cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 262: Derivation of Duchenne Muscular Dystrophy Disease Specific Cardiomyocytes From Patient Urine

Introduction: Human somatic cells can be reprogrammed into primitive stem cells, termed induced pluripotent stem cells (iPSCs). These iPSCs can be extensively expanded in vitro and differentiated into multiple functional cell types, enabling faithful preservation of individual’s genotype and large scale production of disease targeted cellular components. These unique cellular reagents thus hold tremendous potential in disease mechanism study, drugs screening and cell replacement therapy. Due to the genetic mutation of the protein dystrophin, many DMD patients develop fatal cardiomyopathy with no effective treatment. The underlying pathogenesis has not been fully elucidated. Hypothesis: We tested the hypothesis that iPSCs could be generated from DMD patients’ urine samples and differentiated into cardiomyocytes, recapitulating the dystrophic phenotype. Methods: iPSCs generation was achieved by introducing a lentiviral vector expressing Oct4, Sox2, c-Myc and Klf4 into cells derived from patient’s (n=1) and healthy volunteers’ (n=3) urine. Cardiomyocytes were derived by sequentially treating iPSCs with GSK3 inhibitor CHIR99021 and Wnt inhibitor IWP4. Differentiated cardiomyocytes were subjected to calcium imaging, electrophysiology recording, Polymerase Chain Reaction (PCR) analysis, and immunostaining. Results: iPSCs were efficiently generated from human urine samples and further forced to differentiate into contracting cardiomyocytes. PCR analysis and immunostaining confirmed the expression of a panel of cardiac markers. Both normal and patient iPSC derived cardiomyocytes exhibited spontaneous and field stimulated calcium transients (up to 2Hz), as well as action potentials with ventricular-like and nodal-like characteristics. Anti-dystrophin antibodies stained normal iPSC-derived cardiomyocyte membranes but did not react against DMD iPSC-derived cardiomyocytes. Conclusions: Cardiomyocytes can be efficiently generated from human urine, through the cellular reprogramming technology. DMD cardiomyocytes retained the patient’s genetic information and manifested a dystrophin-null phenotype. Functional assessments are underway to determine differences that may exist between genotypes.
Augmenting the nasal airway: beyond septoplasty.

BackgroundNasal airway obstruction is a common complaint of patients presenting to otolaryngology clinics and can be caused by a variety of anatomic factors. A number of advances in the surgical ma...
A Note on the Differences Between Histamine and Leukotaxine

ConclusionsThe permeability and the chemotactic factors found in inflammatory exudates exist as well in the crystalline nitrogenous substance, leukotaxine, recovered from such exudates by chemical fractionation. There is no evidence to support the contention that the permeability factor is histamine. Extraction by the method of Barsoum and Gaddum has failed to reveal the presence of histamine in leukotaxine. Furthermore, alkaline hydrolysis of leukotaxine does not dissociate the permeability from the chemotactic factor. The foregoing observations add further support to the view that leukotaxine is the substance liberated from injured tissue which is primarily responsible for the basic sequences of the inflammatory reaction, namely, the initial increase in capillary permeability and the prompt migration of polymorphonuclear leukocytes.
Analysis of the Impact of International Monetary Fund Programs on Economic Performance of Kenya

Like most other countries in developing countries, Kenya faces economic challenges as it tries to stabilize its balance of payments, reduce external debts and curb high unemployment rates. Structural adjustment programs (SAPs) are defined as economic programs mainly set for developing countries supported by the Bretton Woods institutions since the beginning of 1980s. As a result of prolonged balance of payments deficits, high unemployment rates and high debts, brought about by poor economic performance, the country has turned to International Monetary Fund for credit assistance. This research sought to examine if there was a relationship between structural adjustment programs and economic performance in Kenya. The results in this study revealed a significant correlation between IMF structural adjustment programs and economic performance in Kenya. The findings showed that the three dependent variables analyzed notably, balance of payments, debts, and unemployment showed a strong correlation with IMF structural adjustment programs.
Evidence, 2000-2001 Survey of New York Law

This article is a survey of developments in evidence rules in 2001-2002. This issue covers Procedure, Relevancy, Witnesses, and Cross-examination and Impeachment.Procedure includes: Preservation, Law of the Case, Presumptions, Res Ipsa Loquitur, Noseworthy Doctrine, Juror Knowledge, and Appeals of Evidentiary Rulings.Relevancy includes: General considerations, Consciousness of Guilt, Missing Witness/Document, Other Crimes, and Documentary Evidence.Witnesses includes: Competency, Court Control, and Refreshing Recollection.Cross-examination and Impeachment includes: General considerations; Impeaching One's Own Witness; Bias, Hostility, and Interest; Prior Convictions; Prior Misconduct; and Prior Inconsistent Statements.
Aqueous Photochemistry of Glyoxylic Acid

Aerosols affect climate change, the energy balance of the atmosphere, and public health due to their variable chemical composition, size, and shape. While the formation of secondary organic aerosols (SOA) from gas phase precursors is relatively well understood, studying aqueous chemical reactions contributing to the total SOA budget is the current focus of major attention. Field measurements have revealed that mono-, di-, and oxo-carboxylic acids are abundant species present in SOA and atmospheric waters. This work explores the fate of one of these 2-oxocarboxylic acids, glyoxylic acid, which can photogenerate reactive species under solar irradiation. Additionally, the dark thermal aging of photoproducts is studied by UV–visible and fluorescence spectroscopies to reveal that the optical properties are altered by the glyoxal produced. The optical properties display periodicity in the time domain of the UV–visible spectrum of chromophores with absorption enhancement (thermochromism) or loss (photobleaching)...
Social Workers as Workplace-Based Instructors of Alcohol and Drug Screening, Brief Intervention, and Referral to Treatment (SBIRT) for Emergency Medicine Residents

ABSTRACTProblem: Residency education is challenged by a shortage of personnel and time, particularly for teaching behavioral interventions such as screening, brief intervention, and referral to treatment (SBIRT) to reduce hazardous drinking and drug use. However, social workers may be well placed to teach SBIRT in clinical training settings. Intervention: We describe a curriculum with social workers as SBIRT trainers of emergency medicine (EM) residents during actual clinical shifts in an EM residency training program. The curriculum required 1 EM faculty member working with social workers and 1 additional hour of formal residency conference teaching time. Context: We implemented the curriculum at both a university tertiary care hospital emergency department and a county trauma center. We trained 8 social workers at both sites as SBIRT superusers to teach and assess EM resident SBIRT performance with actual patients. We measured the length and number of sessions to attain SBIRT competence, residents' sati...
Predicting phenotypic variation in growth and metabolism of marine invertebrate larvae

Abstract Understanding the mechanisms that establish variation in growth and metabolism is fundamental in evolutionary and physiological ecology. Although a genetic basis is frequently invoked to explain variation in performance, it remains challenging to study such processes in marine animals due to the lack of genetically-enabled “model” organisms. The Pacific oyster Crassostrea gigas is a species for which pedigreed genetic lines have been established. In this study, a series of larval families was produced by crossbreeding pedigreed lines to yield large-volume larval cultures to provide sufficient biomass for biochemical and physiological analyses. Major phenotypic contrasts in larval growth rate were evident. A primary goal of this study was to investigate the physiological bases for this variation in growth and to identify biomarkers that are predictive of growth potential. To that end, measurements were undertaken to define the relationship between rates of growth, respiration, and ion transport by the sodium-potassium pump (in vivo Na+,K+-ATPase activity). The relationship of respiration and ion transport during larval growth showed that, on average, 17% of total energy demand was allocated to support ion transport. Further analyses of total Na+,K+-ATPase activity (in vitro enzyme assay) revealed that 41% of the total metabolic rate could be accounted for by this single process if all of the enzyme was physiologically active. Significant biological variation was evident, however, when size-specific comparisons were made across different larval families. These differences were up to (i) 2.2-fold in ion transport rates; (ii) 2.8-fold in the allocation of energy to support the metabolic demand of ion transport; (iii) 3.5-fold in total enzyme activity; (iv) 3.9-fold in the physiologically active fraction of total enzyme; and (v) 3.1-fold in gene expression. These differences among families highlight the need to distinguish genetic from environmental causes of biological variation. Notably, for inferences of physiological changes based upon molecular biological analyses, the measured rates of ion transport were not predicted from concurrent measurements of gene expression or enzyme activity. Size-corrected rates of ion transport were predictive of variation in growth rates among different larval families, supporting the application of physiological rates of ion transport as a predictor of growth differences. Evolutionary variation in physiological performance has important implications for understanding the ecology of larval forms. Developing physiological indices will be of value in predicting growth and metabolism and corresponding survival of larval forms of different genotypes in response to environmental change.
Is It Safe to Shunt Anticoagulated NPH Patients

Long-term anticoagulation is often considered to be a relative contraindication to shunt surgery for patients with normal pressure hydrocephalus (NPH). While the overall risk of bleeding associated with shunt placement is low, the risk of bleeding in the elderly is increased, particularly with regard to immediate intracerebral hemorrhage or delayed subdural hematoma (SDH) during or after CSF shunting. Furthermore, NPH patients receiving antithrombotic therapy are at a significantly increased risk of hemorrhagic complication compared to patients who are not on antithrombotic therapy. Given the advanced age, gait impairment, and dementia associated with NPH, the bleeding and thrombotic risk may be even higher in NPH than the general population receiving antithrombotic therapy. Therefore, consultation with a hematologist and/or cardiologist is warranted in order to determine which patients can safely suspend antithrombotic therapy prior to surgery versus those who require bridging. Preoperatively, antiplatelet therapy should be stopped at least 7–14 days prior to surgery, whereas warfarin therapy should be stopped at least 5–7 days prior to surgery and/or bridged with a short-acting anticoagulant, in general. Operative considerations that can reduce the risk of hemorrhagic complication include incision of the pia mater prior to ventricular catheter insertion, potential use of intraoperative imaging guidance, and placement of an adjustable and gravity-assisted shunt valve to lower the risk of overdrainage. In the outpatient setting, gradual lowering of the pressure setting should be performed over time until a balance is reached between maximum symptomatic improvement and the onset of symptoms suggestive of low intracranial pressure (e.g., orthostatic headache and dizziness). Postoperatively, the time to resumption of antithrombotic therapy depends on the patients’ individual risk of thrombosis and bleeding as well as radiographic evaluation for intracranial hemorrhage. In summary, patients on long-term antithrombotic therapy can be safely and effectively evaluated and treated for NPH, with the use of appropriate perioperative and postoperative management.
Antitrust and Patent Policies

The topic I have been asked to cover is formidably complex. How can justice be done to it in the short time available? I know of only one way: to expose the heart of the issue through heroic economic abstractions before attempting to tackle the intricacies of practical policy considerations. In so doing I may to some extent duplicate or (much worse) contradict the papers presented by others and the conclusions reached by them. But backtracking seems in this instance the most efficient way to move forward.
Empirical results of an experimental study on the role of password strength and cognitive load on employee productivity

The demand for information system authentication has significantly increased over the last decade. Research has shown that the majority of user authentications remain to be passwordbased, however, it is well documented that passwords have significant limitations. To address this issue, companies have been placing increased requirements on the user to ensure their passwords are more complex and consequently stronger with little consideration on the impact on employee productivity. Thus, this study was set to determine the effects of changing the password strength (cognitive load) over time and its impact on employee productivity. An experiment with two experimental groups and one control group was conducted. Data was collected on the number of failed operating system logon attempts, users’ logon times, task completion times, and number of reset requests. The data collected from 72 participants was analyzed for group differences and when controlling for computer experience, age, and gender. Our results showed significant differences on all measures between the three groups. However, no significant differences were observed when controlling for computer experience, age, and gender. Furthermore, the results indicated a significant difference between the user’s perceptions about passwords before and after the experiment. Our results may help organizations to realize the point at which increasing authentication places a higher cognitive load on the users, which in turn affects their productivity.
Jeffersonian Republicanism and Resourcing the Civil War

On the eve of the Civil War, the Confederacy had reason to be confident about its chances for success. Although outnumbered and under resourced compared to its northern counterpart, the Confederate leadership believed it possessed a more unified political philosophy centered around the preservation of slavery, a favorable geographic position, superior military leadership, and the ultimate economic weapon, cotton, all of which would inevitably lead to foreign recognition of the South as an independent nation. However, as Meagher chronicles, these advantages proved to be illusory as the North slowly but persistently pursued a strategy designed to economically and financially strangle the Confederacy, aided by several critical errors in terms of political, military, and economic policies, all of which contributed to the eventual defeat of the South .
Fabrication of Photothermal Stable Gold Nanosphere/Mesoporous Silica Hybrid Nanoparticle Responsive to Near-Infrared Light

Various gold nanoparticles have been explored in biomedical systems and proven to be promising in photothermal therapy and drug delivery. Among them, nanoshells were regarded as traditionally strong near infrared absorbers that have been widely used to generate photothermal effect for cancer therapy. However, the nanoshell is not photo-thermal stable and thus is not suitable for repeated irradiation. Here, we describe a novel discrete gold nanostructure by mimicking the continuous gold nanoshell-gold/mesoporous silica hybrid nanoparticle (GoMe). It possesses the best characteristics of both conventional gold nanoparticles and mesoporous silica nanoparticles, such as excellent photothermal converting ability as well as high drug loading capacity and triggerable drug release.
Abstract 161: Alternate Day Fasting With a High Fat and Low Fat Diet: Is Brachial Artery Flow Mediated Dilation Mediated by Adipokine Physiology?

BackgroundCalorie restriction (CR) with variable macronutrient distributions has yielded inconsistent effects on brachial artery flow mediated dilation (FMD) related to weight loss and adipocyte ph...
Thermochemical Investigations of Hydrated Nickel Dication Complexes by Threshold Collision-Induced Dissociation and Theory

The experimental bond energies of Ni2+(H2O)x complexes, where x = 4–11, are determined by threshold collision-induced dissociation using a guided ion beam tandem mass spectrometer with an electrospray ionization source. The electrospray ionization source produces a distribution of Ni2+(H2O)x complexes, where an in-source fragmentation technique is employed to access the x = 4–6 complexes and control the population of excited isomers. The kinetic energy-dependent cross sections are modeled to yield 0 K bond energies for sequential loss of neutral water molecules, which are converted to 298 K binding energies. Analysis of the primary and secondary water losses from the Ni2+(H2O)x reactant ion complexes, x = 4–11, provide accurate thermochemistry for the hydration energies of Ni2+ and yield the first experimental values for x = 4 and 5 binding energies. Speculative thermochemistry for excited isomers of the x = 4–6 complexes is also obtained. Quantum chemical calculations explore the relative energies of pos...
Comparing the Ecological Stoichiometry in Green and Brown Food Webs - A Review and Meta-analysis of Freshwater Food Webs.

The framework of ecological stoichiometry was developed primarily within the context of “green” autotroph-based food webs. While stoichiometric principles also apply in “brown” detritus-based systems, these systems have been historically understudied and differ from green ones in several important aspects including carbon (C) quality and the nutrient (nitrogen (N) and phosphorus (P)) contents of food resources for consumers. In this paper, we review work over the last decade that has advanced the application of ecological stoichiometry from green to brown food webs, focusing on freshwater ecosystems. We first review three focal areas where green and brown food webs differ: (1) bottom-up controls by light and nutrient availability, (2) stoichiometric constraints on consumer growth and nutritional regulation, and (3) patterns in consumer-driven nutrient dynamics. Our review highlights the need for further study of how light and nutrient availability affect autotroph-heterotroph interactions on detritus and the subsequent effects on consumer feeding and growth. To complement this conceptual review, we formally quantified differences in stoichiometric principles between green and brown food webs using a meta-analysis across feeding studies of freshwater benthic invertebrates. From 257 datasets collated across 46 publications and several unpublished studies, we compared effect sizes (Pearson’s r) of resource N:C and P:C on growth, consumption, excretion, and egestion between herbivorous and detritivorous consumers. The meta-analysis revealed that both herbivore and detritivore growth are limited by resource N:C and P:C contents, but effect sizes only among detritivores were significantly above zero. Consumption effect sizes were negative among herbivores but positive for detritivores in the case of both N:C and P:C, indicating distinct compensatory feeding responses across resource stoichiometry gradients. Herbivore P excretion rates responded significantly positively to resource P:C, whereas detritivore N and P excretion did not respond; detritivore N and P egestion responded positively to resource N:C and P:C, respectively. Our meta-analysis highlights resource N and P contents as broadly limiting in brown and green benthic food webs, but indicates contrasting mechanisms of limitation owing to differing consumer regulation. We suggest that green and brown food webs share fundamental stoichiometric principles, while identifying specific differences toward applying ecological stoichiometry across
Exploring horseback riding as a means to build physical competence among adolescent girls

Horseback riding is a novel, physically-based intervention that deemphasizes physical appearance and focuses on overall enjoyment. While evidence supports the effectiveness of riding in improving self-esteem and confidence in a number of special populations, there is little research into whether riding can help to improve the physical self-perceptions of adolescent girls. PURPOSE: The purpose was to explore the use of horseback riding to enhance physical competence in adolescent girls. METHODS: Participants included adolescent girls (N=3; Mage=13) engaged in a 12-week riding program, their parents (N=3), and their riding instructors (N=2). The girls and their parents completed pre- and post-program qualitative semi-structured self-reports while riding instructors completed post-program questionnaires. All measures explored the girls' riding experiences and how they related to their perceptions of physical competence, body image and self-efficacy. RESULTS: Thematic analysis was used and the child and parent reports were examined for convergent and divergent themes and then triangulated with the riding instructors' responses. All three sources highlighted an increased level of physical skill and confidence among the participants post program; this was directly related to positive experiences with the horse. While the girls' felt their physical skills had improved, the parents and riding instructors spoke to an improvement in self-confidence among the girls. Other notable themes were openness to new experiences, fun, and formation of new bonds. CONCLUSION: These findings provide initial evidence that horseback riding can help adolescent girls develop physical competence through mastery experiences, eliciting positive changes in confidence and body image. Acknowledgments: This study was done in collaboration and with the help of the Free Spirit Therapeutic Riding Association
Gold(I)-assisted catalysis - a comprehensive view on the [3,3]-sigmatropic rearrangement of allyl acetate

ABSTRACTThe unified reaction valley approach (URVA) combined with the local mode, ring puckering and electron density analysis is applied to elucidate the mechanistic differences of the non-catalys...
Helping Young Children with Autism Spectrum Disorder Develop Social Ability: The Early Start Denver Model Approach

The Early Start Denver Model (ESDM) is a comprehensive approach for young children with autism spectrum disorder 12–60 months of age that focuses particular attention on social communication and social learning in everyday routines as the primary learning vehicle for young children. ESDM principles and practices were derived from decades of research in developmental psychology (i.e., cognitive, social, emotional, linguistic, and communicative development) and learning science. ESDM is a manualized intervention that focuses on the skills and learning opportunities available to young children in everyday routines involving play and caregiving across their life environments. ESDM defines both teaching procedures and teaching content aligned to the strengths and needs learning profiles seen in early autism, and it allows for individualization of both content and procedures via a detailed hierarchical curriculum and a decision tree that determines when teaching practices should be modified. While the approach is specified, the delivery is highly flexible and can be carried out in any setting involving children and adults, and by anyone who has learned the principles: parents and caregivers, professionals across disciplines, and paraprofessionals. ESDM integrates the principles used by applied behavior analysis, allied health professions, and early childhood intervention and its efficacy in improving social communication and overall learning rates has been demonstrated by a variety of studies. This chapter focuses on how ESDM draws from empirical studies to conceptualize the problems and process of social-communicative development in autism spectrum disorder, and how it translates those concepts into a manualized intervention that improves children’s social communication.
Improving the hemocompatibility of catheters via NO release/generation

Abstract Biomedical devices that offer direct vascular access, such as intravascular (IV) catheters, are essential to modern patient care. To improve the hemocompatibility of IV catheters, significant complications associated with thrombus formation and bacterial infections/biofilm formation must be addressed. Current approaches used in the hospital setting to address these issues include use of: (a) systemic anticoagulant treatment or catheters that deliver localized anticoagulants to prevent thrombus formation on catheter surfaces; (b) catheters that contain antibiotics, bacteriophages, biofilm dispersal agents, or Ag+ ion release to prevent bacterial infection/biofilm; or (c) catheter lock solutions for localized delivery of either anticoagulants or antibiotics. Each of these methods have had some success, yet both the blood-material interactions and bacterial biofilm formation remain very serious problems and efforts aimed at devising novel solutions are still needed. Nitric oxide (NO), a naturally produced gas molecule, holds great potential for the development of the next generation of more thromboresistant and antimicrobial catheters because of NO's ability to inhibit platelet activation and prevent bacterial cell proliferation/biofilm formation. This chapter provides an overview of some of the most commonly used approaches for preparing NO release hemocompatible IV catheters, including chemical-based NO releasing catheters, catalyst-based NO generating catheters, and electrochemical-based NO generating catheters.
Anabolic Steroid Users' Misuse of Non-Traditional Prescription Drugs.

Abstract Background Few anabolic-androgenic steroid (AAS) users disclose their performance enhancing drug (PED) use with their healthcare providers. AAS users practice polypharmacy with prescription medications to counter adverse effects of AAS, to further their muscular gains, or to lose weight. Objectives To compare and contrast AAS using and non-AAS using gym clients regarding PED use, in particular prescription drugs. Methods The CASTRO (Castro Anabolic Steroid Research Observation) study was a 108-item cross-sectional survey that took place at four gyms in San Francisco, California between August 2015 and January 2016. 40 AAS users and 179 non-AAS users completed the survey. Results The prevalence of AAS use in the study cohort was 18.3%. AAS users reported using a greater number of total PEDs (8.7 ± 4.2 vs. 3.7 ± 2.1, p Conclusions AAS users practice polypharmacy and misuse multiple prescription drugs. These findings allow researchers and clinicians to be more knowledgeable and to anticipate potential misuse of prescription medications that traditionally are not thought to be abused.
Assessing the Reliability of Amplified RNA Used in Microarrays

A certain minimal amount of RNA from biological samples is necessary to perform a microarray experiment with suitable replication. In some cases, the amount of RNA available is insufficient, necessitating RNA amplification prior to target synthesis. However, there is some uncertainty about the reliability of targets that have been generated from amplified RNA, because of nonlinearity and preferential amplification. This current work develops a straightforward strategy to assess the reliability of microarray data obtained from amplified RNA. The tabular method we developed, which utilises a Down-Up-Missing-Below (DUMB) classification scheme, shows that microarrays generated with amplified RNA targets are reliable within constraints. There was an increase in false negatives because of the need for increased filtering. Furthermore, this analysis method is generic and can be broadly applied to evaluate all microarray data. A copy of the Microsoft® Excel® spreadsheet is available upon request from Edward Bearden.
Biosolids management--sustainable development status and future direction.

The role of biosolids management continues to gain priority in terms of holistic waste management/reuse. Recommended options should lead to simple and safe management alternatives that stress reclamation of resources. This paper addresses current sustainability strategies, priorities and future direction of waste management as it relates to residuals and in particular to sludges/biosolids. Sludge management and resource recovery approaches must be diversified and flexible. They should be based on actual needs of the affected society and community. It is also important that the chosen strategy be appropriate to the conditions of the site under consideration. Processes which promote sustainability will become viable options for resource management if conversion into a “value-added product” can be realized.
High-throughput combinatorial screening reveals interactions between signaling molecules that regulate adult neural stem cell fate

Advancing our knowledge of how neural stem cell (NSC) behavior in the adult hippocampus is regulated has implications for elucidating basic mechanisms of learning and memory as well as for neurodegenerative disease therapy. To date, numerous biochemical cues from the endogenous hippocampal NSC niche have been identified as modulators of NSC quiescence, proliferation, and differentiation; however, the complex repertoire of signaling factors within stem cell niches raises the question of how cues act in combination with one another to influence NSC physiology. To help overcome experimental bottlenecks in studying this question, we adapted a high-throughput microculture system, with over 500 distinct microenvironments, to conduct a systematic combinatorial screen of key signaling cues and collect high-content phenotype data on endpoint NSC populations. This novel application of the platform consumed only 0.2% of reagent volumes used in conventional 96-well plates, and resulted in the discovery of numerous statistically significant interactions among key endogenous signals. Antagonistic relationships between fibroblast growth factor 2, transforming growth factor β (TGF-β), and Wnt-3a were found to impact NSC proliferation and differentiation, whereas a synergistic relationship between Wnt-3a and Ephrin-B2 on neuronal differentiation and maturation was found. Furthermore, TGF-β and bone morphogenetic protein 4 combined with Wnt-3a and Ephrin-B2 resulted in a coordinated effect on neuronal differentiation and maturation. Overall, this study offers candidates for further elucidation of significant mechanisms guiding NSC fate choice and contributes strategies for enhancing control over stem cell-based therapies for neurodegenerative diseases.
Effect of Electron Beam Sterilization on Three-Dimensional-Printed Polycaprolactone/Beta-Tricalcium Phosphate Scaffolds for Bone Tissue Engineering.

Three-dimensional printing of composite materials such as polycaprolactone/beta-tricalcium phosphate (PCL/β-TCP) enables the design and manufacturing of scaffolds with advanced geometries, along wi...
Safety Analysis of Patients Who Received Ruxolitinib for the Treatment of Steroid-Refractory Acute Graft-Vs-Host Disease in Expanded Access Programs

Introduction Graft-vs-host disease (GVHD) is a serious, potentially fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ruxolitinib (RUX), a Janus kinase (JAK)1/JAK2 inhibitor, is in phase 3 development for patients with steroid-refractory (SR) acute and chronic GVHD. Outside of clinical trials, access to RUX is provided to patients with GVHD through Incyte- and Washington University (WU)–sponsored expanded access programs (EAPs) and single-patient investigational new drug (IND) applications. Objective To report pooled safety data from a subset of patients with SR acute GVHD (aGVHD) enrolled in these programs. Methods Eligible patients were ≥12 years of age, developed SR acute or chronic GVHD after allo-HSCT, and were not eligible for Incyte-sponsored GVHD clinical trials. Patients enrolled in the 2 EAPs received oral RUX at a starting dose of 5 mg twice daily (BID; maximum dose 10 mg BID); those on single-patient INDs received RUX as agreed to by Incyte and the treating physician. Concurrent therapy with other treatments for GVHD was permitted. Serious adverse events (SAEs) were assessed. Data from patients with aGVHD were pooled across the 3 programs; summary statistics are reported. Results At data cutoff (02 Apr 2018), 28 patients with SR aGVHD (Incyte EAP, n=13; WU EAP, n=9; single-patient IND, n=6) and 104 patients with SR chronic GVHD (Incyte EAP, n=33; WU EAP, n=31; single-patient IND, n=40) had enrolled in the programs. Mean (range) age of patients with SR aGVHD was 48 (13–73) years; 71.4% of patients were male. aGVHD was reported in the gastrointestinal (GI) tract (57.1%), skin (53.6%), liver (17.9%), lungs (7.1%), and eyes (3.6%). Most patients (75.0%) received ≥3 prior treatments for GVHD, including corticosteroids; 71.4% of patients received calcineurin inhibitors, and 28.6% of patients received prior RUX. Most patients (n=25) initially received 5 mg RUX BID; 1 patient received 10 mg RUX BID, and 2 patients received RUX 5 mg once daily. Five patients (17.9%) received 10 mg RUX BID as their last dose. Treatment was ongoing in 13 patients (46.4%) at data cutoff; discontinuations were due to death (n=7), withdrawn consent (n=3), disease progression (n=2), primary disease relapse (n=2), or drug refusal (n=1). The mean (range) duration of treatment was 79.6 (1–326) days. SAEs were reported in 13 patients (46.4%). There were no cytopenia, fungal infection, or cytomegalovirus SAEs. Respiratory failure (n=3) and GVHD (n=2) were the only SAEs reported in >1 patient. Ten patients had fatal outcomes following an SAE. Sepsis (n=1) was the only fatal SAE suspected to be related to RUX; no others SAEs were considered related to RUX. Conclusion Patients in the RUX EAPs were heavily pretreated, and more than half of the patients reported GI GVHD. SAEs were reported in almost half of the patients (46.4%), but no new or unexpected SAEs have been reported.
Clinical features of prolonged tilt-induced hypotension with an apparent vasovagal mechanism, but without syncope.

Abstract Background A previous study of electroencephalography (EEG) changes with syncope led to a finding that some young patients develop prolonged periods of tilt-induced hypotension, but they do not lose consciousness. The present study aim was to compare patterns of hemodynamic changes, measures of duration, and sweating between these patients and patients with tilt-induced vasovagal syncope. Methods In an observational study, qualitative changes in hemodynamic parameters were compared between patients with prolonged hypotension (n = 30) and with syncope (n = 30). To demonstrate that periods of hypotension far-exceed the typical presyncope period, several parameters were used to compare the durations of events between groups. Differences in sweating patterns were explored. Results Parallels in hemodynamic changes were present in both groups suggesting similar vasovagal mechanisms. Patients with prolonged hypotension had longer durations of hypotension (165 ± 44 versus 57 ± 13 s, p Conclusions Similarities are present among hemodynamic changes with prolonged hypotension and with tilt-induced vasovagal syncope, suggesting a possible vasovagal mechanism for prolonged hypotension. If true, understanding why some individuals develop a vasovagal response that does not culminate in rapid syncope may help to elucidate the physiologic underpinnings of the vasovagal reflex.
A TWO-STAGE 80 K/140 K SORPTION CRYOCOOLER

The development and experimental testing of a laboratory breadboard 80 K/140 K sorption cooler is reported. The upper stage 140 K carbon/krypton physisorption cooler is used to precool the oxygen generated by the praseodymium cerium oxide chemisorption compressors for the 80 K stage. The experimental hardware, including both compressor stages and the cryostat containing the Joule-Thomson expansion valves and thermoelectric precooler stages, are described. The performance of the laboratory cooler, as well as analytical predictions for a flight cooler design, are summarized. This work has been a major step in demonstrating the feasibility of using sorption coolers for long duration (> 5 years), vibrationless spaceborne cryogenic cooling applications.
Impact of professional women athletes' media representations on collegiate women athletes

There is a lack of representation of women athletes from professional to collegiate sports in U.S. media. For example, Fink (2015) studied the inequities between male and women athletes to understand the harmful nature of the implication of these inequities. Other social constructs arise with the objectification of women athletes. Harrison and Fredrickson (2013) found a connection between aging of adolescent girls to women and an increase of self-objectification. They explained their results using Objectification Theory, which teaches young women to “regard themselves in an objectified gaze” from adolescence. The purpose of this study was to examine women collegiate athletes’ thoughts and feelings about the ways their elite representatives are presented within sports media. Women collegiate athletes viewed images displaying four different types of identity portrayals, and were then interviewed about their perceptions of the images. Each participant asked to answer five questions, and that data was analyzed using open coding methods.
The Irish Literature in Transition: Irish Literature in Transition, 1780–1830, edited by Claire Connolly, Cambridge, Cambridge UP, 2020, 456 pp., $110 (hardback), ISBN: 978-1-1084-9298-0; Irish Literature in Transition, 1830–1880, edited by Matthew Campbell, Cambridge, Cambridge UP, 2020, 340 pp., $120 (hardback), ISBN: 978-1-1084-8048-2

The Irish Literature in Transition series – six books mapping Irish literature from 1700 to present – have real institutional heft. Reflecting on what literature means in Ireland and how it connect...
Safety stock determination with serially correlated demand in a periodic-review inventory system

We consider a periodic-review inventory replenishment model with an order-up-to-R operating doctrine for the case of deterministic lead times and a covariance-stationary stochastic demand process. A method is derived for setting the inventory safety stock to achieve an exact desired stockout probability when the autocovariance function for Gaussian demand is known. Because the method does not require that parametric time-series models be fit to the data, it is easily implemented in practice. Moreover, the method is shown to be asymptoticaly valid when the autocovariance function of demand is estimated from historical data. The effects on the stockout rate of various levels of autocorrelated demand are demonstrated for situations in which autocorrelation in demand goes undetected or is ignored by the inventory manager. Similarly, the changes to the required level of safety stock are demonstrated for varying levels of autocorrelation.
Whiteflies weaponize a plant defense via horizontal gene transfer

Co-opting enemy weapons is a proven strategy in warfare. The war of nature is no different. In this issue of Cell, Xia and colleagues show how a major crop pest stole a plant phenolic glucoside malonyltransferase gene, allowing neutralization of a large class of plant defense compounds.
Political Action, Protest, and the Functioning of Democratic Governance:

The current debate on the vitality of affluent democracies often cites the changing patterns of citizens’ political participation as signs of this malaise. Fewer citizens are voting, and more are t...
Selective methylation: an incorrect hypothesis.

“Selective methylation,” a hypothesis proposed to explain the discrepancy found in the degree of methyl deficiency of transfer ribonucleic acid, cannot be explained on the basis of some biological phenomenon.
Reducing Manual Abstraction in Formal Verification of Out-of-Order Execution

Several methods have recently been proposed for verifying processors with out-of-order execution. These methods use intermediate abstractions to decompose the verification process into smaller steps. Unfortunately, the process of manually creating intermediate abstractions is very laborious. We present an approach that dramatically reduces the need for an intermediate abstraction, so that only the scheduling logic of the implementation is abstracted. After the abstraction, we apply an enhanced incremental-flushing approach to verify the remaining circuitry by comparing the processor description against itself in a slightly simpler configuration. By induction, we demonstrate that any reachable configuration is equivalent to the simplest possible configuration. Finally, we prove correctness on the simplest configuration. The approach is illustrated with a simple example of an out-of-order execution core.
Parallel Task Assignment by Graph Partitioning

A technique is described that performs the mapping of tasks to processors in parallel. The technique first partitions a task graph into subgraphs and then applies mapping algorithms on the individual subgraphs in parallel. The assignment of all subgraphs are combined in the final phase to form the assignment for the entire task graph. This technique has a number of important advantages including (1) enabling the use of more expensive algorithms on the subgraphs, (2) allowing different mapping techniques to be applied to different parts of the task graph, (3) reducing the space requirements during mapping and (4) accommodating modifications to a program without remapping of the entire task graph. Simulation results demonstrate that parallelism can be found in the mapping process and the scheduling performance of our technique using scheduling heuristics is either close or better than when the same mapping algorithm is applied to the entire graph.
Modulating the innate immune response to influenza A virus: potential therapeutic use of anti-inflammatory drugs

Infection by influenza A viruses (IAV) is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV are consequences of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. Indeed, some anti-inflammatory agents have been shown to be effective in animal models in reducing IAV pathology as a proof of principle. The main challenge in developing such therapies is to selectively modulate signaling pathways that contribute to lung injury while maintaining the ability of the host cells to mount an antiviral response to control virus replication. However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e., NF kappa B transcription factors) and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies.
System identification methods for aircraft flight control development and validation

System-identification methods compose a mathematical model, or series of models, from measurements of inputs and outputs of dynamic systems. The extracted models allow the characterization of the response of the overall aircraft or component subsystem behavior, such as actuators and on-board signal processing algorithms. This paper discusses the use of frequency-domain system-identification methods for the development and integration of aircraft flight-control systems. The extraction and analysis of models of varying complexity from nonparametric frequency-responses to transfer-functions and high-order state-space representations is illustrated using the Comprehensive Identification from FrEquency Responses (CIFER) system-identification facility. Results are presented for test data of numerous flight and simulation programs at the Ames Research Center including rotorcraft, fixed-wing aircraft, advanced short takeoff and vertical landing (ASTOVL), vertical/short takeoff and landing (V/STOL), tiltrotor aircraft, and rotor experiments in the wind tunnel. Excellent system characterization and dynamic response prediction is achieved for this wide class of systems. Examples illustrate the role of system-identification technology in providing an integrated flow of dynamic response data around the entire life-cycle of aircraft development from initial specifications, through simulation and bench testing, and into flight-test optimization.
Aging, Spirituality, and Time: A Qualitative Study

We examined the concepts of aging, time, spirituality, and future care needs in four randomly selected informants from a group of 54 never-married childless older women. Using data from the Generativity and Lifestyles of Older Women (GLOW) study, we questioned how women's perceptions of these concepts came together in current older age. We employed cultural theory, (our theoretical framework), ethnography, (our methodological framework), and phenomenology, (our philosophical foundation) to produce a portrait of each woman interviewed. Through a three-session interview process, we elicited the women's life stories, reasons for childlessness, and topics that emerged as significant to the women, including aging, a sense of time remaining, and spirituality. A key finding was that the context of each woman's life, both biographical and historical, transpired as a foundation for these concepts. That is, a woman's "place in time" shaped their experiences of aging, as well as her reasons for childlessness and perceptions of finitude.
The serine/threonine phosphatase, PP2A: endogenous regulator of inflammatory cell signaling.

We have investigated the regulation of kinases and phosphatases in early gene activation in monocytes because these cells are implicated in the pathogenesis of acute inflammatory states, such as sepsis and acute lung injury. One early gene up-regulated by endotoxin is c-Jun, a member of the activating protein (AP) family. C-Jun is phosphorylated by c-Jun N-terminal kinase (JNK) and associates with c-Fos to form the AP-1 transcriptional activation complex that can drive cytokine expression. Inhibition of the serine/threonine phosphatase, PP2-A, with okadaic acid resulted in a significant increase in JNK activity. This finding was associated with increased phosphorylation of c-Jun, AP-1 transcriptional activity, and IL-1β expression. Activation of PP2A inhibited JNK activity and JNK coprecipitated with the regulatory subunit, PP2A-Aα, supporting the conclusion that PP2A is a key regulator of JNK in the context of an inflammatory stimulus.