cssi/SciSciGPT-SciSciNet huggingface dataset:
Protection from respiratory virus infections can be mediated by antigen-specific CD4(+) T cells that persist in the lungs.

Although CD4+ T cells have been shown to mediate protective cellular immunity against respiratory virus infections, the underlying mechanisms are poorly understood. For example, although phenotypically distinct populations of memory CD4+ T cells have been identified in different secondary lymphoid tissues, it is not known which subpopulations mediate protective cellular immunity. In this report, we demonstrate that virus-specific CD4+ T cells persist in the lung tissues and airways for several months after Sendai virus infection of C57BL/6 mice. A large proportion of these cells possess a highly activated phenotype (CD44hi, CD62Llo, CD43hi, and CD25hi) and express immediate effector function as indicated by the production of interferon γ after a 5-h restimulation in vitro. Furthermore, intratracheal adoptive transfer of lung memory cells into β2m-deficient mice demonstrated that lung-resident virus-specific CD4+ T cells mediated a substantial degree of protection against secondary virus infection. Taken together, these data demonstrate that activated memory CD4+ T cells persisting at mucosal sites play a critical role in mediating protective cellular immunity.
Effects of Early Captopril Treatment and Its Removal on Plasma Angiotensin Converting Enzyme (ACE) Activity and Arginine Vasopressin in Hypertensive Rats (SHR) and Normotensive Rats (WKY)

The purpose of this study was to evaluate the effects of early administration and removal of the ACE inhibitor, captopril (CAP) on the plasma ACE activity, AVP levels, and mean arterial pressure (MAP) in groups of rats, control and CAP treated SHR and WKY (SHR, WKY SHRCAP, WKYCAP, respectively and in SHR taken off CAP (OFFCAP) and their progeny (2nd generation, 2ndG). Plasma ACE activity in SHRCAP (54.8 +/- 2.1 mU/ml/min) was significantly greater than in SHR (25.96 +/- 0.34 mU/ml/min) and their offspring (OFFCAP, 26.32 +/- 2.71 and 2ndG, 17.62 +/- 2.47 mU/ml/min, P < 0.001, respectively). Plasma level of AVP in SHR (14.18 +/- 0.98 pg/ml) were greater than in SHRCAP (9.1 +/- 1.01 pg/ml, P < 0.01). A decrease in plasma AVP levels were also noted in OFFCAP (10.48 +/- 0.51 pg/ml) and their offspring 2ndG (10.34 +/- 0.46 pg/ml). Our results did not show a relationship between plasma ACE activity and blood pressure reduction. However, treatment of SHR with captopril produced a decrease in plasma AVP levels which may participate in its antihypertensive mechanism of action.
Oral Infection With a Periodontal Pathogen Accelerates Early Atherosclerosis in Apolipoprotein E–Null Mice

Objective— Because recent epidemiologic evidence suggests that periodontal infections may increase the risk of atherosclerosis and related events in humans, we assessed the impact of oral inoculati...
Age-dependent regression analysis of male gonadal axis

The mechanisms by which aging progressively depletes testosterone (Te) availability in the male are unknown. Accordingly, the objective was to estimate brain gonadotropin-releasing hormone (GnRH) outflow (release and action), which cannot be observed directly, on the basis of downstream effects on pituitary luteinizing hormone (LH) secretion. LH, in turn, feeds forward on (stimulates) gonadal Te secretion, which then feeds back on (inhibits) GnRH-driven LH secretion. LH and Te concentrations were measured repetitively (every 10 min) over 18 h during graded pharmacological blockade of endogenous GnRH outflow in 24 healthy 20- to 72-yr-old men. Data were analyzed using a new age-dependent regression model of GnRH-LH-Te interactions to estimate pulsatile LH secretion and elimination, GnRH outflow, LH feedforward, and Te feedback. By incorporating regression on age within the dose-response model, we show that aging erodes all three primary forward and reverse pathways linking the brain, pituitary gland, and testes. Aging is associated with concomitant deficits in GnRH → LH feedforward, LH → Te feedforward, and Te → GnRH/LH feedback. The analytical formalism should be generalizable to other ensemble regulatory systems, such as those that control growth, reproduction, stress adaptations, and glucose metabolism.
The Areva Integrated and Sustainable Concept of Fatigue Design, Monitoring and Re-assessment The paper was given at the "ANSYS Conference & 26th CADFEM Users' Meeting 2008", Darmstadt/Germany, October 22 to 24, 2008

Fatigue is a focus of Areva's R&D activities in the view of changing boundary conditions for the operation of nuclear power plants: modification of the code-based approaches, lifetime extension, new plants with scheduled operating periods of 60 years and improvement of availability. An integrated approach to the fatigue issue is the way to an optimisation of costs and plant operation as well as a minimisation of non-destructive testing requirements.
Reactivity Gains in NRX Irradiated Slugs

A number of samples of uranium irradiated in NRX have had their reactivities measured in CP-2 by the danger coefficient technique. By means of measurements on enriched, depleted, and poisoned unirr...
Genetic Diversity Affects the Daily Transcriptional Oscillations of Marine Microbial Populations

Marine microbial communities are genetically diverse but have robust synchronized daily transcriptional patterns at the genus level that are similar across a wide variety of oceanic regions. We developed a microarray-inspired gene-centric approach to resolve transcription of closely-related but distinct strains/ecotypes in high-throughput sequence data. Applying this approach to the existing metatranscriptomics datasets collected from two different oceanic regions, we found unique and variable patterns of transcription by individual taxa within the abundant picocyanobacteria Prochlorococcus and Synechococcus, the alpha Proteobacterium Pelagibacter and the eukaryotic picophytoplankton Ostreococcus. The results demonstrate that marine microbial taxa respond differentially to variability in space and time in the ocean. These intra-genus individual transcriptional patterns underlie whole microbial community responses, and the approach developed here facilitates deeper insights into microbial population dynamics.
Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens. WIREs Nanomed Nanobiotechnol 2017, 9:e1403. doi: 10.1002/wnan.1403 For further resources related to this article, please visit the WIREs website.
Distribution and Origin of Groundwater Methane in the Wattenberg Oil and Gas Field of Northern Colorado

Public concerns over potential environmental contamination associated with oil and gas well drilling and fracturing in the Wattenberg field in northeast Colorado are increasing. One of the issues of concern is the migration of oil, gas, or produced water to a groundwater aquifer resulting in contamination of drinking water. Since methane is the major component of natural gas and it can be dissolved and transported with groundwater, stray gas in aquifers has elicited attention. The initial step toward understanding the environmental impacts of oil and gas activities, such as well drilling and fracturing, is to determine the occurrence, where it is and where it came from. In this study, groundwater methane data that has been collected in response to a relatively new regulation in Colorado is analyzed. Dissolved methane was detected in 78% of groundwater wells with an average concentration of 4.0 mg/L and a range of 0–37.1 mg/L. Greater than 95% of the methane found in groundwater wells was classified as hav...
A PDZ-binding motif is essential but not sufficient to localize the C terminus of CFTR to the apical membrane

Localization of ion channels and transporters to the correct membrane of polarized epithelia is important for vectorial ion movement. Prior studies have shown that the cytoplasmic carboxyl terminus of the cystic fibrosis transmembrane conductance regulator (CFTR) is involved in the apical localization of this protein. Here we show that the C-terminal tail alone, or when fused to the green fluorescent protein (GFP), can localize to the apical plasma membrane, despite the absence of transmembrane domains. Co-expression of the C terminus with full-length CFTR results in redistribution of CFTR from apical to basolateral membranes, indicating that both proteins interact with the same target at the apical membrane. Amino acid substitution and deletion analysis confirms the importance of a PDZ-binding motif D-T-R-L> for apical localization. However, two other C-terminal regions, encompassing amino acids 1370-1394 and 1404-1425 of human CFTR, are also required for localizing to the apical plasma membrane. Based on these results, we propose a model of polarized distribution of CFTR, which includes a mechanism of selective retention of this protein in the apical plasma membrane and stresses the requirement for other C-terminal sequences in addition to a PDZ-binding motif.
Volumetric structured illumination microscopy enabled by tunable focus lens(Conference Presentation)

We present a volumetric imaging method for biological tissue that is free of mechanically scanning components. The optical sectioning in the system is obtained by structured illumination microscopy (SIM) with the depth of focus being varied by the use of an electronic tunable-focus lens (ETL). The performance of the axial scanning mechanism was evaluated and characterized in conjunction with SIM to ensure volumetric images could be recorded and reconstructed without significant losses in optical section thickness and lateral resolution over the full desired scan range. It was demonstrated that sub-cellular image resolutions were obtainable in both microsphere films and in ex vivo oral mucosa, spanning multiple cell layers, without significant losses in image quality. The mechanism proposed here has the ability to be integrated into any wide-field microscopy system to convert it into a three-dimensional imaging platform without the need for axial scanning of the sample or imaging optics. The ability to axially scan independent of mechanical movement also provides the opportunity for the development of endoscopic systems which can create volumetric images of tissue in vivo.
Seismic Response Analysis of Large-scale Unanchored Tank under Three Dimensional Excitation

The seismic response of 15×104m3 unanchored tanks under three dimensional excitation is analyzed by ADINA finite element technique using spring element to simulate the foundation.The results show that: the acceleration increases along the height of tank wall;as the site turning softer,the acceleration turning smaller; liquid sloshing heights turning bigger;base shear force turning bigger.The sloshing height and the bottom plate shear force calculated by the formula of tank code are a little smaller compared to the results from three dimension excitation by FE technique,so we should consider multi-dimensional excitation for the seismatic design of tanks.
The role of cultural psychiatry in improving the policy response to Central America’s unaccompanied minors at the American border: local and global implications

Since 2014, children from El Salvador, Guatemala, and Honduras unaccompanied by their parents have fled in large numbers to the United States to escape violent crime and social disadvantage. Current mental health policies in the U.S. government's response can be improved based on guidelines from professional psychiatric and psychological organizations. These guidelines emphasize the importance of immigration and culture, raising questions into how the field of cultural psychiatry can offer conceptual frameworks and methods to research unaccompanied minor migration as a humanitarian problem. This paper conducts a policy analysis by reviewing shortcomings in the U.S. response and explores the potential contributions of cultural psychiatrists in optimizing services to address the needs of these children in the U.S. and their countries of origin.
Effects of Cyclosporine A on Lentiviral Transduction of Mouse Hematopoietic Stem Cells and Transplantation Using Nonmyeloablative Conditioning.

Achieving high level transduction of murine hematopoietic stem cells (HSCs) using lentiviral vectors has been a challenge for many laboratories. We investigated the efficiency of lentiviral transduction of murine stem cell antigen-1+ (sca-1+) cells with and without cyclosporine A (CSA), which has previously been shown to increase the transduction efficiency of other types of murine cells. Sca-1+ cells were isolated from C57BL/6 mice and transduced with lentiviral vectors encoding green fluorescent protein (GFP) at various multiplicity of infections (MOI) and with various concentrations of CSA. Twenty-four hours after a single transduction, 1.5 x 104 or 4.5 x 104 cells were plated in methylcellulose containing the appropriate cytokines for progenitor cell growth, and colonies were counted on days 8–12. In the absence of CSA only 4± 2% of progenitor colonies were GFP+. However, when CSA (10 μM) was added within 3 hours of sca-1 cell isolation, transduction efficiency increased to 44 ± 6%. Although the transduction efficiency increased 10-fold, the number of progenitor colonies significantly decreased when CSA was added (up to 90% decrease). Lower concentrations of CSA (e.g. 1 μM) were less toxic to sca-1+ cells but resulted in inconsistent transduction efficiencies. We next determined the effects of CSA when applied at various times after sca-1 cell isolation. We found that the number of sca-1+ cells decreased within the first two days of culture but then begin to increase on day 3, and by day 7 there is a 7-fold increase compared to the number of cells originally isolated. Cells cultured with virus alone had an average increase of 3.5-fold on day 7, but only 3% of cells cultured in CSA survived to day 7. Cells cultured with both virus and CSA had no viability on day 7. However, by delaying the addition of virus and CSA until day 3, a 1.4-fold increase in sca-1+ cells was observed by day 7, which was achieved without affecting the efficiency of transduction. Sca-1+ cells were then transduced with the lentiviral vector in the presence of CSA and transplanted into transgenic sickle mice using a nonmyeloablative conditioning regimen that consisted of busulfan (25 mg/kg) administered on day -1 and costimulation blockade with CTLA-4Ig and anti-CD40 ligand administered on days 0, 2, 4, and 7. We were able to achieve donor engraftment levels of 98% with a 40% engraftment of gene-modified cells. These results show that using CSA in lentiviral transductions of murine HSCs can be an effective method for increasing overall transduction efficiency, and may aid in the use of lentiviral vectors in animal studies.
514. Clinical Trials of Oncolytic Adenovirus-Mediated Gene Therapy

For the past 20 years we have been developing a multi-modal, gene therapy-based approach for the treatment of cancer. Our therapeutic platform utilizes an oncolytic adenovirus to deliver a pair of cytotoxic “suicide” genes to the tumor. The oncolytic adenovirus generates an anti-tumor effect by replicating in, and destroying, cancer cells (oncolytic viral therapy). The therapeutic effect of the oncolytic adenovirus is enhanced by invoking two cytotoxic gene systems, which render malignant cells sensitive to specific pharmacological agents (cytotoxic gene therapy) and sensitize them to ionizing radiation (radiosensitization). The combined effects of these three modalities result in significant tumor cell destruction and release of tumor antigens, which, when coupled with the robust immune response elicited by the oncolytic adenovirus, generate an environment suitable for tumor antigen processing and cross-presentation that may culminate in the development of anti-tumor immunity. Under four Investigational New Drug (IND) applications, we have evaluated the toxicity and efficacy of our multi-modal approach in six phase 1/2 trials of prostate cancer using four different oncolytic adenoviruses (Figure 1Figure 1). These studies have demonstrated that our approach is safe and evidence of efficacy has been obtained. With respect to safety, there were no dose-limiting toxicities (DLTs) or treatment-related serious adverse events (SAEs) in over 100 patients treated to date. Only 6% of the adverse events were ≥ grade 3 with the vast majority being transient and asymptomatic. With respect to efficacy, in the locally recurrent setting following radiation failure, men who received the gene therapy exhibited a significant lengthening of PSA doubling time (PSADT), a surrogate endpoint that is highly prognostic for the development of distant metastases and prostate cancer-specific mortality. At 7 years, there was an improvement in disease-specific survival relative to well-matched historical controls. When combined with radiation therapy in the newly-diagnosed setting, the gene therapy reduced by 42% the percentage of men who had a positive prostate biopsy 2 years after treatment in a prospective, randomized, controlled phase 2 trial. An even greater treatment effect (i.e., 60% reduction) was observed in men with a low tumor burden at baseline. Together, the results demonstrate that oncolytic adenovirus-mediated gene therapy has the potential to improve tumor control in multiple settings of prostate cancer. To improve our approach further, we have generated a new oncolytic adenovirus expressing IL-12, which is now in the clinic. Updated results of our randomized controlled phase 2 trial (median follow-up 6 years) will be presented along with early results of our ongoing phase 1 trial with the oncolytic adenovirus expressing IL-12.View Large Image | Download PowerPoint Slide
On the Use of Information in Humanitarian Operations

Obtaining reliable information for decision-making to prepare and respond to disasters is difficult. Governments and humanitarian organizations often have to plan complex disaster responses based on forecasts or without having reliable field assessments. Decision aid models can help governments and humanitarian organizations by improving their forecasts during disaster preparedness and by facilitating data collection during field assessments in disaster response. Decision aid models can also facilitate collaboration and coordination between different parties involved in disaster management. This book is an academic study of decision aid models for disaster management.
Building structured theories

We provide a set of syntactic tools for structuring large collections of logical theories. Their use is demonstrated by a formalisation of algebras that are used in describing the semantics of concepts in programming languages, but also of more general systems.
Philatelic Propaganda: U.S. Postage Stamps during the Cold War

Throughout the Cold War, the leading powers used postage stamps to promote their foreign policy goals. This brief research note cites illustrative examples of U.S. and Cuban postage stamps and discusses how and why they were produced.
Human Factors in the Wild Delivering Safety in the Pediatric World (Discussion Panel)

The pediatric healthcare environment is arguably more complex than the general, adult, healthcare settings (e.g., weight based dosing, caring for patients who cannot advocate for themselves, etc.)....
Explicit calculations with Eisenstein series

Abstract We find explicit change-of-basis formulas between Eisenstein series attached to cusps, and newform Eisenstein series attached to pairs of primitive Dirichlet characters. As a consequence, we prove a Bruggeman–Kuznetsov formula for newforms of square-free level and trivial nebentypus. We also derive, in explicit form, the Fourier expansion, Hecke eigenvalues, Atkin–Lehner pseudo-eigenvalues, and other data associated to these Eisenstein series, with arbitrary integer weight, level, and nebentypus.
Alterations in mGlu5 receptor expression and function in the striatum in a rat depression model.

Major depressive disorder is a common form of mental illness. Many brain regions are implicated in the pathophysiology and symptomatology of depression. Among key brain areas is the striatum that controls reward and mood and is involved in the development of core depression-like behavior in animal models of depression. While molecular mechanisms in this region underlying depression-related behavior are poorly understood, the glutamatergic input to the striatum is believed to play a role. In this study, we investigated changes in metabotropic glutamate (mGlu) receptor expression and signaling in the striatum of adult rats in response to prolonged (10-12 weeks) social isolation, a pre-validated animal paradigm modeling depression in adulthood. We found that mGlu5 receptor protein levels in the striatum were increased in rats that showed typical depression- and anxiety-like behavior after chronic social isolation. This increase in mGlu5 receptor expression was seen in both subdivisions of the striatum, the nucleus accumbens and caudate putamen. At subcellular and subsynaptic levels, mGlu5 receptor expression was elevated in surface membranes at synaptic sites. In striatal neurons, the mGlu5-associated phosphoinositide signaling pathway was augmented in its efficacy after prolonged social isolation. These data indicate that the mGlu5 receptor is a sensitive substrate of depression. Adulthood social isolation leads to the up-regulation of mGlu5 receptor expression and function in striatal neurons.
Associations Between Lean Mass, Muscle Strength and Power, and Skeletal Size, Density and Strength in Older Men.

Studies examining the relationship between muscle parameters and bone strength have not included multiple muscle measurements and/or both central and peripheral skeletal parameters. The purpose of this study was to explore the relationship between lean mass, muscle strength and power, and skeletal size, bone density, and bone strength. We studied the association between appendicular lean mass (ALM), grip strength, and leg power, and central quantitative computed tomography (QCT) parameters in 2857 men aged 65 years or older; peripheral QCT was available on a subset (n = 786). ALM, grip strength, and leg power were measured by dual-energy X-ray absorptiometry (DXA), Jamar dynamometer, and the Nottingham Power Rig, respectively. Multivariable models adjusting for potential confounders including age, race, study site, BMI, and muscle measurements were developed and least squares means were generated from linear regression models. For the multivariable model, percent differences of bone parameters between lowest (Q1) and highest quartiles (Q4) of ALM, grip strength, and leg power were reported. ALM was significantly associated with central and peripheral QCT parameters: percent higher values (Q4 versus Q1) ranging from 3.3% (cortical volumetric bone mineral density [vBMD] of the femoral neck) to 31% (vertebral strength index of the spine). Grip strength was only significantly associated with radial parameters: percent higher values (Q4 versus Q1) ranging from 2.5% (periosteal circumference) to 7.5% (33% axial strength index [SSIx]). Leg power was associated with vertebral strength and lower cross-sectional area with percent lower values (Q4 versus Q1) of -11.9% and -2.7%, respectively. In older men, stronger associations were observed for ALM compared to muscle strength and power. Longitudinal studies are needed to examine the relationship between independent changes in muscle measurements and skeletal size, density and strength. © 2018 American Society for Bone and Mineral Research.
Impaired associative inference in the early stage of psychosis

Abstract Relational memory is impaired in chronic schizophrenia. It is unclear if similar deficits are already present in the early stage of psychosis. We used the Associative Inference Paradigm to test relational memory ability in the early stage of a non-affective psychotic disorder. Eighty-two early stage psychosis patients and 67 healthy control subjects were trained on 3 sets of 30 paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), F3-F4 (two new faces). Subjects who reached 80% recall accuracy of the paired associates during training were then tested for their ability to recall the previously seen pairs and solve a novel, inferential pairing F1-F2 (faces linked through association to same house). Sixty early psychosis patients (73%) and 67 healthy control subjects (100%) successfully reached the accuracy threshold (80%) during training and were included in the analysis of relational memory. The early stage psychosis patients showed less of an associative inference effect than the healthy controls (pair type by group interaction: F (1,125) = 5.04, p
Peptidase activity in the membranes of Mycoplasma laidlawii

Abstract Membrane-bound peptidase activity was found in Mycoplasma laidlawii . Similar activity was also found in the cytoplasm and to a small extent in the medium. Aminopeptidase and dipeptidase activities were present in the membranes as well as small amounts of carboxypeptidase activity.
The Impact of Prolonged Breast-Feeding on Birth Intervals and on Postpartum Amenorrhoea

Many mothers in low income countries, particularly in rural areas, nurse their children from 1 to 2 years. The main purpose of this practice is, of course, to provide newborn children with the nutrition necessary for their survival. Many mothers continue to nurse for a long time, often until or after the next pregnancy occurs, because they believe it to be beneficial for their children (1, 2).
Spiral Waves in Excitable Media

The beautiful spiral waves of oxidation in the Belousov-Zhabotinskii reaction [20] are the source of many interesting questions about periodic structures in excitable media. Because they are easy to produce and photograph, pictures of these spirals have appeared in a number of popular science oriented magazines. The study of spirals takes on a more personal interest when one realizes that fibrillation and sudden cardiac arrest from heart attacks may also be due to the appearance of rotating spiral waves of electrical activity on the ventricular myocardium [1], [14]. Immediately questions like “How do spirals form?” and “Can Spirals be prevented?” or “Can one predict if a heart attack will be fatal?” spring to mind. Going beyond questions of self preservation, we may also ask about the properties of spirals, such as their wavelength and frequency, or the conditions necessary to. sustain spiral activity in a given medium.
Localization of acetyl-coenzyme A synthetase on peroxisomes in Tetrahymena.

Abstract The intracellular localization of acetyl-CoA synthetase was studied in the protozoan, Tetrahymena pyriformis . In cells grown under conditions which favor a conversion of acetate to carbohydrate via the glyoxylate bypass, this enzyme was found almost exclusively in the large particle fraction. The sedimentation pattern of this enzyme followed that of isocitrate lyase and lactate oxidase, but not of succinate dehydrogenase when the large particle fraction was subjected to further differential or density-gradient centrifugation. These results suggest that acetyl-CoA synthetase is localized on the peroxisome in TetrahymenaM .
Percutaneous valve replacement and repair: fiction or reality?

Greater advances in the use of percutaneous techniques for the treatment of coronary artery disease and cardiac non-coronary interventions have occurred during the last few years. Among them, percutaneous techniques for the treatment of stenotic valvular lesions were developed, and their benefits
Selective Distribution of Ions, Sugars, and Free Amino Acids

There are few subjects in cell physiology that have played as large a role in the development of concepts of the cell as the selective accumulation and exclusion of solutes. Certainly, investigation of this subject helped the formulation of Troshin’s sorption theory as well as the association-induction (AI) hypothesis. In particular, the unusual distribution patterns of K+ and Na+ gave important clues to the molecular mechanisms that underlie the general patterns of solute distribution in, as well as the physicochemical makeup of, living cells.
An Introduction to Epigenetics in Cardiovascular Development, Disease, and Sexualization.

Epigenetic regulation of gene expression is integral to cell differentiation, development, and disease. Modes of epigenetic regulation—including DNA methylation, histone modifications, and ncRNA-based regulation—alter chromatin structure, promotor accessibility, and contribute to posttranscriptional modifications. In the cardiovascular system, epigenetic regulation is necessary for proper cardiovascular development and homeostasis, while epigenetic dysfunction is associated with improper cardiac development and disease.
Tracking and controlling microservice dependencies

Dependency cycles will be familiar to you if you have ever locked your keys inside your house or car. You can’t open the lock without the key, but you can’t get the key without opening the lock. So...
Medial prefrontal cortex guides goal-directed decision-making about hunger and thirst

Abstract Decision-making guided by self-evaluation of bodily need states (interoception) is thought to be important for cognitive control over eating or drinking1. However, interoception of body states is notoriously unreliable2–4 because hunger and thirst have similar motivational characteristics5. Consequently, individuals may inaccurately assess their need state and consume food when dehydrated, leading some healthcare professionals to advise overweight patients to drink water before eating6–8. Neuroimaging in humans9–11 and recordings in rodents12–15 indicate medial prefrontal frontal cortex (mPFC) involvement in need state-dependent decisions about hunger and thirst, but mPFC surgical lesions16,17 and electrical activity perturbations have little influence on eating or drinking18,19. To investigate need-state dependent decision-making as well as the function of mPFC in hunger and thirst, we developed an instrumental foraging task for mice that mimics key elements of human decisions. When homeostatic need state was variable, mice did not show intrinsic knowledge of hunger or thirst state but, instead, rapidly identified their need after consumption of small portions of food and water (outcome evaluation). We observed a food-seeking bias, even in thirsty mice, that required outcome evaluation for mice to correctly seek water. mPFC was required for need state-dependent decisions about hunger and thirst, specifically under variable need state conditions. Food-seeking or water-seeking choices were controlled by multiple decision-making processes, and mPFC was involved in goal-directed decisions about the identity of need states. Thus, we have discovered a role for mPFC in decision-making about hunger and thirst, which is relevant for human behaviors that contribute to obesity.
γδ T cells in livestock: Responses to pathogens and vaccine potential

The immediate objective of our research is to understand the molecular mechanisms underlying activation and potentiation of the protective functional response of WC1+ γδ T cells to pathogens afflicting livestock species. The long-term goal is to incorporate stimulation of these cells into the next generation of vaccine constructs. γδ T cells have roles in the immune response to many infectious diseases including viral, bacterial, protozoan and worm infections, and their functional responses overlap with those of canonical αβ T cells, for example they produce cytokines including interferon-γ and IL-17. Stimulation of non-conventional lymphocytes including γδ T cells and αβ natural killer T (NKT) cells has been shown to contribute to protective immunity in mammals, bridging the gap between the innate and adaptive immune responses. Because of their innate-like early response, understanding how to engage γδ T-cell responses has the potential to optimize strategies of those that aim to induce pro-inflammatory responses as discussed here.
Water Diffusion and Transport in Oil Paints as Studied by Unilateral NMR and 1H High-Resolution MAS-NMR Spectroscopy

Heavy metal carboxylate degradation severely affects thousands of oil paintings. Relative humidity has been reported to accelerate the rate of the reactions. To evaluate its role further, water diffusion and molecular mobility of protons in linseed oil-based lead white paints were studied by unilateral NMR and 1 H HRMAS spectroscopy. The results indicate that exposure to high %RH for relatively long times affects the dynamics of the oil paint's mobile fraction and that the effect is more pronounced as the thickness of the film increases. It was found that the paint can absorb appreciable amounts of water and has a porosity of approximately 6 % available for the diffusion of water, for which a regime of restricted diffusion was observed. Furthermore, the presence of bound and free-moving water, due to the possible formation of hydrated ionic-group clusters, supports the hypothesis of a polymeric/ionomeric network, as well as regions of essentially water free to move as in the bulk. The findings allow a better understanding of the role of water as a factor activating the degradation process in linseed oil-based lead white paints.
Comparison of echocardiographic and fluoroscopic sizing of the left atrial appendage prior to percutaneous closure

Sizing of the left atrial appendage (LAA) ostium prior to occlusion (LAAO) is routinely performed with transesophageal echocardiography (TEE). We sought to compare the utility of sizing via fluoroscopy to TEE for percutaneous LAAO. We retrospectively evaluated all patients undergoing percutaneous LAAO at our institution from April 2015 through January 2018 (n = 195). We evaluated baseline characteristics, maximum measured ostium size (for both TEE and fluoroscopy), and differences in measured size to device size for both techniques. Of the total cohort, 185 (95%) had both intraoperative TEE and fluoroscopic images available for analysis and were included in the final analysis. The mean age was 74 years and 64% were male. Hypertension was present in 89%, diabetes in 30%, and stroke in 32% of patients. The mean ejection fraction was 51%. The most common LAA morphology was “wind sock” (52%). Measured ostial diameter on fluoroscopy was larger compared with TEE (2.04 ± 3.43 mm larger on fluoroscopy, p < 0.001). Ostium diameter on TEE was more closely correlated to the size of the device implanted compared with fluoroscopy (0.76 vs. 0.61, p = 0.001). Fluoroscopy results in larger estimated LAA ostium diameter compared with TEE. Despite this, TEE was more strongly correlated to operator choice in device sizing, which may reflect practice patterns. Because compression of the ostium on the device is necessary for long-term procedural success, under-sizing may lead to a higher rate of leaks. Prospective evaluation of the utility of routine fluoroscopic sizing compared with TEE is warranted.
Immunomodulatory stromal cell interactions in the eye

Single-cell sequencing of eye stroma reveals cell-cell interactions essential for suppressing ocular inflammation.
On Aggregability of Risk Averse and Risk Seeking Preferences into One Representative Agent

This study provides formal theoretical evidence for nesting of probability measures that are generated by risk aversion in probability measures that are generated by risk seeking preferences. In presence of highlighted nesting, conditional on independent parameterization of expectations (probability distributions) that are conditioned on either of risk aversion, or risk seeking preferences, the two sets of preferences aggregate into one representative agent. This is a novel result that simultaneously is not trivial. Non-triviality is evident in the accompanying prediction that formation of expectations (probability distributions) over entirety of assets within stock markets, this without recourse to heterogeneity of preferences, does not induce existence of a single representative agent. The formal theoretical evidence demonstrates that the value-growth anomaly - the superior return performance of `value' stocks in relation to `growth' stocks - is induced by deviations from rational expectations equilibriums, as such lacks characterization as an anomaly.
Illness perceptions and beliefs about medication: impact on health-related quality of life in adolescent kidney transplant recipients.

Adolescents diagnosed with chronic kidney disease (CKD) who undergo kidney transplantation have to adjust to pervasive effects of chronic illness and life-long treatment maintenance, alongside normative developmental stressors. The way in which adolescent transplant recipients experience and think about their illness as well as their medication regimen can be a crucial factor impacting psychosocial outcomes. Participants were 26 adolescent kidney transplant recipients (μ = 16.8 years, σ = 1.69 years) who completed self-report surveys during a clinic visit. Multiple linear regressions were used to investigate whether adolescents' beliefs about medications and attitudes and perceptions of their illness are associated with their overall quality of life. Adolescents' negative illness perceptions contributed to lower transplant-specific health-related quality of life ratings (ΔR2 =.305, p < .01). Additionally, adolescent beliefs about their specific medication regimens (ie, personal medication concerns) (ΔR2 =.342, p < .01), and general beliefs about medication use (ie, harm, overuse) (ΔR2 =.241, p < .05) also contribute significantly to the variance in their overall quality of life ratings. Adolescent transplant patients in older grades and those in special education endorsed lower quality of life. Cognitive components (eg, beliefs, perceptions) of an adolescent kidney transplant recipient's experience contribute to transplant-related quality of life outcomes. This highlights a point of intervention where cognitive change interventions may be utilized and efficacious in improving health outcomes.
Para-aminobenzoic acid (PABA) enhances the in-vitro tumor response of ovarian cancer to Topotecan (TTN) through mitochondrial-mediated apoptosis

5319 Objectives: We tested the effect of PABA when combined with TTN on ovarian cancer cell proliferation, and generation of reactive oxygen species (ROS) as a marker for mitochondrial-mediated apoptosis. We also examined the effect of duration of exposure to PABA. Methods: SKOV-3 cells were maintained in DMEM media with 10% FBS. 5x103 cells were plated in 96 well plates overnight. Cells were treated with PABA at 100 ug/ml for either 7 or 18 days and were then treated with varying concentrations of TTN (0 to 5uM). At the end of treatment (24 hours), cell proliferation and viability was measured using a Cell Proliferation Assay Kit (Chemicon International, Inc, Temecula, CA). For measurement of ROS, PABA- treated and PABA-free cells were exposed to either 1 or 2.5 uM TTN. Treated cells were incubated in 5 uM dihydroethidine (Molecular Probes, Eugene, OR) at 37°C for 15 min, harvested by trypsinization and washed. ROS generation was determined by measuring the number of ethidium-positive cells via FACS analysis. Mixed model analysis of variance was used to assess the impact of the treatment components on the fraction of cells surviving compared to untreated cells. Results: For both 7 day and 18 day exposure to PABA, and at all concentrations of TTN, PABA caused significantly greater growth inhibition (GI) in the SKOV-3 cells compared to TTN treatment alone (p=0.043). However, the length of exposure to PABA had no significant effect (p=0.807) on GI. There was no statistically significant interaction (p>0.39) between TTN and either PABA (presence versus absence) or length of exposure to PABA (7 versus 18 days) suggesting an absence of synergism between PABA and TTN in SKOV-3 cells. At 1 uM TTN, the GI achieved with 7 days PABA exposure was improved by 18% over TTN alone and for 18 days’exposure by 21% over TTN alone. Five-week treatment of the cells with PABA even without TTN increased the percent of ethidium-positive cells 36-fold from 6.71 ± 0.95 (S.D.) without PABA to 240.24 ± 13.31 with PABA. Treatment with TTN showed no effect on ROS generation. Conclusions: PABA, which has been shown to upregulate cdc25a (Peter Brooks, unpublished data), increases the growth inhibition caused by TTN in ovarian cancer cells. This is associated with an increase in mitochondrial stress in these cells as indicated by an increased ROS generation. This implies that addition of PABA to TTN chemotherapy in ovarian cancer might improve tumor response through mitochondrial-mediated apoptosis. Supported by DOD OC010016 and the Chemotherapy Foundation.
Intraosseous Anchorage of a Collagen Matrix Graft to Enhance Repair of Peroneus Brevis Tendon Degeneration

INTRODUCTION Chronic degeneration of the peroneus brevis tendon (PBT) at its insertion to the base of the fifth metatarsal is uncommon; however, when present it can be a challenge to treat. Repair of the PBT often requires tubularization with or without a peroneus longus tendon transfer. These repairs, however, may not provide resultant full muscle strength, especially if ostectomy of the fifth metatarsal base is required. We report outcomes following a novel technique for anatomic repair of degenerative PBT with intraosseous fifth metatarsal base fixation of a collagen matrix graft. METHODS Thirteen consecutive patients (14 procedures) with degeneration of PBT that underwent tendon repair augmented with collagen matrix graft from 2011 to 2019 were reviewed retrospectively. We present outcome data of these 13 patients that were followed for at least 12 months. RESULTS Muscle strength, complications, and patient-reported subjective outcomes were reported. There were 10 females and 3 males. Average age was 49.1 years, and average follow-up was 34.9 months. Muscle strength was reported at 5/5 to the PBT by the final follow-up for 92% of patients. There were minimal complications, 84.6% (11/13) of patients had no limitation in activity level, and 92% (12/13) would recommend this procedure to a friend. CONCLUSION Outcomes for this novel repair technique for insertional degenerative PBT have never been reported before and show excellent results with long-term follow-up.
Common iliac vein stenting for May-Thurner syndrome and subsequent pregnancy.

Abstract Background For women with left common iliac vein compression (ie, May-Thurner syndrome) who undergo venous stenting and subsequently become pregnant, concerns have been raised regarding a possible compromise of stent patency due to compression from the gravid uterus and the hypercoagulability induced by pregnancy. Only a small body of literature exists on this subject, and limited management guidelines are available. The present study was designed to evaluate the safety of iliac vein stenting for May-Thurner syndrome (MTS) with subsequent pregnancy. Methods Female patients who had undergone common iliac vein stenting at our center who were aged 18 to 45 years and had subsequently become pregnant were identified. A retrospective medical record review of eight eligible patients was conducted, recording the demographics, procedural characteristics, and anticoagulation strategies. The primary outcome evaluated was stent patency. Results All eight patients had undergone left common iliac vein stenting for MTS. A total of eight stents were placed, and all demonstrated duplex ultrasound patency throughout pregnancy and postpartum. Seven patients delivered healthy pregnancies, and one experienced a stillbirth. The clinical CEAP (clinical, etiologic, anatomic, pathophysiologic) class remained unchanged or improved from pregnancy to postpartum for all patients. The average age at stent placement was 31 ± 5 years, and the average interval from stent placement to pregnancy was 28 ± 19 months. One patient developed nonobstructive deep vein thrombosis (DVT) of the left femoral vein during pregnancy and was treated with therapeutic enoxaparin. The nonobstructive DVT did not compromise the iliac vein stent. Two patients received low-dose aspirin and prophylactic doses of enoxaparin, one for a history of DVT and factor V Leiden and one for a recent history of fertility treatment. The five remaining patients received no anticoagulation, three received low-dose aspirin, and two received no antiplatelet therapy. Conclusions Common iliac vein stent patency was not compromised by subsequent pregnancy in our eight patients with MTS. Furthermore, the stents remained patent throughout pregnancy in patients receiving a wide range of anticoagulation and antiplatelet treatments, suggesting that no uniform therapeutic threshold exists and treatment should be individualized. For most patients, low-dose aspirin alone or no treatment was adequate. This could have implications for counseling women who require intervention for MTS and are of child-bearing age.
Environmental control and life support testing at the Marshall Space Flight Center

The Space Station Environmental Control and Life Support System (ECLSS) test program at the Marshall Space Flight Center (MSFC) is addressed. The immediate goals and current activities of the test program are discussed. Also described are the Core Module Integration Facility (CMIF) and the initial ECLSS test configuration. Future plans for the ECLSS test program and the CMIF are summarized.
Towards a Privacy Preserving e-Commerce Protocol

Every time a user performs a transaction over the Internet, a wealth of personal information is revealed, either voluntarily or involuntarily. This causes serious breach of privacy for the user, in particular, if the personally identifying information is misused by the different players involved in the transaction. Ideally, therefore, the user would like to have a considerable degree of control over what personal information to reveal and to whom. In this paper we propose a new e-commerce protocol that helps the user protect her privacy while purchasing products over the Internet. The proposed scheme provides a flexible and powerful approach for the secure handling of private data and offers the user considerable control over how she wishes to disseminate her personal data.