cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-Term Outcomes Following a Single Corticosteroid Injection for Trigger Finger

Background: The outcomes of corticosteroid injection for trigger finger are well documented only with short-term follow-up. The purpose of this investigation was to determine the long-term effectiveness of a single injection and to examine predictors of success up to ten years after injection. Methods: This case series analyzed 366 first-time corticosteroid injections in flexor tendon sheaths from January 2000 to December 2007 with a minimum follow-up duration of five years. Two hundred and forty patients (66%) were female, 161 patients (44%) had multiple trigger fingers, and eighty-eight patients (24%) had diabetes at the time of injection. The primary outcome of treatment failure was defined as subsequent injection or surgical trigger finger release of the affected digit. Medical records were reviewed, and any patients without documented failure or a return office visit in 2012 to 2013 were contacted by telephone regarding symptom recurrence and the need for additional treatment. Kaplan-Meier analyses with log-rank test and Cox regression analysis assessed the effect of baseline patient and disease characteristics on injection success. Results: Forty-five percent of patients demonstrated long-term treatment success after a single injection. In the final regression model, the interaction of sex and the number of trigger fingers was the single predictor of treatment success. Exploring this association revealed a ten-year success rate of 56% for female patients presenting for the first time with a trigger finger compared with 35% in male patients presenting for the first time with a trigger finger, 39% in female patients with multiple trigger fingers, and 37% in male patients with multiple trigger fingers. Eighty-four percent of treatment failures occurred within the first two years following injection. Patient age, symptom type, and undifferentiated diabetes status were not predictive of treatment success. Conclusions: Female patients presenting with their first trigger finger have the highest rate of long-term treatment success after a single corticosteroid injection. Patients who continue to experience symptom relief two years after injection are likely to maintain long-term success. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Latitudinal variation in spongivorous fishes and the effectiveness of sponge chemical defenses

It has been proposed that predation pressure declines with increasing latitude and a positive correlation exists between predation intensity and the investment into chemical defenses. However, little direct evidence supports the idea that tropical species are better defended chemically than their temperate counterparts. Temperate reefs of the South Atlantic Bight (SAB) off Georgia, USA, provide a unique opportunity to study tropical sponges in a temperate environment. We documented sponge species richness and abundance, sponge predator density, and examined the ability of eight sponge species to chemically deter predation by fishes on two reefs in the SAB. We used rarefaction analysis and ANOVA to compare our results for sponge species richness and density, respectively, with similar published studies conducted on reefs of the sub-tropical Atlantic (i.e., Florida Keys). These analyses were combined with similar statistical comparisons for spongivorous fish species richness and density. Results showed that sponge species richness was lower, but sponge density was higher, on the temperate SAB reefs than on the subtropical reefs. Both spongivorous fish diversity and density were lower on the SAB reefs. The greater abundance of sponges and lower density of predators on SAB reefs suggest a lower frequency of predation on sponges on SAB reefs. Of the eight sponge species assayed from the SAB reefs, five possessed chemical extracts that were significantly less deterrent to fish predators than their tropical/subtropical conspecifics. When the results were combined across all sponge species, the chemical deterrence of fish predators was significantly lower for extracts obtained from the temperate sponge community as compared to the tropical/subtropical assemblage. These results support the more general hypothesis that a lower density and diversity of sponge predators occurs at high as compared to low latitudes in the western Atlantic and may contribute to decreased investment in chemical defenses.
Deep typechecking and refactoring

Large software systems are typically composed of multiple layers, written in different languages and loosely coupled using a string-based interface. For example, in modern web-applications, a server written in Java communicates with a database back-end by passing in query strings. This widely prevalent approach is unsafe as the analyses developed for the individual layers are oblivious to the semantics of the dynamically constructed strings, making it impossible to statically reason about the correctness of the interaction. Further, even simple refactoring in such systems is daunting and error prone as the changes must also be applied to isolated string fragments scattered across the code base. We present techniques for deep typechecking and refactoring for systems that combine Java code with a database back-end using the Java Persistence API [10]. Deep typechecking ensures that the queries that are constructed dynamically are type safe and that the values returned from the queries are used safely by the program. Deep refactoring builds upon typechecking to allow programmers to safely and automatically propagate code refactorings through the query string fragments. Our algorithms are implemented in a tool called QUAIL. We present experiments evaluating the effectiveness of QUAIL on several benchmarks ranging from 3,369 to 82,907 lines of code.We show that QUAIL is able to verify that 84% of query strings in our benchmarks are type safe. Finally, we show that QUAIL reduces the number of places in the code that a programmer must look at in order to perform a refactoring by several orders of magnitude.
Endurance training enhances lactate clearance during hyperlactatemia

Constant infusions of cold molar lactate (178.0 +/- 1.6 mumol.kg-1.min-1), [U-14C]lactate (0.50 muCi/min), and [6-3H]glucose (0.5 muCi/min) were employed to study the effects of endurance training (running 1 h/day, at 38 m/min, 10% grade) on lactate clearance in resting, hyperlactatemic rats. Before infusion, resting blood lactate levels were not significantly different between controls, 1.10 +/- 0.04 mM, and trained animals, 1.16 +/- 0.04 mM. Lactate levels increased significantly during the infusion period, attaining steady-state mixed venous concentrations of 11.32 +/- 0.24 mM and 5.44 +/- 0.09 mM, respectively, for controls and trained animals. Lactate clearance rates, based on net lactate removal (i.e., not tracer-estimated lactate removal), were twofold greater in trained animals vs. controls, 33.0 +/- 0.7 and 15.4 +/- 0.4 ml.kg-1. min-1, respectively. Lactate specific activity values during the infusion period were not significantly different between controls, 22,243 +/- 236 dpm/mumol, and trained animals, 21,270 +/- 374 dpm/mumol, indicating similar endogenous dilution of the pyruvate-lactate pool. For both control and trained animals, essentially 100% of the 14C infused as lactate was recovered as either glucose or CO2; however, trained animals demonstrated a 25% greater rate of gluconeogenesis. At a given lactate production rate, trained animals maintain lower lactate levels through enhanced clearance via gluconeogenesis and oxidation.
A Summary of 2009 Inflation Adjustments Affecting Individuals

Without inflation adjustments to key portions of the tax system, individuals would be faced with an erosion of their purchasing power. Beginning in 1985, Congress implemented an indexation procedure to adjust various income tax components, including the tax rate schedules, standard deduction, and personal and dependency exemptions. Although suspended by the Tax Reform Act of 1986, indexation resumed in 1989 and now applies to many items in the tax system. In this report, Young discusses 2009 inflation adjustments to specific portions of the individual tax system that are tied to a Consumer Price Index year ending in August. Items adjusted by this indexation procedure include the tax rate schedules, standard deductions, exemptions (and related phaseout), the overall limit on itemized deductions, the annual gift tax exclusion, and some computational elements related to the unearned income of minor children, the child credit, the earned income tax credit, adoption expenses, educational savings bonds, education credits, education loan interest, qualified transportation fringe benefits, medical savings accounts (Archer MSAs), health savings accounts, long-term care insurance premiums, long-term care insurance benefits, traditional and Roth IRA income phaseouts and contribution limits, and the section 179 expense election.
Retention of Children and Their Families in the Longitudinal Outcome Study of the Comprehensive Community Mental Health Services for Children and Their Families Program A Multilevel Analysis

Predictors of retention of participants in a longitudinal study and heterogeneity between communities were investigated using a multilevel logistic regression model. Data from the longitudinal outcome study of the national evaluation of the Comprehensive Community Mental Health Services for Children and Their Families program and information on communities participating in the evaluation were used to examine retention of participants at 6-, 12-, 18-, and 24-month follow-up interviews. Findings revealed that both child and family characteristics and community characteristics significantly influenced participation for up to 24-month follow-up. Specifically, behavioral and emotional problems at intake, referral source, proportion of total staff devoted to interviewers, and total amount of incentive paid out at baseline influenced retention of participants. In addition, significant random effects at both Level 2 and Level 3 indicated that retention varied significantly between communities and among children e...
Zeroth-Order Resonator Antennas Using Composite Right/Left-Handed Microstrip Transmission Lines

The left-handed metamaterials have the negative permittivity epsiv and permeability mu simultaneously. These provide the left-handed metamaterials with various new properties in comparison with the traditional right-handed (RH) materials. Many applications for the left-handed metamaterials are possible. A new type of the microstrip resonant antenna with small physical size will be presented using composite right/left-handed (CRLH) transmission lines (TL). The antennas are implemented by the series microstrip unit cells. The verifications are done by the detailed simulations. Two zero order (ZOR) CRLH antennas were designed that operate at 2.4 GHz and 915 MHz. The antenna at 915-MHz is also experimentally processed and tested for RFID applications.
Inhalant Use Disorders in the United States

Abstract Inhalant misuse is among the most prevalent and pernicious forms of drug use in the United States. Hundreds of low-cost and widely available commercial products containing volatile hydrocarbons are inhaled for their psychoactive effects. Inhalant use is prevalent among adolescents, indigenous populations, persons involved with the juvenile and criminal justice systems, and other marginalized groups. Acute inhalant intoxication can lead to “sudden sniffing death” and is associated with many adverse health and social outcomes. Chronic inhalant use, such as occurs among persons with inhalant use disorder, is associated with significant neurotoxicity and a range of cognitive impairments, psychosocial deficits, and organ pathologies. Limited, though important, progress has been made in understanding the pharmacology and toxicology of inhalant misuse. However, little is known regarding the treatment and prevention of inhalant use disorders.
Effects of Short-and Long-Term Exposure to Boat Noise on Cortisol Levels in Juvenile Fish

Anthropogenic noise can elicit a significant elevation in plasma cortisol levels in fish (Smith et al. 2004; Wysocki et al. 2006). In response to a stressor, fish attempt to compensate by using a series of biochemical and physiological changes that start with a neuroendocrine response. This response includes the release of cortisol into the circulatory system (Wendelaar Bonga 1997).
Molecular Phylogeny of Oxygenic Cells and Organelles Based on Small-Subunit Ribosomal RNA Sequences

The evolution of oxygenic photosynthesis stands apart as the most significant event in the biogeochemical history of our earth. It would be difficult to imagine a more far-reaching occurrence — the planetary atmosphere was modified forever towards an opposite end of the chemical spectrum. The early atmosphere was reducing, could support the abiotic synthesis of simple organic compounds from which life could evolve, and left a geological legacy in the form of an extensive deposition of reduced minerals. Among the earliest forms of life were those able to harvest biochemical energy from the oxidation and reduction of inorganic compounds, and phototrophs able to trap energy from another readily available source — light.
Structural operability analysis of heat exchanger networks

Methode basee sur une formulation modifiee du probleme, qui tient compte de la structure sous-jacente du processus pour les courants du reseau, ce qui reduit les dimensions du probleme. Exemples numeriques
Methylation of SOCS3 is inversely associated with metabolic syndrome in an epigenome-wide association study of obesity

Epigenetic mechanisms, including DNA methylation, mediate the interaction between gene and environment and may play an important role in the obesity epidemic. We assessed the relationship between DNA methylation and obesity in peripheral blood mononuclear cells (PBMCs) at 485,000 CpG sites across the genome in family members (8-90 y of age) using a discovery cohort (192 individuals) and a validation cohort (1,052 individuals) of Northern European ancestry. After Bonferroni-correction (Pα=0.05 = 1.31 × 10-7) for genome-wide significance, we identified 3 loci, cg18181703 (SOCS3), cg04502490 (ZNF771), and cg02988947 (LIMD2), where methylation status was associated with body mass index percentile (BMI%), a clinical index for obesity in children, adolescents, and adults. These sites were also associated with multiple metabolic syndrome (MetS) traits, including central obesity, fat depots, insulin responsiveness, and plasma lipids. The SOCS3 methylation locus was also associated with the clinical definition of MetS. In the validation cohort, SOCS3 methylation status was found to be inversely associated with BMI% (P = 1.75 × 10-6), waist to height ratio (P = 4.18 × 10-7), triglycerides (P = 4.01 × 10-4), and MetS (P = 4.01 × 10-7), and positively correlated with HDL-c (P = 4.57 × 10-8). Functional analysis in a sub cohort (333 individuals) demonstrated SOCS3 methylation and gene expression in PBMCs were inversely correlated (P = 2.93 × 10-4) and expression of SOCS3 was positively correlated with status of MetS (P = 0.012). We conclude that epigenetic modulation of SOCS3, a gene involved in leptin and insulin signaling, may play an important role in obesity and MetS.
Using social norm to promote energy conservation in a public building

Abstract In the last decade, there have been an increasing number of interventions that rely on social norms to leverage support for changes in behavior. Many of these interventions target environmentally relevant behaviors such as water and energy consumption, most commonly at the household level. In this paper, we present a field experiment that examines the impact of social norms on petition signing addressing energy consumption in a University campus building. Our results indicate that social norms have an impact on student’s support for the initiative, with 5% more students signing a petition to adjust the building’s thermostat by 2 °F when informed that 90% of students initially agreed to sign the petition. Our research highlights that social norms can be used to influence individual behavior in a petition signing context, which is more likely to lead to permanent change, than those contexts where individuals need to repeatedly sustain these changes individually over time.
The Corridor: Using GIS to Propose Satisfactory Transportation Paths between the West Bank and the Gaza Strip

Connection between theWest Bank and the Gaza Strip is a critical factor in the success of the prospective Palestinian state. Such a connection cannot be guaranteed without providing Palestinians with a transportation path or “corridor” through Israel that includes roads, a rail link, and infrastructure. The Palestinian Ministry of Planning needs a flexible processmodelling tool to propose a range of acceptable ground-based transportation paths between the two territories. The tool's flexibility will be used in the future to modify the weight of each criterion so as to adapt to the terms of negotiations with the Israeli side. This article describes how to use multi-criteria evaluation (MCE) with weighted linear combination (WLC) to create a map of suitability and then shows how this map can be used as friction surface of cost to calculate the least-cost pathways between Gaza's main crossing points and the West Bank's major roads. The article reflects Palestinian-recommended criteria that take into account ...
Palo Alto and the NASA Ames Research Center

In the mid-1960s I was fascinated by the developing NASA space program. We had been working on the effects of gravity on the lung, and it was natural to wonder what would happen in the absence of gravity in space. I therefore decided to try to get my foot in the door. With the help of John Billingham at the NASA Ames Research Center, I was awarded a 1-year fellowship to work in that institution. We flew to San Francisco at the end of 1967 and spent the year in Palo Alto. The most productive project of the year was exploiting the excellent digital computing facilities of the Center to analyze pulmonary gas exchange. I carried out a study looking at the effects of ventilation-perfusion inequality on pulmonary gas exchange that was very innovative at the time. However a remarkable opportunity occurred when I was invited to give a seminar at the new medical school being developed by the University of California in San Diego. Dr. Eugene Braunwald who was chief of medicine was looking for someone to take charge of the physiology course for first-year medical students. This was to be taught out of the department of medicine. My skills fitted this well and I agreed to take up the position. As a consequence, Penelope and I returned to London to sell our house and make other arrangements.
A nonsurgical protocol for management of postarthroplasty wound drainage

Abstract Persistent wound drainage after total joint arthroplasty can potentiate periprosthetic joint infection. Although current recommendations are to treat persistent wound drainage with surgical debridement, we believe nonoperative treatment may be successful in selected patients. We performed a retrospective analysis of 25 persistently draining hip and knee arthroplasty wounds treated with a protocol consisting of a combination of surgical site aspiration, closure of open wound edges, cessation of anticoagulants, activity modification, and antibiotics (in select patients). Wound drainage ceased in 24 of 25 wounds treated with this protocol. One patient who continued to drain for 3 more days was successfully treated with surgical debridement and evacuation of hematoma. No patient developed infection. We believe this protocol can be successful in many arthroplasty patients.
Superpixels based marker tracking vs. hue thresholding in rodent biomechanics application

Examining locomotion has improved our basic understanding of motor control and aided in treating motor impairment. Mice and rats are premier models of human disease and increasingly the model systems of choice for basic neuroscience. High frame rates (250 Hz) are needed to quantify the kinematics of these running rodents. Manual tracking, especially for multiple markers, becomes time-consuming and impossible for large sample sizes. Therefore, the need for automatic segmentation of these markers has grown in recent years. We propose two methods to segment and track these markers: first, using SLIC superpixels segmentation with a tracker based on position, speed, shape, and color information of the segmented region in the previous frame; second, using a thresholding on hue channel following up with the same tracker. The comparison showed that the SLIC superpixels method was superior because the segmentation was more reliable and based on both color and spatial information.
Automated Centerline Delineation to Enrich the National Hydrography Dataset

A common problem in the automated generalization of basemaps is extraction of important features for cartographic visualization purposes. The delineation of a stream network centerline poses unique challenges especially when variables such as stream order, channel depth, or flow rate are not available. This paper presents an algorithm for automated delineation of a continuous cartographic centerline through a flowline network encompassing a single subbasin. Six datasets testing the algorithm are drawn from the U.S. National Hydrography Dataset (NHD) to compare among delineations in landscapes with varying terrain and precipitation regimes. Centerline delineation provides a database enrichment, which adds functionality and enables cartographic generalization. A user-defined cutoff value permits progressively inclusive centerline delineations which may be targeted to multiple map scales and purposes.
ErbB3 Targeting Enhances the Effects of MEK Inhibitor in Wild-Type BRAF/NRAS Melanoma

MEK-ERK1/2 signaling is elevated in melanomas that are wild-type for both BRAF and NRAS (WT/WT), but patients are insensitive to MEK inhibitors. Stromal-derived growth factors may mediate resistance to targeted inhibitors, and optimizing the use of targeted inhibitors for patients with WT/WT melanoma is a clinical unmet need. Here, we studied adaptive responses to MEK inhibition in WT/WT cutaneous melanoma. The Cancer Genome Atlas data set and tumor microarray studies of WT/WT melanomas showed that high levels of neuregulin-1 (NRG1) were associated with stromal content and ErbB3 signaling. Of growth factors implicated in resistance to targeted inhibitors, NRG1 was effective at mediating resistance to MEK inhibitors in patient-derived WT/WT melanoma cells. Furthermore, ErbB3/ErbB2 signaling was adaptively upregulated following MEK inhibition. Patient-derived cancer-associated fibroblast studies demonstrated that stromal-derived NRG1 activated ErbB3/ErbB2 signaling and enhanced resistance to a MEK inhibitor. ErbB3- and ErbB2-neutralizing antibodies blocked the protective effects of NRG1 in vitro and cooperated with the MEK inhibitor to delay tumor growth in both cell line and patient-derived xenograft models. These results highlight tumor microenvironment regulation of targeted inhibitor resistance in WT/WT melanoma and provide a rationale for combining MEK inhibitors with anti-ErbB3/ErbB2 antibodies in patients with WT/WT cutaneous melanoma, for whom there are no effective targeted therapy options.Significance: This work suggests a mechanism by which NRG1 regulates the sensitivity of WT NRAS/BRAF melanomas to MEK inhibitors and provides a rationale for combining MEK inhibitors with anti-ErbB2/ErbB3 antibodies in these tumors. Cancer Res; 78(19); 5680-93. ©2018 AACR.
Roles of Environmental Pollution and Pesticides in Diabetes and Obesity: The Epidemiological Evidence

Abstract There are several factors that contribute to the development of type 2 diabetes, such as obesity, sedentary lifestyle, and family history, which are widely accepted in the medical community. However, the role of environmental contaminants or pollutants in diabetes is not yet well understood. The strongest body of epidemiological evidence is that linking certain persistent organic pollutants (POPs) to diabetes. POPs include dioxins, furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides. A metaanalysis of six studies of dioxins and furans produced a relative risk (RR) of 1.91 (95% CI 1.44–2.54) for diabetes when comparing the highest category versus the lowest category. A metaanalysis of 13 cross-sectional studies of PCBs and diabetes produced an RR of 2.90 (95% CI 2.14–3.92), and a metaanalysis of 8 prospective studies of PCBs and diabetes produced an RR of 1.65 (95% CI 1.16–2.34). Comparing the top versus the bottom tertile, a metaanalysis of any organochlorine pesticide and diabetes in 22 studies found a summary odds ratio of 1.68 (95% CI 1.37–2.07). Bisphenol A (BPA) is an endocrine disrupter that is found in many consumer products; human exposure is believed to be mainly from food product packaging containing BPA. A metaanalysis of BPA and type 2 diabetes, using five studies, produced a summary RR of 1.45 (95% CI 1.13–1.87) comparing the fourth quartile with the first quartile of urinary BPA. Phthalates are chemicals added to plastics to increase their flexibility, transparency, durability, and longevity. A metaanalysis of four studies produced a summary RR of 1.48 (95% CI 0.98–2.25) for diabetes when comparing the highest category of total phthalates with the lowest category. Although this summary RR is not significant, there is evidence that some individual phthalate metabolites are related to diabetes. Other environmental pollutants that have been studied include carbon monoxide, lead, nitrogen dioxide, ozone, particulate matter and sulfur dioxide in air pollution, and toxic heavy metals such as arsenic, cadmium, and mercury. Notably, a metaanalysis of 12 studies of arsenic in drinking water and type 2 diabetes had a pooled RR of 1.75 (95% CI 1.20–2.54). There is growing support for the “developmental obesogen” theory. It promotes the concept that certain chemicals may be capable of disrupting developmental processes related to metabolic homeostasis during early life and thus increasing the risk for obesity and other related metabolic diseases. However, most of the work relating environmental pollutants to obesity has produced inconsistent results. An exception is DDE (dichlorodiphenyldichloroethylene), a metabolite of dichlorodiphenyltrichloroethane. For DDE, there are seven studies showing positive associations with adiposity and two studies having null relationships.
Housing trajectories of immigrants and their children in France: Between integration and stratification:

Immigrants have been found to exhibit different housing tenure patterns from the rest of the population in a number of contexts. This article tests whether observed differences in tenure in France ...
Tetrahydrocurcumin epigenetically mitigates mitochondrial dysfunction in brain vasculature during ischemic stroke.

Abstract The objectives of this study are to identify the mechanism of mitochondrial dysfunction during cerebral ischemic/reperfusion (I/R) injury and the therapeutic potential of tetrahydrocurcumin (THC) to mitigate mitochondrial dysfunction in experimental stroke model. In our study, 8–10 weeks old male C57BL/6 wild-type mice were subjected to middle cerebral artery occlusion (MCAO) for 40 min, followed by reperfusion for 72 h. THC (25mg/kg-BW/day) was injected intraperitoneally once daily for 3 days after 4 h of ischemia. The experimental groups were: (i) sham, (ii) I/R and (iii) I/R + THC. We noticed that THC treatment in ischemic mice significantly improved the functional capacity and motor co-ordination along with reduced neuroscore, infarct volume, brain edema and microvascular leakage in brain parenchyma. The study revealed that level of total homocysteine (tHcy), homocysteine metabolizing enzymes, mitochondrial oxidative stress were significantly altered in I/R mice compared to sham. We also observed alteration in mitochondrial transition pore, ATP production and O2 consumption in the ischemic brain as compared to sham. Further, elevated matrix metalloproteinases-9 (MMP-9) activity and reduced tight junction protein expressions intensified the brain vascular impairment in I/R mice compared to sham. Interestingly, we found that levels of mitophagy markers, fusion and fission proteins were significantly altered. However THC treatment in I/R mice almost normalized the above functional and molecular changes. Mechanistic study demonstrated that DNA Methyltransferase 1 (DNMT1) expression was higher and was associated with reduced mitochondrial tissue inhibitor of metalloproteinases 2 (TIMP-2) expression through hyper-methylation of CpG island of TIMP-2 promoter in I/R mice compared to sham. However, administration of epigenetic inhibitor, 5-Azacytidine (5-Aza) abrogated I/R induced hyper-methylation of TIMP-2 promoter and maintaining the extracellular matrix (ECM) integrity. In conclusion, this study suggests that THC epigenetically ameliorates mitochondrial dysfunction in brain vasculature during Ischemic Stroke.
Primordial Blasts, a population of blood borne stem cells responsible for whole body regeneration in a basal chordate

Abstract The invertebrate chordate Botrylloides leachii regenerates entire new bodies from small fragments of blood vessels in a process called whole body regeneration (WBR). During the early stages of WBR, proliferation occurs only in small, blood borne cells expressing integrin-alpha-6, pou3 and vasa. Proliferating blood cells can be ablated using Mitomycin C (MMC), and MMC treatment blocks regeneration. However, regeneration could be rescued by injection of blood borne cells from healthy individuals, and using limiting dilution approaches we found that injection of a single Integrin-alpha-6 (IA6)-positive cell is capable of rescuing whole body regeneration. The contribution of IA6+ cells to WBR was confirmed via lineage tracing: following transplantation of EdU-labeled IA6+ cells into MMC treated recipients, EdU label is detected in regenerating tissues. Our data suggest that ia6+pou3+ cells are proliferating blood borne stem cells that are responsible for whole body regeneration, and we named these cells Primordial Blasts. Primordial Blasts express notch and frizzled receptors, and inhibitors of either Notch or canonical Wnt signaling block regeneration and proliferation of Primordial Blasts.
In Search of Excellence: A Tool for Teaching Marketing Management?

An experiment is presented in which a failing corporation is described by executive MBA students as performing well on all of Peters and Watermans’ eight principles of excellence. Implications for using In Search of Excellence as a teaching tool are discussed.
Positive Allosteric Modulation of CD11b as a Novel Therapeutic Strategy Against Lung Cancer

Lung cancer is one of the leading causes of cancer-related deaths in the United States. A major hurdle for improved therapies is immune suppression mediated by the tumor and its microenvironment. The lung tumor microenvironment (TME) contains large numbers of tumor-associated macrophages (TAMs), which suppress the adaptive immune response, increase neo-vascularization of the tumor, and provide pro-tumor factors to promote tumor growth. CD11b is highly expressed on myeloid cells, including TAMs, where it forms a heterodimeric integrin receptor with CD18 (known as CD11b/CD18, Mac-1, CR3, and αMβ2), and plays an important role in recruitment and biological functions of these cells, and is a validated therapeutic target. Here, we describe our pre-clinical studies targeting CD11b in the context of lung cancer, using pharmacologic and genetic approaches that work via positive allosteric modulation of CD11b function. GB1275 is a novel small molecule modulator of CD11b that is currently in Phase 1/2 clinical development. We assess GB1275 treatment effects on tumor growth and immune infiltrates in the murine Lewis Lung Carcinoma (LLC) syngeneic tumor model. Additionally, as an orthogonal approach to determine mechanisms of action, we utilize our recently developed novel CD11b knock-in (KI) mouse that constitutively expresses CD11b containing an activating isoleucine to glycine substitution at residue 332 in the ligand binding CD11b A-domain (I332G) that acts as a positive allosteric modulator of CD11b activity. We report that pharmacologic modulation of CD11b with GB1275 significantly reduces LLC tumor growth. CD11b KI mice similarly show significant reduction in both the size and rate of LLC tumor growth, as compared to WT mice, mimicking our observed treatment effects with GB1275. Tumor profiling revealed a significant reduction in TAM infiltration in GB1275-treated and in CD11b KI mice, increase in the ratio of M1/M2-like TAMs, and concomitant increase in cytotoxic T cells. The profiling also showed a significant decrease in CCL2 levels and a concomitant reduction in Ly6Chi monocytes in circulation in both groups. These findings suggest that positive allosteric modulation of CD11b reduces TAM density and reprograms them to enhance the adaptive immune response and is a novel therapeutic strategy against lung cancer.
Coupled Flight Dynamics and Thermoelasticity Model of Maneuvering Aircraft

The stress and strain tensors in maneuvering aircraft are affected not only by the aerodynamic and propulsive forces but also by the body translational and angular velocities and high rate temperat...
Causal Inference for Nonlinear Outcome Models with Possibly Invalid Instrumental Variables

Instrumental variable methods are widely used for inferring the causal effect of an exposure on an outcome when the observed relationship is potentially affected by unmeasured confounders. Existing instrumental variable methods for nonlinear outcome models require stringent identifiability conditions. We develop a robust causal inference framework for nonlinear outcome models, which relaxes the conventional identifiability conditions. We adopt a flexible semi-parametric potential outcome model and propose new identifiability conditions for identifying the model parameters and causal effects. We devise a novel three-step inference procedure for the conditional average treatment effect and establish the asymptotic normality of the proposed point estimator. We construct confidence intervals for the causal effect by the bootstrap method. The proposed method is demonstrated in a large set of simulation studies and is applied to study the causal effects of lipid levels on whether the glucose level is normal or high over a mice dataset.
Continuous quasiperiodic Schrödinger operators with Gordon type potentials

Let us concern the quasi-periodic Schrodinger operator in the continuous case (Hy)(x) = −y′′(x) + V(x, ωx)y(x), where V:(R/Z)2→R is piecewisely γ-Holder continuous with respect to the second variable. Let L(E) be the Lyapunov exponent of Hy = Ey. Define β(ω) as β(ω)=lim supk→∞−ln||kω||k. We prove that H admits no eigenvalue in regime {E∈R:L(E)<γβ(ω)}.
PPAD Activity Promotes Outer Membrane Vesicle Biogenesis and Surface Translocation by Porphyromonas gingivalis.

ABSTRACT Many bacteria switch between a sessile and a motile mode in response to environmental and host-related signals. Porphyromonas gingivalis, an oral anaerobe implicated in the etiology of chronic periodontal disease, has long been described as a nonmotile bacterium. And yet, recent studies have shown that under certain conditions, P. gingivalis is capable of surface translocation. Considering these findings, this work aimed to increase our understanding of how P. gingivalis transitions between sessile growth and surface migration. Here, we show that the peptidylarginine deiminase secreted by P. gingivalis (PPAD), an enzyme previously shown to be upregulated during surface translocation and to constrain biofilm formation, promotes surface translocation. In the absence of PPAD, the production of outer membrane vesicles (OMVs) was drastically reduced. In turn, there was a reduction in gingipain-mediated proteolysis and a reduced zone of hydration around the site of inoculation. Transcriptome sequencing (RNA-Seq) and metabolomics analyses also showed that these changes corresponded to a shift in arginine metabolism. Overall, this report provides new evidence for the functional relevance of PPAD and proteases, as well as the importance of PPAD activity in OMV biogenesis and release. Our findings support the model that citrullination is a critical mechanism during lifestyle transition between surface-attached growth and surface translocation by modulating OMV-mediated proteolysis and arginine metabolism. IMPORTANCE Gram-negative bacteria produce nanosized OMVs that are actively released into their surroundings. The oral anaerobe P. gingivalis is prolific in OMV production, and many of the proteins packaged in these vesicles are proteolytic or protein-modifying enzymes. This includes key virulence determinants, such as the gingipains and PPAD (a unique peptidylarginine deiminase). Here, we show that PPAD activity (citrullination) is involved in OMV biogenesis. The study revealed an unusual mechanism that allows this bacterium to transform its surroundings. Since OMVs are detected in circulation and in systemic tissues, our study results also support the notion that PPAD activity may be a key factor in the correlation between periodontitis and systemic diseases, further supporting the idea of PPAD as an important therapeutic target.
Neoadjuvant endocrine therapy use in early stage breast cancer during the covid-19 pandemic.

Physician treatment preferences for early stage, estrogen positive breast cancer (ER + BC) patients were evaluated during the initial surge of the COVID-19 pandemic in the US when neoadjuvant endocrine therapy (NET) was recommended to allow safe deferral of surgery. A validated electronic survey was administered May–June, 2020 to US medical oncologists (MO), radiation oncologists (RO), and surgeons (SO) involved in clinical trials organizations. Questions on NET use included practice patterns for locoregional management following NET. 114 Physicians from 29 states completed the survey—42 (37%) MO, 14 (12%) RO, and 58 (51%) SO. Before COVID-19, most used NET ‘rarely’ (49/107, 46%) or ‘sometimes’ (36, 33%) for ER + BC. 46% would delay surgery 2 months without NET. The preferred NET regimen was tamoxifen for premenopausal and aromatase inhibitor for postmenopausal women. 53% planned short term NET until surgery could proceed. Most recommended omitting axillary lymph node dissection (ALND) for one micrometastatic node after 1, 2, or 3 months of NET (1 month, N = 56/93, 60%; 2 months, N = 54/92, 59%; 3 months, N = 48/90, 53%). With longer duration of NET, omission of ALND decreased, regardless of years in practice, percent of practice in BC, practice type, participation in multidisciplinary tumor board, or number of regional COVID-19 cases. More physicians preferred NET for ER + BC during the pandemic, compared with pre-pandemic times. As the duration of NET extended, more providers favored ALND in low volume metastatic axillary disease. The Covid-19 pandemic affected practice of ER + BC; it remains to be seen how this may impact outcomes.
Collateral Damage: An Analysis of the Achievements and Unintended Consequences of Batterer Intervention Programs and Discourse

This paper reviews and critiques two prevailing program models for batterer intervention in order to highlight both their valuable achievements and attendant costs and consequences. We analyze these batterer intervention program models at 3 levels. First, we describe the historical development and basic program components of the intervention models. Second, we trace differences in the models to their grounding in different psychological assumptions and theories about behavior change, masculinity, and violence. Third, differences between the models are mapped onto contrasting approaches to the regulation of human deviance in the criminal justice and mental health systems. Based on this analysis, we conclude that further attention to structural and contextual factors, such as class, race, economic stress, and substance abuse in explanations of domestic violence is needed, together with alternative approaches to collaboration between victim advocates and batterer intervention providers.
High-performance chiral displacement chromatographic separations in the normal-phase mode

Abstract A normal-phase displacement chromatographic method has been developed for the preparative-scale separation of the enantiomers of 1,2-O-dihexadecyl- rac -glycerol-3-O-(3,5-dinitrophenyl)carbamate using the Pirkle-type covalently bonded naphthylalanine silica chiral stationary phase. The separation selectivity of the system has been maximized by varying the tetrahydrofuran concentration and the temperature of the tetrahydrofuran—hexane eluent within the range constrained by the solubility of the sample and the displacer. The 3,5-dinitrobenzoyl ester of n -heptanol, which is more retained under the selected separation conditions than any of the enantiomers of the glycerol ether derivative, was selected and used as displacer in a preparative displacement chromatographic separation of a 20-mg sample of the glycerol ether derivative. For comparison purposes, an analogous overloaded elution mode separation was also completed under identical separation conditions. A large number of product fractions were collected during both the displacement chromatographic run and the corresponding overloaded elution mode run; these were analyzed for enantiomeric purity such that the percent recoveries and the production rates for both separation methods could be calculated.
CRI: symbolic debugger for MCAPI applications

We present a trace-driven SMT-based symbolic debugging tool for MCAPI (Multicore Association Communication API) applications. MCAPI is a newly proposed standard that provides an API for connectionless and connection-oriented communication in multicore applications. Our tool obtains a trace by executing an instrumented MCAPI. The collected trace is then encoded into an SMT formula such that its satisfiability indicates the existence of a reachable error state such as an assertion failure.
High-efficiency transformation of Pichia stipitis based on its URA3 gene and a homologous autonomous replication sequence, ARS2.

Abstract This paper describes the first high-efficiency transformation system for the xylose-fermenting yeast Pichia stipitis. The system includes integrating and autonomously replicating plasmids based on the gene for orotidine-5'-phosphate decarboxylase (URA3) and an autonomous replicating sequence (ARS) element (ARS2) isolated from P. stipitis CBS 6054. Ura- auxotrophs were obtained by selecting for resistance to 5-fluoroorotic acid and were identified as ura3 mutants by transformation with P. stipitis URA3. P. stipitis URA3 was cloned by its homology to Saccharomyces cerevisiae URA3, with which it is 69% identical in the coding region. P. stipitis ARS elements were cloned functionally through plasmid rescue. These sequences confer autonomous replication when cloned into vectors bearing the P. stipitis URA3 gene. P. stipitis ARS2 has features similar to those of the consensus ARS of S. cerevisiae and other ARS elements. Circular plasmids bearing the P. stipitis URA3 gene with various amounts of flanking sequences produced 600 to 8,600 Ura+ transformants per micrograms of DNA by electroporation. Most transformants obtained with circular vectors arose without integration of vector sequences. One vector yielded 5,200 to 12,500 Ura+ transformants per micrograms of DNA after it was linearized at various restriction enzyme sites within the P. stipitis URA3 insert. Transformants arising from linearized vectors produced stable integrants, and integration events were site specific for the genomic ura3 in 20% of the transformants examined. Plasmids bearing the P. stipitis URA3 gene and ARS2 element produced more than 30,000 transformants per micrograms of plasmid DNA. Autonomously replicating plasmids were stable for at least 50 generations in selection medium and were present at an average of 10 copies per nucleus.
Supplemental Appendix for 'Non-Bayesian Updating: A Theoretical Framework'

This appendix applies the model in Non-Bayesian Updating: A Theoretical Frame-Work to address the question: What do non-Bayesian updaters learn?
Connecting the candidates: : consultant networks and the diffusion of campaign strategy in American congressional elections

Modern American political campaigns are typically conceptualized as �candidate-centered� and treated as conditionally independent in quantitative analyses. In reality, however, these campaigns are linked by professional consulting firms, which are important agents of campaign strategy diffusion within the extended party networks of the contemporary era. To test our hypothesis that consultants disseminate campaign strategies among their clients, we analyze new data on U.S. House elections derived from Federal Election Commission records. Using spatial autoregressive models, we find that candidates who share consultants are more likely to use similar campaign strategies than we would otherwise expect, conditional on numerous explanatory variables. These results, which largely withstand an extensive series of robustness and falsification tests, suggest that consultants play a key role in diffusing strategies among congressional campaigns.
Containerless laser-induced flourescence study of vaporization and optical properties for sapphire and alumina

Evaporation of aluminum oxide was studied from 1800 to 2327 K by laser-induced flourescence (LIF) detection of Al atom vapor over sapphire and alumina spheres that were levitated in an argon gas jet and heated with a continuous wave CO2 laser. Optical properties were determined from apparent specimen temperatures measured with an optical pyrometer and true temperatures deduced from the LIF intensity versus temperature measurements using the known temperature dependence of the Al atom vapor concentration in equilibrium with Al2O3. The effects of impurities and dissolved oxygen on the high-temperature optical properties of aluminum oxide were discussed.
Theory of Collective Intelligence

In this chapter an analysis of the behavior of an arbitrary (perhaps massive) collective of computational processes in terms of an associated “world” utility function is presented We concentrate on the situation where each process in the collective can be viewed as though it were striving to maximize its own private utility function. For such situations the central design issue is how to initialize and update the collective's structure, in particular the private utility functions, so as to induce the overall collective to behave in a way that has large values of the world utility. Traditional “team game” approaches to this problem simply set each private utility function equal to the world utility function. The “collective intelligence” (COIN) framework is a semiformal set of heuristics that have recently been used to construct private utility functions that in many experiments have resulted in world utility values up to orders of magnitude superior to that ensuing from use of the team game utility. In this chapter we introduce a formal mathematics for analyzing and designing collectives. We also use this mathematics to suggest new private utilities that should outperform the COIN heuristics in certain kinds of domains. In accompanying work we use that mathematics to explain previous experimental results concerning the superiority of COIN heuristics. In that accompanying work we also use the mathematics to make numerical predictions, some of which we then test. In this way these two papers establish the study of collectives as a proper science, involving theory, explanation of old experiments, prediction concerning new experiments, and engineering insights.