cssi/SciSciGPT-SciSciNet huggingface dataset:
Decitabine in myelodysplastic syndromes

Decitabine (5-aza-2’-deoxycytidine), a cytosine analog, inhibits DNA methylation and has dual effects on neoplastic cells, including the reactivation of silenced genes and differentiation at low doses, and cytotoxicity at high doses. Decitabine has promising clinical efficacy in the treatment of myelodysplastic syndromes (a heterogeneous group of bone marrow malignancies), with evidence of target modulation (hypomethylation) and a favorable toxicity profile. Optimal dosing schedules of decitabine in myelodysplastic syndrome are those that maximize hypomethylation (low dose, high dose intensity, multiple cycles). However, the molecular mechanisms of in vivo response to decitabine are still unclear. Combination therapies that augment decitabine’s epigenetic effect, or take advantage of gene activation, will likely improve clinical responses and may extend its use to the treatment of other malignancies.
Centipede envenomation: bringing the pain to Hawai'i and Pacific Islands.

Scolopendra subspinipes is the only clinically significant centipede found in Hawai‘i. Envenomation typically leads to extreme localized pain, erythema, induration, and tissue necrosis and possible lymphedema or lymphangitis. Mortality is uncommon and results from secondary infection or anaphylaxis. Management is supportive and includes wound care, pain control, and treatment with topical or oral antihistamines and anti-inflammatory medications.
The Physiological Significance of Thylakoid Membrane Protein Phosphorylation

The regulation of the process of light absorption and the regulation of the rate of electron transport between the main three integral thylakoid membrane complexes has attracted considerable interest among investigators in photosynthesis. Since the beginning of the present decade, two aspects of this regulation have developed independently and almost simultaneously. The first involved the discovery by Bennett [1] of a reversible phosphorylation of the LHC II of photosystem II. The physiological significance attributed to this phenomenon was the regulation of excitation energy distribution between PSII and PSI in higher plant chloroplasts [2]. It was hypothesized that phospho-LHC II separates from the PSII complex in the grana partition region and upon migration in the nonappressed membrane region it couples energetically to PSI complexes where it serves as a PSI accessory antenna [3]. The first part of this model has received considerable support from a variety of experimental approaches. The energetic coupling of phospho-LHC II with PSI, however, is currently a controversial issue with more research required to provide unambiguous answers.
Abuse, Adoption, and Attention Deficit Disorder

This piece discusses how adoption is affected by abuse of disabled children, particularly those who suffer from Attention Deficit/Hyperactivity Disorder (ADHD). Children who have attention difficulties are more apt to be abused by their parents than are those who do not. Unfortunately, the problems that plague these children do not end when they are removed from their parents. They are more likely to be hard to place in permanent homes than children without disabilities, and may only leave foster care as they age out, or become emancipated. Further, even if they are adopted, the adoptions may be disrupted at a higher rate than those of children without such difficulties. Finally, even when the adoptions remain intact, the children may not turn out as well as adopted children without known problems.
Airspace Security Measures Employed For the UN General Assembly Meeting: Analysis and Impact

The FAA plays a pivotal role in maintaining security within the National Airspace System (NAS). This paper discusses employment of temporary flight restrictions, use of air interdiction assets and establishment of an Aviation Security Operations Center as air domain security measures during the September 2007 United Nations General Assembly meeting. Also discussed are some of the Tracks of Interest that were detected during the event and some of the impacts that airspace security measures had on the NAS and its users.
Abstract SY31-03: Genome regulation by long noncoding RNAs.

The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serves as the template for protein synthesis. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long noncoding RNAs (lncRNAs) provide an important new perspective on the centrality of RNA in gene regulation. An emerging theme from multiple model systems is that LncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, long noncoding RNAs can function as modular scaffolds to specify higher order organization in RNP complexes and in chromatin states. I will discuss how this mode of regulation is particularly relevant to cancer and the maintenance of genome integrity. Citation Format: Howard Y. Chang. Genome regulation by long noncoding RNAs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY31-03. doi:10.1158/1538-7445.AM2013-SY31-03
Longevity and Efficacy of Pyrethroid and Organophosphate Termiticides in Field Degradation Studies using Miniature Slabs

Organophosphate (chlorpyrifos, fenitrothion, and isofenphos) and pyrethroid (bifenthrin, cypermethrin, lamda-cyhalothrin, and permethrin) formulations were applied in sand and covered by miniature slabs in a field study in southern Florida. Sub-slab sands were sampled annually for up to 5 yr to evaluate their barrier efficacy against the Formosan subterranean termite, Coptotermes formosanus Shiraki, and the eastern subterranean termite, Reticulitermes flavipes (Kollar). The bioassay results showed that at the rates tested under these miniature slabs, pyrethroids generally provided longer protection than organophosphates, but microencapsulated formulations extended longevity of some organophosphates. According to the half-life regression model, permethrin had the longest half-life (21.9 mo) among the 7 insecticides selected for residue analysis. Because the foundation size of a typical house is much larger than the miniature plots used in this study, our results should be interpreted with caution.
FD-CADRE 2.0: A Flexible, MPI-based Framework for Moving Body and Multi-Disciplinary Simulations

FD-CADRE provides a framework for control and communication between multiple legacy software packages for multidisciplinary simulations and has been used for several years for complex store separation simulations using computational fluid dynamics (CFD) to compute forces and moments. While the code interface is flexible, the underlying methodology led to inefficient operation for extremely complex or long-duration simulations. A method based on MPI-2 has been developed which employs a client-server approach allowing more efficient operation and memory-based storage of the data while minimizing the application program interface changes. This improved method has been demonstrated for two multicomponent moving body simulations. In addition the framework has been extended to handle the transfer and utilization of surface data for multidisciplinary applications including conjugate heat-transfer and fluid-structure interaction.
BACILLUS CEREUS: FOOD POISONING ORGANISM. A REVIEW

This paper is devoted to a review of information pertinent to the role of Bacillus cereus as a food-borne pathogen. Primary emphasis is on the properties of B. cereus and published accounts of its involvement in animal and human disease. Methods for isolation, identification, and enumeration are discussed. Research needs pertaining to (a) recognition of the potential public health hazard and (b) further investigation of the food poisoning syndrome are presented.
Tech Fever in the Health Sector

The use of information and communication technologies (ICT) in health—e-health—has been nothing short of epidemic. In developed countries, e-health has developed quickly from the provision of online medical content for health professionals and patients to the implementation of e-commerce solutions for billing, epide-miological surveillance, monitoring of health system performance, logistical support for clinical tasks, e-management of medical care processes, and support for treatment of patients with chronic conditions or disabilities. In the United States, the greatest potential for ICT may lie in systems that improve communication between health care institutions, support the ordering and management of medications, and help monitor and improve patient compliance with care regimens (Blaya, Fraser, and Holt, 2010). Mobile devices can also improve the timeliness and quality of data collection. However, before the fever becomes too contagious, there is an urgent need for more rigorous evaluations of the effectiveness and cost-effectiveness of e-health systems, especially in less developed countries (Blaya, Fraser and Holt, 2010; Kahn, Yang, and Kahn, 2010).
Discharge, Waiver, and the Behavioral Undercurrents of Debtor-Creditor Law

An individual in financial distress enjoys two important rights. First, she can protect some of her assets from her creditors, whether in bankruptcy or not. A creditor cannot seize the clothes on the debtor’s back, her tools of trade, basic household goods, her wedding ring, or her homestead.1 Second, the “honest but unfortunate debtor” has a right to bankruptcy’s “fresh start.”2 She can file a bankruptcy petition and obtain a discharge of past debt. She keeps only the property creditors could not reach outside of bankruptcy, but she enjoys her future income free of the claims of her old creditors. Each right allows the debtor to put some assets (existing property such as household goods in one case and future earnings in the other) beyond the reach of creditors. But the rights differ in a crucial respect. A debtor can allow creditors to take household goods and assets otherwise beyond the creditors’ reach by granting a security interest in them. With a security interest, a creditor can seize and sell the assets. By contrast, a debtor cannot give up her right to enjoy future earnings. She has no ability to waive her right to file a bankruptcy petition at the time she borrows.3 Liens on future income do not survive bankruptcy. This Essay explores the difference between these two rights through the lens of behavioral economics.
PET DAQ system for compressed sensing detector modules

We developed a data acquisition (DAQ) system for positron emission tomography (PET) that can efficiently process detector module signals with compressed sensing multiplexing schemes. This multiplexing scheme has a multiplexing ratio of 8:1 and the capability to resolve multi-hit events or light sharing events even at very high singles rates. To process the compressed signals, a conventional DAQ system structure had to be modified. It needs to process 16 ADC channels simultaneously and process large coincidence packets efficiently. We design simultaneous 32 channel ADC sampling scheme to process 16 channel simultaneously at the FPGA. The "asymmetric coincidence processing" was used for coincidence identification which reduced the required network speed. The measured maximum singles events rate was 3.6 Mevent/s per compressed sensing processor which will be 74.7 Mevent/s for all the system. Identified coincidences could be downloaded to a data acquisition PC at 1.2 Mevent/s at maximum. Other free-running analog-to-digital converter (A DC) based systems can also benefit from the proposed asymmetric processing scheme to increase system throughput. Index TermsPositron emission tomography (PET), data acquisition system (DAQ), compressed sensing, coincidence event processing, asymmetric coincidence processing.
Comparison of tomographic fluorescence spectral and lifetime multiplexing

Multispectral and lifetime imaging in turbid media can be mathematically described in two steps, involving spectral or temporal mixing of the fluorophores and the diffuse light transport in the turbid medium. We show that the order of fluorophore mixing and diffuse propagation is reversed in spectral and lifetime multiplexing, resulting in a fundamental difference in their multiplexing capabilities, regardless of the measurement conditions. Using the resolution matrix to define a quantitative measure for inter-fluorophore cross-talk, we show that lifetime multiplexing, using the asymptotic time domain approach, provides zero cross-talk, while spectral multiplexing can achieve zero cross-talk under special conditions. We also compare the performance of spectral and lifetime multiplexing for tomographic inversion of two overlapping fluorophores in a heterogeneous digital mouse atlas.
Continuous Liquid-Phase Hydrogenation of 1,4-Butynediol to High-Purity 1,4-Butanediol over Particulate Raney Nickel Catalyst in a Fixed Bed Reactor

The work describes the results on the hydrogenation of the 2-butyne-1,4-diol (BYD) to 1,4-butanediol (BAD) over both slurry and particulate Raney nickel catalysts (Ra Ni) in batch and in a fixed bed reactor system. The detailed study on the kinetics of the reaction obtained in batch conditions revealed the existence of four stages in the overall hydrogenation network. In the first region, A, the starting BYD produces exclusively cis-2-butene-1,4-diol (cis-BED) and to a lesser degree the respective 4-hydroxybutanal (γ-HALD). In the second region, B, the cis-BED takes part in three parallel reactions of hydrogenation to BAD, isomerization to trans-2-butene-1,4-diol (trans-BED), and the formation of additional γ-HALD. In the third region, C, the trans-BED is mostly engaged in further hydrogenation to BAD, and surprisingly, starts producing the main byproduct, n-butanol (BOL). In the last kinetic region, D, the accumulated 4-hydroxybutanal is slowly hydrogenated to BAD. A completely different reaction profile...
Brachytherapy Boost Utilization and Survival in Unfavorable-risk Prostate Cancer

Abstract Background There are limited comparative survival data for prostate cancer (PCa) patients managed with a low-dose rate brachytherapy (LDR-B) boost and dose-escalated external-beam radiotherapy (DE-EBRT) alone. Objective To compare overall survival (OS) for men with unfavorable PCa between LDR-B and DE-EBRT groups. Design, setting, and participants Using the National Cancer Data Base, we identified men with unfavorable PCa treated between 2004 and 2012 with androgen suppression (AS) and either EBRT followed by LDR-B or DE-EBRT (75.6–86.4Gy). Outcome measurements and statistical analysis Treatment selection was evaluated using logistic regression and annual percentage proportions. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards, and propensity score matching. Results and limitation We identified 25038 men between 2004 and 2012, during which LDR-B boost utilization decreased from 29% to 14%. LDR-B was associated with better OS on univariate (7-yr OS: 82% vs 73%; p Conclusions Between 2004 and 2012, LDR-B boost utilization declined and was associated with better OS compared to DE-EBRT alone. LDR-B boost is probably the ideal treatment option for men with unfavorable PCa, pending long-term results of randomized trials. Patient summary We compared radiotherapy utilization and survival for prostate cancer (PCa) patients using a national database. We found that low-dose rate brachytherapy (LDR-B) boost, a method being used less frequently, was associated with better overall survival when compared to dose-escalated external-beam radiotherapy alone for men with unfavorable PCa. Randomized trials are needed to confirm that LDR-B boost is the ideal treatment.
Beyond Belmont: Ensuring Respect for AI/AN Communities Through Tribal IRBs, Laws, and Policies.

We concur with Friesen and colleagues (2017) that it is timely to reflect on the history of the Belmont Report and its role in the development of research regulations, especially its failure to acc...
Just Say No: Corporate Taxation and Corporate Social Responsibility

This article will address the question whether publicly traded US corporations owe a duty to their shareholders to minimize their corporate tax burden in any way that they may be able to get away with from a purely legal perspective. First, however, to render the subsequent discussion a bit more concrete, I will describe a recently unveiled case study of corporate tax aggressiveness.
Outcomes of Patients With Relapsed Core Binding Factor-Positive Acute Myeloid Leukemia

Abstract Purpose To determine the factors associated with outcomes in patients with core binding factor acute myeloid leukemia (CBF-AML) in first relapse. Material and Methods We conducted a retrospective analysis of 92 patients with CBF-AML in first relapse who presented to our institution from 1990-2014. Clinical and demographic parameters were included in univariate and multivariate Cox proportional hazards regression model to predict overall survival. Results Among the 92 relapsed patients, 60 (65%) patients had inv (16) and 32 (35%) had t (8;21). The median survival for patients with inv(16) cytogenetic group was 15.6 months (range 10.32 to 20.88 months) while for the t(8;21) group was 9 months (range 3.68 to 14.32) ( P = .004). Univariate Cox model analysis showed that increased age, high white blood cell count, t (8;21) cytogenetic group, and high bone marrow blast percentage were associated with poor overall outcome, while stem cell transplant intervention was associated with better survival. Additional cytogenetic aberrations at relapse were not associated with survival outcomes ( P = .4). Multivariate Cox model analysis showed that t(8;21) cytogenetic group has more hazard of death after adjusting, age, marrow blast percentage, blood cell count, and stem cell transplant(hazard ratio 1.802; P = .02). Conclusion Among patients with relapsed CBF-AML, median survival was less than a year and half and the outcome was worse in patients with t (8;21). Despite the relatively better outcomes, dedicated clinical trials are needed to improve the outcome in all patients with relapsed CBF-AML.
Promoting Spiritual Formation in Distance Education

For many in Christian higher education, modeling Christ-likeness in the classroom is considered a primary means and evidence of integrating faith and learning. But when the face-to-face relational ...
Knowledge, Time, and Paradox: Introducing Sequential Epistemic Logic

Epistemic logic in the tradition of Hintikka provides, as one of its many applications, a toolkit for the precise analysis of certain epistemological problems. In recent years, dynamic epistemic logic has expanded this toolkit. Dynamic epistemic logic has been used in analyses of well-known epistemic “paradoxes”, such as the Paradox of the Surprise Examination and Fitch’s Paradox of Knowability, and related epistemic phenomena, such as what Hintikka called the “anti-performatory effect” of Moorean announcements. In this paper, we explore a variation on basic dynamic epistemic logic—what we call sequential epistemic logic—and argue that it allows more faithful and fine-grained analyses of those epistemological topics.
Narrative: Why It's Important, and How It Works

Behavior analysts have said little about narrative and storytelling, emphasizing instead the functional/pragmatic aspects of verbal behavior. Nevertheless, these are ubiquitous human activities, and they are important to understand. Stories are prominent in essays on social issues, fund-raising appeals and political speeches, and they are the bedrock of theater. Foundational narratives are at the roots of major religions and of conflicts between them, and narrative has been proposed as an organizing basis for psychological wellbeing as well as a source of empathetic reactions. The ongoing process of reading or hearing a good story entails interlocking relations between establishing stimuli and their related, differentiated reinforcing consequences, with a story's coherence providing a key to its reinforcing effects. What are the behavioral principles that underlie the repertoires involved in all this? Behavior analysts have defined and studied some-the basic verbal classes, of course, although temporally extended sequences require some adjustments in these. Intraverbal behavior needs to be parsed into sub-categories to delineate highly varied sequences such as occur in paraphrase and translation. These two, along with imitation, generalized imitation and re-telling of stories, entail a salient role of complex invariance. The terms pliance and tracking help to balance the roles of speaker and listener, and to account for joint attention, which appears important in early verbal development. Transfer and transformation of function are additional ubiquitous processes, addressed through stimulus equivalence, relational frames, and other higher-order operants, especially naming, which entails the fusion of speaking and listening. Finally, we should consider ways in which a behavioral understanding of narrative can serve both behavior analysis and its surrounding culture.
Enacting food sovereignty in Aotearoa New Zealand and Peru: revitalizing Indigenous knowledge, food practices and ecological philosophies

This article reports on a cross-cultural study of two Indigenous1 knowledge and food security systems: Quechua2 people of Peru and Māori3 of Aotearoa – New Zealand, and implications for food system...
Leveraging pH profiles to direct enzyme production (cellulase, xylanase, polygalacturonase, pectinase, α-galactosidase, and invertase) by Aspergillus foetidus.

Abstract Aspergillus foetidus was found to have different optimal pH conditions for producing different carbohydrases including cellulase, xylanase, pectinase, α-galactosidase, polygalacturonase, and invertase. Designs to trigger these conditions sequentially using controlled pH gradients were evaluated for directing the culture through multiple production stages optimal for different enzymes. For production of enzyme mixtures with particularly high pectinase and α-galactosidase activities, for more effective hydrolysis of the complex carbohydrate in soybean meal, the best method tested was a pH gradient started at pH 7.0, decreased to pH 6.0 over 72 h, held constant for 24 h, and then decreased to pH 5 over 24 h.
The Prebiotic Synthesis and Replication of RNA Oligomers: The Transition from Prebiotic Molecules to the RNA World

The problems and possibilities of the formation of the RNA world from prebiotic molecules will be discussed here. Experiments describing the poymerization of activated mononucleotides to oligonucleotides under primitive Earth conditions will be presented as well as initial studies on the replication of these oligomers. These experiments suggest a possible route from the prebiotic world to the RNA world.
Boundary Control and Stabilization for a Viscous Burgers’ Equation

This paper is concerned with the use of a boundary control to stabilize a viscous Burgers’ equation on a finite interval. The main result of the paper parallels a result found in [1], The main differences are that our original uncontrolled system is not asymptotically stable. Indeed, using a center manifold argument, it can be shown that the trajectories of the uncontrolled problem approach constant equilibria as t goes to infinity. By tuning a boundary control parameter (gain) we show that the resulting controlled system is exponentially stable for initial data small enough in the so-called “zero dynamics” subspace. Following [7], we define the zero dynamics to be the system corresponding to a positive infinite value of the gain parameter. Furthermore the margin of stability is monotone increasing with increasing k and converges to that obtained for the zero dynamics (i.e., infinite gain). Thus, we obtain that the controlled Burgers’ system is locally exponentially stable uniformly in k → ∞.
Applications of the Calculus of Moving Surfaces

The applications of the calculus of moving surfaces are remarkably broad. Of course, many of the applications come from problems in physics and engineering in which physical surfaces move. On the other hand, numerous applications come from problems in which, at least in the statement of the problem, there are no moving surfaces. There are at least three categories of such problems: shape optimization, boundary perturbation, and a third category illustrated by the proof of a version of the Gauss–Bonnet theorem.
Selecting Antiplatelet Therapy at the Time of Percutaneous Intervention for an Acute Coronary Syndrome Weighing the Benefits and Risks of Prasugrel Versus Clopidogrel

Background—On average, acute coronary syndrome patients treated with prasugrel experience fewer ischemic complications, but more bleeding, than those receiving clopidogrel. However, heterogeneity in treatment effects can alter the likelihood of benefits and risks of an individual patient. We developed predictive models of the benefits (reduced ischemic events) and risks (increased bleeding) to support targeting prasugrel to those who benefit most from treatment. Methods and Results—Using 12 579 patients from Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38), we fit risk models for ischemic events (cardiovascular death, spontaneous myocardial infarction, stroke) and bleeding (TIMI major/minor) over a 14.8-month follow-up and then calculated each patient’s predicted risk for major ischemia and bleeding with both prasugrel and clopidogrel. We found substantial heterogeneity of the treatment effect of ...
Deep learning of biomimetic visual perception for virtual humans

Future generations of advanced, autonomous virtual humans will likely require artificial vision systems that more accurately model the human biological vision system. With this in mind, we propose a strongly biomimetic model of visual perception within a novel framework for human sensorimotor control. Our framework features a biomechanically simulated, musculoskeletal human model actuated by numerous skeletal muscles, with two human-like eyes whose retinas have spatially nonuniform distributions of photoreceptors not unlike biological retinas. The retinal photoreceptors capture the scene irradiance that reaches them, which is computed using ray tracing. Within the sensory subsystem of our model, which continuously operates on the photoreceptor outputs, are 10 automatically-trained, deep neural networks (DNNs). A pair of DNNs drive eye and head movements, while the other 8 DNNs extract the sensory information needed to control the arms and legs. Thus, exclusively by means of its egocentric, active visual perception, our biomechanical virtual human learns, by synthesizing its own training data, efficient, online visuomotor control of its eyes, head, and limbs to perform tasks involving the foveation and visual pursuit of target objects coupled with visually-guided reaching actions to intercept the moving targets.
Commentary Response for "LARC Provision by Family Physicians: Low But on the Rise".

Family physicians (FPs) are well poised to offer comprehensive contraceptive services to their patients, since they see patients across the life cycle and often provide maternity care and many preventative health services, including Papanicolaou smears and sexually transmitted infections (STI)
Management of Virologic Failure in Patients with Chronic Hepatitis B Treated with Nucleos(t)ide Analogues

Poorly controlled hepatitis B increases the risk for liver-related morbidity. Although there are now six approved nucleos(t)ide analogues (NA) for the treatment of chronic hepatitis B (CHB), drug resistance and thus virologic breakthrough still exist. This review outlines a systematic approach to the management of virologic failure in patients with CHB treated with NAs. Current NAs can be divided into older generation and newer generation agents, with newer generation agents associated with lower rates of virologic breakthrough. Both tenofovir dipovoxil fumarate (TDF) and tenofovir alafenamide (TAF) are equally as effective in addressing virologic breakthrough while on all other NAs. Entecavir is an effective treatment option for NA naive patients only, with high rates of resistance to entecavir in those exposed to older NAs. The management of virologic breakthroughs should focus on identifying risk factors for future drug resistance and escalation to appropriate newer generation drug options to avoid long-term liver-related morbidity.
Deletion of ΔdblGata motif leads to increased predisposition and severity of IgE-mediated food-induced anaphylaxis response.

Background Previous studies have revealed an important role for the transcription factor GATA-1 in mast cell maturation and degranulation. However, there have been conflicting reports with respect to the requirement of GATA-1 function in mast cell dependent inflammatory processes. Herein, we examine the requirement of GATA-1 signaling in mast cell effector function and IgE-mast cell-dependent anaphylaxis. Objective To study the requirement of GATA-1 dependent signaling in the development and severity of IgE-mast cell-dependent anaphylaxis in mice. Methods Wild type (Balb/c) and mutant ΔdblGata (Balb/c) mice were employed to study the role of GATA-1 signaling in in vitro IgE-mediated activation of bone marrow derived mast cells (BMMCs). Murine models of passive IgE-mediated and oral antigen-induced IgE-mediated anaphylaxis were employed in mice. Frequency of steady state mast cells in various tissues (duodenum, ear, and tongue), peritoneal cavity, and clinical symptoms (diarrhea, shock, and mast cell activation) and intestinal Type 2 immune cell analysis including CD4+ Th2 cells, type 2 innate lymphoid cells (ILC2), and IL-9 secreting mucosal mast cells (MMC9) were assessed. Results In vitro analysis revealed that ΔdblGata BMMCs exhibit a reduced maturation rate, decreased expression of FceRIα, and degranulation capacity when compared to their wildtype (WT) counterparts. These in vitro differences did not impact tissue resident mast cell numbers, total IgE, and susceptibility to or severity of IgE-mediated passive anaphylaxis. Surprisingly, ΔdblGata mice were more susceptible to IgE-mast cell-mediated oral antigen induced anaphylaxis. The increased allergic response was associated with increased Type 2 immunity (antigen-specific IgE, and CD4+ TH2 cells), MMC9 cells and small intestine (SI) mast cell load. Conclusion Diminished GATA-1 activity results in reduced in vitro mast cell FceRIα expression, proliferation, and degranulation activity. However, in vivo, diminished GATA-1 activity results in normal homeostatic tissue mast cell levels and increased antigen-induced CD4+ Th2 and iMMC9 cell levels and heightened IgE-mast cell mediated reactions.
Preventing the need for revision surgery after penile plication reconstruction of Peyronie's deformities

Background: The need for repeat penile plication (PP) for persistent penile deformity has previously been associated with (I) poor initial erectile response to intracavernosal injection (ICI), (II) an inadequate number of corrective sutures, and (III) a lack of sutures along the proximal shaft of the penis. We present our current experience with PP after implementing corrective measures to assess whether our need for revision surgery was reduced. Methods: We performed a retrospective review of patients who underwent PP for Peyronie’s disease (PD) between 2009–2018 and had a minimum follow-up of 6 months. We updated our surgical technique in 2016 by (I) using supplemental intracorporal saline injections if the initial erection response to prostaglandin E1 injection was inadequate, (II) increasing numbers of corrective plication sutures, and (III) emphasizing more proximal suture placement. Patients were stratified into two groups and outcomes compared (prior technique versus current technique). Results: Of 472 PP patients who met inclusion criteria, 340 (72%) plication patients before 2016 were compared to 132 (28%) performed after 2016. The revision rate in the current cohort (1.5%, 2/132) decreased by more than half compared to the previous cohort (3.8%, 13/340). Mean preoperative angle of curvature was similar between the two groups (50.4 vs . 51.4 degrees, P=0.64), while the average residual postoperative degree was smaller in the current group (7.36 vs . 2.14 degrees, P vs . 8.38, P=0.04). After revision, all cases were functionally straight, with a mean postoperative curvature of 4 degrees at a median follow-up of 10.6 months (IQR, 2.08–20.7). Conclusions: Ensuring adequate rigidity with additional ICI and focusing a greater number of corrective sutures in a more proximal location appears to help prevent the need for revision plication surgery.
Visualizing a Moving Target: A Design Study on Task Parallel Programs in the Presence of Evolving Data and Concerns

Common pitfalls in visualization projects include lack of data availability and the domain users' needs and focus changing too rapidly for the design process to complete. While it is often prudent to avoid such projects, we argue it can be beneficial to engage them in some cases as the visualization process can help refine data collection, solving a “chicken and egg” problem of having the data and tools to analyze it. We found this to be the case in the domain of task parallel computing where such data and tooling is an open area of research. Despite these hurdles, we conducted a design study. Through a tightly-coupled iterative design process, we built Atria, a multi-view execution graph visualization to support performance analysis. Atria simplifies the initial representation of the execution graph by aggregating nodes as related to their line of code. We deployed Atria on multiple platforms, some requiring design alteration. We describe how we adapted the design study methodology to the “moving target” of both the data and the domain experts' concerns and how this movement kept both the visualization and programming project healthy. We reflect on our process and discuss what factors allow the project to be successful in the presence of changing data and user needs.
HIV Latency and the noncoding RNA therapeutic landscape.

The Human Immunodeficiency Virus (HIV) belongs to the subfamily of lentiviruses that are characterized by long incubation periods and chronic, persistent infection. The virus integrates into the genome of infected CD4+ cells and, in a subpopulation of cells, adopts a transcriptionally silent state, a process referred to a viral latency. This property makes it exceedingly difficult to therapeutically target the virus and eradicate infection. If left untreated, the inexorable demise of the infected individual’s immune system ensues, a causal result of Acquired Immunodeficiency Syndrome (AIDS). Latently infected cells provide a reservoir that maintains viral infection indefinitely. In this chapter we explore the role of noncoding RNAs in HIV infection and in the establishment and maintenance of viral latency. Both short and long noncoding RNAs are endogenous modulators of epigenetic regulation in human cells and play an active role in gene expression. Lastly, we explore therapeutic modalities based on expressed RNAs that are capable of countering infection, transcriptionally regulating the virus, and suppressing or activating the latent state.
The Occupational Medicine Perspective on Behavioral Health Concerns

In occupational medicine, the main issue with psychological and psychosocial issues is the treatment of workers with injuries or illness is often attributed to work and thus treated in the workers’ compensation system. Psychosocial problems are more common in workers’ compensation patients than in general medical patients. The same personality traits that make many orthopedic and neurosurgeons good surgeons give them “blinders” to the psychological issues occurring with their workers’ compensation patients. Another barrier to the recognition of psychosocial issues within the workers’ compensation system is the workers’ compensation system itself. When psychosocial factors are delaying or preventing recovery, they must be identified and addressed within the treatment process. In closing, there is a discussion regarding essential strategies to better address many of the problematic issues within the workers’ compensation system.
Selective Estrogen Receptor β Agonists: a Therapeutic Approach for HIV-1 Associated Neurocognitive Disorders.

The persistence of HIV-1 associated neurocognitive disorders (HAND) in the post-cART era, afflicting between 40 and 70% of HIV-1 seropositive individuals, supports a critical need for the development of adjunctive therapeutic treatments. Selective estrogen receptor β agonists, including S-Equol (SE), have been implicated as potential therapeutic targets for the treatment of neurocognitive disorders. In the present study, the therapeutic efficacy of 0.2 mg SE for the treatment of HAND was assessed to address two key questions in the HIV-1 transgenic (Tg) rat. First, does SE exhibit robust therapeutic efficacy when treatment is initiated relatively early (i.e., between 2 and 3 months of age) in the course of viral protein exposure? Second, does the therapeutic utility of SE generalize across multiple neurocognitive domains? Treatment with SE enhanced preattentive processes and stimulus-response learning to the level of controls in all (i.e., 100%) HIV-1 Tg animals. For sustained and selective attention, statistically significant effects were not observed in the overall analyses (Control: Placebo, n = 10, SE, n = 10; HIV-1 Tg: Placebo, n = 10, SE, n = 10). However, given our a priori hypothesis, subsequent analyses were conducted, revealing enhanced sustained and selective attention, approximating controls, in a subset (i.e., 50%, n = 5 and 80%, n = 8, respectively) of HIV-1 Tg animals treated with SE. Thus, the therapeutic efficacy of SE is greater when treatment is initiated relatively early in the course of viral protein exposure and generalizes across neurocognitive domains, supporting an adjunctive therapeutic for HAND in the post-cART era.
Histologic evaluation of disease activity in inflammatory bowel disease

Abstract Histologic examination of the gastrointestinal (GI) tract plays an essential role in the diagnosis and differential diagnosis of inflammatory bowel disease (IBD). With the availability of more potent anti-IBD therapies and subspecialization of GI pathology, the evaluation of GI specimens either biopsy or resection specimens from patients suspicious for IBD or IBD patients suffering from disease relapse or in surveillance, becomes more detail-oriented. The benefit of histologic mucosal healing in the clinical outcome of patients with ulcerative colitis (UC) has emerged calling for a tiered, precise, and reliable scoring system in IBD pathology practice. This chapter is to review the previously published histopathology scoring systems in UC and Crohn’s disease and the daily pathology practice pattern in IBD care. As a thorough histologic assessment of IBD activity is time-consuming, how to achieve a cost-effective histologic evaluation of IBD specimens to meet the ever-increasing clinical demands remains a challenge.
Abstract 3421: Identifying mechanisms of immune evasion in microsatellite instable endometrial cancers

Inherited or sporadic defects in mismatch repair genes (MLH1, MSH2, MSH6, and PSM2) can lead to microsatellite instable (MSI) tumors, most commonly colon, endometrial or gastric tumors. High mutation rates in MSI tumors have been associated with greater immunogenicity, but these tumors can evade immune response. Recently developed mouse models of MSI endometrial cancer (EC) were used to evaluate immune surveillance mechanisms. Uterine-targeted MSH2 knockout (PR-Cre+MSH2flox/flox) mice were characterized and determined that 22% of mice develop spontaneous EC by 12-16 months of age. Microsatellite instability was evaluated by PCR. Immune infiltration was quantified by immunohistochemistry (IHC) using FoxP3 (Tregs), CD11b (myeloid cells) and CD8 (tumor infiltrating lymphocytes, TILs) antibodies. Tumors were divided into TILHigh and TILLow ( All endometrial tumors from PR-Cre+MSH2flox/flox mice were MSI and included endometrioid, serous, and mixed histologies. Tumors showed varying degrees of immune infiltrate, irrespective of histology. Of 7 tumors, 4 (57%) were TILHigh and 3 (43%) were TILLow. Transcriptome analysis showed TILHigh tumors upregulated innate immunity related pathways including, pattern recognition-associated factors, Type I IFN signaling molecules and CXCL5. Activation of adaptive immunity was observed by an increase in T cell chemoattractants, CXCL9 and CCL21. TILHigh tumors displayed at least a 2-fold increase in MHC class I molecules and CD86 needed for T cell activation. IL1A, CSF1, and TGFB2 (cytokines involved in immunosuppressive cell recruitment and induction) were also highly expressed. IHC confirmed co-localization of TILs with myeloid cells and Tregs in TILHigh tumors. TILLow tumors had decreased expression of several members in the IFN family responsible for initiating innate responses. Primary cell lines from TILHigh and TILLow tumors used in an orthotopic syngeneic mouse model retained the immune profile of the original tumor. Understanding mechanisms of immune evasion is critical for improving immunotherapy. This model of MSI EC reflects the spectrum of immunogenicity observed in clinical studies. TILHigh tumors express a wide range of factors involved in innate and adaptive anti-tumor responses, while TILLow tumors lack key mediators needed for immune activation. These new models for MSI EC will be essential to test the efficacy of immunotherapies and study mechanisms of resistance. Citation Format: Brenda Melendez, Emily Hinchcliff, Nisha Gokul, Elizabeth Whitley, Russell R. Broaddus, Rosemarie E. Schmandt, Karen H. Lu, Melinda S. Yates. Identifying mechanisms of immune evasion in microsatellite instable endometrial cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3421.
Malic Enzyme Couples Mitochondria with Aerobic Glycolysis in Osteoblasts.

Summary The metabolic program of osteoblasts, the chief bone-making cells, remains incompletely understood. Here in murine calvarial cells, we establish that osteoblast differentiation under aerobic conditions is coupled with a marked increase in glucose consumption and lactate production but reduced oxygen consumption. As a result, aerobic glycolysis accounts for approximately 80% of the ATP production in mature osteoblasts. In vivo tracing with 13C-labeled glucose in the mouse shows that glucose in bone is readily metabolized to lactate but not organic acids in the TCA cycle. Glucose tracing in osteoblast cultures reveals that pyruvate is carboxylated to form malate integral to the malate-aspartate shuttle. RNA sequencing (RNA-seq) identifies Me2, encoding the mitochondrial NAD-dependent isoform of malic enzyme, as being specifically upregulated during osteoblast differentiation. Knockdown of Me2 markedly reduces the glycolytic flux and impairs osteoblast proliferation and differentiation. Thus, the mitochondrial malic enzyme functionally couples the mitochondria with aerobic glycolysis in osteoblasts.
Optimal Financial Ratios in a Public Bank versus a Private Bank

This article explores factors that explain the coexistence of public and private banks in the debt market. Starting from the objective function that underpins each institution type, the article identifies the sources of growth in a public bank relative to a private bank under the constraint that both types of institutions compete for the same funds in the debt market. The optimal response functions associated with each objective function also underscore differences in the correlation across key financial ratios for a public bank versus a private bank. Theoretical results also serve as a reference for the role of assumptions on projections of financial ratios for a public bank versus a private bank.
A Survey of Metal Lines at High Redshift. II. SDSS Absorption Line Studies—O VI Line Density, Space Density, and Gas Metallicity at z abs ~ 3.0

We have analyzed a large data set of Ovi absorber candidates found in the spectra of 3702 Sloan Digital Sky Survey (SDSS) quasars, focusing on a subsample of 387 active galactic nuclei sight lines with an average S/N 5.0, allowing for the detection of absorbers above a rest-frame equivalent width limit of Wr 0.19 A for the Ovi 1032 A component. Accounting for random interlopers mimicking an Ovi doublet, we derive for the first time a secure lower limit for the redshift number density ΔN/Δz for redshifts zabs 2.8. With extensive Monte Carlo simulations, we quantify the losses of absorbers due to blending with the ubiquitous Lyα forest lines and estimate the success rate of retrieving each individual candidate as a function of its redshift, the emission redshift of the quasar, the strength of the absorber, and the measured signal-to-noise ratio (S/N) of the spectrum by modeling typical Lyman forest spectra. These correction factors allow us to derive the “incompleteness and S/N-corrected” redshift number densities of Ovi absorbers: ΔNOvi,c/Δzc (2.8 <z< 3.2) = 4.6 ± 0.3, ΔNOvi,c/Δzc (3.2 <z< 3.6) = 6.7 ± 0.8, and ΔNOvi,c/Δzc (3.6 <z< 4.0) = 8.4 ± 2.9. We can place a secure lower limit for the contribution of Ovi to the closure mass density at the redshifts probed here: ΩOvi(2.8 <z< 3.2) 1.9 × 10 −8 h −1 .W e show that the strong lines we probe account for over 65% of the mass in the Ovi absorbers; the weak absorbers, while dominant in line number density, do not contribute significantly to the mass density. Making a conservative assumption about the ionization fraction, Ovi O , and adopting the Anders & Grevesse solar abundance values, we derive the mean metallicity of the gas probed in our search: ζ (2.8 <z< 3.2) 3.6 × 10 −4 h, in good agreement with other studies. These results demonstrate that large spectroscopic data sets such as SDSS can play an important role in QSO absorption line studies, in spite of the relatively low resolution.
High-Order Methods for Simulations in Engineering

Engineers create new things and hence always have to deal with incomplete information. A critical review is made of the accuracy of the available physical and modeling parameters. It shows that in many cases key physical and modeling parameters such as viscosities, boundary conditions, geometry, and even basic physics are not known to within 1%. This raises the question as to whether any numerical method needs to be of even higher quality than a fraction of this threshold. Thereafter work estimates for traditional high-order elements are derived. The comparison of error and work estimates shows that even for relative accuracy in the 0.1% range, which is one order below the typical accuracy of engineering interest (1% range), linear elements may outperform all higher order elements. The chapter concludes with some recent LES results that indicate that eight-order schemes on a grid of size 2h are similar to second-order schemes on a grid of size h, and some open questions.