient and compared with other Crohn's phenotypes, ulcerative colitis, and non-Crohn's patients. A unique pattern of STAT3 phosphorylation emerged: high STAT3(S727) and low STAT3(Y705) in strictures and the opposite in unaffected intestine. TGFB1 transcriptional activity was regulated by phospho-STAT3(S727) and was decreased by Stattic or dominant-negative STAT3(S727A). TGF-β1, COL1A1, and CTGF expression was inhibited by Stattic or dominant-negative STAT3(S727A). Treatment of normal muscle cells with IL-6 or expression of constitutively active STAT3(S727E) phenocopied muscle cells from strictured intestine. Neutralization of autocrine IL-6 reversed STAT3 phosphorylation and normalized expression of TGF-β1 in strictured intestinal muscle. The ability of Stattic to improve development of fibrosis was confirmed in mice with 2,4,6-trinitrobenzenesulfonic acid-induced colitis. We observed a unique phospho-STAT3(S727) response in patients with Montreal B2 Crohn's disease, particularly in response to IL-6 leading to increased TGF-β1, collagen, and CTGF production in ileal strictures.
Chronic nephrotoxicity complicating cyclosporine treatment of chronic inflammatory demyelinating polyradiculoneuropathy

We elected to use cyclosporin A (CsA) in a woman debilitated by refractory chronic inflammatory demyelinating polyradiculoneuropathy. Although strength improved coincident with CsA therapy, after 21 months she developed congestive heart failure and had a precipitous loss of renal function with chronic renal failure requiring hemodialysis. While most CsA-induced nephrotoxicity is dose related and reversible, the kidney biopsy in our patient showed chronic nephropathy, a complication previously unreported in the native kidney of a nontransplant patient. A slow rise in blood pressure preceded serum creatinine changes and was an early indicator of impending irreversible nephrotoxicity.
A case of exuberant candidal onychomycosis in a child with hyper IgE syndrome.

An 8-year-old girl with recurrent oral thrush as an infant and toddler, multiple diaper yeast infections, recurrent ear infections that required multiple ear-tube placements, a long history of mild atopic dermatitis, and at least 7 Staphylococcus aureus abscesses on the extremities presented with new-onset thickening of the thumbnail that had failed therapy with 40% urea cream (Figure 1). Of note, she had no history of bronchopulmonary infections. Periodic acidSchiff stained sections of a nail-plate clipping revealed yeast
Efficient algorithms for clique problems

The k-clique problem is a cornerstone of NP-completeness and parametrized complexity. When k is a fixed constant, the asymptotically fastest known algorithm for finding a k-clique in an n-node graph runs in O(n^0^.^7^9^2^k) time (given by Nesetril and Poljak). However, this algorithm is infamously inapplicable, as it relies on Coppersmith and Winograd's fast matrix multiplication. We present good combinatorial algorithms for solving k-clique problems. These algorithms do not require large constants in their runtime, they can be readily implemented in any reasonable random access model, and are very space-efficient compared to their algebraic counterparts. Our results are the following:*We give an algorithm for k-clique that runs in O(n^k/(@elogn)^k^-^1) time and O(n^@e) space, for all @e>0, on graphs with n nodes. This is the first algorithm to take o(n^k) time and O(n^c) space for c independent of k. *Let k be even. Define a k-semiclique to be a k-node graph G that can be divided into two disjoint subgraphs U={u"1,...,u"k"/"2} and V={v"1,...,v"k"/"2} such that U and V are cliques, and for all i=
Single genome analysis reveals genetic characteristics of Neuroadaptation across HIV-1 envelope

The widespread use of highly effective, combination antiretroviral therapy (cART) has led to a significant reduction in the incidence of HIV-associated dementia (HAD). Despite these advances, the prevalence of HIV-1 associated neurocognitive disorders (HANDs) has been estimated at approximately 40%-50%. In the cART era, the majority of this disease burden is represented by asymptomatic neurocognitive impairment and mild neurocognitive disorder (ANI and MND respectively). Although less severe than HAD, these diagnoses carry with them substantial morbidity. In this cross-sectional study, single genome amplification (SGA) was used to sequence 717 full-length HIV-1 envelope (env) clade B variants from the paired cerebrospinal fluid (CSF) and blood plasma samples of fifteen chronically infected HIV-positive individuals with normal neurocognitive performance (NCN), ANI and MND. Various degrees of compartmentalization were found across disease states and history of cART utilization. In individuals with compartmentalized virus, mean HIV-1 env population diversity was lower in the CSF than plasma-derived variants. Overall, mean V1V2 loop length was shorter in CSF-derived quasispecies when compared to contemporaneous plasma populations, and this was found to correlate with a lower mean number of N-linked glycosylation sites in this region. A number of discrete amino acid positions that correlate strongly with compartmentalization in the CSF were identified in both variable and constant regions of gp120 as well as in gp41. Correlated mutation analyses further identified that a subset of amino acid residues in these compartmentalization “hot spot” positions were strongly correlated with one another, suggesting they may play an important, definable role in the adaptation of viral variants to the CSF. Analysis of these hot spots in the context of a well-supported crystal structure of HIV-1 gp120 suggests mechanisms through which amino acid differences at the identified residues might contribute to viral compartmentalization in the CSF. The detailed analyses of SGA-derived full length HIV-1 env from subjects with both normal neurocognitive performance and the most common HAND diagnoses in the cART era allow us to identify novel and confirm previously described HIV-1 env genetic determinants of neuroadaptation and relate potential motifs to HIV-1 env structure and function.
Loneliness, Depression, and Social Activity after Determination of Legal Blindness

In 84 blind clients, incidence of depression was 6% (5 subjects), and symptoms changed markedly as a function of time since determination of legal blindness. Self-reports of feelings of loneliness ...
Effects of L-lysine and L-arginine on in vitro replication of feline herpesvirus type-1

Objective—To determine the effects of varios concentrations of L-lysine and L-arginine on in vitro replication of feline herpesvirus type-1 (FHV-1). Sample Population—Cultured Crandell-Reese feline kidney (CRFK) cells and FHV-1 strain 727. Procedure—Uninfected CRFK cells or CRFK cells infected with FHV-1 were cultured in Dulbecco's modified Eagle's medium or in 1 of 7 test media containing various concentrations of lysine and arginine. Viral titer and CRFK growth rate were assessed in each medium. Results—Media depleted of arginine almost completely inhibited viral replication, whereas 2.5 or 5.0 µg of arginine/ml of media was associated with a significant increase in FHV-1 replication. In media with 2.5 µg of arginine/ml, supplementation with 200 or 300 µg of lysine/ml reduced viral replication by 34.2 and 53.9%, respectively. This effect was not seen in media containing 5.0 µg of arginine/ml. Growth rates of CRFK cells also were suppressed in media containing these concentrations of amino acids, but the...
Colloidal graphene—Scalable processing for advanced materials

Abstract A context for the burgeoning emergence of colloidal graphene in various states of oxidation is provided for a collection of detailed reviews and perspectives on the exfoliation, synthesis, and use of colloidal graphene as a functional material in diverse advanced materials. Methods of generation cover orders of magnitude in scale, from bench top to manufacturing, and special attention is given to overlap with extant dispersion technology. Syntheses range from redox manipulations of coal extracts and graphite to multistep synthesis of polycyclic aromatic hydrocarbons. The advanced materials discussed include diverse sensing materials, including an introduction to optoelectronic devices, and numerous energy materials. Challenges for refining our understanding of basic properties of graphene on various length scales are presented.
Testing the hybrid-3-D hillslope hydrological model in a controlled environment

Hillslopes are important for converting rainfall into runoff, influencing the terrestrial dynamics of the Earth's climate system. Recently, we developed a hybrid-3-D (h3D) hillslope hydrological model that gives similar results as a full 3-D hydrological model but is up to 2–3 orders of magnitude faster computationally. Here h3D is assessed using a number of recharge-drainage experiments within the Landscape Evolution Observatory (LEO) with accurate and high-resolution (both temporally and spatially) observations of the inputs, outputs, and storage dynamics of several hillslopes. Such detailed measurements are generally not available for real-world hillslopes. Results show that the h3D model captures the observed storage, base flow, and overland flow dynamics of both the larger LEO and the smaller miniLEO hillslopes very well. Sensitivity tests are also performed to understand h3Ds difficulty in representing the height of the saturated zone close to the seepage face of the miniLEO hillslope. Results reveal that a temporally constant parameters set is able to simulate the response of the miniLEO for each individual event. However, when one focuses on the saturated zone dynamics at 0.15 m from the seepage face, a stepwise evolution of the optimal model parameter for the saturated lateral conductivity parameter of the gravel layer occurs. This evolution might be related to the migration of soil particles within the hillslope. However, it is currently unclear whether and where this takes place (in the seepage face or within the parts of the loamy sand soil).
Impact of Progression during Neoadjuvant Chemotherapy on Operative Management of Breast Cancer.

Background: Neoadjuvant chemotherapy (NCT) is the standard of care for locally advanced breast cancer, but remains controversial in early stage disease. Some have raised concerns that disease progression may make breast-conserving therapy (BCT) or even mastectomy impossible. The goal of this study was to determine the impact of disease progression during NCT on operative management. Methods: We reviewed clinicopathologic data on patients receiving NCT for Stage I-III breast cancer at a cancer center between 1994 and 2007. Chemotherapy regimens were anthracycline and/or taxane-based as determined by the medical oncologist. Results: 1928 patients received NCT, of which 1762 (91%) had a response (minor, partial, or complete), 107 (6%) had stable disease (SD), and 59 (3%) progressed (PD) on at least one regimen. Of the 59 patients with progression, 13 (22%) had tumor response and 7 (12%) had SD with their first regimen, but progressed on their second regimen. Thirty-nine (66%) had progression on their first regimen of which 4 (10%) proceeded to surgery, 1 (3%) developed metastasis, and 1 (3%) refused further therapy. Thirty-three (85%) received a second chemotherapy regimen after progression on the first regimen; 18 (55%) had response to the second regimen, 5 (15%) had SD, and 10 (30%) had further progression. Eight (14%) had XRT to control local progression. In the 59 patients with progression at any point during NCT, 40 (68%) underwent mastectomy, 12 BCT (20%), and 7 (12%) had no surgery. In patients who had mastectomies, 3 (8%) were BCT candidates before progression, one (3%) was converted to mastectomy for technical reasons, and 2 (5%) were not evaluable from available data. Overall, disease progression changed the operative plan in 11 (0.5%): 2 developed distant metastasis, 2 developed clinical lymphadenopathy, 3 required mastectomy instead of BCT, 3 became inoperable, and 1 required flap closure. Conclusion: Patients treated with NCT should be evaluated by multi-disciplinary team members for response to therapy. Progression on NCT is infrequent (3%), but the optimal management in these patients needs further study. Overall, progression on NCT changes the operative management in only a small proportion of patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1090.
Electronic Structure of Underdoped Superconductors and Related Mott Insulators

In this short paper, we give a brief review of our experimental effort to investigate the issue of normal state pseudogap in the underdoped regime, and the connection of the pseudogap of the electronic structure of the insulator.
Measuring Electricity from Space

Introduction On September 4, 1882, Thomas Edison flipped a switch at his Pearl Street Station and electric lights flickered on across lower Manhattan. So began the era of electric power transmission, setting off the proliferation of power plants distributing electrical power across the world. Yet today, 1.3 billion people continue to lack electricity, relying instead on kerosene, wood, and agricultural residues to meet their energy needs (International Energy Agency 2013). Where do these 1.3 billion people reside? And what do they reveal about how their governments choose to electrify some before others, and some not at all? Despite its significance, there are little reliable data on how electricity is distributed in much of the developing world. High levels of uncertainty pervade official estimates of electrification rates, a vital and basic public service that is typically provided by governments in most of the rural world. Surveys from the World Bank, the Demographic and Health Surveys (DHS), and household survey programs provide invaluable data on household electrification rates and use. But these exist only for a subset of countries and rarely enable estimation of electrification rates at lower sub-national levels. Moreover, such surveys are expensive and difficult to conduct in areas that are remote, dangerous, or without the cooperation of local officials. This book proposes a new method to estimate the provision of electrification using satellite imagery of the earth at night to identify lit and unlit areas across the globe. Stable concentrations of outdoor lighting are a uniquely good indicator of electricity access, because electricity is the most reliable energy source for outdoor illumination of streets and buildings and the only source that can do so at the levels required for satellite detection. Compared with traditional data on energy production and consumption, the satellite images explicitly reveal the geographic distribution of electrical power, providing a clearer picture of who benefits from electricity across every corner of the globe. Satellite Imagery of Nighttime Lights Since the early 1970s, the Defense Meteorological Satellite Program's Operational Linescan System (DMSP-OLS) has been flying in polar orbit capturing high-resolution images of the entire earth each night, typically between 7PM and 10PM local time.
Cybersecurity in Japan

This chapter provides an analysis of Japan’s internal and external CS dynamics as well as the responses and the relevant actors involved in enhancing cyber-defense capabilities. Japan has realized the need for a new regulatory and institutional order on the cyber-front. While substantial progress has been made in recent years, Japan’s CS progress remains far behind most industrialized countries. Recent developments are, however, likely to have far-reaching and significant effects on the country’s economic, political, and military spheres. Also examined are major jolts and shocks that woke the country up to a new level of CS awareness and recent regulatory developments on this front. The analysis also highlights major challenges and barriers facing Japan in strengthening CS. Finally it examines similarities and differences between Japan’s approach to CS and those of other major world economies.
Re-establishment of nucleosome occupancy during double-strand break repair in budding yeast.

Abstract Homologous recombination (HR) is an evolutionarily conserved pathway in eukaryotes that repairs a double-strand break (DSB) by copying homologous sequences from a sister chromatid, a homologous chromosome or an ectopic location. Recombination is challenged by the packaging of DNA into nucleosomes, which may impair the process at many steps, from resection of the DSB ends to the re-establishement of nucleosomes after repair. However, nucleosome dynamics during DSB repair have not been well described, primarily because of a lack of well-ordered nucleosomes around a DSB. We designed a system in budding yeast Saccharomyces cerevisiae to monitor nucleosome dynamics during repair of an HO endonuclease-induced DSB. Nucleosome occupancy around the break is lost following DSB formation, by 5′–3′ resection of the DSB end. Soon after repair is complete, nucleosome occupancy is partially restored in a repair-dependent but cell cycle-independent manner. Full re-establishment of nucleosome protection back to the level prior to DSB induction is achieved when the cell cycle resumes following repair. These findings may have implications to the mechanisms by which cells sense the completion of repair.
A potential role for Periostin in Barrett’s carcinogenesis

B28 Introduction: Periostin is a secreted extracellular matrix protein important in embryonic development and wound repair. It is a potential inducer of epithelial-mesenchymal transition and cell motility in normal development and cancer; although, whether it has a tumor suppressive or tumor promoting role is controversial. Overexpression of periostin mRNA was recently reported in Barrett’s (BE) and oesophageal adenocarcinoma (OAC) tissues (Hao Y, Gastroenterology 2006). >Aims: 1. Use gene expression data to determine whether periostin is overexpressed in the Barrett’s-dysplasia- carcinoma sequence. 2. Validate array data in independent samples at the protein level. 3. Investigate the capacity for periostin to promote invasion in vitro. >Methods: RNA expression was determined using Agilent microarrays from samples representing different stages of OAC development (normal squamous-oesophagus (NE); n=6, intestinal metaplasia (IM); n=21, Low-grade-dysplasia (LGD); n=17, High-grade-dysplasia (HGD); n=13, OAC; n=8). Periostin protein expression was examined immunohistochemically on an independent data-set (abcam14041). Oesophageal stromal fibroblasts were isolated from normal (NAFs), Barrett’s (BAFs), and tumor-associated patient tissues (CAFs) and characterized using vimentin and CK8/18. Periostin expression was determined by Western blotting and QPCR in primary fibroblasts, oesophageal adenocarcinoma (SEG, FLO, OE33, BIC) and dysplastic epithelial cell lines (GohTert, ChTert, GihTert). Effects of recombinant periostin (100-400ng/ml) and addition of primary fibroblasts on FLO invasiveness and motility were investigated in vitro using matrigel and wound healing assays. >Results: Periostin was significantly overexpressed in OAC compared to NE (4.36 fold, p=0.0035), IM (2.76 fold, p=0.0275), LGD (3.61 fold, p=0.0027) and HGD (14 fold, p=8.83E-08), (One-Way ANOVA). IHC showed that periostin protein expression was restricted to the stroma of BE and cancer tissues, with an apparent concentration at the epithelial-stromal interaction front in OAC. Purified cell types (primary stromal fibroblasts and established epithelial cell lines) were used to further characterize the cell specific expression of periostin. Apart from SEG cells, dysplastic and OAC epithelial cell lines expressed lower levels of periostin mRNA compared to oesophageal fibroblast lines derived from patients with dysplasia and cancer (2 fold, p Conclusion: Overexpression of periostin in primary fibroblasts and in stroma of cancer related tissues, combined with periostin-induced promotion of invasion in vitro, suggests a role for fibroblast derived periostin in cancer. The isolation of stage-specific primary stromal fibroblasts offers a valuable tool for further functional studies of stromal-epithelial interactions in Barrett’s carcinogenesis.
Trajectories for Flyby Sample Return at Saturn's Moons

Ballistic trajectories are computed which would enable a sample return mission to Titan or Enceladus without capturing, descending, or landing. The low-cost mission concept utilizes a free return trajectory that also involves a close flyby of the moon. This work extends the concept, and related trajectory analysis methodology, previously applied to a Europa mission. Specifically, a broad search algorithm is employed to systematically locate potentially feasible itineraries over an entire Saturn period. High-quality approximate solutions are then optimized to be continuous using high-fidelity dynamics. Techniques and software from the Europa analysis, were readily adapted and able to find numerous mission enabling trajectories. A direct mission to Titan is possible with flight time under 16 years and Earth-relative speeds below 11.0 km/sec. The VEEGA option is shown to substantially reduce launch C3, but flight times exceed 21 years. Unfortunately, an Enceladus mission requires a flight time of 25 years or more, and incurs fairly high relative speeds. Nevertheless, an optimized reference mission is computed.
Using a chelating agent to generate low ash bioenergy feedstock

Inorganic elements present in lignocellulosic biomass and introduced during harvesting and handling of the feedstock negatively affect biomass conversion to fuels and products. In particular, alkali and alkaline earth metals act as catalysts during thermochemical conversion, contribute to reactor degradation, and decrease the yield and quality of the reaction products. In this study, we investigated an approach to reduce ash content of switchgrass. Several reagents (chelating agents ethylenediaminetetraacetic acid (EDTA) and citric acid, as well as acetic acid, sulfuric acid, and water) under various extraction times (5, 10, 15, and 20 min) were tested using a microwave-assisted extraction method. After the extraction, mass loss, total ash, individual inorganics, and concentration of sugars in the hydrolyzates were measured. EDTA afforded the highest inorganics removal, with near complete extraction of alkali and alkaline earth metals K, Ca, and Mg, and high removal of S and Si. Citric acid and sulfuric acid removed similarly high amounts of K, Ca, and Mg as EDTA, but less Mg, P, S, and Fe. Additionally, extraction with water resulted in near complete removal of K; however, more modest removal of other inorganics was observed compared to other treatments. The mass loss was significantly higher in the sulfuric acid extractions due to hydrolysis of the structural carbohydrates, while EDTA resulted in little carbohydrate degradation due to the more neutral pH conditions. This study illustrated the benefits of extracting with chelating agents, as opposed to mineral acids, to remove inorganics and improve biomass quality.
Darwin Comes to Clinic

What might be the benefits of whole-genome rather than whole-exome sequencing (WES) for identifying the genetic causes of human disabilities? A recent paper by Doan et al. focuses attention on mutations in human accelerated regions (HARs), a subset of genomic regulatory elements showing accelerated evolution between chimpanzees and humans.
Nonlinear Stabilization Control of Multiple-RTAC Systems Subject to Amplitude-Restricted Actuating Torques Using Only Angular Position Feedback

Multiple rotational translational actuator (RTAC) systems are nonlinear complicated mechatronic systems introduced to investigate the self-synchronized phenomenon in mechanical engineering, which consist of a series of single-RTAC subsystems connected one by one through elastic springs. This paper studies the globally stabilizing control problem for multiple-RTAC systems by considering that the actuators are constrained in torque amplitudes and velocity signals are unavailable for feedback. More precisely, by carefully analyzing the system energy storage function and respecting the maximum allowable control torques, a novel amplitude-restricted control law is developed without requiring velocity feedback, which can stabilize multiple-RTAC systems from any initial condition theoretically. It is beneficial that the proposed control law does not involve any plant parameters, which consequently makes it insensitive to parameter uncertainties. The stability and convergence characteristics of the designed control system are rigorously supported with Lyapunov techniques. To the best of our knowledge, the proposed controller is the first one that can stabilize a multiple-RTAC system while simultaneously ensuring the practical control amplitude-restricted constraints, by using only output feedback. Both numerical simulation and hardware experiments are included to verify the effectiveness of the proposed control approach.
Extremely low-income households, housing affordability and the Great Recession

The effects of the Great Recession on housing equity and homeownership have been well-documented. However, we know little about how rental households fared and the efficacy of housing subsidies in addressing affordability gaps. This paper examines the extent to which rental housing became less affordable for Extremely Low-Income (ELI) households - those earning less than 30% of the Area Median Income (AMI). I then run regression models to determine the local characteristics most strongly associated with larger affordability gaps, with a focus on whether housing subsidies are effective at combating such gaps. Rental affordability gaps became more pronounced during the Great Recession. In nearly 70% of the counties in my sample, there was an increase from 2007 to 2010 in the number of ELI households per affordable rental unit. Across the country, the increase was 17%, a dramatic increase in only three years. There is considerable variation across the country, with acute affordability crises often concentrated in the South, particularly Florida. Regression models provide compelling evidence that housing vouchers, public housing, and project-based Section 8 subsidies play an important role in limiting the extent to which large numbers of ELI households are competing for a shortage of low-cost rental units. However, these programmes do not respond quickly to local needs - such as those brought about by the Great Recession. A pilot study where local housing authorities had funding to be more agile and responsive would be an important step toward crafting better policy.
Durable Resistance in the Pathosystems: Maize -Northern and Southern Leaf Blights

Monogenic resistance to northern leaf blight (Setosphaeria turcica) in maize is race-specific. Monogenic and oligogenic resistance to southern leaf blight (Cochliobolus heterostrophus) is not known to be race-specific, but it has not been tested extensively. Cytoplasmic susceptibility reduces effectiveness of maize resistance to race T of C. heterostrophus. Polygenes for resistance to northern leaf blight occur on 12 of 20 chromosome arms of maize. There is evidence of some specificity in this polygenic resistance. Recurrent selection significantly enhanced virulence of S. turcica to polygenically resistant inbreds, but the specificity of this increased virulence was not determined. Generation means analysis estimated up to 11 polygenes for resistance to southern leaf blight in resistant inbreds. Three generations of recurrent selection for virulence to a polygenically resistant inbred gave an 18% increase in lesion size on that inbred and a 7–10% increase on four unrelated maize cultivars. Thus, artificial selection can increase both virulence (cultivar specific) and aggressiveness (cultivar nonspecific) in C. heterostrophus.
A Hypothesis and Review of the Relationship between Selection for Improved Production Efficiency, Coping Behavior, and Domestication.

Coping styles in response to stressors have been described both in humans and in other animal species. Because coping styles are directly related to individual fitness they are part of the life history strategy. Behavioral styles trade off with other life history traits through the acquisition and allocation of resources. Domestication and subsequent artificial selection for production traits specifically focused on selection of individuals with energy sparing mechanisms for non-production traits. Domestication resulted in animals with low levels of aggression and activity, and a low hypothalamic-pituitary-adrenal (HPA) axis reactivity. In the present work we propose that, vice versa, selection for improved production efficiency may to some extent continue to favor docile domesticated phenotypes. It is hypothesized that both domestication and selection for improved production efficiency result in the selection of reactive style animals, which are both characterized by low levels of aggression and activity, and increased serotonin neurotransmitter levels. Whereas domestication quite consistently results in a decrease in the functional state of the HPA axis, the reactive coping style is often found to be dominated by a high HPA response. This may suggest that fearfulness and coping behavior are two independent underlying dimensions to the coping response. Although it is generally proposed that animal welfare improves with selection for calmer animals that are less fearful and reactive to novelty, animals bred to be less sensitive with fewer desires may be undesirable from an ethical point of view.
Perioperative Management of Hyperlipidemia Medications.

Background Coronary artery disease is a common comorbidity encountered during the perioperative period. Whether patients are scheduled for cardiac or noncardiac surgery, this cardiovascular disease must be addressed in the preoperative period to decrease the accompanying risks and potential postoperative problems. Lipid-lowering medications are often used to treat hyperlipidemia, a risk factor for the development of atherosclerosis and coronary artery disease. Objective To discuss the medications most commonly used to treat hyperlipidemia and to describe strategies for handling these treatment regimens in the perioperative period. Method An online search of studies and review articles was conducted through PubMed and Medline that addressed pharmacology and perioperative management of hyperlipidemia medications. Results Statins are the most commonly prescribed lipid-lowering agents, with benefits that extend beyond correcting lipid levels. However, statins can have clinically significant adverse effects that may necessitate the use of other lipid-lowering medications with different mechanisms of action. Alternative medications such as nicotinic acid and omega-3 fatty acids should be withheld in the preoperative period because these agents have been associated with hypotension and increased bleeding. Conclusion Clinicians must be familiar with the various lipid-lowering agents because it is very likely they will encounter such medications during preoperative visits.
Trauma-focused cognitive behavioural therapy for young children: clinical considerations.

ABSTRACTTrauma-focused Cognitive Behavioural Therapy (TF-CBT) has been utilized with children of a wide age range and with diverse trauma experiences. This article will focus on the application of ...
T185. DIFFERENTIAL ACTIVITY OF TRANSCRIBED ENHANCERS IN THE PREFRONTAL CORTEX OF 592 CASES WITH SCHIZOPHRENIA AND CONTROLS

AbstractBackgroundTranscription at enhancers is a widespread phenomenon, which produces so-called enhancer RNA (eRNA) and occurs in an activity dependent manner. The role of eRNA and its utility in exploring disease-associated changes in enhancer function and the downstream coding transcripts that they regulate is however not well established. We here used transcriptomic and epigenomic data to interrogate the relationship of eRNA transcription to disease status and how genetic variants alter enhancer transcriptional activity in the human brain.MethodsWe combined RNA-seq data from 537 post mortem brain samples from the CommonMind Consortium with cap analysis of gene expression and enhancer identification, using the assay for transposase-accessible chromatin followed by sequencing.ResultsWe find 118 differentially transcribed eRNAs in schizophrenia and identify schizophrenia-associated gene/eRNA co-expression modules. Perturbations of a key module are associated with the polygenic risk scores. Further, genetic variants affecting expression of 927 enhancers, which we refer to as enhancer expression quantitative loci or eeQTLs, are identified. Enhancer expression patterns are consistent across studies, including differentially expressed eRNAs and eeQTLs. Combining eeQTLs with a genome-wide association study of schizophrenia identifies a genetic variant that alters enhancer function and expression of its target gene, GOLPH3L.DiscussionHere, we expanded the scope of the CommonMind Consortium to interrogate enhancer function in schizophrenia, to examine how genetic variation affects enhancers, and to evaluate specific effects on enhancer and gene expression for previously identified schizophrenia risk variants. Our novel approach to analyzing enhancer transcription is adaptable to other large-scale, non-poly-A depleted, RNA-seq studies.
Inverse agonism of retinoic acid receptors directs epiblast cells into the paraxial mesoderm lineage.

Abstract We have investigated the differentiation of paraxial mesoderm from mouse embryonic stem cells utilizing a Tbx6-EYFP/Brachyury (T)-Cherry dual reporter system. Differentiation from the mouse ESC state directly into mesoderm via Wnt pathway activation was low, but augmented by treatment with AGN193109, a pan-retinoic acid receptor inverse agonist. After five days of differentiation, T+ cells increased from 12.2% to 18.8%, Tbx6+ cells increased from 5.8% to 12.7%, and T+/Tbx6+ cells increased from 2.4% to 14.1%. The synergism of AGN193109 with Wnt3a/CHIR99021 was further substantiated by the increased expression of paraxial mesoderm gene markers Tbx6, Msgn1, Meox1, and Hoxb1. Separate to inverse agonist treatment, when mouse ESCs were indirectly differentiated into mesoderm via a transient epiblast step the efficiency of paraxial mesoderm formation markedly increased. Tbx6+ cells represented 65–75% of the total cell population after just 3 days of differentiation and the expression of paraxial mesoderm marker genes Tbx6 and Msgn increased over 100-fold and 300-fold, respectively. Further evaluation of AGN193109 treatment on the indirect differentiation protocol suggested that RARs have two distinct roles. First, AGN193109 treatment at the epiblast step and mesoderm step promoted paraxial mesoderm formation over other mesoderm and endoderm lineage types. Second, continued treatment during mesoderm formation revealed its ability to repress the maturation of presomitic mesoderm into somitic paraxial mesoderm. Thus, the continuous treatment of AGN193109 during epiblast and mesoderm differentiation steps yielded a culture where ~90% of the cells were Tbx6+. The surprisingly early effect of inverse agonist treatment at the epiblast step of differentiation led us to further examine the effect of AGN193109 treatment during an extended epiblast differentiation protocol. Interestingly, while inverse agonist treatment had no impact on the conversion of ESCs into epiblast cells based on the expression of Rex1, Fgf5, and pluripotency marker genes Oct4, Nanog, and Sox2, after three days of differentiation in the presence of AGN193109 caudal epiblast and early paraxial mesoderm marker genes, T, Cyp26a1, Fgf8, Tbx6 and Msgn were all highly up-regulated. Collectively, our studies reveal an earlier than appreciated role for RARs in epiblast cells and the modulation of their function via inverse agonist treatment can promote their differentiation into the paraxial mesoderm lineage.
The Heat Is on: A Mixed-Method Examination of Eating Behavior and Executive Functions among Low Income Minority Girls during Summertime.

Despite evidence that youth gain weight disproportionately over the summer months, few studies examine contributing obesogenic behaviors. Utilizing a mixed-methods approach, this study examined ass...
Introduction to Behavior Medicine

Before going into a detailed consideration of the issues with which this unit deals, it is in order to introduce the reader to the historical and theoretical contexts out of which behavioral medicine has emerged. To understand what is new about behavioral medicine it is necessary first to consider how it differs from that field which has traditionally concerned itself with the links between emotions and illness: “psychosomatic medicine.” Historically, psychosomatic medicine focused its main attention on the role of specific personality traits and the neurotic conflicts growing out of those traits in the etiology and pathogenesis of disease. While the focus initially was on seven disorders—duodenal ulcer, asthma, Grave’s disease, essential hypertension, ulcerative colitis, neurodermatitis, and rheumatoid arthritis—in recent years the scope has enlarged to include all illness. Yet the historical concern with such intrapsychic phenomena as personality and neurotic conflict determined to a large extent that interventions in psychosomatic medicine would be directed toward correcting or reducing conflicts or changing personality. Thus therapy focused on the spontaneous verbal productions of the patient with the goal of achieving insights that would hopefully ameliorate the disease process.
A locally linear regression model for boundary preserving regularization in stereo matching

We propose a novel regularization model for stereo matching that uses large neighborhood windows. The model is based on the observation that in a local neighborhood there exists a linear relationship between pixel values and disparities. Compared to the traditional boundary preserving regularization models that use adjacent pixels, the proposed model is robust to image noise and captures higher level interactions. We develop a globally optimized stereo matching algorithm based on this regularization model. The algorithm alternates between finding a quadratic upper bound of the relaxed energy function and solving the upper bound using iterative reweighted least squares. To reduce the chance of being trapped in local minima, we propose a progressive convex-hull filter to tighten the data cost relaxation. Our evaluation on the Middlebury datasets shows the effectiveness of our method in preserving boundary sharpness while keeping regions smooth. We also evaluate our method on a wide range of challenging real-world videos. Experimental results show that our method outperforms existing methods in temporal consistency.
Large Eddy Simulations and Acoustic Predictions in Automotive Applications

The emergence of the computational tools capable of accurately predicting the flow properties around complex geometries has opened new opportunities in the design of automotive components and their integrations. In particular, one may now be able to predict the acoustic noise produced by the unsteady fluid motion induced by the individual parts and quantitatively evaluate their loudness and spectral (i.e. frequency content) without relying on semi-empirical models. To demonstrate this capability the flow noise produced by two configurations typical of automotive applications – namely the outside rear view mirrors and the rain gutters – are examined quantitatively. Relevant details regarding the prediction methods as well as a selection of results are discussed.
The Cytosolic Redox is Coupled to VO2. A Working Hypothesis

In aerobic tissues the match between energy demand (ATPase activity) and energy supply (ATP production) requires close integration of the glycolytic and mitochondrial metabolic controls. Since most ATPase activity occurs in the cytosol this integration must be mediated by cytosolic signals. While there is uncertainty about the mechanism, there is general agreement that recruitment of mitochondrial ATP production is strongly coupled to changes in cytosolic phosphorylation state. Although the role of mitochondrial redox has been identified, cytosolic redox has been left out of models of mitochondrial control. Results from three different kinds of studies suggest that in the cell there is a strong interaction between the mitochondrial and cytosolic redox states and mitochondrial metabolism. These results include studies on: 1) intact tissues such as liver (Berry et al, 1980), heart (Kauppinen et al, 1983) and red skeletal muscle (Connett et al, 1986); 2) reconstituted glycolytic and mitochondrial systems (Jong & Davis, 1983) and 3) metabolic models of heart metabolism that include kinetic submodels of most of the individual enzymes (Kohn, 1983). The objective of this paper is to describe a distributed equilibrium hypothesis that accounts for a cooperative interaction between the glycolytic and oxidative metabolic systems under aerobic conditions.
A drug-drug interaction study of capecitabine and celecoxib in patients with advanced solid malignancies.

e14066Background: Warfarin is an anticoagulant and CYP2C9 substrate commonly used in oncology patients. Several studies suggest a drug-drug interaction between capecitabine and warfarin that may be...
Building strength, endurance, and mobility using an astaxanthin formulation with functional training in elderly.

Author(s): Liu, Sophia Z; Ali, Amir S; Campbell, Matthew D; Kilroy, Kevin; Shankland, Eric G; Roshanravan, Baback; Marcinek, David J; Conley, Kevin E | Abstract: BackgroundBuilding both strength and endurance has been a challenge in exercise training in the elderly, but dietary supplements hold promise as agents for improving muscle adaptation. Here, we test a formulation of natural products (AX: astaxanthin, 12 mg and tocotrienol, 10 mg and zinc, 6 mg) with both anti-inflammatory and antioxidant properties in combination with exercise. We conducted a randomized, double-blind, placebo-controlled study of elderly subjects (65-82 years) on a daily oral dose with interval walking exercise on an incline treadmill.MethodsForty-two subjects were fed AX or placebo for 4 months and trained 3 months (3×/week for 40-60 min) with increasing intervals of incline walking. Strength was measured as maximal voluntary force (MVC) in ankle dorsiflexion exercise, and tibialis anterior muscle size (cross-sectional area, CSA) was determined from magnetic resonance imaging.ResultsGreater endurance (exercise time in incline walking, g50%) and distance in 6 min walk (g8%) accompanied training in both treatments. Increases in MVC by 14.4% (±6.2%, mean ± SEM, P l 0.02, paired t-test), CSA by 2.7% (±1.0%, P l 0.01), and specific force by 11.6% (MVC/CSA, ±6.0%, P = 0.05) were found with AX treatment, but no change was evident in these properties with placebo treatment (MVC, 2.9% ± 5.6%; CSA, 0.6% ± 1.2%; MVC/CSA, 2.4 ± 5.7%; P g 0.6 for all).ConclusionsThe AX formulation improved muscle strength and CSA in healthy elderly in addition to the elevation in endurance and walking distance found with exercise training alone. Thus, the AX formulation in combination with a functional training programme uniquely improved muscle strength, endurance, and mobility in the elderly.
Accelerator Physics Center at Fermilab : History and Accomplishments (2007-2018)

Fermilab’s Accelerator Physics Center (APC) was created in June 2007 with mission to carry out research and development to keep the US leading high-energy physics laboratory at the forefront of accelerator science, technology and facility operation. In support of the FNAL high-energy physics research mission, APC scientists and enginners conducted accelerator RD provided accelerator physics support for existing operational programs and the evolution thereof; trained accelerator scientists and engineer and established experimental programs for a broad range of accelerator R&D that can be accessed by both Fermilab staff and the US and world HEP community. APC was a center-place for in-depth design, research and development efforts which allowed the Laboratory to make intelligent decisions on the ILC in the US, on the Muon Collider, as well as originate projects like PIP-II (through the Proton Driver/Project-X work), LHC-AUP (via LARP) and the IOTA/FAST R&D facility. APC was also the birthplace and host of many national and international collaborations and several educational/training programs in beam physics resulted in 27 PhD theses. In the Fall 2018, following an important milestone of the first beam circulating in the IOTA ring, the APC was re-organized into several departments in Accelerator Division, charged to carry out the accelerator physics research with IOTA/FAST beams and making it relevant for future upgrades of the Fermilab accelerator complex.
The use of coercion in the treatment of incarcerated juveniles adjudicated on sexual offenses: consequences and implications.

Since the inception of specialized treatment for juveniles accused of and adjudicated on sexual offenses (JASOs), denial has been an organizing principle. Most clinicians believe that “breaking through” denial is a necessary prerequisite for successful treatment. Unfortunately, there is little empirical evidence to support this claim. Further, when admitting to one's sexually offensive behavior in treatment becomes paramount, the risk that other therapeutic issues are missed or ignored increases. This article calls attention to the dangers of coercion, in its varied forms, when attempting to get youth to “take responsibility” for their sexually offensive behavior. Based on interviews with 40 incarcerated JASOs, the author suggests that using “presumptive realities” as an organizing principle rather than denial, helps to focus treatment providers on their role in the therapeutic process. In using “presumptive realities” the JASO's story or interpretation of the abuse event is considered therapeutically relevant and reflective of the context in which treatment occurs.
Boosting Publicity: Old and New Media, Deliberations, and Organic Ideology Articulation

Publicizing campaigns need not only be far-reaching but also empowering. Mobilization, thus, requires all forms of traditional and emergent media, at the same time that venues for iterative knowing, probing, and problem-solving and formulating and articulating an organic ideology are created and sustained. With climate denial deeply entrenched in governments and traditional mass media channels, a new hegemony that support emancipatory and transformative climate actions can be promoted using new channels provided by social media; albeit ensuring authentic participation. Strengthening proven modes of face-to-face public engagement remains important. Authentic and influential deliberations can be tapped not only to increase public knowledge but also to open up a culture for reflexive problem solving, which has long-lasting effects to people.