cssi/SciSciGPT-SciSciNet huggingface dataset:
In Silico Identification of an Aryl Hydrocarbon Receptor Antagonist with Biological Activity In Vitro and In Vivo

The aryl hydrocarbon receptor (AHR) is critically involved in several physiologic processes, including cancer progression and multiple immune system activities. We, and others, have hypothesized that AHR modulators represent an important new class of targeted therapeutics. Here, ligand shape–based virtual modeling techniques were used to identify novel AHR ligands on the basis of previously identified chemotypes. Four structurally unique compounds were identified. One lead compound, 2-((2-(5-bromofuran-2-yl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (CB7993113), was further tested for its ability to block three AHR-dependent biologic activities: triple-negative breast cancer cell invasion or migration in vitro and AHR ligand–induced bone marrow toxicity in vivo. CB7993113 directly bound both murine and human AHR and inhibited polycyclic aromatic hydrocarbon (PAH)– and TCDD-induced reporter activity by 75% and 90% respectively. A novel homology model, comprehensive agonist and inhibitor titration experiments, and AHR localization studies were consistent with competitive antagonism and blockade of nuclear translocation as the primary mechanism of action. CB7993113 (IC50 3.3 × 10−7 M) effectively reduced invasion of human breast cancer cells in three-dimensional cultures and blocked tumor cell migration in two-dimensional cultures without significantly affecting cell viability or proliferation. Finally, CB7993113 effectively inhibited the bone marrow ablative effects of 7,12-dimethylbenz[a]anthracene in vivo, demonstrating drug absorption and tissue distribution leading to pharmacological efficacy. These experiments suggest that AHR antagonists such as CB7993113 may represent a new class of targeted therapeutics for immunomodulation and/or cancer therapy.
Current Problems in Combustion Research

Publisher Summary This chapter focuses on current problems in combustion research with emphasis on advances achievable by asymptotic analysis. Combustion research can be defined as the study of chemically reacting flows in which heat is liberated. Exothermically reacting flows can be described by a set of partial differential equations. Writing these equations and their boundary conditions in forms, which provide well-posed problems, constitutes one way to accomplish the modeling. In chemically reacting flows, changes in concentrations of chemical species must be described. These concentrations can be defined by local, instantaneous values of the mass fractions of each species. The chapter describes the effects of chemical reactions in a general, nondimensional form. Conservation of energy, a key equation in combustion, can be expressed in several different forms, depending in part on whether attention is focused on thermal energy or on total energy. The most common approaches to turbulence modeling are moment methods, in which equations are written for averages of the dependent variables for some of their variances and occasionally for some higher moments.
Vitamin B6 nutritional status and cellular availability of pyridoxal 5′-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions☆

The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine → cystathionine → cysteine) is largely maintained even during vitamin B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/h per kg body weight. The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B6 status suggests that the resulting modulation of H2S production may have physiological consequences in a subset of people. Supported by NIH grant DK072398. This paper refers to data from studies registered at clinicaltrials.gov as NCT01128244 and NCT00877812.
Responding artfully to student-initiated departures in the adult ESL classroom

Abstract Teachers constantly endeavor to strike a balance between the arguably competing tasks of maintaining control on the one hand and encouraging student participation on the other ( Paoletti & Fele, 2004 ). How precisely such a balance is accomplished, however, remains largely a mystery. Based on videotaped data from the adult English as a Second Language (ESL) classroom, we describe two teacher practices for responding to student-initiated departures, where teacher control is maintained in the service of participation and learning. Findings of this conversation analytic study contribute to a growing understanding of how certain learner contributions in the language classroom may be tactfully and efficiently handled while offering increasing specificity for strengthening the foundations of language teacher education.
Reoperation for Margins After Breast Conservation Surgery: What's Old Is New Again.

More than 30 years after demonstration that survival after breast conservation surgery (BCS) and adjuvant radiotherapy is equivalent to survival after mastectomy,1 significant variability in the implementation of BCS remains, particularly in the rates of reoperation for margins. Breast conservation surgery is the most common oncologic operation performed in the United States, with a measurable financial and physical burden caused by repeated excisions. In this issue of JAMA Surgery, the study by Isaacs et al2 reports a mean 90-day reoperation rate of 30.9% from 2003 to 2013 in New York State, with a significant decrease over time from 38.5% to 23.1%. This study shows that almost onethird of the reoperations results in mastectomy. In 2014, Wilke et al3 similarly demonstrated that within the National Cancer Database from 2004 to 2010, the rates of repeated operations after BCS decreased from 25% to 22%. This change is seen within the context of efforts to define adequate margins for BCS.4 The recent Society for Surgical Oncology–American Society for Radiation Oncology (SSOASTRO) consensus guidelines encourage the use of “no ink on tumor” as the current standard in an era of multimodal treatment and evolving understanding of tumor biology along with tumor burden. In fact, this approach to reexcisions echoes the conclusion of Fisher et al5(p1722) in 1986 after review of pathologic findings from the National Surgical Adjuvant Breast Project that “it is most appropriate to regard lines of resection involved only when cancer is transected,” because subjective designations of close margins resulted in second operations with a low yield of residual cancer. Isaacs et al2 report notable intersurgeon variability, with rates of reoperations ranging from 0% to 100%. Studies have shown significant surgeon and institutional variation in clinical practice,6 althoughwithout data regardingmarginwidth, the proportion of this variation attributable to interpretation ofmargin status isunknown. Sourcesof inconsistencymay include surgeon training and volume, radiographic evaluation, andpathologic processing. In addition, subjective elements of surgeon bias may play a role because the authors’ multivariable analysis demonstrated that repeated excisions were significantlymore likely inyoungerpatients and thosewith fewer comorbidities.2 Establishing a rational, evidence-based approach to reexcision as originally proposedbyFisher et al5 and that has been supported by the new SSO-ASTRO guidelines has the potential to provide substantial national cost savings by eliminating reexcisions for closebutnegativemargins.7As theseguidelines for margin status are widely adopted, identification of persistent outliers to these guidelines and assessment of the effect of this practice change on surgical outcomes and value of care for early stage breast cancer should remain important goals.
Dimolybdenum(III) Complexes of −OSi(OtBu)3, −O2P(OtBu)2, and −OB[OSi(OtBu)3]2 as Single-Source Molecular Precursors to Molybdenum-Containing, Multi-Component Oxide Materials

The following dimolybdenum complexes containing −OSi(OtBu)3, −O2P(OtBu)2, and −OB[OSi(OtBu)3]2 ligands have been synthesized and structurally characterized: Mo2(NMe2)4[OSi(OtBu)3]2 (1), Mo2(OtBu)4[OSi(OtBu)3]2 (2), Mo2(NMe)4{OB[OSi(OtBu)3]2}2 (3), Mo2(NMe2)2[μ-O2P(OtBu)2]2[O2P(OtBu)2]2 (4), Mo2(NMe2)2[OSi(OtBu)3]2[μ-O2P(OtBu)2]2 (5), and Mo2(NMe2)2[μ-O2P(OtBu)2]2{OB[OSi(OtBu)3]2}2 (6). The isolation and structural characterization of trans- and cis-isomers of complexes 4 and 5 (4a and 4b, 5a and 5b, respectively) are also reported. Studies of the thermal decompositions of the complexes (by thermogravimetric analysis and solution 1H NMR spectroscopy) were performed. Xerogels with approximate compositions of 2MoO1.5·2P2O5 and 2MoO1.5·2P2O5·2SiO2 were derived from 4a and 5a or 5b, respectively, via solution thermolyses (toluene). The as-synthesized (and dried) xerogels contain one equiv of HNMe2 per molybdenum center (by combustion analysis, IR spectroscopy, and thermogravimetric analysis), and these materi...
Pronouns and Thoughts on Neutrality: Gender Concerns in Modern Grammar

With increased social awareness of transgender and non-binary individuals, universities across the United States have implemented policies, made suggestions for inclusive language practices, and provided gender-neutral pronoun guides to avoid marginalizing these groups of people through adjusting personal pronoun usage. However, these measures have been met with mixed reception from students, parents, administrators, legislators, and others. As linguists, the authors looked at the situation with gender-neutral pronouns on campuses and investigated 1) an overview of how exactly language plays a role in identifying someone’s gender; and 2) the historical linguistics and social contexts that surround this issue. The paper concludes with recommendations for gender-neutral pronouns in compliance with federal policies and university visions, missions, and goals to be more inclusive of genderqueer and non-binary individuals.
Effect of environmental exposure to hydrogen sulfide on central nervous system and respiratory function: a systematic review of human studies

Background: Assessment of the health effects of low-level exposure to hydrogen sulfide (H2S) on humans through experiments, industrial, and community studies has shown inconsistent results.Objective: To critically appraise available studies investigating the effect of H2S on the central nervous system (CNS) and on respiratory function.Methods: A search was conducted in 16 databases for articles published between January 1980 and July 2014. Two researchers independently evaluated potentially relevant papers based on a set of inclusion/exclusion criteria.Results: Twenty-seven articles met the inclusion criteria: 6 experimental, 12 industry-based studies, and 10 community-based studies (one article included both experimental and industry-based studies). The results of the systematic review varied by study setting and quality. Several community-based studies reported associations between day-to-day variations in H2S levels and health outcomes among patients with chronic respiratory conditions. However, eviden...
Building an endoscopic ear surgery program.

Purpose of review This article discusses background, operative details, and outcomes of endoscopic ear surgery. This information will be helpful for those establishing a new program. Recent findings Endoscopic ear surgery is growing in popularity. The ideal benefit is in totally transcanal access that would otherwise require a larger incision. The endoscope carries a number of advantages over the microscope, as well as some disadvantages. Several key maneuvers can minimize disadvantages. There is a paucity of studies directly comparing outcomes between endoscopic and microscopic approaches for the same procedure. Summary The endoscope is gaining acceptance as a tool for treating otologic diseases. For interested surgeons, this article can help bridge the transition from microscopic to totally transcanal endoscopic ear surgery for appropriate disease.
Affected Sib Methods

The affected sib pair method is used extensively to distinguish between simple modes of inheritance of HLA associated diseases. Certain diseases, such as insulin dependent diabetes mellitus (IDDM), appear more complex than simple recessive or dominant traits. This finding has led to the development of several tests and extensions of the affected sib pair method to more complex models.
Human-Robot Mutual Force Borrowing and Seamless Leader-Follower Role Switching by Learning and Coordination of Interactive Impedance

This research developed a bilateral human-robot mutual adaptive impedance control strategy. The developed interactive impedance coordination methods can let human and robot arbitrarily switch the role between leader and follower seamlessly. Also, through iteratively increasing the impedance in the intended moving direction, human and robot can mutually borrow the force from each other to facilitate the task execution.
Critical perspectives on mainstream, groundlevel, and alternative comics in The Comics Journal, 1977 to 1996

The Comics Journal, the premiere venue for comics criticism in the United States since its inception in 1977, built its reputation on its harsh criticism of mainstream comics and its championing of alternative comics, but the Journal did not arrive fully at this position for two decades. During this time its critical perspective was complex and contradictory, with the Journal continuing to hold out hope for the eventual improvement of superhero comics. However, the Journal focused most of its critical energies on what were known at the time as groundlevel comics, small, independently published comics that utilised the genres of science fiction, fantasy, horror and superheroes. The Journal largely ignored alternative comics until the late 1980s, and it wasn’t until the 1990s that the Journal fully embraced them as the driving force for the evolution and improvement of American comics.
Parenting of children with Down syndrome compared to fragile X syndrome.

Children with Down syndrome (DS) and fragile X syndrome (FXS) struggle with language development. Parenting variables, such as responsiveness to children’s communication attempts (Maternal Responsi...
“Operation abolition” vs. “operation correction”

demonstrations by college students and others at hearings of the House UnAmerican Activities Committee (HUAC) in San Francisco during May 1960 were Communist inspired and led. Since its release two years ago, over 1,300 prints of the film (at $100 each) have been purchased outright in addition to widespread rental of prints for single showings (4). Corporations, colleges, women's clubs, fraternal groups, and religious organizations, among others, have presented the film to countless thousands, and then, depending on their motives in exhibiting it, commended or condemned its creators. Supporters maintain that the film fairly and accurately describes the manner in which well-meaning Americans can fall prey to Communist wiles. Detractors claim it is a travesty of doctored filmstrips, a fairy-tale narrative, and a gross injustice on the part of the producer, if not of the Committee itself for releasing it. The controversy continues, and indeed has become more intense. In January of 1962, the House Un-American Activities Committee issued a point-by-point reply to 28 charges against the film, concluding that ". .. the Communist Party, in typical fashion, has efficiently capitalized on the considerable number of
Preparation of clean surfaces and Se vacancy formation in Bi2Se3 by ion bombardment and annealing

Bismuth Selenide (Bi2Se3) is a topological insulator (TI) with a structure consisting of stacked quintuple layers. Single crystal surfaces are commonly prepared by mechanical cleaving. This work explores the use of low energy Ar+ ion bombardment and annealing (IBA) as an alternative method to produce reproducible and stable Bi2Se3 surfaces under ultra-high vacuum (UHV). It is found that a clean and well-ordered surface can be prepared by a single cycle of 1 keV Ar+ ion bombardment and 30 min of annealing. Low energy electron diffraction (LEED) and detailed low energy ion scattering (LEIS) measurements show no differences between IBA-prepared surfaces and those prepared by in situ cleaving in UHV. Analysis of the LEED patterns shows that the optimal annealing temperature is ~450 °C. Angular LEIS scans reveal the formation of surface Se vacancies when the annealing temperature exceeds 520 °C.
Forcing Variable: The Climatic System

Chapter 6 describes climate controls and the climate zones in the United States as well as the glaciation and glacial areas. Climate is controlled by latitude, proximity to large water bodies, global wind patterns, and mountains. These produce eight climate zones in the United States: wet-dry savanna, humid subtropical, humid continental, steppe, desert, Mediterranean, moist coastal, and mountain. The glaciation during the past 2.4 million years has had a profound effect on landscape, producing areas of erosion, old drift, young drift, and alpine glaciation. The most recent glacial retreat beginning 18,000 years ago deposited a landscape of moraines and other glacial features in the area of young drift across the central United States. Older features are largely destroyed in areas of old drift. Mountain areas in the Cordillera were sculpted into jagged rock faces during the glaciation.
Bending behavior of sandwich composite structures with tunable 3D-printed core materials

Abstract We combine 3D printing technique, numerical analysis, and experiments to design a new class of sandwich composites that exhibit various bending behaviors. These programmed sandwich structures contain 3D printed core materials with truss, conventional honeycomb, and re-entrant honeycomb topologies. Three-point bending tests are performed to investigate the bending behavior of these sandwich composites with two types of carbon fiber reinforced polymer face sheets. Under bending deformation, sandwich composites with truss core materials provide highest flexural stiffness and strength that are desirable in structural components. The sandwich composites with re-entrant honeycomb core exhibit a sequential snap-through instability which significantly enhances the energy absorption abilities. Our experimental and numerical results indicate that architected core structures can be utilized to tailor the bending properties as well as failure mechanisms. These findings offer new insights into the study of nonlinear mechanical response of sandwich structures, which can benefit a wide range of industries and applications.
Abstract 33: Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor

Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 are present in the heart and signal via decreased and increased cAMP production, respectively. Previously we reported that cardiomyocyte-specific EP4 KO mice develop a phenotype of dilated cardiomyopathy with reduced ejection fraction. We thus hypothesized that PGE2 decreases contractility via EP3. To test this hypothesis, the effects of PGE2 and the EP1/EP3 agonist sulprostone (sulp) were examined in the mouse langendorff preparation and in adult mouse cardiomyocytes (AVM) using the IonOptix cell contractility system. Isolated hearts of 18-20 wk old male C57Bl/6 mice were mounted and equilibrated for 10 min, then perfused with PGE2 (10 -6 mol/l) or sulp (10 -6 mol/l) for 30 min. Values at the end of equilibration were set to 100%. Compared to vehicle, PGE2 decreased +dp/dt (77.8±3% vs 96.7±3%, p -6 mol/l). Myocyte contractility was evaluated on the IonOptix system with pacing at 1Hz. Treatment with PGE2 (10 -9 M) for 10 min reduced contractility as measured by peak height (3.69 ± 0.48% for vehicle vs 2.00 ± 0.22% for PGE2, p
No Time for College? An Investigation of Time Poverty and Parenthood.

Postsecondary outcomes are significantly worse for student parents even though they earn higher GPA’s on average. This study used institutional records and survey data from a large urban U.S. unive...
Pituitary Adenomas: Surgery Perspective

The first recorded attempt at surgical resection of a pituitary tumor was a two-stage lateral subtemporal decompression in an acromegalic patient performed by Caton and Paul [1]. They used a temporal approach as suggested by Sir Victor Horsley, who later used both a subfrontal approach and a lateral middle fossa approach in operating on 10 pituitary tumors [2]. The first successful removal of a pituitary tumor via a superior nasal transsphenoidal approach was in 1907 (Fig. 27-1) [3]–[5]. Open image in new window Figure 27-1 Schloffer’s transnasal transsphenoidal operation. (A) Incision made along the left nasolabial furrow around the left ala nasi and continued up to the glabella. (B) The incision cuts through the skin, nasal bone, philtrum, and the anterior part of the septum. The whole external nose is reflected to the right exposing the remainder of the septum. (C) The rest of the nasal septum has been removed exposing the rostrum of the sphenoid sinus. (D) The anterior wall of the sphenoid sinus is opened, the mucosal lining of the sinus is removed with a sharp spoon, and the floor of the sella is removed with a small chisel or punch forceps. (From: Cope VZ. The pituitary fossa and the methods of surgical approach thereto. Br J Surg 1916; 4:107–144. Used with permission.)
On a Newton Polygon Approach to the Uniformization of Singularities of Characteristic p

This paper is a report about some results of uniformization of singularities in characteristic p under the guidance of Prof H. Hironaka.
Evaluating the effects of four VR locomotion methods: joystick, arm-cycling, point-tugging, and teleporting

In this work we present two novel methods of exploring a large immersive virtual environment (IVE) viewed through a head-mounted display (HMD) using the tracked controllers that come standard with commodity-level HMD systems. With the first method, "Point-Tugging," users reach and pull the controller trigger at a point in front of them and move in the direction of the point they "tug" with the controller. With the second method, "Arm-Cycling," users move their arms while pulling the trigger on the hand-held controllers to translate in the yaw direction that their head is facing. We perform a search task experiment to directly compare four locomotion techniques: Joystick, Arm-Cycling, Point-Tugging, and Teleporting. In the joystick condition, a joystick is used to translate the user in the yaw direction of gaze with physical rotations matching virtual rotations. In the teleporting condition, the controllers create an arched beam that allows the user to select a point on the ground and instantly teleport to this location. We find that Arm-Cycling has advantages over the other methods and could be suitable for wide-spread use.
Secular trends in success rate of catheter ablation for atrial fibrillation: The SMASH-AF cohort

Background Approaches, tools, and technologies for atrial fibrillation (AF) ablation have evolved significantly since its inception. We sought to characterize secular trends in AF ablation success rates. Methods We performed a systematic review and meta-analysis of AF ablation from January 1, 1990, to August 1, 2016, searching PubMed, Scopus, and Cochrane databases. Major exclusion criteria were insufficient outcome reporting and ablation strategies that were not prespecified and uniform. We stratified treatment arms by AF type (paroxysmal AF; nonparoxysmal AF) and analyzed single-procedure outcomes. Multivariate meta-regressions analyzed effects of study, patient, and procedure characteristics on success rate trends. Registered in PROSPERO (CRD42016036549). Results A total of 180 trials and observational studies with 28,118 patients met inclusion. For paroxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 73.1% in 2003 to 77.1% in 2016, increasing by 0.9%/year (95% CI 0.4%-1.4%; P = .001; I2 = 90%). After controlling for study design and patient demographics, rate of improvement in success rate summary estimate increased (1.6%/year; 95% CI 0.9%-2.2%; P = .001; I2 = 87%). For nonparoxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 70.0% in 2010 to 64.3% in 2016 (1.1%/year; 95% CI −1.3% to 3.5%; P = .37; I2 = 85%), with no improvement in multivariate analyses. Conclusions Despite substantial research investment and health care expenditure, improvements in AF ablation success rates have been incremental. Meaningful improvements may require major paradigm or technology changes, and evaluation of clinical outcomes such as mortality and quality of life may prove to be important going forward.
Why M&A advice rarely pays off: Ineffective advisors or experience incompatibility?

Hiring an investment bank as financial advisor in acquisitions is a prevalent phenomenon although prior research disagrees on whether acquirers ‘get their money’s worth’ from their financial adviso...
Quercetin and Sodium Butyrate Synergistically Increase Apoptosis in Rat C6 and Human T98G Glioblastoma Cells Through Inhibition of Autophagy

This study investigated the efficacy of quercetin (QCT) in combination with sodium butyrate (NaB) in enhancing apoptosis in rat C6 and human T98G glioblastoma cells though blockage of autophagy under nutrient-starvation. The most synergistic doses of the drugs were determined to be 25 µM QCT and 1 mM NaB in both cell lines. After QCT and QCT + NaB treatments, autophagy quantification with acridine orange staining showed a drastic decrease in protective autophagy in the cells under nutrient-starvation. Decrease in autophagy was correlated with decreases in expression of Beclin-1 and LC3B II. Combination treatment increased the morphological signs of apoptosis including membrane blebbing, nuclear fragmentation, and chromatin condensation. Annexin V staining was also performed for detection and quantification of increases in apoptosis. Western blotting results showed that combination of QCT and NaB increased apoptosis by decreasing anti-apoptotic Bcl-2 and increasing pro-apoptotic Bax, decreasing survivin, activating caspase-3, and degrading poly (ADP-ribose) polymerase (PARP). This study demonstrated the therapeutic potentials of a novel combination therapy in inhibiting protective autophagy to enhance apoptosis in rat C6 and human T98G glioblastoma cells.
Experimental Traumatic Brain Injury during Adolescence Enhances Cocaine Rewarding Efficacy and Dysregulates Dopamine and Neuroimmune Systems in Brain Reward Substrates.

Although clinical studies identify traumatic brain injury (TBI) as a risk factor for the development of substance use disorder, much remains unknown about the possible underlying pathogenesis and age-specific effects. Thus, the aim of this study is to test the hypothesis that at an age of ongoing maturation, adolescent TBI alters elements of the reward pathway, resulting in increased sensitivity to the rewarding effects of a subthreshold dose of cocaine that does not induce significant behavioral changes in naive, non-injured mice. Specifically, these results were derived from the combination of the controlled cortical impact model of TBI, performed on either adolescent (6 weeks) or young adult (8 weeks) mice, followed by the cocaine-induced conditioned place preference assay 2 weeks later. Using three-dimensional isosurface rendering and volumetric image analysis, TBI was found to induce neuromorphological changes such as decreased dendritic complexity and reduced spine density in brain regions essential for reward perception and processing of drug-induced euphoria. Further, we demonstrated that these neuronal changes may affect the differential expression of dopamine-associated genes. Our analysis also provided evidence for age-related differences in immune response and the distinct involvement of augmented microglial phagocytic activity in the remodeling of neuronal structures in the adolescent TBI brain. Our studies suggest that TBI during adolescence, a period associated with ongoing maturation of dopaminergic systems, may subsequently enhance the abuse liability of cocaine in adulthood.
Lineage does not regulate the sensory synaptic input of projection neurons in the mouse olfactory bulb

Lineage regulates the synaptic connections between neurons in some regions of the invertebrate nervous system. In mammals, recent experiments suggest that cell lineage determines the connectivity of pyramidal neurons in the neocortex, but the functional relevance of this phenomenon and whether it occurs in other neuronal types remains controversial. We investigated whether lineage plays a role in the connectivity of mitral and tufted cells, the projection neurons in the mouse olfactory bulb. We used transgenic mice to sparsely label neuronal progenitors and observed that clonally related neurons receive synaptic input from olfactory sensory neurons expressing different olfactory receptors. These results indicate that lineage does not determine the connectivity between olfactory sensory neurons and olfactory bulb projection neurons.
Advancing health equity by integrating intersectionality into epidemiological research: applications and challenges.

Epidemiological research increasingly recognises that health disparities are driven by complex interplay among factors including housing, education and employment.1 Intersectionality—‘the relationships among multiple dimensions and modalities of social relations and subject formations’—offers a theoretical approach for expanding our understanding of health disparities beyond independent systems of privilege and oppression (eg, racism and sexism).2 Intersectionality theory was developed more than 30 years ago to better understand how various identities interact and produce cumulative impacts across the life course. Still, traditional public health approaches of examining a single exposure and health outcome continue to limit our understanding of how health disparities are experienced across varying classes, races, ethnicities, genders and sexualities.3 Intersectionality theory in health research is often relegated to social science literature, highlighting a missed opportunity for epidemiological research to consider how larger structural inequities shape health. Kimberle Crenshaw, a leader in Black feminist legal theory, …
1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP)-Cysteine Conjugates: Metabolic Formation and Binding to Cellular DNA.

1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP) is a potential proximate carcinogenic metabolite of pyrrolizidine alkaloids. In the present study, we determined that reaction of 1-CHO-DHP...
Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences.

Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM. We obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS. 99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612–1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773–1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886–2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743–0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784–0.835], p < 0.001). Increasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.
Facilitating Content Discovery and the Value of the Publisher Platform—An Overview

Libraries invest heavily in content, both through purchase and licensing. This money is wasted, however, if faculty and students are unable to easily locate and use content for research and teaching. Designing and promoting tools to assist in navigating a variety of information sources have been the purview of both librarians and information providers—from the card catalog to sophisticated indexing and abstracting databases to discovery products such as Summon and Primo. Where, however, do publishers fall into the information discovery mix? Should they be investing resources and time into the development of their product platforms, or should they cede content discovery to third parties? Publishers have a vested interest in making their content discoverable through as many paths as possible, and once discovered, publishers want to offer the user additional related content to prolong their stay on the publisher’s own site. Librarians also want to provide as many options to our users as possible, rather than investing in a single discovery option.
Microgrids and the transition toward decentralized energy systems in the United States: A Multi-Level Perspective

Abstract The increasing penetration of microgrids in appears to be part of a transition toward electricity distribution systems that are more decentralized than the current system. With microgrids gaining space as a competing and parallel distribution grid model and challenging the current centralized grid system, studying their adoption presents an opportunity to understand this socio-technical transition in the energy system. This study looks at this ongoing change in the United States and applies the Multi-Level Perspective framework to explore the drivers, contexts, processes, policies, institutions, and interactions that affect the adoption of microgrids. Through a qualitative case study analysis of California, New York, and Oregon, the study finds that natural disasters, massive power outages and climate change concerns have acted as key pressures for the adoption of microgrids. At the same time, the electric power system maintains important stabilization mechanisms, such as the availability of cheap and abundant electricity, as well a market structure that limits the opportunities of entry and profit for third-party developers, which make it harder for niche innovations like microgrids to break in. In addition, this study finds that state support in the form of funding and legislation is crucial for nurturing the microgrid niche market.
Abortion in women with severe preeclampsia and eclampsia prior to 24 weeks gestation

Abstract Objective Due to poor prognosis, obstetric care providers often recommend abortion for women diagnosed with severe preeclampsia prior to fetal viability. However, there is limited available evidence to guide the counseling regarding risks. Study design This study is a retrospective case series that describes outcomes of all women who underwent abortions with the diagnosis of severe preeclampsia or eclampsia prior to 24 weeks gestation. Results This case series describes 11 women who underwent abortion prior to 24 weeks gestation due to severe preeclampsia or eclampsia, 9 by dilation and evacuation and 2 by labor induction. The majority of women underwent dilation and evacuation and no women undergoing either induction of labor or dilation and evacuation had severe complications directly related to the abortion. Conclusions This case series provides information on the safety of abortion procedures in women with severe preeclampsia and eclampsia syndrome.
Efficacy of a modified-live IBR-BVD-PI3-BRSV-Mannheimia haemolytica toxoid vaccine against challenge with virulent BHV-1 and PI3 viruses in calves 60 days of age

Efficacy of attenuated (att) bovine herpesvirus type 1 (BHV-1) and bovine parainfluenza type-3 (PI3) viruses as antigen fractions in a modified-live virus (MLV) multivalent vaccine was evaluated following single, subcutaneous (SC) administration and intranasal (IN) challenge 28 days after vaccination, with either virulent BHV-1 or PI3 viruses in young calves. A total of 80 seronegative calves, 50 to 63 days of age at the time of vaccination, were used in 2 separate studies with 40 animals per study. Calves were allocated to 2 treatment groups with 20 animals per group which received either a single dose of a MLV IBR-BVD-PI3-BRSV vaccine, Mannheimia haemolytica toxoid, or corresponding placebo formulation without targeted test antigen fractions attBHV-1 (Study 1) or attPI3 (Study 2). Incidence and duration of clinical signs associated with respiratory disease, rectal temperatures, virus shedding, and serologic responses were compared between treatment groups in each study to assess vaccine efficacy. The 5-way vaccine induced significantly higher (p<0.0001) virus neutralizing antibody responses and reduction in fever (p<0.0001), mean rectal temperatures, and lower incidence or shorter duration of clinical disease related to BHV-1 and PI3 infection than placebo-treated calves. Infectious bovine rhinotracheitis (IBR) disease, hallmark of BHV-1 infection, was observed in 95% of control calves and in only 10% of vaccinates. Vaccinated animals in Study 1 and Study 2 demonstrated a 98.8 and 98.9% reduction in virus shedding, respectively, and significantly (p<0.0001) shorter duration of virus shedding compared to control calves, demonstrating protective vaccine efficacy.
Hope, Optimism, and Clinical Pain: A Meta-Analysis.

BACKGROUND Generalized expectancies have been theorized to play key roles in pain-related outcomes, but the empirical findings have been mixed. PURPOSE The primary aim of this meta-analysis was to quantify the relationships between two of the most researched positive generalized expectancies (i.e., hope and optimism) and pain-related outcomes (i.e., pain severity, physical functioning, and psychological dysfunction) for those experiencing clinical pain. METHODS A total of 96 studies and 31,780 participants with a broad array of pain diagnoses were included in analyses, using random-effects models. RESULTS Both hope and optimism had negative correlations with pain severity (hope: r = -.168, p < .001; optimism: r = -.157, p < .001), positive correlations with physical functioning (hope: r = .199, p < .001; optimism: r = .175, p < .001), and negative correlations with psychological dysfunction (hope: r = -.349, p = .001; optimism: r = -.430, p <.001). CONCLUSION The current findings suggest that hope and optimism are similarly associated with adaptive pain-related outcomes. Future research should examine the efficacy of interventions on hope and optimism in ameliorating the experience of clinical pain.
Examining a new prosocial risk-taking scale in a longitudinal sample of ethnically diverse adolescents.

Abstract Introduction This longitudinal study designed and tested the validity of a new measure of prosocial risk taking — risks that individuals take in order to help others. Methods The sample was racially and ethnically diverse adolescents in the rural Southeastern United States (N = 867; Mage = 12.82 years, 10–14 years at Wave 1; 50% Girls, 33% White non-Latinx, 27% Latinx, 20% Black, 20% Mixed/Other race/ethnicity). Adolescents completed self-report measures of the new prosocial risk-taking scale at baseline and one- and two-year follow-ups. Results Confirmatory factor analysis demonstrated excellent model fit with a 6-item single factor score. Further, the scale demonstrated good test-retest reliability at one and two-year follow ups. The scale also demonstrated convergent validity, such that prosocial risk taking was positively correlated with prosocial tendencies, empathy, and sensation seeking, and negatively correlated with negative risk-taking behavior and risk tolerance. Finally, we found significant differences by race/ethnicity (but not by gender) in prosocial risk taking, which were not attributable to measurement invariance, and should be interpreted in the context of ongoing societal inequalities between youth. Conclusions The new Prosocial Risk-Taking Scale yielded reliable scores in our sample. It may be used in future research to investigate individual differences in adolescents' prosocial risk taking, developmental change in prosocial risk taking, and the significance of prosocial risk taking for adolescents' emotional and social adaptation.
Early goal-directed therapy in the treatment of sepsis: the times have changed but not the therapy and benefit to patients.

Dear Editor, A review and meta-analysis published by Angus and colleagues [1] concludes: ‘‘EGDT (early goal-directed therapy) does not decrease mortality but increases costs’’ and suggests: ‘‘EGDT should not be part of the Surviving Sepsis Campaign (SSC) guidelines’’. This conclusion, while interesting, is incorrect for numerous methodological reasons. EGDT was the result of a series of studies over two decades identifying poor care, early sepsis mortality, early identification (SIRS), risk stratification (lactate), cultures and antimicrobials, identifying cryptic shock and early hemodynamic optimization to treat global tissue hypoxia in the emergency department (ED) [2]. While considered standard care in the ICU setting, these principles were applied to the most proximal part of hospitalization as ischemic stroke, acute myocardial infarction, or trauma was treated. EGDT is more than optimizing central venous pressure (CVP) and oxygen saturation (ScvO2) as hypothesized by Angus et al. EGDT was a prospective randomized trial where resuscitation was conducted in the ED and blinded to the ICU team. Angus et al. incorrectly labels the EGDT unblinded. The trial Trilogy, completed a decade later, was unblinded and included as
Image-Blogs: Consumer Adoption and Usage

Bloggers are now turning to more creative ways to share their knowledge, thoughts, ideas, and opinions (information) while making it an easier experience for them and their viewers. image-blogging has become a tool for those looking to share information through multimedia with their viewers. This paper is part of a larger project looking into a broader investigation of image-blog usage. Understanding what encourages adoption and use of a image blog by its audience is of interest to companies looking to utilize such technologies to their benefit.
Algorithmic noise-tolerance for low-power signal processing in the deep submicron era

In deep submicron (DSM) VLSI technology, deviations in node voltages due to DSM noise can lead to erroneous system outputs in VLSI implementations of DSP and communication algorithms degrading their performance in terms of signal-to-noise ratio (SNR) or bit-error-rate (BER). We present algorithmic noise-tolerance schemes for digital filtering to detect such errors in system output and mitigate their effect on the system performance. The errors in the system output are detected by employing a low-complexity prediction scheme. It is shown that, the proposed scheme improves the performance of the filtering algorithm by up to 10dB with less than 10% hardware overhead. It is also shown that the proposed scheme can be employed to achieve substantial energy savings with marginal degradation in performance by deliberately introducing errors in DSP hardware by overscaling the supply voltage.
Ten-Step Survival Guide for the Emerging Business Web

Webservices technology is converging, and today we are at least able to define what we mean if we use the term webservice (SOAP, XML, WSDL). Given the maturing technology, it is opportune to get concrete about the future of webservices-based technologies. An area that traditionally has been assumed to become a major beneficiary of webservices technology is that of business-to-business interactions. In this paper we try to get to the core issues we face in creating this emerging ‘business web,’ these dynamic, digital business ecosystems.
Cosmological Structure Formation With and Without Hot Dark Matter

Cold + Hot Dark Matter (CHDM) is perhaps the best theory of cosmic structure formation {\it if} the cosmological matter density is near critical (i.e., $\Omega_0 \approx 1$) and {\it if} the expansion rate is not too large (i.e. $h \equiv H_0/(100 \kmsMpc) \lsim 0.6$). I discuss CHDM together with its chief competitor among CDM variants, low-$\Omega_0$ CDM with a cosmological constant (\lcdm). \lcdm\ with $\Omega_0 \sim 0.3$ has the possible virtue of allowing a higher expansion rate $H_0$ for a given cosmic age $t_0$, but the defect of predicting too much fluctuation power on small scales. Also, except for the $H_0-t_0$ problem, there is not a shred of evidence in favor of a nonzero cosmological constant, only increasingly stringent observational upper bounds on it. CHDM has less power on small scales, in good agreement with data, although it remains to be seen whether it predicts early enough galaxy formation to be compatible with the latest high-redshift data. CHDM has the advantage among $\Omega=1$ CDM-type models of requiring little or no tilt, which appears to be an advantage in fitting recent small-angle cosmic microwave background anisotropy data. The presence of a hot component that clusters less than cold dark matter lowers the effective $\Omega_0$ that would be measured on small scales, which appears to be in accord with observations, and it may also avoid the discrepancy between the high central density of dark matter halos from CDM simulations compared to evidence from rotation curves of dwarf spiral galaxies.
Performance Surface Prediction for WAN-Based Clusters

The last five years have been a period of exponential growth in the number of machines connected to the Internet and the speed at which these machines communicate. The infrastructure is now in place to consider a nationwide cluster of workstations as a viable parallel processing platform. In order to achieve acceptable performance on this kind of a machine, performance prediction tools must provide information on where to place computational objects. Incorrect object placement can result in poor performance and congestion in the network. This research develops a new paradigm for predicting performance in the Wide Area Network (WAN) based cluster arena. Statistical samples of the performance of clusters and applications are used to build characteristic surfaces. These surfaces are then used to provide guidance in placement of new applications. This prediction method is intended to minimize both the execution time of the application and the impact of the application on the nationwide virtual machine. Performance prediction tools are an important prerequisite to effectively utilizing WAN based clusters.
Anforderungen an das Rechenzentrum der Zukunft

Lassen Sie mich mit einer Prognose beginnen, die vor einiger Zeit ein sehr renommierter Kenner der DV-Szene gemacht hat.