cssi/SciSciGPT-SciSciNet huggingface dataset:
Clinical characteristics of chronic heart failure patients with an augmented peripheral chemoreflex

Aims The peripheral chemoreflex may be augmented in chronic heart failure and may play a role in its pathophysiology including the mediation of exercise hyperpnoea and sympathetic activation. The objective of this study was to characterize the patients with an augmented peripheral chemoreflex. Methods and results Peripheral chemoreflex sensitivity was assessed by measuring the ventilatory response to hypoxia using transient inhalations of pure nitrogen in 50 patients with chronic heart failure (age 58·±12·1 (SD) years; radionuclide left ventricular ejection fraction 26·5±13·0%). The peripheral chemoreflex of 12 healthy controls with similar demographic characteristics was 0·272±0·201 1.min−1. %Sao2−1 compared with 0·673±0·4101.min−1.%Sao2−1 ( P <0·0001) in the chronic heart failure patients. Using 2 standard deviations above the mean level of the controls' peripheral chemoreflex sensitivity as the upper limit of normal, we defined an augmented chemoreflex as greater than 0·6751.min−1.%Sao2−1 Twenty of the chronic heart failure patients (40%) demonstrated such an augmented peripheral chemoreflex. Compared with patients with peripheral chemoreflex sensitivity within the normal range, they had a reduced peak oxygen consumption during cardiopulmonary exercise (15·1±4·4 vs 18·5±5·8 ml.kg−1.min−1, P =0·02), reduced radionuclide left ventricular ejection fraction (21·8±11·8 vs 29·4±13·1%, P =0·046) and were in a worse New York Heart Association functional class (2·8 vs 2·4 P =0·05). The ventilatory response to exercise, as characterized by the regression slope relating minute ventilation to carbon dioxide output during exercise, was also higher (40·48±9·32 vs 34·54±7·19, P =0·02), consistent with the role of the peripheral chemoreflex in mediating exercise hyperpnoea. There was also an increased proportion of patients with non-sustained ventricular tachycardia in the group with an augmented peripheral chemoreflex (61% vs 21%, chisquared 7·08, P <0·01). No difference was seen in the age, height, weight and lung function measurements of these patients compared with the normal chemoreflex group. Conclusion An augmented peripheral chemoreflex is a common finding in chronic heart failure patients, one associated with increasing severity and with the exercise hyperpnoea seen in the condition. That there was an excess of patients with non-sustained ventricular tachycardia in the group with an augmented peripheral chemoreflex may be related to the chemoreflex-driven sympathetic stimulation. The peripheral chemoreflex may be important in the pathophysiology of chronic heart failure, both in terms of symptoms and exercise limitation.
Generational differences on craft workers’ perceptions of the factors affecting labour productivity11This paper is one of a selection of papers in this Special Issue on Construction Engineering and Management.

Although the current economic downturn has eased the stress of broad skilled labour shortages, it is reasonable to believe that the shortage will return when the U.S. economy rebounds. The shortage...
Accurate delay models for ECL logic synthesis

The usage of logic synthesis tools for ECL logic has been questionable, among other reasons, because of the discrepancy between the simple, computationally efficient models required by synthesis and the more and more sophisticated models required for accurate simulation. The paper demonstrates that with appropriate choice of modelling parameters, it is possible to map an existing ECL simulation library to a synthesis library with errors below 1%. The authors review the basic delay calculation algorithms provided by a prominent commercial ECL Logic Synthesis tool (Synopsys). They show how delay data is generated by their proprietary delay calculator DECAL. They develop a simplification scheme that enables the algorithms given in Synopsys to produce accurate results. Finally, they present some results on accuracy. >
Ingenious strategies of microbial pathogens

Presentations at the Minisymposium “Pathogens and Parasites” featured the unexpected ways in which pathogens have adapted to their parasitic lifestyles.
Overcurrent protection issues for radial distribution systems with distributed generators

The integration of distributed generators (DGs) into distribution systems is being proposed as a solution to meet increasing load demands and to utilize more renewable energy. Existing overprotection schemes must be modified to address the new system characteristics of radial distribution systems with DGs. Minimum “off-the-shelf” overcurrent protection devices and distributed generators were added to the 123 Nodes Radial Test feeder. A commercial power systems analysis tool was used to determine the coordination issues that arise in the distribution system due to the integration of DGs. The results of these studies are presented and discussed.
Helicobacter pylori eradication: are there alternatives to antibiotics?

It is now generally accepted that infection with Helicobacter pylori is an important cause of peptic ulcer disease and that eradication of this organism greatly reduces the recurrence rate of ulcers. H. pylori also can cause chronic gastritis and hypochlorhydria and is a risk factor for gastric cancer. Conventional eradication therapies, which consist of two antibiotics plus either a proton-pump inhibitor or a bismuth compound, are highly effective, but can cause significant side effects in some cases. Alternative methods of eradicating H. pylori are therefore being investigated. To date, the research in this area is still preliminary, and no treatment has emerged as a clear alternative to the conventional triple-therapy regimens. (Altern Med Rev 2001;6(4):355-366)
The roles of cis- and trans-regulation in the evolution of regulatory incompatibilities and sexually dimorphic gene expression

Evolutionary changes in gene expression underlie many aspects of phenotypic diversity within and among species. Understanding the genetic basis for evolved changes in gene expression is therefore an important component of a comprehensive understanding of the genetic basis of phenotypic evolution. Using interspecific introgression hybrids, we examined the genetic basis for divergence in genome-wide patterns of gene expression between Drosophila simulans and Drosophila mauritiana. We find that cis-regulatory and trans-regulatory divergences differ significantly in patterns of genetic architecture and evolution. The effects of cis-regulatory divergence are approximately additive in heterozygotes, quantitatively different between males and females, and well predicted by expression differences between the two parental species. In contrast, the effects of trans-regulatory divergence are associated with largely dominant introgressed alleles, have similar effects in the two sexes, and generate expression levels in hybrids outside the range of expression in both parental species. Although the effects of introgressed trans-regulatory alleles are similar in males and females, expression levels of the genes they regulate are sexually dimorphic between the parental D. simulans and D. mauritiana strains, suggesting that pure-species genotypes carry unlinked modifier alleles that increase sexual dimorphism in expression. Our results suggest that independent effects of cis-regulatory substitutions in males and females may favor their role in the evolution of sexually dimorphic phenotypes, and that trans-regulatory divergence is an important source of regulatory incompatibilities.
Erdös-Rényi laws for dynamical systems

We establish Erdos-Renyi limit laws for Lipschitz observations on a class of non-uniformly expanding dynamical systems, including logistic-like maps. These limit laws give the maximal average of a time series over a time window of logarithmic length. We also give results on maximal averages of a time series arising from Holder observations on intermittent-type maps over a time window of polynomial length. We consider the rate of convergence in the limit law for subshifts of finite type and establish a one-sided rate bound for Gibbs-Markov maps.
CALCIUM UPTAKE BY BOVINE MUSCLE MITOCHONDRIA AND SARCOPLASMIC RETICULUM

Mitochondria and sarcoplasmic reticulum were isolated from prerigor bovine muscle, and their anaerobic calcium uptake activities and stabilities were determined at temperatures, pH values, and ATP concentrations selected to simulate conditions in postmortem muscle. Both organelles were relatively active at 1 mM ATP and showed optimum activity at 3 mM. The pH optimum was 7.2 for mitochondria and 6.0–6.5 for sarcoplasmic reticulum; activities of both increased with increasing temperatures. Under simulated postmortem conditions both organelles initially increased in activity, but mitochondria were first to decline below their initial value. Stabilities declined with decreasing, pH values and increasing temperatures, especially above 25°C for mitochondria and above 40°C for sarcoplasmic reticulum.
Galactomannan and Polymerase Chain Reaction–Based Screening for Invasive Aspergillosis Among High-Risk Hematology Patients: A Diagnostic Meta-analysis

BACKGROUND Screening of high-risk patients for invasive aspergillosis (IA) has the potential to decrease the use of empiric antifungal agents. However, the performance of different screening methods has not been studied. METHODS We performed a meta-analysis of published studies to assess the diagnostic performance of galactomannan (GM) and polymerase chain reaction (PCR) as weekly screening tests in high-risk populations. The sensitivity and specificity of 6 approaches combining GM and PCR were estimated using the bivariate model. RESULTS Thirteen studies with 1670 patients met our inclusion criteria. Single positive test results had modest sensitivity and specificity for screening (respectively, 92% and 90% for GM; 84% and 76% for PCR). The screening approach with the highest sensitivity was the one that used at least 1 GM- or PCR-positive result to define a positive episode, achieving a sensitivity of 99%, significantly higher than any single test (P = .0018 compared with GM and P < .0001 compared with PCR). Meanwhile, when both GM and PCR were positive for the same patient, the specificity increased to 98%, which was not significantly different compared to the specificity of at least 2 positive GM (95%, P = .56 for the comparison) or PCR results (93%, P = .07 for the comparison). CONCLUSIONS When screening high-risk patients for IA with GM and PCR tests, the absence of any positive test can obviate the need for antifungal agents with a negative predictive value of 100%, whereas the presence of at least 2 positive results is highly suggestive of an active infection with a positive predictive value of 88%.
MR imaging of large hypothalamic hamartomas in two infants.

Case 1 was an 11-month-old boy referred for the evaluation of apnea and seizures, which he had had since birth. He had syndactyly, polydactyly, a cleft epiglottis, and developmental delay. He was hypoglycemic, hypothyroid, and deficient in growth hormone. Case 2 was a 6-month-old boy referred because of mild developmental delay. A large suprasellar mass was found in both patients on CT and MR (Figs. 1 and 2). Because of the central location of the masses, neither patient had a biopsy. Clinically, the infants remained unchanged 1 year after their initial visits. Discussion Histologically, hamartomas of the hypothalamus most closely re­ semble the posterior hypothalamus. The masses typically are small and pedunculated and look like a collar button. They fill the space between the optic chiasm and pons [1 ]. Signs and symptoms usually are seen early in life. The most frequent presentations are precocious puberty (35- 70%), seizures (48%), and developmental changes [2). Usually, no focal neurologic signs are seen. Precocious puberty rarely occurs with large hamartomas [3). CT typically shows a mass situated posterior to the dorsum sellae and the pituitary stalk, anterior to the pons and cerebral peduncles,
The Integration of China into the Global Political Economy: Trade, Foreign Direct Investment, and Tourism

How integrated is China with East Asia and ‘the West’? Especially given the belief of many analysts that China is slowly rising in power to one day command the global system in much the way the United states controls the global system now, empirically valid data demonstrating the structure of China’s connections with the rest of the world is sorely needed. Using macro level theories of cooperation and conflict, combined with a statistical analysis of global trade, foreign direct investment (FDI), and tourism flows, the intensity of China’s integration with the global political economy is measured.
Superfluid phases of He 3 in nanoscale channels

Confinement of superfluid $^{3}\mathrm{He}$ on length scales comparable to the radial size of the $p$-wave Cooper pairs can greatly alter the phase diagram by stabilizing broken symmetry phases not observed in bulk $^{3}\mathrm{He}$. We consider superfluid $^{3}\mathrm{He}$ confined within long cylindrical channels of radius $100\phantom{\rule{4.pt}{0ex}}\text{nm}$, and report new theoretical predictions for the equilibrium superfluid phases under strong confinement. The results are based on the strong-coupling formulation of Ginzburg-Landau (GL) theory with precise numerical minimization of the free energy functional to identify the equilibrium phases and their regions of stability. We introduce an extension of the standard GL strong-coupling theory that accurately accounts for the phase diagram at high pressures, including the tricritical point and ${T}_{AB}(p)$ line defining the region of stability for the bulk A phase. We also introduce tuneable boundary conditions that allow us to explore boundary scattering ranging from maximal to minimal pairbreaking, and report results for the phase diagram as a function of pressure, temperature, and boundary conditions. Four stable phases are found: a polar phase stable in the vicinity of ${T}_{c}$, a strongly anisotropic, cylindrical analog of the bulk B phase stable at sufficiently low temperatures, and two chiral A-like phases with distinctly different orbital symmetry, one of which spontaneously breaks rotation symmetry about the axis of the cylindrical channel. The relative stability of these phases depends sensitively on pressure and the degree of pairbreaking by boundary scattering. The broken symmetries exhibited by these phases give rise to distinct signatures in transverse nuclear magnetic resonance (NMR) spectroscopy. We present theoretical results for the transverse NMR frequency shifts as functions of temperature, the rf pulse tipping angle, and the static NMR field orientation.
A Methodology to Analyze Multi-Agent Systems Modeled in High Level Petri Nets

This paper presents a methodology for analyzing multi-agent systems modeled in nested predicate transition nets. The objective is to automate the model analysis for complex systems, and provide a foundation for tool development. We formally define the translation rules that translate the multi-agent model to an executable PROMELA model, and demonstrate the translation with an example.
Spread-Wing Postures and Their Possible Functions in the Ciconiidae

IN two recent papers Clark (19'69) and Curry-Lindahl (1970) have reported spread-wing postures in storks and other birds and discussed some of the functions that they may serve. During recent field studies (1959-69) of all 17 species of storks, I have had opportunities to observe spread-wing postures. in a number of species and under different environmental conditions (Table i). The contexts in which these postures occur shed some light on their possible functions.
Investigation of the Noise from a Rectangular Supersonic Jet

An experimental investigation of a low aspect ratio rectangular nozzle’s flow field was completed. Over, ideally, and under expanded operating conditions were presented for nozzle temperature ratios of between unity and three. The aim of this study was threefold, first to validate the newly constructed heated jet noise rig at the University of Cincinnati, second to provide data for future computational validation, and third to compile acoustic baselines for future noise reduction studies. Validation of the experimental results was achieved through comparison to jet noise theories and empirical relations, particularly the fine and large scale similarity spectrum, screech frequency predictions, and scaling of acoustic intensity with powers of the expansion factor β. Excellent comparisons were achieve with limited deficiencies identified, such as possible nonlinear propagation and/or rig noise contamination at high frequencies for elevated temperatures. It was found for the current experimental setup that screech was eliminated at highly elevated temperatures. This phenomena that is still currently debated and bears further investigation. Additionally, the noise source known as crackle was briefly investigated, and it was found that at elevated temperature and pressure ratios the measured acoustics met the criteria for a crackling jet.
Modeling the effects of extracellular potassium on bursting properties in pre-Bötzinger complex neurons

There are many types of neurons that intrinsically generate rhythmic bursting activity, even when isolated, and these neurons underlie several specific motor behaviors. Rhythmic neurons that drive the inspiratory phase of respiration are located in the medullary pre-Botzinger Complex (pre-BotC). However, it is not known if their rhythmic bursting is the result of intrinsic mechanisms or synaptic interactions. In many cases, for bursting to occur, the excitability of these neurons needs to be elevated. This excitation is provided in vitro (e.g. in slices), by increasing extracellular potassium concentration (Kout) well beyond physiologic levels. Elevated Kout shifts the reversal potentials for all potassium currents including the potassium component of leakage to higher values. However, how an increase in Kout, and the resultant changes in potassium currents, induce bursting activity, have yet to be established. Moreover, it is not known if the endogenous bursting induced in vitro is representative of neural behavior in vivo. Our modeling study examines the interplay between Kout, excitability, and selected currents, as they relate to endogenous rhythmic bursting. Starting with a Hodgkin-Huxley formalization of a pre-BotC neuron, a potassium ion component was incorporated into the leakage current, and model behaviors were investigated at varying concentrations of Kout. Our simulations show that endogenous bursting activity, evoked in vitro by elevation of Kout, is the result of a specific relationship between the leakage and voltage-dependent, delayed rectifier potassium currents, which may not be observed at physiological levels of extracellular potassium.
Exercise and the Reproductive System in Women

Exercise was long thought to suppress female reproductive function but has been shown to have no suppressive effect beyond the impact of its energy cost on energy availability, defined as dietary energy intake minus exercise energy expenditure. To preserve reproductive function, exercising women need to maintain an energy availability (dietary energy intake minus exercise energy expenditure) of ∼45 kilocalories per kilogram of fat-free mass per day (kcal/kgFFM/day) under normal circumstances and no less than 30 kcal/kgFFM/day during weight-loss programs.
Deficient cMyBP-C protein expression during cardiomyocyte differentiation underlies human hypertrophic cardiomyopathy cellular phenotypes in disease specific human ES cell derived cardiomyocytes.

Abstract Aims Mutations of cardiac sarcomere genes have been identified to cause HCM, but the molecular mechanisms that lead to cardiomyocyte hypertrophy and risk for sudden death are uncertain. The aim of this study was to examine HCM disease mechanisms at play during cardiac differentiation of human HCM specific pluripotent stem cells. Methods and results We generated a human embryonic stem cell (hESC) line carrying a naturally occurring mutation of MYPBC3 ( c . 2905 + 1 G > A ) to study HCM pathogenesis during cardiac differentiation. HCM-specific hESC-derived cardiomyocytes (hESC-CMs) displayed hallmark aspects of HCM including sarcomere disarray, hypertrophy and impaired calcium impulse propagation. HCM hESC-CMs presented a transient haploinsufficiency of cMyBP-C during cardiomyocyte differentiation, but by day 30 post-differentiation cMyBP-C levels were similar to control hESC-CMs. Gene transfer of full-length MYBPC3 during differentiation prevented hypertrophy, sarcomere disarray and improved calcium impulse propagation in HCM hESC-CMs. Conclusion(s) These findings point to the critical role of MYBPC3 during sarcomere assembly in cardiac myocyte differentiation and suggest developmental influences of MYBPC3 truncating mutations on the mature hypertrophic phenotype.
SOC design challenges for embedded systems

Nowadays, LSIs can integrates billions of transistors on a chip. This means that a system or systems can be implemented in a LSI. Therefore in order to support new requirements of SOC (System on Chip) the LSI design methodology is required to be changed. SOC's are used inside embedded systems. In SOC design, it is required to achieve (1) system level optimization (2) application specific solution (3) reduction of LSI design cost (4) reduction of embedded software design cost. Platform approaches are proposed to solve these problems, but the lack of the flexibility in a platform is the most critical problem to use in the practical design. We proposed EXREAL Platform, which is the mother platform to generate application specific platforms. We are proposing the heterogeneous multi-core is better than the software solution on the standardized hardware platform. In order to achieve EXREAL Platform, we are developing three fundamental technologies that is (1) hardware interconnect technology (2) software interconnect technology (3) evaluation/validation technology. In this paper, the key concepts of EXREAL platform and some practical examples to achieve system level optimization are described.
Augmented Lower Urinary Tract

Augmentation cystoplasty (AC) is an outstanding option for patients with a threatened upper urinary tract who have failed conservative or minimally invasive therapy. However, AC is a nonphysiologic option putting a patient in need for lifelong medical surveillance. Urodynamics have an important role in assessing patients with lower urinary tract dysfunction prior to AC. In addition, many patients will require some type of intervention after AC. Urodynamics may be part of the post-AC diagnostic evaluation for patients with suboptimal outcomes after lower urinary tract reconstruction.
Do patients with submassive pulmonary embolism benefit from thrombolytic therapy

Despite growing interest in thrombolytic agents to treat submassive pulmonary embolism, their role in this scenario remains controversial. Needed is a way to identify patients with this condition who are at risk of clinical deterioration and who would benefit from thrombolytic therapy. Here, we review the use of thrombolytic agents in submassive pulmonary embolism to help distinguish the risk and benefits of this therapy.
The Potential Utility of Ashwagandha for Improving Cognitive Dysfunction in Persons with Bipolar or Other Neurocognitive Disorders

Bipolar Disorder is a mood disorder that can be quite severe for subgroups of patients, and often such patients manifest deficits in attention, concentration, memory, and executive functions that persist even when they are relatively well. Cognitive concerns can impair daily life functioning and impact employment, education, and interpersonal relationships. Main line treatments for bipolar disorder typically do not address cognitive impairments, and some treatments may actually worsen cognitive deficits. Treatment development for cognitive impairments in bipolar disorder is truly in its infancy; extracts of Ashwagandha (Withania somnifera) may hold promise as a potential treatment option. The bioactive constituents of Ashwagandha, including withanolides, indosides, Withaferin A, and others, possess anti-inflammatory-immunomodulatory, anti-oxidant, cortisol lowering, anti-stress, pro-cholinergic, anti-glutamatergic and neuroprotective properties, the very processes that are thought to underlie cognitive impairments not only in in bipolar disorder but also in other psychiatric disorders like schizophrenia and major depression. This chapter reviews this in detail and highlights the preliminary randomized controlled study assessing an extract of Ashwagandha for improving cognition in bipolar disorder. The chapter also explores the potential role of Ashwagandha extracts in the treatment of other neurocognitive disorders, and it concludes by summarizing additional future research needed to realize the potential of this ancient medicinal plant for the treatment of human ailments.
Sustainable Urban Ecosystems: Problems and Perspectives

In urban ecosystems, the main problems are drinking water supply, energy supply, drainage, waste disposal, land use change, pollution, mitigation of natural disasters, and protecting the integrity of ecosystems. These problems are being compounded by population explosion including migration, sociocultural upheaval, and climate change. In order to discuss these problems from a hydrologic perspective, this paper first revisits ecology, ecosystems, ecosphere, and biosphere. It then looks at ecosystems in the hierarchy of biological organization. This then leads to stating the sciences that are allied with ecology and ecosystems. The next question that needs to be addressed is the one of sustainability. Defining sustainability is, some aspects of sustainable development and sustainability imperatives are enumerated. With this background in hand, urban ecosystems and their components are formulated. This leads to stating the main urban hydrology problems and challenges. These problems and challenges are being complicated by growing global population, particularly urban population and especially in India and its cities. Emphasizing water as the source of life, food, fiber, and energy, the question of meeting the challenges of water security, energy security, and food supply arises. To that end, water use, including individual, virtual water use, water withdrawals, and water use in different sectors, is discussed. The use of water in energy production is then highlighted. There is a dualism of energy use in India, and this gives rise to India’s energy challenge. Without sustainable energy supply in the long term, development will be impeded, for this is one of the sustainability imperatives. The problem of drinking water which is still plaguing cities in India is then examined. Like energy, it is related to human health and development. These challenges must be met with an integrated approach to water management under the specter of looming climate change. The discussion is concluded with a personal perspective on water, food, and energy security and on development itself.
Synthesis and Properties of Polymers with an Organosilicon–Acetylene Backbone

Acetylene- and diacetylene-containing organosilicon polymers continue to be of great interest in academia, government, and industry due to their high thermo-oxidative stability combined with excellent solubility and processability characteristics. Progress in this field over the past 30 years is reported herein. We present and discuss the synthesis, characterization, and structure–property relationships related to these materials. Furthermore, properties for specific applications of these polymers are briefly summarized, such as absorption and emission spectroscopy, composite mechanical analysis, four-probe conductivity measurements, and electroluminescence.
A Model of Respiratory Variability During Non-Rem Sleep

A number of studies have noted the frequent occurrence of periodic breathing (PB) during the transition from wakefulness to sleep and during the light stages of non-rapid eye movement (NREM) sleep1,2. The onset of sleep is also known to be accompanied by a shift of the CO2 response line to the right, as well as a slight-to-moderate depression in slope1,2. However, these observations appear to be inconsistent with theoretical and experimental studies of PB, which have shown that a decrease in controller gain would enhance the stability of respiratory control3,4,5. Existing models of PB are also unable to explain why subjects with primary alveolar hypoventilation syndrome (PAHS), who have very low ventilatory CO2 responses, experience large fluctuations in ventilation and blood gases during sleep1.
The Nexus Approach to Managing Water, Soil and Waste under Changing Climate and Growing Demands on Natural Resources

The human population has increased more than a thousand times from 2–20 million at the dawn of settled agriculture about 10–12 millennia ago to 7.2 billion in 2013. It is projected to reach 9.6 billion by 2050 and ~11 billion by 2100 (UN in World population prospects: The 2012 revision. UN Department of Economic and Projection Section, New York, 2012)
Magic Type Labelings of Digraphs

Early labeling results were all on undirected graphs. However, in the mid-1980s Bloom and Hsu defined graceful labelings on directed graphs [16]. Not much work was done with directed graph labeling until the early 2000s when Marr worked with directed graph labelings in her dissertation [65]. As part of that work, Bloom et al. defined magic labelings on directed graphs [17]. The results in this chapter are from [17] unless otherwise noted.
Abstract 4347: Integrated single-cell DNA and RNA analysis of intratumoral heterogeneity and immune lineages in colorectal and gastric tumor biopsies

Intratumoral heterogeneity and immune cellular infiltration are important indicators for both prognosis and prediction of treatment efficacy. Intratumoral heterogeneity, arising from the backdrop of ongoing mutation accrual and genome instability, drives Darwinian evolutionary selection for therapy-resistant cells. Infiltrating immune cell lineages are repressed in their function, thus enabling tumors to evade the immune system. Currently, conventional bulk sequencing does not resolve features from individual cancer cells and other cellular components present in a tumor. Thus, one loses critical granular information describing the overall complexity of the tumor and its local microenvironment. To achieve a complete analysis of intratumoral heterogeneity and immune response to a tumor, we developed and applied a strategy for parallel single cell DNA-Seq and single cell RNA-Seq on excised tumors - our approach used tumor biopsies obtained directly after surgery with immediate processing and dissociation into single cell suspensions for genomic analysis. For thousands of cells, single-cell DNA-Seq analysis was used to generate genome wide copy number results and total quantification of chromosomal aneuploidy. With these results, we determined the intratumoral phylogenetic distributions at single cell resolution. Single-cell copy number variant detection performance in cancer cell lines was cross-validated with traditional whole genome sequencing and karyotyping from established cell lines. Remarkably, we distinguished between replicating and non-replicating cells - this was defined by discrete and localized fluctuations in read coverage across the genome. Our findings were confirmed by flow cytometry analysis. Single-cell RNA-Seq provided an overview of the different subpopulations with distinct transcriptional phenotypes. We resolved multiple subsets of tumor epithelial cells reflecting transcriptional heterogeneity as well as stromal components including endothelial, muscle, fibroblast and immune cells. Among immune cells, we further resolved phenotypes including T, B, NK, dendritic cells and monocytes. We also detected a small number of cells with expression of markers of immune exhaustion. Overall, our study successfully demonstrated the feasibility of conducting integrated single-cell DNA-Seq and RNA-Seq on patient tumors. As supported by our results, single cell genomics offers an unprecedented perspective on the genomic and cellular complexities of primary tumor biopsies. Citation Format: Billy Lau, Noemi Andor, Anuja Sathe, Christina Wood-Bouwens, George Poultsides, Hanlee Ji. Integrated single-cell DNA and RNA analysis of intratumoral heterogeneity and immune lineages in colorectal and gastric tumor biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4347.
Application of risk factors for venous thromboembolism in patients with multiple myeloma starting chemotherapy, a real‐world evaluation

Introduction Within the first year of diagnosis, up to 1 in 3 multiple myeloma (MM) patients will experience a venous thromboembolism (VTE). The International Myeloma Working Group (IMWG) has thromboprophylaxis guidelines that stratify patients into low or high risk for thrombosis and subsequently recommend thromboprophylaxis, but it is unknown if these recommendations are being followed or if they are effective. The purpose of this study was to assess efficacy of the IMWG guidelines and investigate other potential VTE risk factors. Methods Study participants were treated at the University of Kansas Medical Center between 2007 and 2013, and charts were reviewed to extract data. Cases (MM and VTE) were matched to controls (MM and no VTE) at approximately 1:3 ratio based on gender, age (±5 years), and time of MM diagnosis (±5 years). Results A total of 80 cases and 211 controls were matched. Most patients (82%) were considered high risk for experiencing a VTE at the time of their MM diagnosis and 18% were considered low risk. Neither risk category (P = 0.16) nor thromboprophylaxis at baseline (P = 0.37) predicted VTE, though cases were more likely than controls to have an increased risk of thrombosis at the time of clot compared to their baseline risk (P = 0.09). Conclusion Our results suggest that IMWG guidelines are not being consistently followed and therefore could not be validated. Additional risk factors were not identified, but risk for VTE may change over time suggesting patients may require ongoing assessment of VTE risk and thromboprophylaxis throughout the disease course.
Idiopathic Pulmonary Fibrosis Guideline Recommendations. Need for Adherence to Institute of Medicine Methodology

Rationale: The 2018 idiopathic pulmonary fibrosis (IPF) guidelines were developed using an approach that adhered to the Institute of Medicine (IOM) standards, in which each recommendation was informed by a systematic review. The convergence of opinion on recommendations and evidence (CORE) process is a modified Delphi process that does not require a systematic review but yields similar recommendations. Objectives: To determine the importance of systematic reviews to the recommendations made by the IPF guidelines. Methods: IPF experts who were not on the IPF guideline panel and had no knowledge of the guideline's evidence synthesis or recommendations were recruited to answer the same questions as the guidelines but using a modified CORE process. Recommendations derived from the modified CORE process and IOM-adherent process were then compared. Concordance of the course of action, strength of recommendation, and quality of evidence was measured. Results: Ten questions were addressed. The modified CORE process and IOM-adherent process yielded concordant recommendations for 9 of 10 (90%) questions (ĸ-agreement, 0.84; 95% confidence interval, 0.55-1.00). The strength of the recommendations was the same for seven of eight (88%) graded recommendations (ĸ-agreement, 0.75; 95% confidence interval, 0.31-1.00), but ratings of the quality of evidence were discordant. The modified CORE process was less expensive and required less time and effort than the IOM-adherent process. Conclusions: The modified CORE process developed recommendations that were concordant with those developed by an experienced guideline panel using the robust standards of the IOM; however, it was less expensive and less burdensome.
Discovery of Noncancer Drug Effects on Survival in Electronic Health Records of Patients With Cancer: A New Paradigm for Drug Repurposing.

PURPOSEDrug development is becoming increasingly expensive and time consuming. Drug repurposing is one potential solution to accelerate drug discovery. However, limited research exists on the use o...
Development of Mo recovery and concentration column processes for production of 99Mo from accelerator-driven irradiation of aqueous uranyl-sulfate solution

Recovery and concentration columns were designed for separation of Mo from highly concentrated uranyl–sulfate solution. Molybdenum uptake on titania sorbent, from concentrated uranium solutions, is...
Prefrontal Cortex Predicts State Switches during Reversal Learning

Summary Reinforcement learning allows organisms to predict future outcomes and to update their beliefs about value in the world. The dorsal-lateral prefrontal cortex (dlPFC) integrates information carried by reward circuits, which can be used to infer the current state of the world under uncertainty. Here, we explored the dlPFC computations related to updating current beliefs during stochastic reversal learning. We recorded the activity of populations up to 1,000 neurons, simultaneously, in two male macaques while they executed a two-armed bandit reversal learning task. Behavioral analyses using a Bayesian framework showed that animals inferred reversals and switched their choice preference rapidly, rather than slowly updating choice values, consistent with state inference. Furthermore, dlPFC neural populations accurately encoded choice preference switches. These results suggest that prefrontal neurons dynamically encode decisions associated with Bayesian subjective values, highlighting the role of the PFC in representing a belief about the current state of the world.
Radioactive Decays of Au 194 , Au 196 , and Au 198

The de-excitations of the 2+ second excited states of ${\mathrm{Pt}}^{194}$ and ${\mathrm{Pt}}^{196}$ have been studied to compare crossover transition intensities to the 0+ ground states relative to the known cascade transitions to the 2+ first excited states. An intermediate-image beta-ray spectrometer was used to measure the internal-conversion electron spectra occurring in the decays of ${\mathrm{Au}}^{194}$ and ${\mathrm{Au}}^{196}$. A conversion line is found in the decay of ${\mathrm{Au}}^{194}$ corresponding to a 0.618-Mev crossover having a transition intensity of 25% relative to the 0.290-Mev cascade, provided the latter is assumed to be $E2$. In ${\mathrm{Pt}}^{196}$ an upper limit of 0.04% is placed on the intensity of a possible crossover transition compared with the 0.331-Mev cascade. ${\mathrm{Au}}^{194}$ exhibits the internal-conversion lines of 36 gamma-ray transitions which fit energetically into a proposed energy level scheme for ${\mathrm{Pt}}^{194}$. A search in the electron spectrum of ${\mathrm{Au}}^{198}$ showed no gamma-ray transitions other than the three already known.
Knowledge, Stories, and Culture in Organizations

Organizations are full of stories; organizational economics, not so much. Rather, organizational economics has little work that conceptualizes the role or measures the incidence of stories in organizations. This shortage concerns us not only because stories are prevalent in organizations but more importantly because we think some stories play a role in organizations that sheds light on why organizations exist and how they might be improved. In brief, we explore the idea that stories in organizations may induce a particular kind of organizational knowledge, of which organizational culture is a leading example.
History of share prices and market efficiency of the Madrid general stock index

Abstract We apply Moving Average (MA), Relative Strength Indicator (RSI), Moving Average Convergence Divergence (MACD), and trading breakout (TBO) techniques to investigate the weak-form market efficiency of the Madrid General Stock Index, Indice General de la Bolsa de Madrid (IGBM), from 1/2/1975 to 12/31/2012. The empirical results not only strongly validate the predictive power of trading rules with robust statistical significance in all three sub-periods over the thirty-eight years, but also provide the possible strategies to outperform the buy-and-hold strategy with the consideration of transaction costs and risk. This supports the argument against weak-form market efficiency of the IGBM.
National patterns of injury and outcomes of gunshot wounds to the penis: A Trauma Quality Programs retrospective cohort analysis.

Aim Gunshot wounds (GSW) to the penis represent a rare type of traumatic injury in the civilian United States population. Although small, single-center studies have reported results of care for these types of injured patients, no national analyses have examined this group. Methods A cohort of patients with GSW to the penis was identified using the 2017 American College of Surgeons Trauma Quality Programs database, a comprehensive national database of 753 accredited trauma centers. Results Gunshot wounds to the penis occurred in 722 patients, which represents 1.7% of all GSW patients (n = 41,017). Gunshot wounds from altercations with law enforcement or accidental discharge of a firearm were rare; the vast majority (n = 655, 90.7%) occurred as a result of assault, intentional self-harm, attempted suicide, or attempted homicide. Patients with a major concomitant non-genitourinary injury comprised 119 (16.5%) patients of the cohort. Most patients (n = 499, 69.1%) underwent a genitourinary procedure during their trauma admission. Penile salvage was successful in most cases, with only 13 (1.8%) patients requiring completion penectomy. Most patients (87.8%) required admission with a median length of stay of 49.8 h. Most patients were treated at the initial trauma center without requiring transfer to another center, and complications during admission were rare. Conclusions This analysis, the first national examination of care of patients with GSW to the penis, reveals overall favorable outcomes. Admission and surgical intervention were required in most patients, but penectomy was rare and length of stay was generally short. These results will guide resource utilization and quality improvement efforts in this patient cohort.
Prenatal diagnosis of hemoglobinopathies.

Hemoglobinopathies are very frequent disorders for which prenatal diagnosis has now been applied for nearly 15 years. They are caused by a wide range of molecular defects requiring a variety of molecular techniques for diagnosis. Clinical, technical, and ethical problems of prenatal diagnosis for the hemoglobinopathies are being presented and can serve as paradigms for most other Mendelian genetic disorders.
Challenges and opportunities in verification and validation of low temperature plasma simulations and experiments

This paper describes the verification and validation (V&V) framework developed for the stochastic Particle-in-Cell, Direct Simulation Monte Carlo code Aleph. An ideal framework for V&V from the viewpoint of the authors is described where a physics problem is defined, and relevant physics models and parameters to the defined problem are assessed and captured in a Phenomena Identification and Ranking Table (PIRT). Numerous V&V examples guided by the PIRT for a simple gas discharge are shown to demonstrate the V&V process applied to a real-world simulation tool with the overall goal to demonstrably increase the confidence in the results for the simulation tool and its predictive capability. Although many examples are provided here to demonstrate elements of the framework, the primary goal of this work is to introduce this framework and not to provide a fully complete implementation, which would be a much longer document. Comparisons and contrasts are made to more usual approaches to V&V, and techniques new to the low-temperature plasma community are introduced. Specific challenges relating to the sufficiency of available data (e.g., cross sections), the limits of ad hoc validation approaches, the additional difficulty of utilizing a stochastic simulation tool, and the extreme cost of formal validation are discussed.
AKT controls protein synthesis and oxidative metabolism via combined mTORC1 and FOXO1 signalling to govern muscle physiology.

BACKGROUND Skeletomuscular diseases result in significant muscle loss and decreased performance, paralleled by a loss in mitochondrial and oxidative capacity. Insulin and insulin-like growth factor-1 (IGF-1) are two potent anabolic hormones that activate a host of signalling intermediates including the serine/threonine kinase AKT to influence skeletal muscle physiology. Defective AKT signalling is associated with muscle pathology, including cachexia, sarcopenia, and disuse; however, the mechanistic underpinnings remain unresolved. METHODS To elucidate the role of AKT signalling in muscle mass and physiology, we generated both congenital and inducible mouse models of skeletal muscle-specific AKT deficiency. To understand the downstream mechanisms mediating AKT's effects on muscle biology, we generated mice lacking AKT1/2 and FOXO1 (M-AKTFOXO1TKO and M-indAKTFOXO1TKO) to inhibit downstream FOXO1 signalling, AKT1/2 and TSC1 (M-AKTTSCTKO and M-indAKTTSCTKO) to activate mTORC1, and AKT1/2, FOXO1, and TSC1 (M-QKO and M-indQKO) to simultaneously activate mTORC1 and inhibit FOXO1 in AKT-deficient skeletal muscle. Muscle proteostasis and physiology were assessed using multiple assays including metabolic labelling, mitochondrial function, fibre typing, ex vivo physiology, and exercise performance. RESULTS Here, we show that genetic ablation of skeletal muscle AKT signalling resulted in decreased muscle mass and a loss of oxidative metabolism and muscle performance. Specifically, deletion of muscle AKT activity during development or in adult mice resulted in a significant reduction in muscle growth by 30-40% (P < 0.0001; n = 12-20) and 15% (P < 0.01 and P < 0.0001; n = 20-30), respectively. Interestingly, this reduction in muscle mass was primarily due to an ~40% reduction in protein synthesis in both M-AKTDKO and M-indAKTDKO muscles (P < 0.05 and P < 0.01; n = 12-20) without significant changes in proteolysis or autophagy. Moreover, a significant reduction in oxidative capacity was observed in both M-AKTDKO (P < 0.05, P < 0.01 and P < 0.001; n = 5-12) and M-indAKTDKO (P < 0.05 and P < 0.01; n = 4). Mechanistically, activation and inhibition of mTORC1/FOXO1, respectively, but neither alone, were sufficient to restore protein synthesis, muscle oxidative capacity, and muscle function in the absence of AKT in vivo. In a mouse model of disuse-induced muscle loss, simultaneous activation of mTORC1 and inhibition of FOXO1 preserved muscle mass following immobilization (~5-10% reduction in casted M-indFOXO1TSCDKO muscles vs. ~30-40% casted M-indControl muscles, P < 0.05 and P < 0.0001; n = 8-16). CONCLUSIONS Collectively, this study provides novel insights into the AKT-dependent mechanisms that underlie muscle protein homeostasis, function, and metabolism in both normal physiology and disuse-induced muscle wasting.