cssi/SciSciGPT-SciSciNet huggingface dataset:
Congenic Strains for Genetic Analysis of Virulence Traits in Cryptococcus gattii

Cryptococcus gattii is responsible for a large outbreak of potentially fatal disease that started in the late 1990s on Vancouver Island, Canada. How this fungus and the outbreak isolates in particular cause disease in immunocompetent people is unknown, with differing hypotheses. To explore genetic contributions, a pair of congenic a and α mating type strains was generated by a series of 11 backcrosses to introgress the MAT locus from a nonoutbreak strain into the background of strain R265, isolated from a Vancouver Island patient. The congenic pair was used to investigate three traits: mitochondrial inheritance, the effect of the MAT alleles on virulence, and the impact of a predicted virulence factor on pathogenicity. The two congenic strains show the same virulence in different models of cryptococcosis and equivalent levels of competition in coinfection assays. These results rule out a role of the MAT locus and mitochondrial genotype as major virulence factors in the outbreak strains. Disruption of Bwc2, a light-dependent transcription factor, resulted in reduced virulence, consistent with a similar function in the related species Cryptococcus neoformans. The C. gattii congenic strains represent a new resource for exploring the evolution of virulence in the C. neoformans-C. gattii clade.
Heart Valve Structure and Function in Development and Disease

The mature heart valves are made up of highly organized extracellular matrix (ECM) and valve interstitial cells (VICs) surrounded by an endothelial cell layer. The ECM of the valves is stratified into elastin-, proteoglycan-, and collagen-rich layers that confer distinct biomechanical properties to the leaflets and supporting structures. Signaling pathways have critical functions in primary valvulogenesis as well as the maintenance of valve structure and function over time. Animal models provide powerful tools to study valve development and disease processes. Valve disease is a significant public health problem, and increasing evidence implicates aberrant developmental mechanisms underlying pathogenesis. Further studies are necessary to determine regulatory pathway interactions underlying valve pathogenesis in order to generate new avenues for novel therapeutics.
CMEIAS Color Segmentation: An Improved Computing Technology to Process Color Images for Quantitative Microbial Ecology Studies at Single-Cell Resolution

Quantitative microscopy and digital image analysis are underutilized in microbial ecology largely because of the laborious task to segment foreground object pixels from background, especially in complex color micrographs of environmental samples. In this paper, we describe an improved computing technology developed to alleviate this limitation. The system’s uniqueness is its ability to edit digital images accurately when presented with the difficult yet commonplace challenge of removing background pixels whose three-dimensional color space overlaps the range that defines foreground objects. Image segmentation is accomplished by utilizing algorithms that address color and spatial relationships of user-selected foreground object pixels. Performance of the color segmentation algorithm evaluated on 26 complex micrographs at single pixel resolution had an overall pixel classification accuracy of 99+%. Several applications illustrate how this improved computing technology can successfully resolve numerous challenges of complex color segmentation in order to produce images from which quantitative information can be accurately extracted, thereby gain new perspectives on the in situ ecology of microorganisms. Examples include improvements in the quantitative analysis of (1) microbial abundance and phylotype diversity of single cells classified by their discriminating color within heterogeneous communities, (2) cell viability, (3) spatial relationships and intensity of bacterial gene expression involved in cellular communication between individual cells within rhizoplane biofilms, and (4) biofilm ecophysiology based on ribotype-differentiated radioactive substrate utilization. The stand-alone executable file plus user manual and tutorial images for this color segmentation computing application are freely available at http://cme.msu.edu/cmeias/. This improved computing technology opens new opportunities of imaging applications where discriminating colors really matter most, thereby strengthening quantitative microscopy-based approaches to advance microbial ecology in situ at individual single-cell resolution.
Nonlinear perturbations for linear semi-infinite optimization problems

A perturbation method for solving semi-infinite optimization problems is introduced. The approach is to use the continuous structure of the problem rather than an a priori discretization of the constraint set. A duality theory for infinite-dimensional convex programs is used to construct a nonlinear dual problem which is a finite-dimensional unconstrained concave problem. This induced dual problem penalizes the classical semi-infinite problem. This formulation lends itself to computing a solution of the dual by Newton's type method and allows for solving both the primal and dual problems. Implementation of a primal-dual algorithm, the connection with interior point methods, and further results are briefly discussed. >
Margin requirements and stock volatility

Since 1934 the Federal Reserve Board has had the power to set separate limits on the amount of credit that can be extended to purchasers of common stock. There has been much recent debate about the efficacy of these margin regulations. This article argues that the Fed has responded to increases in stock prices by raising margin requirements. The increase in prices has been associated with a decrease in volatility. There is no evidence that changes in margin requirements reduce subsequent stock return volatility. Also, trading halts have not had much effect on volatility in the past. Trading halts that were associated with banking panics were associated with high stock return volatility, but halts without bank panics were not associated with high levels of volatility.
Solubility and prediction of the heat of solution of sodium naproxen in aqueous solutions.

ABSTRACT: The solubility of sodium naproxen was determined over a range of temperatures from 15.2°C to 39.7°C by two methods: analyses of samples from equilibrated solutions and a recently developed procedure utilizing a focused-beam reflectance method (FBRM). The results demonstrate the utility of the newer and, in some cases, simpler method. A discontinuity in the solubility was observed at 29.8°C, identifying the temperature as which the dihydrate and anhydrous forms of sodium naproxen trade places as being the more stable of the two forms. The heats of solution for the two pseudopolymorphs were obtained from van't Hoff plots of the solubility data. These results were used to demonstrate how the heat of solution of one form can be estimated using the heat of dehydration obtained from differential scanning calorimetry (DSC) and the heat of solution from another form. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.
The Epidaurus Project: holism in Department of Defense health facilities.

ABSTRACTThe Epidaurus Project, an advanced initiative in holistic (or whole-person) medicine, has operated in the Military Health System (MHS) since 2001. Its purpose has been to engage prominent civilian authorities on evidence-based building design, family-centered approaches, interdisciplinary care integration, and wellness, to optimize outcomes in the MHS. Over the past decade, many of the Epidaurus idea sets have been incorporated into MHS facility designs and therapeutic programs. The MHS owes a debt of gratitude to the numerous civilian thought leaders who participated in this project.
Measurement of Thermal Conductivity and Interface Thermal Resistance of Multilayered Thin-Films Using Variable Pulse-Width Transient Thermoreflectance

This work discusses the use of a non-contact, non-invasive and in-situ measurement approach for determining the thermal conductivity of thin films used in the microelectronics industry, along with the interface thermal resistance between the films. The approach is based on the thermoreflectance method, where the change in the surface temperature is measured by detecting the change in the reflectivity of the sample. The results presented in this paper show that by using different pulse-widths for the heating laser, as well as a variable wavelength for the probing laser, the proposed method enables the measurement of several unknown parameters in a multi layered sample, which is representative of modern devices developed by the microelectronics industry. In addition, it is shown that the method can be further improved to minimize the measurement uncertainties by estimating a-priori the optimum thickness of the metal absorption layer that needs to be used. A property called responsivity is described, and it is shown that maximizing its value is indeed producing the lowest measurement uncertainties. An objective of this work is to provide guidance to investigators building similar systems and help others improve existing systems.Copyright © 2012 by ASME
Liver fat: effect of hepatic iron deposition on evaluation with opposed-phase MR imaging.

Purpose: To retrospectively determine the effect of liver iron deposition on the evaluation of liver fat by using opposed-phase magnetic resonance (MR) imaging. Materials and Methods: Committee on Human Research approval was obtained, and compliance with HIPAA regulations was observed. Patient consent was waived by the committee. Thirty-eight patients with cirrhosis (30 men, eight women; mean age, 58 years; range, 34–76 years) who underwent abdominal MR imaging and had contemporaneous liver biopsy were retrospectively identified. Two radiologists independently quantified liver fat according to the relative loss of signal intensity and compared this loss on opposed-phase and in-phase T1-weighted gradient-echo images. Liver fat percentage and presence of iron deposition were independently recorded by a pathologist. Generalized linear models, which included a mixed–random effects model, were used to determine the effect of iron deposition on the Spearman correlation coefficient for relative signal intensity ...
Forces between Dislocations due to Dislocation Core Fields

Atomistic dislocation models were used to determine the properties of dislocation core fields in Al using an EAM potential. Equilibrium atom configurations were compared with initial configurations displaced according to the Volterra field to determine core displacement fields for edge, screw, and mixed (60° and 30°) geometries. The core field was approximated by a line force defect field lying parallel to the dislocation line direction. Best-fit parameters for the core fields were obtained in terms of the anisotropic elastic solution for a line force defect, from which the line force strengths and the origin of the line forces were determined. The line force stress fields were then used to compute the forces between dislocations for several dislocation configurations. The Volterra field dominates beyond 50b but core field forces modify the equilibrium angle of edge dislocation dipoles and determine the force between otherwise noninteracting edge and screw dislocations at distances out to 50b compared to the Volterra-only forces.
Pediatric Giant Right Atrial Aneurysm: A Case Series and Review of the Literature

Giant right atrial aneurysm is a rare form of congenital heart disease with a wide spectrum of clinical presentation varying from asymptomatic patients to those with refractory atrial arrhythmias or severe airway obstruction. Diagnosis is often confused with other causes of right atrial dilation such as Ebstein disease. Because of its rare occurrence and variable clinical presentation, inconsistencies in medical and surgical management strategies exist between centers. We present five cases of giant right atrial aneurysm managed at our institution and discuss the clinical presentation, diagnostic challenges, and medical and surgical management.
A design based approach to constructing computational solutions to diagnostic problems

Troubleshooting problems in real manufacturing environments impose constraints on admissible solutions that make the computational solutions offered by "troubleshooting from first principles" and the conventional experience based expert systems approaches infeasible. In this paper we present a computational theory for a solution to these problems that is based on the Principle of Locality and exploits the domain specific weak methods of troubleshooters and debugging knowledge of the designers. The computational theory is evaluated by generating focus of attention heuristics for a moderately complex digital device.
Severity, etiology and possible consequences of treatment-related lymphopenia in patients with newly diagnosed high-grade gliomas

SUMMARY Lymphopenia is a common consequence of therapy for malignant glioma. Current standard therapy includes corticosteroids, temozolomide and radiation therapy, all of which are toxic to lymphocytes. The resulting immunosuppression has serious clinical consequences. Decreased lymphocyte counts can result in opportunistic infections, decreased efficacy of immunotherapy and reduced overall survival. The exact mechanisms underlying the association between decreased survival and lymphopenia in malignant glioma patients are unclear. However, as lymphocytes are key effector cells in the immune response to cancer, it is likely that depleting their numbers renders the immune system less effective at eliminating malignant cells. Currently, no strategies exist for the prevention or reversal of treatment-related immunosuppression in malignant glioma patients, although there are several promising theoretical approaches. This article reviews the current state of knowledge regarding the severity, etiology and possib...
Evidence-based guidelines for teaching patient-centered interviewing

In a rare study of effectiveness of an interviewing method, we previously reported a randomized controlled trial demonstrating that training in a step-by-step patient-centered interviewing method improved residents' knowledge, attitudes, and skills and had a consistently positive effect on trained residents' patients. For those who wish to use this evidence-based patient-centered method as a template for their own teaching, we describe here for the first time our training program--and propose that the training can be adapted for students, physicians, nurse practitioners, physician assistants, and other new learners as well. Training was skills-oriented and experiential, fostered positive attitudes towards patient-centered interviewing, and used a learner-centered approach which paid special attention to the teacher-resident relationship and to the resident's self-awareness. Skills training was guided by a newly identified patient-centered interviewing method that described the step-by-step use of specific behaviors.
The search for meaning: eventfulness in the lives of homeless mentally ill persons in the Skid Row district of Los Angeles

In the past two decades, the field of psychiatry has seen the once dominant psychoanalytic theories overtaken by biological explanations and approaches to severe mental illness. With this change in perspective, the significance of fantasies and delusions have been reduced to being merely symptoms of psychopathology rather than reflections of human needs and motivations. Using ethnographic evidence from a long-term research project. this paper explores one method by which mentally ill homeless individuals in the Skid Row district of Los Angeles attempted to wrest meaningful lives for themselves out of an environment that featured disaffiliation, violence, boredom, and extreme poverty.
Adrenal cortical cell replacement in the mouse.

The mode of cell replacement in the adrenal cortex of the adult female mouse was studied bjr radioautography after labeling cells with tritiated thymidine. The fate of the labeled cells was followed in a series of animals killed at time periods up to twenty-one days after thymidine injection. It was found that the vast majority of labeled cells were located in the peripheral region of the cortex and that very few radioactive cells were present in the inner fasciculata and reticularis. Calculations made from cell counts indicated that the mitotically active outer cortex would be replaced within one to three months. Since no shift in the distribution pattern of the labeled cells occurred during the twenty-one day period studied it was concluded that no appreciable migration of cortical cells occurs. In accordance with these findings it was further concluded that the “escalator” concept should be abandoned.
Differential Effects of 20-Hydroxyeicosatetraenoic Acid on Intrarenal Blood Flow in the Rat

We recently demonstrated that endothelin-1-induced medullary vasodilation despite a potent cortical vasoconstriction in the rat kidney may be accounted for by 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study characterized the effects of 20-HETE and its metabolites, 20-hydroxy prostaglandin E2 (20-OH PGE2) and 20-hydroxy prostaglandin F2α (20-OH PGF2α), and the contribution of nitric oxide (NO) and prostanoids to the changes evoked in cortical blood flow (CBF) and medullary blood flow (MBF). We tested the hypothesis that 20-HETE produces qualitatively different regional hemodynamic effects in the kidney with 20-OH PGF2α or 20-OH PGE2, accounting for the vasoconstriction or vasodilation, respectively, in the cortex and medulla. Renal intra-arterial infusion of 1, 2.5, 5, and 10 ng/min 20-HETE decreased CBF by 10 ± 3, 24 ± 4, 40 ± 7, and 58 ± 9 perfusion units (PU), respectively, but increased MBF by 4 ± 2, 16 ± 4, 27 ± 3, and 41 ± 10 PU, respectively. 20-OH PGF2α mimics the effects of 20-HETE, as did PGF2α. However, 20-OH PGE2 increased both CBF and MBF, as did PGE2. Indomethacin (5 mg/kg) blunted the effects of 20-HETE but not that of 20-OH PGE2 and 20-OH PGF2α. However, SQ29548 ([1 S -[1α,2α( Z ),3α,4α]]-7-[3[[2-[(phenylamino)carbonyl[hydrazino]methyl]-7-oxabicyclo]2.2.1]hept-2-yl]-5-heptenoic acid) (0.1 mg/kg), a prostaglandin H2/thromboxane A2 receptor antagonist, blunted the cortical and medullary hemodynamic effects elicited by 20-HETE, 20-OH PGE2, 20-OH PGF2α, and PGF2α but not PGE2. N ω-l-nitro arginine methyl ester (5 mg/kg), the inhibitor of NO synthase, exacerbated the cortical constrictor effects of 20-HETE and 20-OH PGF2α without affecting the medullary perfusion produced by 20-HETE or its metabolites. These findings suggest that 20-HETE, through its hydroxyl metabolites, produced differential effects in the kidney. The medullary perfusion appears to be independent of NO.
Mathematical model of edema in the isolated rabbit lung perfused with oleic acid.

The development of edema by the isolated, perfused rabbit lung in response to oleic acid was analyzed with the equations of Kedem and Katchalsky (Biochim. Biophys. Acta 27: 229–246, 1958). A perfused cylinder and annulus surround was chosen as a model. Isolated lungs, perfused with an isosmotic solution containing dextran as an oncotic agent, received a bolus injection of oleic acid into the pulmonary artery, resulting in marked edema without a rise in mean pulmonary arterial pressure. Hydrostatic pressure was kept constant and in the model was converted to its equivalent concentration of osmotically active impermeant solute, with a reflection coefficient (sigma) of 1. Fluid changes could be analyzed with three principal components as follows: the capillary permeability to solute (Pk), the hydraulic coefficient (Lp), and sigma. The equations were solved using Euler's method for integration, and the values for the three coefficients were adjusted to fit the data. The analysis indicated that the edema measured experimentally could be simulated by a progressive increase in Lp at constant or increasing values of Pk and decreasing values for sigma but not after selective increases in Pk and/or decreases in sigma alone. The analysis suggests that an expanding hydraulic conductivity may be the rate-limiting factor in oleic acid-induced pulmonary edema in the isolated, perfused rabbit lung.
Why more women than men

The anxiety disorders share a non-specific proneness to negative affectivity with depressive disorders and other forms of emotional distress. Such negative affectivity is presumed to enhance the salience of fear and anxiety as well as other negative emotions. When combined with a style of responding to negative affect that is characterized by high threat value and avoidance, the proneness to anxiety in particular is enhanced. The higher the loading on negative affectivity and the more pervasive the threat-based style of responding, the greater are the chances of becoming anxious over a broader array of stimuli. Females are at greater risk than males for anxiety disorders as well as depression. The divergence between males and females increases postpuberty, when female propensity intensifies whereas male risk for anxiety as well as depression remains relatively unchanged. Results from longitudinal analyses confirm the hazard rate curves, in that childhood anxiety predicts adolescent anxiety in girls only, and that anxiety is more stable in females than males throughout adolescence and early adulthood. The divergence may progressively widen through later middle-age as well. Closer examination suggests that most sex differentiation occurs not in the propensity to fear per se but in the level of anxious and avoidant responding. This chapter describes the parts of the origins model at which greater risk is conferred upon females than males and the social and evolutionary underpinnings of such risk.
The Dipole Magnet System for the Jlab THz/IR/UV Light Source Facility

Abstract Six families of dipoles were designed, manufactured and tested for the THz/IR/UV Light Source Facility at the Thomas Jefferson National Accelerator Facility (Jlab). These magnets obtained core field and field integral uniformities at the parts in 10,000 level. They form the basis of an ERL transport system with considerable operational flexibility (e.g. independently, order-by-order tuneable momentum compaction) and very large momentum acceptance − in the order of 10%. They were modelled in 3D using ANSYS, Radia or Opera 3D. The highlights of dipole magnet system design are presented along with summaries of family characteristics. Operational experience is presented. These dipoles run at two core field ranges, 0.05 T and 0.22 to 0.71 T. PACScodes: 41.85.Lc, 41.85 Ja
Abstract 15553: The Incidence of Emergency Department Visits for ST-Elevation Myocardial Infarction is Decreasing in the U.S

Introduction: The incidence and longitudinal trends of patients with ST-elevation myocardial infarction (STEMI) presenting to U.S. emergency departments (EDs) are currently unknown. Efforts to streamline door-to-balloon times by ED bypass, as well as greater use of effective treatments for cardiovascular disease, may decrease ED STEMI presentation. These estimates play an essential role in hospital resource allocation strategies. Hypothesis: The incidence of STEMIs presenting to EDs is decreasing. Methods: We conducted a descriptive epidemiological analysis of STEMI visits to EDs between 2006 through 2011 using the Nationwide Emergency Department Sample data which is the largest source of U.S. ED data. We included adult ED visits with an ICD-9CM diagnosis of STEMI and calculated incidence rates for STEMI ED visits using U.S. census population data. Incidence calculations were stratified by age group, geographic region, and year. Results: From 2006-2011, there was a mean of 258,106 STEMIs presenting to EDs per year, declining from 300,466 in 2006 to 227,343 in 2011. Incidence of ED STEMI visits per 10,000 adults declined from 10.1 (95% CI 9.8,10.8) in 2006 to 7.3 (95% CI 6.8,7.8) in 2011. The Midwest had the highest rate at 10.0 (95% CI 9.2,10.8) and the West had the lowest with 6.6 (95% CI 6.1,7.0). The incidence of STEMI decreased for all age groups ( Figure ) and regions during the study period. Conclusions: We report the first national estimates of STEMI presentation to U.S. EDs, which demonstrate decreasing incidence across all age groups and all geographic regions between 2006 and 2011. ![][1] [1]: /embed/graphic-1.gif
Hurricanes and the Local Sales Tax Base: Evidence from the 2004 Florida Disasters

The authors look at the effect of Florida's 2004 hurricanes on the local sales tax base. There is typically an increase in sales tax revenue after a storm. However, the most severe storms may fail to quickly bring a double-digit increase in sales tax revenue.
DESAL^\beta : A Framework For Implementing Self-stabilizing Embedded Network Applications

The Dynamic Embedded Sensor-Actuator Language (DESAL) [2] is a rule-based programming language, without events, interrupts, or hidden control. Nodes have built-in access to their neighbors’ state, with automatic node discovery and health monitoring. Applications communicate via shared variables, rather than explicit message passing. Shared variables naturally represent the state of self-stabilizing algorithms. DESAL simplifies the construction of self-stabilizing embedded applications by eliminating network programming, while offering significant reliability improvements.
Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.
Leveraging Managed Runtime Systems to Build, Analyze, and Optimize Memory Graphs

Optimizing memory management is a major challenge of embedded systems programming, as memory is scarce. Further, embedded systems often have heterogeneous memory architectures, complicating the task of memory allocation during both compilation and migration. However, new opportunities for addressing these challenges have been created by the recent emergence of managed runtimes for embedded systems. By imposing structure on memory, these systems have opened the doors for new techniques for analyzing and optimizing memory usage within embedded systems. This paper presents GEM (Graphs of Embedded Memory), a tool which capitalizes on the structure that managed runtime systems provide in order to build memory graphs which facilitate memory analysis and optimization. At GEM's core are a set of fundamental graph transformations which can be layered to support a wide range of use cases, including interactive memory visualization, de-duplication of objects and code, compilation for heterogeneous memory architectures, and transparent migration. Moreover, since the same underlying infrastructure supports all of these orthogonal functionalities, they can easily be applied together to complement each other.
Comparisons of interfacial Phe, Tyr, and Trp residues as determinants of orientation and dynamics for GWALP transmembrane peptides.

Aromatic amino acids often flank the transmembrane alpha helices of integral membrane proteins. By favoring locations within the membrane–water interface of the lipid bilayer, aromatic residues Trp, Tyr, and sometimes Phe may serve as anchors to help stabilize a transmembrane orientation. In this work, we compare the influence of interfacial Trp, Tyr, or Phe residues upon the properties of tilted helical transmembrane peptides. For such comparisons, it has been critical to start with no more than one interfacial aromatic residue near each end of a transmembrane helix, for example, that of GWALP23 (acetyl-GGALW5(LA)6LW19LAGA-[ethanol]amide). To this end, we have employed 2H-labeled alanines and solid-state NMR spectroscopy to investigate the consequences of moving or replacing W5 or W19 in GWALP23 with selected Tyr, Phe, or Trp residues at the same or proximate locations. We find that GWALP23 peptides having F5, Y5, or W5 exhibit essentially the same average tilt and similar dynamics in bilayer membranes o...
Response to Insecticides of the Sugarcane Borer in Louisiana and Texas1

In studies conducted to monitor the development of insecticide resistance among populations of Diatraea saccharalis (F.), Louisiana cultures remained unchanged in their response to azinphosmethyl and monocrotophos. Cultures from 2 locations in the Lower Rio Grande Valley of Texas gave similar responses to those of Louisiana to azinphosmethyl but were 4.5–9X more resistant to monocrotophos, 10–12X more resistant to carbofuran, and 2–8X more resistant (or cross-resistant) to methomyl and methyl parathion. Responses of Louisiana and Texas strains to 2 synthetic pyrethroids, fenvalerate and permethrin, were similarly susceptible.
Computational Prediction of microRNA Targets

Computational prediction of microRNA (miRNA) targets is a fundamental step towards the characterization of miRNA function and the understanding of their role in disease. A single miRNA can regulate hundreds of different gene transcripts through partial sequence complementarity and a single gene may be regulated by several miRNAs acting cooperatively. The remarkable advances made in recent years have allowed the identification of key features for functional miRNA binding sites. A plethora of prediction tools are now available, but their accuracies remain rather poor, as miRNA target recognition has revealed itself to be a very complex and dynamic mechanism, still only partially understood.
Diagnosis of Normal and Abnormal Color Vision with Cone-Specific VEPs

Purpose Normal color vision depends on normal long wavelength (L), middle wavelength (M), and short wavelength sensitive (S) cones. Hereditary “red-green” color vision deficiency (CVD) is due to a shift in peak sensitivity or lack of L or M cones. Hereditary S cone CVD is rare but can be acquired as an early sign of disease. Current tests detect CVD but few diagnose type or severity, critical for linking performance to real-world demands. The anomaloscope and newer subjective tests quantify CVD but are not applicable to infants or cognitively impaired patients. Our purpose was to develop an objective test of CVD with sensitivity and specificity comparable to current tests.
Non-Hodgkin's lymphoma of the paranasal sinuses: clinical and pathological features, and response to combined-modality therapy.

Purpose Lymphomas of the paranasal sinuses may have poorer prognoses compared with other extranodal lymphomas of the head and neck, and are not well defined as a particular clinicopathologic entity. The outcome of combined-modality therapy and central nervous system (CNS) prophylaxis has not been fully determined. Patients and methods We retrospectively reviewed our experience with 16 consecutive, carefully defined patients, all treated with both chemotherapy and radiotherapy. Results There were 11 men and five women, mean age 52. All presented with local symptoms; 13 had stage I or II disease. Thirteen had diffuse large cell lymphoma, two diffuse mixed, and one small noncleaved. Phenotyping revealed 10 B-cell, four T-cell, and two T or natural killer (NK). Most received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy; the order of chemotherapy and radiotherapy varied. Twelve received CNS prophylaxis. Of 12 complete responses, six relapsed, all at distant sites, and two died during initial therapy. Five-year survival was 29%, and median survival 18 months. Four of 10 B-lineage patients were relapse-free at 4 years; all six T- or T/NK-lineage patients relapsed or were dead within 6 months. Tumors of T or NK lineage often expressed CD56 and showed evidence of Epstein-Barr viral infection; otherwise, pathological features were not predictive of lineage or outcome. Neither age nor lactate dehydrogenase predicted prognosis. No complete responder recurred in the CNS as site of first relapse. Conclusion Despite localized stage at presentation, sinus lymphoma is an aggressive disease, characterized by distant relapse and early mortality. Combined-modality therapy with CNS prophylaxis improves outcome compared with radiotherapy alone; however, prognosis remains poor. Patients with T-lineage disease appear to have a particularly bad outcome. Autologous bone marrow transplantation should be evaluated as first-line therapy for those at high risk of relapse.
Clinical, surgical, and molecular prognostic factors for survival after spinal sarcoma resection

OBJECTIVE The goal of this study was to investigate the local recurrence rate and long-term survival after resection of spinal sarcomas. METHODS A retrospective review of patients who underwent resection of primary or metastatic spinal sarcomas between 1997 and 2015 was performed. Tumors were classified according to the Enneking classification, and resection was categorized as Enneking appropriate (EA) if the specimen margins matched the Enneking recommendation, and as Enneking inappropriate (EI) if they did not match the recommendation. The primary outcome measure for all tumors was overall survival; local recurrence was also an outcome measure for primary sarcomas. The association between clinical, surgical, and molecular (tumor biomarker) factors and outcomes was also investigated. RESULTS A total of 60 patients with spinal sarcoma were included in this study (28 men and 32 women; median age 38 years). There were 52 primary (86.7%) and 8 metastatic sarcomas (13.3%). Thirty-nine tumors (65.0%) were clas...
Acute myeloid leukaemia

There has been considerable progress in the understanding and treatment of childhood acute myeloid leukaemia over the past two decades. In particular, cytoand molecular genetics offer the potential for more specific diagnosis of what is basically a heterogeneous disease.To date treatment has been based on a steady increase in cytotoxic chemotherapy with or without the addition of bone marrow transplantation. Randomised therapeutic trials are difficult to perform in what is a rare disease.The best way forward is for paediatric trial groups worldwide to collaborate in developing common, or parallel, therapeutic protocols. Acute myeloid leukaemia (AML) in children is a rare disease. There are about 70 newly diagnosed cases in the UK per year and AML accounts for 15% of all childhood leukaemia. The incidence of AML is relatively stable throughout the childhood years but then slowly rises through early adult life before a progressive rise occurs above the age of 55.
The Struggle of Integration: James Baldwin and Melanie Klein in the Context of Black Lives Matter

Recent killings of unarmed black citizens are a fresh reminder of the troubled state of racial integration in the United States. At the same time, the unfolding Black Lives Matter protest movements and the responses by federal agencies each testify to a not insignificant capacity for addressing social pathologies surrounding the color line. In order to respond to this ambivalent situation, this article suggests a pairing between the work of James Baldwin and that of the psychoanalyst Melanie Klein. I will argue that we cannot fully appreciate the depths of what Baldwin called the “savage paradox” of race without the insights provided by Klein and object relations psychoanalysis. Conversely, Baldwin helps us to sound out the political significance of object relations approaches, including the work of Klein and those influenced by her such as Hanna Segal and Wilfred Bion. In conversation with the work of Baldwin, object relations theory can help to identify particular social settings and institutions that might allow concrete efforts toward racial justice to take root.
An experimental/theoretical investigation of interfacial instabilities in superposed pressure-driven channel flow of Newtonian and well-characterized viscoelastic fluids Part II. Nonlinear stability

The interfacial stability of pressure driven channel flow consisting of a highly elastic Boger fluid superposed on as silicone oil is investigated experimentally and theoretically. The viscosity of the two fluids used in the experiments are closely matched, hence any interfacial instability observed in this flow is primarily caused by elastic effects. In Part I of this study (Khomami and Su, 1999) it was demonstrated experimentally and theoretically that this flow system is linearly unstable for a range of depth ratios. In Part II, the dynamics of interfacial waves in the weakly nonlinear regime is examined. Specifically, the Stuart-Landau equation is used to examine the shape of saturated waves. It is shown that the bifurcations are primarily supercritical and the theoretical wave forms compare favorably with experimental measurements. Moreover, it is found that in the weakly nonlinear regime most of the energy transfer occurs between the primary mode and the second harmonic for the fluid system considered. ©2000 Elsevier Science B.V. All rights reserved.
Self-Reported Driving Difficulty in Veterans With Traumatic Brain Injury: Its Central Role in Psychological Well-Being

Background The ability to drive is a core function supporting independent living. Traumatic brain injury (TBI) may impair driving capacity in numerous ways. Previous research has documented that individuals with TBI have more driving-related problems than other people and has identified predictors of driving status or capacity, mostly among civilians; however, no research has examined the implications of driving limitations for the well-being of individuals with TBI. Objective To examine the association between self-reported difficulty in driving with important domains of psychological well-being in veterans with TBI, with adjustment for posttraumatic stress disorder (PTSD) and years since most recent TBI. Design Cross-sectional. Setting Veterans' homes. Participants A total of 61 veterans of the Global Wars on Terrorism diagnosed with TBI, all outpatients at a Veterans Affairs medical center rehabilitation service. Methods Home interviews as a baseline assessment for a larger randomized controlled trial. Main Outcome Measures Community reintegration (extent of social participation), depressive symptomatology, and role limitations due to physical health problems and those due to emotional problems. Self-rated competence in driving was the predictor, and sociodemographic characteristics, diagnosis of PTSD, severity of TBI, and time since most recent TBI were covariates. Results Self-rated driving difficulty was associated with decreased community reintegration (β = .280, P =.028), greater depressive symptomatology (β = −.402, P P =.011) and to emotional problems (β = −.324, P = .006), after we adjusted for PTSD and other variables. Discussion The self-reported ability to drive seems to be central to psychological well-being in veterans with TBI, showing clear associations with depression, community reintegration, and health-related role limitations. These associations cannot be attributed to comorbid PTSD. Conclusion Rehabilitation specialists should view driving difficulty as a risk factor for poor psychosocial outcomes in veterans with TBI and seek ways to compensate for the veteran's loss of driving if it is no longer advisable. Level of Evidence II
Precis of Risk and Rationality

My book Risk and Rationality argues for a new alternative to the orthodox theory of rational decision-making. This alternative, risk-weighted expected utility maximization, holds that there are three important components involved in rational decision-making: utilities, probabilities, and risk-attitudes. This essay explains the basic outline of the theory and precisely how it differs from the orthodox theory. It also summarizes the main threads of argument in the book.
Examining caries aetiology in adolescence with structural equation modelling

OBJECTIVES This analysis examines the aetiology of caries development in adolescents using structural equation modelling to identify behavioural mediators of the relationship between socioeconomic status (SES) and caries incidence, and to investigate the role of sex on caries-preventive behaviour and caries. METHODS This analysis was based on data from the Iowa Fluoride Study, a longitudinal study of a birth cohort. We hypothesized that socioeconomic status earlier in life has a direct effect on caries development and an indirect effect from improved behavioural variables-dental visit attendance, toothbrushing frequency and percentage of beverage intake consisting of sugar-sweetened beverages-and that sex also plays a role in behavioural variables, as well as caries. A structural equation model was developed based on these hypotheses, and direct and indirect standardized path coefficients were calculated, as well as their standard errors. RESULTS Based on our proposed model, SES at birth significantly influences SES during adolescence, but not adolescent behaviours. The effect of SES during adolescence on caries in the permanent dentition is mediated by adolescent behaviours. Female participants have worse caries than male participants, despite lower self-reported percentages of sugar-sweetened beverage intake and more frequent brushing and dental attendance. CONCLUSIONS This analysis models the relationships among known causal factors for caries and suggests that the role of SES in caries may not be as important as previously thought and different behaviours that affect oral health between males and females as well as differences in caries between the sexes could begin during adolescence. These findings could help improve caries prevention programmes for adolescents.
Dynamics of intraoperative Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter transmission.

Background Our primary objective was to examine anesthesia work area reservoir isolation of Klebsiella , Acinetobacter , Pseudomonas , and Enterobacter spp (KAPE) pathogens. This is a retrospective analysis of a randomized, prospective, and observational study involving 3 academic medical centers. Methods Patients included adults undergoing general anesthesia. Gram-negative isolates (N = 2,682) were collected from anesthesia work area reservoirs in 274 randomly selected operating room case pairs. Nine hundred and forty-five isolates were included in this study. Chi square tests were used to examine the association of anesthesia work area reservoirs with KAPE genera isolation. Results Acinetobacter pathogens were more likely to be isolated from anesthesia provider hands (risk ratio [RR], 1.07; 95% confidence interval [CI], 1.04-1.10; corrected P = .004) and less likely to be isolated from patients (RR, 0.2; 95% CI, 0.08-0.50; corrected P Enterobacter pathogens were more likely to be isolated from patients (RR, 3.34; 95% CI, 1.92-5.81; corrected P = 0.001) and less likely to be isolated from provider hands (RR, 0.89; 95% CI, 0.83-0.97; corrected P = .007). Conclusions Anesthesia provider hands are important reservoirs for Acinetobacter spp, whereas patient skin surfaces are key reservoirs for Enterobacter spp. Future work should examine the impact of a multimodal program in controlling the intraoperative spread of Acinetobacter and Enterobacter pathogens.
A two-scale generalized finite element method for parallel simulations of spot welds in large structures

Abstract The diameter of spot welds used in the automotive and aerospace industry is orders of magnitude smaller than the dimensions of the structural components. Automotive bodies typically have between three and five thousand spot welds which makes 3-D Direct Finite Element Analysis (DFEA) of this class problem not practical. To circumvent these limitations of the FEM, spot welds are idealized in industrial problems as elastic or rigid beams connecting nodes of the metal sheet meshes. However, parameters used in these spot weld models are often problem dependent. This paper presents a parallel Generalized Finite Element Method (GFEM) for the simulation of spot welds in large structures. The proposed GFEM can adopt structural-scale meshes that ignore the spot welds and thus can be generated much quicker than in a DFEA. The element size in the GFEM mesh is of the same order as those used in the industry for the class of problems considered here. Verification problems show that the proposed method can provide an accuracy comparable to a 3-D DFEA. Numerical experiments on a hat-stiffened panel with 168 spot welds show that the proposed GFEM scales much better than a DFEA on shared memory machines, in particular when nonlinear material behavior near the spot welds is considered.
Pharmacometrics of Viral Infections

Antiviral drugs play a crucial role in the treatment of human infections caused by viral pathogens. In order for antiviral therapy to be efficacious, the optimal dose and dosing interval for each compound must be identified. Optimal dosage regimens are defined as regimens that maximize inhibition of viral replication, prevent the emergence of resistance, and demonstrate minimal toxicity. Pharmacometrics can be applied to guide in the intelligent design of optimal dosage regimens for antiviral compounds. But in order for this approach to be successful, a deep understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) properties of each compound must be delineated. In this chapter, we describe the use of in vitro PD model systems to elucidate the PD and PK/PD interactions for several antiviral agents active against human immunodeficiency virus (HIV), hepatitis C virus (HCV), or influenza A virus. We also discuss how this information derived from “benchtop” experiments can be directly applied to the “bedside” or clinic.
Müllerian Inhibiting Substance: New Insights

In 1947, Alfred Jost first postulated a Mullerian inhibitor, originally called Mullerian inhibiting substance (MIS) and also referred to as anti-Mullerian hormone, as a critical participant in vertebrate sexual differentiation. In his seminal experiments, Jost showed that female rabbit embryos implanted with testicular fragments before sexual differentiation showed Mullerian duct regression as well as the expected preservation of Wolffian ducts and external virilization. However, implantation with testosterone pellets alone could not induce regression of Mullerian ducts; therefore, he suggested the existence of another testicular hormone—Mullerian ‘l inhibitrice. In 1969, Picon demonstrated Mullerian duct regression in organ culture following exposure to testicular fragments. Using this assay, Josso and colleagues identified the Sertoli cell product causing Mullerian duct regression, which lead to a renewed interest in MIS physiology, embryology, and molecular signaling as well as subsequent diagnostic and therapeutic applications.