cssi/SciSciGPT-SciSciNet huggingface dataset:
Purification and Properties of Staphylococcal Delta Hemolysin

Abstract Large amounts (200 mg per liter of culture supernatant fluid) of highly purified staphylococcal soluble delta hemolysin were obtained by adsorption to and selective elution from hydroxyapatite followed by exhaustive dialysis against water, concentration by polyvinylpyrrolidone or polyethylene glycol 20,000 dialysis, and a final water dialysis. No carbohydrate, phosphorus, or inactive 280-nm absorbing material was detected in the preparation; however, analysis by density gradient centrifugation, gel filtration, analytical ultracentrifugation, carboxymethyl cellulose chromatography, polyacrylamide disc gel electrophoresis, isoelectric focusing, and electron microscopy revealed that the lysin was molecularly heterogeneous. The preparation contained an acidic fibrous lysin (S20,w of 11.9) and a basic lysin component composed of a population of granular aggregates of various sizes, with a maximum S20,w of approximately 4.9. No other staphylococcal products were detected in the preparation. The lysin was active against erythrocytes from many animal species and acted synergistically with staphylococcal beta hemolysin against sheep erythrocytes. It was soluble in chloroform-methanol (2:1), was inactivated by various phospholipids, normal sera, and proteolytic enzymes, but was partially resistant to heat inactivation. Activity was not affected by Ca2+, Mg2+, citrate, ethylenediaminetetraacetic acid, or cysteine. The lysin preparation also disrupted bacterial protoplasts and spheroplasts, erythrocyte membranes, lysosomes, and lipid spherules, was growth-inhibitory for certain bacteria, and clarified egg yolk-agar. Large amounts produced dermonecrosis in rabbits and guinea pigs. The minimum lethal intravenous dose for mice and guinea pigs was approximately 110 and 30 mg/kg, respectively.
Pore dimensions for accumulating biomass. II. Microbes that form spores and exhibit mycelial growth

The relationship between the dimensions of a spore and the accumulation of that microbe in a porous, inorganic structure has been determined. In order to achieve high accumulation of mycelial growth, at least 70% of the pores of an inorganic carrier should have pore diameters in the range of one times the smallest dimension of the fungal spore but less than about 16 times the largest dimension of that spore. This relationship was established by varying the physical parameters of the carriers as well as their chemical composition.
Circulating concentrations of proinflammatory cytolcines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Abstract Proinflammatory cytokines are capable of modulating cardiovascular function by a variety of mechanisms. These cytokines are elevated in patients with severe heart failure, but changes in mild or moderate heart failure have not been reported. Therefore, simultaneous arterial and coronary sinus concentrations of interleukin-1α, soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-α were measured in 78 patients with New York Heart Association functional class II to IV heart failure and compared with 17 healthy volunteers. Concentrations of interleukin-1α, soluble interleukin-2 receptor, and interleukin-6 were determined by a “sandwich” enzyme-linked immunosorbent assay and tumor necrosis factor-α by tissue culture technique. There were no statistical differences in interleukin-1α, soluble interleukin-2 receptor, or tumor necrosis factor-α concentrations in mild to moderate heart failure versus control subjects. Interleukin-6 was significantly elevated, 75 ± 16 versus 0.4 ± 0.4 pg/ml (p = 0.002). Cytokine concentrations did not differ by heart failure etiology. Paired arterial and coronary sinus concentrations were not significantly different. Soluble interleukin-2 receptor concentrations were significantly correlated with New York Heart Association functional class (r = 0.59, p = 0.04) and negatively associated with exercise tolerance time (r = −0.59, p = 0.007). Thus, interleukin-6 is significantly elevated in mild or moderate heart failure.
Evaluation of Protein Solubility as an Indicator of Underprocessing of Soybean Meal

Abstract Three experiments were conducted to compare urease activity (UA), orange G-binding capacity (OGBC), and protein solubility (PS) in a potassium-hydroxide solution of soybean meal (SBM) as indicators of overprocessing. In two additional experiments, amino-acid supplementation was employed in an attempt to overcome the growth depression associated with overheating SBM. Subsamples of commercially prepared lots of dehulled SBM were heated for varying periods of time in an autoclave at 121 C. In Experiments 1, 2, and 3, UA dropped to zero (pH change) after approximately 10 min of cooking. The assay was unable to differentiate between meals that were heated for longer periods. The OGBC of SBM was decreased by autoclaving. However, the narrow range of the orange G values that corresponded to degrees of heat treatment indicated that this test may be of limited value in identifying overprocessed SBM. By contrast, PS values decreased with each increase of autoclaving time, and did not approach zero even with 80 min of heating. Adding .2 % lysine either singly or in combination with .2% arginine or. 1% methionine, or both, totally overcame the growth depression due to overprocessing. The weight gains and feed conversions of broiler chicks were negatively correlated with autoclaving times in excess of 10 minutes. In all experiments, PS values more closely reflected the impaired chick performance from overheated SBM than UA or OGBC. The PS values below 70% suggested overprocessed SBM.
Overexpression of the tinman-related genes XNkx-2.5 and XNkx-2.3 in Xenopus embryos results in myocardial hyperplasia

Drosophila tinman is an NK-class homeobox gene required for formation of the dorsal vessel, the insect equivalent of the vertebrate heart. Vertebrate sequences related to tinman, such as mouse Nkx-2.5, chicken cNkx-2.5, Xenopus XNkx-2.5 and XNkx-2.3 are expressed in cardiac precursors and in tissues involved in induction of cardiac mesoderm. Mice which lack a functional Nkx-2.5 gene die due to cardiac defects. To determine the role of tinman-related sequences in heart development, we have overexpressed both XNkx-2.3 and XNkx-2.5 in Xenopus laevis embryos. The resulting embryos are morphologically normal except that they have enlarged hearts. The enlarged heart phenotype is due to a thickening of the myocardium caused by an increase in the overall number of myocardial cells (hyperplasia). Neither ectopic nor precocious expression of cardiac differentiation markers is detectable in overexpressing embryos. These results suggest that both XNkx-2.3 and XNkx-2.5 are functional homologues of tinman, responsible for maintenance of the heart field.
Preemptive strategies for overcoming the forgetting of goals

Maintaining and pursuing multiple goals over varying time scales is an important ability for artificial agents in many cognitive architectures. Goals that remain suspended for long periods, however, are prone to be forgotten. This paper presents a class of preemptive strategies that allow agents to selectively retain goals in memory and to recover forgotten goals. Preemptive strategies work by retrieving and rehearsing goals at triggers, which are either periodic or are predictive of the opportunity to act. Since cognitive architectures contain common hierarchies of memory systems and share similar forgetting mechanisms, these strategies work across multiple architectures. We evaluate their effectiveness in a simulated mobile robot controlled by Soar, and demonstrate how preemptive strategies can be adapted to different environments and agents.
The Need for Self-Expression and the Need to Belong

The need for work as such is the second dimension of human material need. Just as physical need derives from human materiality, so too does the need for work as such. Because all human knowledge is acquired through the senses [John Paul, p. 33], there is no such thing as pure human intellect. Therefore, whether it is as physically demanding as waiting on tables or drilling for oil, or as mentally challenging as composing a symphony or designing a suspension bridge, human work requires a living human being, an embodied human being
Prospective phase II trial of sorafenib combined with doxorubicin eluting bead-transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: Efficacy analysis.

4124 Background: This study reports the final analysis (n=50) of a prospective phase II study evaluating the efficacy of the combination of sorafenib and doxorubicin eluting bead transarterial chem...
Vascular foramina and arterial supply of the distal end of the femur.

1. A number of vascular foramina in the distal end of the femur have been classified according to their anatomical location as supracondylar, condylar, and intercondylar groups. Each group forms a perforated area on the bone.2. In the intercondylar incisura, between the two upper attachments of the
Capacity of Fox’s H-function Fading Channel with Adaptive Transmission

Novel closed-form exact expressions for the capacity of the recently-introduced Fox's H-function fading channel are derived. The expressions are obtained assuming different types of adaptive transmission strategies, namely, channel inversion with fixed rate, truncated channel inversion with fixed rate, optimum rate adaptation with fixed power and optimum power and rate adaptation. The obtained expressions are versatile and can be used to evaluate the capacity for virtually any fading channel one might be interested in as a special case.
Abstract 5724: HER2-mediated resistance of breast cancer stem cells in HER2-negative/low breast cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Despite a recent trend toward improvement, breast cancer (BC) mortality remains high due to resistance of recurrent tumors. A major cause of recurrence is likely a micro-metastatic seeding of cells that developed resistance by activating intrinsic or acquired survival pathways. In this regard, HER2 expression and cancer stem cells (CSCs) are the major cause for recurrence and targeting HER2 is well considered in therapeutic regiments. However, clinical data showed that anti-HER2 also benifit HER2−/low BC patients, suggesting that tumor cells may acquire HER2 gene activation to survive. We have previously reported that NF-κB mediates radioresistance by controlling HER2 gene. Herein, we identified HER2-expressing BC stem cells (HER2+/CD44+/CD24−/low) in radiation-resistant HER2−/low BC cells, MCF7/C6. Matrigel invasion, tumor sphere formation and radioresistance were enhanced in the HER2 mediating radioresistant cells. About 10% of the CD44+/CD24−/low cells sorted from MCF7/C6 cells or irradiated xenografts showed co-expression of HER2/CD44, ALDH and high tumorigenicity compared to HER2−/CD44+/CD24−/low cells, suggesting that the induction of HER2 expression further increased the BCSC aggressiveness. In fact, clinical data indicates that cells co-expressing HER2/CD44 were increased in recurrent tumors (84.6%) compared to the primary tumors (57.1%). Proteomics analysis identified a unique profile of proteins including DNA repair, mitochondrial function, redox, mTOR pathways that may govern the resistance of HER2+/CD44+/CD24−/low CSCs. These results demonstrate that HER2-mediated BC resistance can develop at the level of BCSC. Thus, HER2-expressing BCSCs may serve as an effective target to treat BC recurrence even from primary HER2−/low tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5724. doi:1538-7445.AM2012-5724
Analysis of Fluid-Stent Interaction via Digital Particle Image Velocimetry

Vascular stents are commonly used as a scaffold to hold arteries open after angioplasty. The clinical use of stents has also extended to treatment of cerebral aneurysms and as a graft anchor for endoluminal treatment of abdominal aortic aneurysms. In spite of the clinical success of stents, very little quantitative data exist on how stent structure influences blood flow patterns. Once in place, stents alter the mechanical and geometrical properties of the arterial tree. Such alterations represent an impedance mismatch between stent and unstented vessel. These changes appear to have a profound influence on pressure and flow wave interaction. These alterations may play a role in flow mediated stent failure [1, 2].Copyright © 2002 by ASME
441 EXPLORING THE ROLE OF THE FRLS DOMAIN OF THE CADF PROTEIN IN CAMPLYLOBACTER JEJUNI

Background Camplylobacter jejuni is a leading cause of bacterial gastroenteritis in the United States, with estimated loss of productivity due to illness being eight billion dollars annually. Previous studies have indicated that the CadF protein of C. jejuni is important in adherence to host epithelial cells. Further research indicates that the FRLS domain of the CadF protein possesses Fibronectin (Fn) binding ability, necessary for adhesion. A novel system for expressing foreign peptides in the S-layer of Caulobacter crescentus has been developed, which allows for rapid creation and purification of peptides. Study Design and Methods PCR sequencing was performed on various isolates of C. jejuni to see if the cadF gene is conserved across different isolates. Monoclonal antibodies were created and screened by ELISA to determine their binding efficiency to the FRLS domain of the CadF protein. Recombinant DNA methods were used to create a recombinant plasmid that upon electroporation into C. crescentus expressed a portion of the CadF protein, including the FRLS domain. Results The cadF gene is well conserved across the 23 isolates tested. A monoclonal antibody that binds near the FLRS domain with good specificity was identified. A C. crescentus strain expressing the FRLS domain of the CadF gene from C. jejuni was created and isolated. Conclusion The cadF gene is conserved across 22 isolates at the nucleotide level. A system for rapid expression, purification, and testing for the FRLS domain of the CadF gene has been created.
Solid-State Nanopore Detection of Diverse Nucleic Acid Biomarkers with Drag-Regulated Nanopore Translocation

In the solid-state (SS-) nanopore system, the net force experienced by an analyte dictates its speed and translocation direction. Detection can therefore be hindered if either the molecule translocates through the pore too rapidly to be detected (case 1), or if the net force is very small or negative (i.e. away from the pore, case 2). The DRNT assay utilizes a charged chaperone protein and a short biotinylated nucleic acid, neither of which yields events individually (cases 1 and 2, respectively), but when bound, shift to resolvable translocation speeds. This allows selective detection and quantification of target DNA in solution. Here, we describe two specific applications of DRNT. First, we target single-base modifications, including epigenetic variants and damage elements, by selectively labeling diverse but distinct modified bases with a biotin moiety to enable DRNT analysis. Second, we target microRNAs (miRNAs) and other select nucleic acid sequences by exploiting conformational differences between single- and double-stranded nucleic acids. Our results demonstrate the translational potential of the SS-nanopore platform for biomedical diagnostics.
Resources Utilized by Preclinical Medical Students During Patient Morning Rounds

Information resource utilization by preclinical medical students was studied in the context of a physician-mentored patient rounds (PMPR) exercise. This exercise involved four clinical tasks: creating a differential diagnosis, refining the differential diagnosis, choosing diagnostic tests, and formulating a treatment plan. The assignment required them to record the information resources they used. Individual students typically used a variety of resources. Patient data, prior medical knowledge, Internet resources, and course materials were used by most students. Across clinical tasks, students used progressively less Internet resources and progressively more course materials.
Lithic Source Identification Through Macroscopic Analysis: An Example from Cedar Mesa, Southeastern Utah

ABSTRACTDuring the course of the archaeological survey project conducted between 1972 and 1973 on Cedar Mesa, southeastern Utah, the problem of the sources of prehistoric Anasazi stone tool material and the implications of material distributional variation through time was studied. A methodology for differentiating discrete material types was employed based on macroscopic analysis and differentiation of recovered site materials and comparison with identified potential source or actual prehistoric quarry material. Ten discrete material types, from on and around Cedar Mesa and from as far away as 65 km eastward, could be identified to at least the level of source geologic formation. Discontinuities between the Basketmaker II, Basketmaker III, and Pueblo occupation phases on the mesa, implied by marked temporal differences in the frequencies of certain types, correlate with and support available dendrochronological and ceramic evidence.
Diagnosis and Treatment of Lymphatic Plastic Bronchitis in Adults Using Advanced Lymphatic Imaging and Percutaneous Embolization

Rationale: Plastic bronchitis is a condition characterized by expectoration of branching bronchial casts. Although the mechanism of cast formation in adults with plastic bronchitis remains poorly understood, abnormal pulmonary lymphatic flow resulting in molding of congealing lymphatic fluids in the airway has been documented as a cause of the disease in children with congenital heart disease.Objectives: To use advanced lymphatic imaging techniques, including dynamic contrast-enhanced magnetic resonance (MR) lymphangiography (DCMRL) and intranodal lymphangiography, to investigate the mechanism of cast formation in adult patients with plastic bronchitis, and to evaluate the therapeutic outcome of percutaneous lymphatic embolization for these patients.Methods: Seven adults (male/female = 3/4, mean age = 50 yr) who presented with expectoration of branching bronchial casts were evaluated. Lymphatic imaging included heavy T2-weighted MR imaging and DCMRL. All patients underwent bilateral intranodal lymphangiog...
Dependence of power and efficiency of AlGaN/GaN HEMTs on the load resistance for class B bias

The material properties of GaN and the AlGaN/GaN heterostructure such as high breakdown field and high sheet charge density, allow AlGaN/GaN HEMTs to be operated at significantly higher drain bias voltages as compared to other III-V compound semiconductor FETs. As expected, larger RF voltage and current swings result in higher normalized output power at microwave frequencies. AlGaN/GaN HEMTs are capable of generating output power density in excess of 10 W/mm in the X-band, which is at least an order of magnitude larger than what is obtainable with GaAs FETs. In this paper, we discuss the effect of the load impedance on measured output power (P/sub out/) and efficiency (/spl eta/) at various drain bias conditions in class B mode. Dynamic loadlines; extracted at the device's output are used for analysis of the trade-off between voltage and current swings at different load resistances and its effect on output power and efficiency.
Mir-9 Is Aberrantly Expressed In MPN Patients and Accelerates Erythropoietic Cell Growth and Differentiation

Abstract 1983 The myeloproliferative neoplasms (MPNs), PV, ET and IMF, harbor a common gain-of-function mutation of JAK2V617F but in the past several years other molecular lesions have been noted as well such as mutation of TET2, chromsomal gains and losses, aberrant mRNA expression and aberrant microRNA expression. Since miRNAs are important regulators of hematopoiesis, we measured miRNA expression levels in CD34+ cells isolated from 8 patient samples (4 PV with JAK2V617F, 3 ET with wild-type JAK2 and 1 IMF with unknown JAK2 status) and 4 healthy controls using a Taqman Low Density Array (TLDA) representing 667 known miRNAs. We identified 28 miRNAs that were significantly deregulated in MPN patients compared to controls (p<0.05). Many of these miRNAs (18/24; 75%) were also deregulated in an independent miRNA array study using MPN patient granulocytes (n=39, 25 PV, 14 ET). Among these miRNAs, miR-9 expression was significantly upregulated in MPN patient CD34+ cells as well as in mature granulocytes. Furthermore, miR-9 expression was responsive to modulation of JAK2 activity in both gain of function (overexpression of JAK2V617F in TF-1 cells) and loss of function (inhibition of JAK2 activity in HEL cells) systems, suggesting that miR-9 may be dysregulated by aberrant JAK2V617F signaling. Analysis of miR-9 expression in ex-vivo, uni-lineage human CD34+ cultures, revealed that miR-9 is expressed at low levels during erythropoiesis, while levels gradually increase during myeloid differentiation. To determine how deregulated expression of miR-9 affected erythropoiesis, we transduced human bone marrow CD34+ cells (AllCells) with empty vector or miR-9 lentivirus, and examined erythroid differentiation and proliferation in liquid culture over 12 days. miR-9 expressing cells displayed a consistent growth advantage (∼30%), and accelerated erythroid differentiation (CD71+, GlyA+) at days 7 and 9. HITS-CLIP is a high throughput miRNA target prediction method developed in the Darnell lab based on crosslinking Argonaute protein to miRNA and target mRNA, providing highly specific identification of direct miRNA targets. We previously identified genes differentially expressed in PV patient CD34+ cells compared to normal CD34+ cells using Affymetrix HG-U133A arrays (117 genes, p<0.05). A comparison of predicted miR-9 mRNA targets identified using HITS-CLIP in P13 mouse brain, with genes downregulated in PV patient microarray studies, identified KLF4 which encodes a zinc finger protein involved in pluripotency and YWHAZ a 14-3-3 protein involved in signaling pathways regulating proliferation and survival as potential miR-9 targets relevant to aberrant hematopoiesis in MPN. Dysregulated cell growth in MPN may result in part from aberrant miRNA expression. Disclosures: Carroll: Sanofi Aventis Corporation: Research Funding; Kyowa Hakko Kirin Pharmaceuticals: Research Funding; Agios Pharmaceuticals: Research Funding.
Bilingualism in older Mexican-American immigrants is associated with higher scores on cognitive screening

Bilingualism may protect against cognitive aging and delay the onset of dementia. However, studies comparing monolinguals and bilinguals on such metrics have produced inconsistent results complicated by confounding variables and methodological concerns. We addressed this issue by comparing cognitive performance in a more culturally homogeneous cohort of older Spanish-speaking monolingual (n = 289) and Spanish-English bilingual (n = 339) Mexican-American immigrants from the Sacramento Longitudinal Study on Aging. After adjusting for demographic differences and depressive symptoms, both groups performed similarly at baseline on verbal memory but the bilingual group performed significantly better than the monolingual group on a cognitive screening test, the Modified Mini-Mental State Examination (3MS; p < 0.001). Group differences on the 3MS were driven by language/executive and language/praxis factors. Within the bilingual group, neither language of testing nor degree of bilingualism was significantly associated with 3MS or verbal memory scores. Amongst individuals who performed in the normal or better range on both tests at baseline and were followed for an average of 6 years, both monolinguals and bilinguals exhibited similar rates of cognitive decline on both measures. These findings suggest that bilingualism is associated with modest benefits in cognitive screening performance in older individuals in cross-sectional analyses that persist across longitudinal analyses. The effects of bilingualism should be considered when cognitively screening is performed in aging immigrant populations.
Patient characterization and usage trends of proton beam therapy for localized prostate cancer in the United States: A study of the National Cancer Database.

Abstract Purpose To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer. Patients and Methods The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality. Results In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67–0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65–0.78) or high (0.44; 0.38–0.5) risk, white vs. black race (0.66; 0.58–0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50–0.98), live in higher income counties (1.55; 1.36–1.78), and live in metropolitan areas compared to urban (0.21; 0.18–0.23) or rural (0.14; 0.10–0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%–5.6%; P Conclusion PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified.
Endoluminal ultrasound applicator configurations utilizing deployable arrays, reflectors and lenses to augment and dynamically adjust treatment volume, gain, and depth

Endoluminal high-intensity ultrasound offers spatially-precise thermal ablation of tissues adjacent to body lumens, but is constrained in treatment volume and penetration depth by the effective aperture of integrated transducers, which are limited in size to enable delivery through anatomical passages, endoscopic instrumentation, or laparoscopic ports. This study introduced and investigated three distinct endoluminal ultrasound applicator designs that can be delivered in a compact state then deployed or expanded at the target luminal site to increase the effective therapeutic aperture. The first design incorporated an array of planar transducers which could be unfolded at specific angles of convergence between the transducers. Two alternative designs consisted of fixed transducer sources surrounded by an expandable multicompartment balloon that contained acoustic reflector and dynamically-adjustable fluid lenses compartments. Parametric studies of acoustic output were performed across device design parameters via the rectangular radiator and secondary sources methods. Biothermal models were used to simulate resulting temperature distributions in three-dimensional heterogeneous tissue models. Simulations indicate that a deployable transducer array can increase volumetric coverage and penetration depth by ~80% and ~20%, respectively, while permitting more conformal thermal lesion shapes based on the degree of convergence between the transducers. The applicator designs incorporating reflector and fluid lenses demonstrated enhanced focal gain and penetration depth that increased with the diameter of the expanded reflector-lens balloon. Thermal simulations of assemblies with ~12 mm compact profiles and ~50 mm expanded balloon diameters demonstrated generation of localized thermal lesions at depths up to ~10 cm in liver tissue.
Multivariate Probability Distributions: Applications and Risk Models

Multiple, simultaneous and dependent sources of risks are common to risk modeling. To model their manifestations, we use multivariate probability distributions and models to express their dependence and their interactions. The purpose of this chapter is to summarize a number of approaches to multivariate probability modeling and measurement of dependence. These include statistical and functional models, Bayesian techniques, families of multivariate probability distributions and copula. Both short term and long-run memory and fractal models are relegated to Chap. 5.
Evolutionary Action of de novo missense variants across pathways prioritizes genes linked to autism and predicts patient phenotypic severity

The pathogenicity of individual de novo missense mutations in autism spectrum disorder remains difficult to validate. Here we asked in 2,384 probands whether these variants exhibited collective functional impact biases across pathways. As measured with Evolutionary Action (EA) in 368 gene groupings, we found significant biases in axonogenesis, synaptic transmission, and other neurodevelopmental pathways. Strikingly, both de novo and inherited missense variants in prioritized genes correlated with patient IQ. This general integrative approach thus detects missense variants most likely to contribute to autism pathogenesis and is the first, to our knowledge, to link missense variant impact to autism phenotypic severity.
The Changing Input-Output Network Structure of the U.S. Economy

U.S. industries have become less connected over the last 10 years, and service industries have become more central.
Brief Report: Relationship Between ADOS-2, Module 4 Calibrated Severity Scores (CSS) and Social and Non-Social Standardized Assessment Measures in Adult Males with Autism Spectrum Disorder (ASD)

The ADOS-2 Modules 1-3 now include a standardized calibrated severity score (CSS) from 1 to 10 based on the overall total raw score. Subsequent research published CSS for Module 4 (Hus, Lord, Journal of Autism and Developmental Disorders 44(8):1996-2012, 2014); however more research is needed to examine the psychometric properties of this CSS. Forty males with ASD completed an assessment battery consisting of ADOS-2 Module 4 and other clinical measures assessing core ASD symptomology and comorbidity. Pearson correlation analyses found that CSS did not correlate with measures that assessed core social deficits of ASD or general psychiatric co-morbidity, but CSS did correlate negatively with intellectual quotient. These findings provide information on the limitations and relevance of CSS to be taken into account in future clinical evaluations of ASD.
Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis

Aim To evaluate the efficacy, safety, tolerability and steroid-sparing effect of repository corticotropin injection (RCI), in an open-label clinical trial, in refractory adult polymyositis (PM) and dermatomyositis (DM). Methods Adults with refractory PM and DM were enrolled by two centres. Inclusion criteria included refractory disease defined as failing glucocorticoid and/or ≥1 immunosuppressive agent, as well as active disease defined as significant muscle weakness and >2 additional abnormal core set measures (CSMs) or a cutaneous 10 cm Visual Analogue Scale score of ≥3 cm and at least three other abnormal CSMs. All patients received RCI of 80 units subcutaneously twice weekly for 24 weeks. The primary end point for the trial was the International Myositis Assessment and Clinical Studies definition of improvement. Secondary end points included safety, tolerability, steroid-sparing as well as the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism myositis response criteria (EULAR) Results Ten of the 11 enrolled subjects (6 DM, 4 PM) completed the study. Seven of 10 met the primary end point of efficacy at a median of 8 weeks. There was a significant decrease in prednisone dose from baseline to conclusion (18.5 (15.7) vs 2.3 (3.2); P 10% and the physician global by >40%. RCI was considered safe and tolerable. No patient developed significant weight gain or an increase of haemoglobin A1c or cushingoid features. Conclusion Treatment with RCI was effective in 70% of patients, safe and tolerable, and led to a steroid dose reduction in patients with adult myositis refractory to glucocorticoid and traditional immunosuppressive drugs. Trial registration number NCT01906372; Results.
Providing support through life's final chapter for those who made it home.

ABSTRACTMilitary personnel are exposed to unique environmental hazards and psychological stressors during their service to our nation. As a result, military service personnel are at high risk not only for physical injury but for psychological trauma as well that may result in post-traumatic stress disorder, depression, substance abuse, and homelessness. These medical and psychosocial issues may hasten the development of life-limiting illnesses and may complicate the delivery of end-of-life care. Community-based hospice agencies often lack the resources and expertise to address the special needs of veterans. This article highlights the efforts of the Department of Veterans Affairs to provide comprehensive and co-ordinated end-of-life support for “those who served.”
How (and Whether) to Teach Undergraduates about the Replication Crisis in Psychological Science.

Over the past 10 years, crises surrounding replication, fraud, and best practices in research methods have dominated discussions in the field of psychology. However, no research exists examining ho...
Dynamic Modulus of Syntactic Foam Core - a Non Destructive Approach

Sandwich composites are a special class of composite materials which are widely used because of their high specific strength and bending stiffness. Lower density of these materials makes them well suited for marine and aerospace applications. Developments in aviation posed requirement of lightweight, high strength and highly damage tolerant materials. Sandwich structured composites, fulfilling these requirements became the first choice for many applications including structural components for ground transport and marine vessels. The use of cores such as closed cell structured foam in sandwich structures gives some distinct advantages over open cell structured foams and cores [1]. The specific compressive strength of close cell structured foams is much higher and absorbs less moisture than open cell structured foam.
Comparative pharmacological properties of muscle function in the foregut and the hindgut of the cockroach Leucophaea maderae.

Abstract 1. 5-Hydroxytryptamine (4 × 10−8 M) consistently caused an increase in the frequency and amplitude of spontaneous contractions of the foregut of Leucophaea maderae. The hindgut showed similar responses to this indolalkylamine, but the threshold ranged from 4 × 10−8 M to 4 × 10−6 M. 2. Tyramine (5 × 10−6 M) produced a marked suppression of muscular activity in both organs and served as an antagonist of 5-hydroxytryptamine, glutamate and proctolin. 3. Monosodium glutamate (4 × 10−5 M) generally evoked a large phasic contraction in hindguts. However, glutamate (1 × 10−4 M) had either no effect on foreguts or induced a suppression of contractile activity. 4. Although the pentapeptide proctolin stimulated rhythmic activity in both the foregut and the hindgut, the threshold for activation of the hindgut (3 × 10−11 M) was lower than the foregut (3 × 10−8 M). 5. The results suggests that a dichotomy exists between the neurochemical mechanisms controlling these two organs in L. maderae.
Production of superoxide by phagocytic leukocytes: a paradigm for stimulus-response phenomena.

Publisher Summary Phagocytic leukocytes, for example, neutrophils, eosinophils, monocytes, produce substantial quantities of superoxide (O 2 - ) and hydrogen peroxide (H 2 O 2 ) during phagocytosis, or upon perturbation of their plasmalemma, by any one of a variety of soluble and quasi-soluble agents. The chapter reviews the properties of the superoxide-producing oxidase of neutrophils and the developments cited as they pertain to the activation of the enzyme system. The majority of the biochemical studies on the oxidative metabolism of leukocytes has been performed on neutrophils since these cells are far more abundant than other types of cells capable of producing O 2 - . They are obtainable from blood and, in large quantities and in pure form, by elicitation. “Elicited” neutrophils are cells which migrate into the peritoneum of mammals following the injection of a sterile inflammatory agent, for example, casein, glycogen. The most commonly employed cells are human blood neutrophils and elicited rabbit and guinea pig neutrophils.
Capecitabine maintenance in high risk loco-regional colorectal cancer.

e15695Background: The outcome for patients with high-risk loco-regional colorectal cancer (CRC) remains unsatisfactory despite the use of adjuvant chemotherapy. Based on the SEER data, the worst su...
Continuous accumulation of organic matter-rich sediments associated with Oceanic Anoxic Event 1a in the El Pujal section, Organyà Basin, Catalunyà Spain and its relation to episodic dysoxia

Abstract A detailed lithostratigraphic and geochemical analysis was performed on a 13.77 m sequence consisting of a succession of limestones, argillaceous limestones and marlstones at the El Pujal section in the Organya Basin of the south-central Spanish Pyrenees. Biostratigraphic analysis reveals the presence of the foraminifer Leupoldina cabri positioning the sequence within OAE 1a. Corroborating evidence from stable carbon isotope data permits the correlation of the El Pujal section with other Tethyan sections, namely Roter Sattel (Switzerland), Cismon (Italy) and El Pui (Spain) to within carbon isotope segment C5. Geochemical results reveal periodic increase of redox sensitive trace elements (RSTEs: V, Ni, Co, Cr, Cu, Mo), biolimiting (P, Fe) and terrestrially derived elements (Al, Si, Ti) at argillaceous limestone and marlstone intervals, concurrent with episodes of enhanced organic matter preservation (TOC >1.18%). Further evidence from microfacies characterized by higher pyrite concentration, impoverished benthic fauna and lower degree of bioturbation are in accord with geochemical proxies. Biomarker data shows n-alkanes distributions ranging from nC10 to nC31, suggesting that the organic matter (OM) is a mixture of in-situ produced and terrestrially derived. Calculated average chain length (ACL nC25-nC33) shows lower values in intervals associated with argillaceous limestones and marlstones, suggesting wetter climate during these periods. The results imply that fluvial influences controlled by regional hydrologic variability related to climatic fluctuations probably exacerbated the already sluggish basinal conditions through the development of density stratification in the water column. Integration of the data from the El Pujal section shows that changes in paleoproductivity, terrigenous input, and redox conditions characterize the deposition of OAE 1a in the Organya Basin without the hallmark of an anoxic phase. Conditions remained similar to those recorded in the preceding sequence at El Pui, thus revealing continuous deposition of OM under impoverished oxygen conditions, punctuated by episodes of dysoxia.
Linking Adult Neurogenesis to Epilepsy Through Epigenetics

Diverse environmental stimuli regulate continuous production of new neurons in restricted adult brain regions, such as the mammalian hippocampus. Certain forms of “physiological” stimulation (e.g., exercise, experience, and normal aging) promote neurogenesis, presumably for cellular replacement and function. In contrast, “pathological” stimulation arising from brain injury (e.g., traumatic brain injury and stroke) also promotes neurogenesis, presumably for repair or replacement of dying/degenerating neurons. In most of these cases, the direct cause-and-effect relationship between adult hippocampal neurogenesis and the functional role of adult-generated neurons—whether it is for normal tissue homeostasis or repair of damaged tissue—remains unclear. A major neurological disorder that warrants investigation is epilepsy, where a single seizure episode is sufficient to massively increase neural stem/progenitor cell proliferation and adult hippocampal neurogenesis. Based on morphological and functional changes of adult-generated granule neurons after seizures, it has been postulated that seizure-induced neurogenesis may lead to ectopic dentate granule cell production and neuronal circuit formation (“aberrant neurogenesis”) and spontaneous recurrent seizures (“epileptogenesis”). Moreover, studies show that blocking aberrant neurogenesis leads to a reduction in epileptogenesis, suggesting a causative role of seizure-induced neurogenesis in epilepsy development. Thus, a better understanding of the cellular and molecular mechanisms governing aberrant neurogenesis might prevent epilepsy development. On a molecular level, seizure activity has been shown to mediate epigenetic changes, including DNA methylation and histone modification. Since epigenetic alterations are typically heritable and associated with long-lasting changes in gene expression, epigenetic dysregulation of gene expression may control behavior of hippocampal neural stem cells and their progeny after seizures and contribute to epilepsy. In this chapter, we describe the seizure-induced cellular alterations within the adult hippocampal dentate gyrus that are associated with epilepsy development. We also discuss several recent examples of the molecular control of hippocampal neurogenesis after seizures, focusing on epigenetic mechanisms.
How Does CEO Career Origin Influence Firm’s Risk-Taking?

Does CEO career origin matter for corporate risk-taking? Is the level of corporate risk-taking determined by firm characteristics or by CEO personal/compensation characteristics? Using 3,006 CEO turnover data between 1992 and 2010, we find that outsider CEOs make more risky investment decisions than insider CEOs. After controlling for compensation sensitivity variables, we find that outsider CEOs are more risk-taking than insider CEOs. The board of directors may hire outsider CEOs because of the risk-taking reason. Our results also suggest that the CEO compensation structure difference is not the reason why outsider CEOs take more risk than insider CEOs.
Getting Under Alexa’s Umbrella: Infiltration Attacks Against Internet Top Domain Lists

Top domain rankings such as Alexa are frequently used in security research. Typical uses include selecting popular websites for measurement studies, and obtaining a sample of presumably “benign” domains for model training or whitelisting purposes in security systems. Consequently, an inappropriate use of these rankings can result in unwanted biases or vulnerabilities. This paper demonstrates that it is feasible to infiltrate two domain rankings with very little effort. For a domain with no real visitors, an attacker can maintain a rank in Alexa’s top 100 k domains, for instance, with seven fake users and a total of 217 fake visits per day. To remove malicious domains, multiple research studies retained only domains that had been ranked for at least one year. We find that even those domains contain entries labelled as malicious. Our results suggest that researchers should refrain from using these domain rankings to model benign behaviour.
Discrimination of duration ratios in bisyllabic tokens by native English and Estonian listeners

In an earlier study [Journal of Phonetics (1987), 15, 349–363], we examined the ability of Estonian and English speakers to discriminate among pairs of noise bursts whose durations were in the ratios of 1 : 2, 2: 3, 3 : 2, and 2 : 1. The results obtained showed that both groups of listeners clearly recognized only two contrastive patterns: 1 : 2 and 2 : 3 vs. 3 : 2 and 2: 1. Since there may be a difference in the perception of duration ratios when listeners are in a speech mode of perception rather than a non-speech mode, the present study is a replication of the earlier study using bisyllabic tokens as stimuli instead of noise-burst sequences. Again, the obtained results show the same contrastive patterns. The data support a reanalysis of the three-way quantity contrast in Estonian into two-way contrast based on duration (short-long vs. long-short) and a contrast based upon F0 contours.
NIR-Absorbing Ru II Complexes Containing α-Oligothiophenes for Applications in Photodynamic Therapy.

The design of near-infrared (NIR)-active photosensitizers (PSs) for light-based cancer treatments such as photodynamic therapy (PDT) has been a challenge. While several NIR-RuII scaffolds have been reported, this approach has not been proven in cells. This is the first report of NIR-RuII PSs that are phototoxic to cancer cells, including highly pigmented B16F10 melanoma cells. The PS family incorporated a bis(1,8-naphthyridine)-based ligand (tpbn), a bidentate thiophene-based ligand (nT; n=0-4), and a monodentate 4-picoline ligand (4-pic). All compounds absorbed light >800 nm with maxima near 730 nm. Transient absorption (TA) measurements indicated that n=4 thiophene rings (4T) positioned the PDT-active triplet intraligand charge transfer (3 ILCT) excited state in energetic proximity to the lowest-lying triplet metal-to-ligand charge transfer (3 MLCT). 4T had low-micromolar phototoxicity with PIvis and PI733nm values as large as 90 and 12, respectively. Spectroscopic studies suggested that the longer-lived (τTA =3-6 μs) 3 ILCT state was accessible from the 3 MLCT state, but energetically uphill in the overall photophysics. The study highlights that phototoxic effects can be achieved with NIR-absorbing RuII PSs as long as the reactive 3 ILCT states are energetically accessible from the low-energy 3 MLCT states. It also demonstrates that tissue-penetrating NIR light can be used to activate the PSs in highly pigmented cells where melanin attenuates shorter wavelengths of light.