cssi/SciSciGPT-SciSciNet huggingface dataset:
Benjamin Franklin Unmasked: On the Unity of His Moral, Religious, and Political Thought

Benjamin Franklin Unmasked: On the Unity of His Moral, Religious, and Political Thought. By Jerry Weinberger. Lawrence: University Press of Kansas, 2005. 352p. $34.95. There are two important issues raised by Jerry Weinberger's intricate, probing, and insightful book: whether his portrayal of Franklin is accurate and whether Franklin's understanding of existence is correct. Weinberger's thesis is controversial: From age 15, when Franklin read his father's books on theology until his death at 84, he never wavered in his conviction that God did not exist, religion was superstition, and moral principles were merely longings of the human psyche, unfulfilled in this life or the next. But if he took such a skeptical view of righteousness, why did he pen his Autobiography and promote such homespun virtues as temperance, frugality, justice, chastity, and humility?
A simulation based heuristic approach to a resource investment problem (RIP)

A simulation-based heuristic approach is presented for a resource investment problem (RIP). This version of the RIP considers the trade-off between the number of resources, project makespan and resource utilization. A "win-win" goal is a reduction in project makespan while improving resource utilization. The RIP heuristic is presented as an executive for RCAN, a simulation tool that produces solutions to the multi-mode resource constrained project scheduling problem (RCPSP). The RIP heuristic uses feedback from RCAN to iteratively modify a set of renewable resources. The heuristic is shown to be effective on real-world, large-scale depot maintenance projects. In addition, the simulation tool uses a priority rule approach to schedule project tasks for the RCPSP problem. Therefore the RCPSP priority rule has a major effect on the RIP heuristic. An analysis is presented showing how various priority rules impact the RIP heuristic's ability to reduce the makespan while maintaining or increasing resource utilization.
SITES OF LIPOPROTEIN LIPASE ACTIVITY IN ADIPOSE TISSUE PERFUSED WITH CHYLOMICRONS Electron Microscope Cytochemical Study

Lipoprotein lipase activity was studied in rat parametrial adipose tissue perfused with chylomicrons and in gelatin blocks containing postheparin plasma and chylomicrons. The tissues and blocks were fixed in glutaraldehyde and incubated in 0.035 M CaCl2-0.1 M Tris medium (pH 8.3) at 38°C. The doubly labeled chylomicron triglycerides (glycerol-3H and palmitate-14C) in the tissues and blocks were hydrolyzed during incubation to free fatty acids (FFA) and the FFA remained in the specimens; hydrolysis was inhibited by 0.004 M diethyl paranitrophenyl phosphate (E-600). Incubated blocks and tissue were treated with 0.05 M Pb(NO3)2, postfixed in OsO4, dehydrated with acetone, embedded in Epon, and examined by electron microscopy. The incubated blocks contained electronlucent areas and granular and laminar precipitates at sites of hydrolysis. Similar precipitates were found in incubated tissue, within vacuoles and microvesicles of capillary endothelium, and in the subendothelial space (between the endothelium and pericytes), but not in the capillary lumen or in or near fat cells. The cytochemical reaction was greatly reduced, in blocks and tissues incubated with E-600. It is concluded that plasma glycerides are hydrolyzed by lipoprotein lipase in capillary endothelial cells and in the subendothelial space of adipose tissue and that glycerides across the endothelial cells within a membrane-bounded system.
Interleukin-12 as an Adjuvant Promotes Immunoglobulin G and Type 1 Cytokine Recall Responses to Major Surface Protein 2 of the Ehrlichial Pathogen Anaplasma marginale

Anaplasma marginale is a tick-transmitted pathogen of cattle closely related to the human ehrlichiae, Ehrlichia chaffeensis and the agent of human granulocytic ehrlichiosis (HGE). These pathogens have in common a structurally conserved outer membrane protein (OMP) designated the major surface protein 2 (MSP-2) in A. marginale and HGE and OMP-1 in E. chaffeensis. Protective immunity against ehrlichial pathogens is believed to require induction of gamma interferon (IFN-γ) and opsonizing immunoglobulin (Ig) subclasses directed against OMP epitopes that, in concert, activate macrophages for phagocytosis and killing. Because interleukin-12 (IL-12) acts as an adjuvant for protein immunization to induce IFN-γ and protective immunity against intracellular pathogens, we hypothesized that as an adjuvant with MSP-2, IL-12 would augment type 1 recall responses to A. marginale. IL-12 was coadsorbed with MSP-2 to alum and shown to significantly enhance IFN-γ production by lymph node cells (LNC) and LNC-derived CD4+ T-cell lines from immunized calves following recall stimulation with A. marginale. LNC proliferation and IL-2 production were also enhanced in IL-12-treated calves. Elevated recall proliferative responses by peripheral blood mononuclear cells were still evident 9 months after immunization. Serum IgG levels were consistently increased in IL-12 immunized calves, predominantly due to higher IgG1 responses. The results support the use of IL-12 coadsorbed with OMP of ehrlichial pathogens in alum to amplify both antibody and type-1 cytokine responses important for protective immunity.
Neutrophil-derived oxygen metabolites stimulate thromboxane release, pulmonary artery pressure increases, and weight gains in isolated perfused rat lungs.

Addition of normal human neutrophils and the neutrophil stimulant, phorbol myristate acetate (PMA), caused perfusate thromboxane (TXB2) elevations, pulmonary artery pressure (PAP) increases, and lung weight gains in isolated perfused rat lungs. Addition of PMA and neutrophils that do not generate O2 metabolites from a patient with chronic granulomatous disease (CGD) — or addition of PMA and normal neutrophils with the purported O2 metabolite scavenger, dimethylthiourea (DMTU) — also caused PAP increases but did not cause perfusate TXB2 elevations or lung weight gains in isolated lungs. In parallel, mixtures of normal neutrophils and PMA made hydrogen peroxide (H2O2) concentrations in vitro which exceeded concentrations found in mixtures containing PMA and CGD neutrophils or mixtures containing PMA, normal neutrophils, and DMTU. TXB2 levels were not detectable in mixtures containing normal neutrophils and PMA in vitro. Our results indicate that neutrophil-derived O2 metabolites contribute to perfusate TXB2...
Long-term Outcome of Once Daily Nasal Irrigation for the Treatment of Pediatric Chronic Rhinosinusitis

Objectives/Hypothesis Chronic rhinosinusitis(CRS) results in significant morbidity and health care expenditure. Safety and efficacy of nasal irrigation use in the treatment of pediatric CRS have been demonstrated, but long-term outcomes are unknown. We reviewed characteristics and treatment outcomes after 6 weeks of once daily nasal irrigation in pediatric CRS based on computed tomography (CT) scans, and summarized parental reports of subsequent use of nasal irrigation for recurring symptoms Study Design Retrospective cohort study and cross-sectional survey. Methods Review and survey of 144 pediatric CRS patients diagnosed between July 2003 and January 2012. Results One hundred four patients were reviewed. Mean age was 8.0 years, and 65.4% were male. Presenting symptoms included congestion (95.2%), cough (79.8%), rhinorrhea (60.6%), headache (48.1%), and fatigue (40.4%). Comorbidities included positive allergy test (50%), asthma (57.3%), and gastroesophageal reflux disease (28.2%). After 6 weeks, 57.7% of patients reported complete resolution of symptoms. Reductions in Lund–Mackay CT scores were 4.14 and 4.38 on the left and right sides, respectively (P < .001). Of the 54 parents who completed the prospective surveys, 53.7% reported using irrigation again in the past 12 months (median = 1, interquartile range = 3). Only nine patients underwent functional endoscopic sinus surgery (FESS) after the initial 6 weeks. Patients requiring FESS were, on average, 3.6 years older than those who did not receive FESS (P = 0.0005). Median length of follow-up was 48 months (range = 20–113). There were no significant differences in age, Lund–MacKay score changes, and symptom resolution proportions between those who completed the survey and those who did not. Conclusions Nasal irrigation is effective as a first-line treatment for pediatric CRS and subsequent nasal symptoms, and reduces the need for FESS and CT imaging. Level of Evidence 2b. Laryngoscope, 124:1000–1007, 2014
A Look to the Future of JAMS: Three Years Out, Thirty Years Out...:

I want to take this opportunity to thank all of those in the academy who have encouraged me and mentored me throughout my career.
Specifying and Analyzing Workflows for Automated Identification and Data Capture

Humans use computers to carry out tasks that neither is able to do easily alone: humans provide eyes, hands, and judgment while computers provide computation, networking, and storage. This symbiosis is especially evident in workflows where humans identify objects using bar codes or RFID tags and capture data about them for the computer. This Automated Identification and Data Capture (AIDC) is increasingly important in areas such as inventory systems and health care. Humans involved in AIDC follow simple rules and rely on the computer to catch mistakes; in complex situations this reliance can lead to mismatches between human workflows and system programming. In this paper we explore the design, implementation and formal modeling of AIDC for vital signs measurements in hospitals. To this end we describe the design of a wireless mobile medical mediator device that mediates between identifications, measurements, and updates of Electronic Health Records (EHRs). We implement this as a system Med2 that uses PDAs equipped with Bluetooth, WiFi, and RFID wireless capabilities. Using Communicating Sequential Processes (CSP) we jointly specify workflow and computer system operations and provide a formal analysis of the protections the system provides for user errors.
Meta-analysis of foraging and predation risk trade-offs in terrestrial systems

Although there is ample evidence for the generality of foraging and predation trade-offs in aquatic systems, its application to terrestrial systems is less comprehensive. In this review, meta-analysis was used to analyze experiments on giving-up-densities in terrestrial systems to evaluate the overall magnitude of predation risk on foraging behavior and experimental conditions mediating its effect. Results indicate a large and significant decrease in foraging effort as a consequence of increased predation risk. Whether experiments were conducted under natural or artificial conditions produced no change in the overall effect predation had on foraging. Odor and live predators as a correlate of predation risk had weaker and nonsignificant effects compared to habitat characteristics. The meta-analysis suggests that the effect of predation risk on foraging behavior in terrestrial systems is strongly dependent on the type of predation risk being utilized.
Prostate-specific antigen levels at 6 months after I-125 prostate brachytherapy for localized prostate cancer predicts biochemical relapse free survival

tumor definition and to confirm the adequacy of the brachytherapy catheter placements. These images were projected within the MR room to allow the operator more timely feedback of catheter position. HDR brachytherapy inverse treatment planning (IPSA-PLATO, Nucletron Inc.) was performed using an axial T2-weighted FSE image corrected for spatial distortion obtained at the end of the procedure. The PTV consisted of the prostate gland as well as any visualized extracapsular extension of disease. Dose constraints were applied to the urethra and rectum. Dose-volume histograms were generated for the PTV, urethra, rectum, and path of the NVB on contrast-enhanced MRI. Catheter encroachment on the path of the NVB was documented.
Improving the Quality of Life of African Americans Receiving Palliative Care

The purpose of this pilot study was to examine the effects of personal characteristics on quality of life (QOL) among African Americans receiving palliative care. Although an important goal of palliative care is to improve the client’s QOL, no studies were found examining the QOL of African Americans receiving palliative care. The study sample included African Americans receiving palliative care in inpatient settings or through enrollment in a hospice program. Data were collected using a structured interview guided by five questionnaires to measure QOL, physical performance, spirituality, social support, and family support/satisfaction. Data were analyzed using descriptive statistics, Pearson r correlation coefficients, and multiple regression analysis. The total sample (N = 16) was predominately single, female, and 50 to 59 years old. There was a significant relationship between QOL and religious and spiritual coping and between QOL and social support. Participant recruitment was a significant issue in t...
Preserving Different Pasts: The American National Monuments, by Hal Rothman, University of Illinois Press, Urbana and Chicago, 1989

The national monuments that exist today within our national parks are often perceived as icons of a romantic or even a mythic past Seldom, however, do very personal crusades that were waged to preserve these natural and culture resources intrude upon the public consciousness? Even less frequently are the preservation efforts of the past valued for what they tell us about American culture and how the values of that culture have changed over time. But the archaeological, historic, and natural history sites that comprise our national monuments have layered meanings. Quite apart from their intrinsic value as heritage sites, our effort to preserve perceptions of the past. It is somewhat surprising, therefore, that scholarship on the national monuments proper remained an historiographical backwater. This situation has been rectified, however, with the publication of Hal Rothman's Preserving Different Pasts: The American National Monuments. These national treasurers have at last found an able historian to tell their story.
Determination of left ventricular size and shape

Significant advances have occurred over the past 15 years in the ability to measure ventricular dimensions. Angiocardiography still remains the most reliable method for overall determination of chamber size and shape and serves as a standard for calibration or comparison for newer methods. Improvements in the use of radiographic methods over the next few years are anticipated with more extensive use of multiplane studies associated with repeated injections of improved contrast materials that produce fewer physiological effects or with substances that adhere to the endocardial surfaces. It is also anticipated that existing methods for automatically obtaining dimensional information from X rays will be continued and improved.
Endogeneity Issues in Governmental Research

We examine the issue of endogeneity in government accounting research. Estimation bias and inconsistency can arise when single equation estimation includes an explanatory endogenous variable. We discuss the modeling and estimation issues involving endogenous explanatory variables and we illustrate alternative specification tests for explanatory endogeneity when a system of equations includes a qualitative dependent variable, a common feature in government research. Our specification testing confirms the presence of endogeneity bias in a model used to estimate auditor reputation and audit fees in the government sector. We conclude the paper by offering suggestions for research where examining or considering explanatory endogeneity using simultaneous equations may be appropriate in other government settings.
Suppression of diamondback moth (Lepidoptera: Plutellidae) oviposition by overhead irrigation

Intermittent overhead irrigation caused 7-fold reduction in diamondback moth, Plutella xylostella (L.), oviposition on watercress in greenhouse no-choice tests. Irrigation during the night reduced oviposition as effectively as 24 h of irrigation, but daytime irrigation did not affect oviposition. Eggs were laid mainly on lower leaf surfaces, with an intermediate number on stems and petioles, and fewest on upper leaf surfaces. Oviposition in the greenhouse occurred primarily at night with the peak rate during 2000–2300 hours. Darkness during the day stimulated oviposition. Suppression of oviposition may contribute to previously reported control of the diamondback moth by overhead irrigation.
Monitoring results of food hygiene quality in circulation link of Shiyan City in 2012

[Objective]To understand food hygiene quality status,and provide a scientific basis for strengthening the food quality and safety,preventing and controlling the foodborne illness in Shiyan City.[Methods]The spot cooked meat products,cakes and biscuits were randomly selected from bazaars,supermarkets and street delis in ShiyanCity.The results were analyzed.[Results]A total of 205 samples were collected,69(33.66%) were qualified,116(56.59%) were qualified for total bacterial count,98(47.80%) were qualified for coliform bacteria.The qualified rate of nitrite in cooked meat and meat products was 99.28%,and it was 100% in acid number and peroxide value of cakes.No pathogen was detected in food.There was significant difference between different management premises such as street delis and bazaars(χ2 = 10.05,P 0.05).[Conclusion]The microbial contamination of cooked meat and meat products is more serious,especially the health products in the country trade market.There is a risk of food poisoning hazards in cooked meat and meat products which should attract more attention from the health supervision departments.
The digital universe

In this era of YouTube and Google, information is key. Ever since operational digital computers were first constructed in the mid 20th century, their computational power has grown by leaps and bounds, to the point where the information-processing power of all the computers on Earth is becoming comparable, by some measures, to the information-processing power of the entire human population.
Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 04: On 3D Fabrication of Phantoms and Experimental Verification of Patient Dose Computation Algorithms

Purpose: Transport based dose calculation algorithm Acuros XB (AXB) has been shown to accurately account for heterogeneities mostly through comparisons with Monte Carlo simulations. This study aims at providing additional experimental verification for AXB for flattened and unflattened clinical energies in low density phantoms of the same material. Materials and Methods: Polystyrene slabs were created using a bench-top 3D printer. Six slabs were printed at varying densities from 0.23 g/cm3 to 0.68 g/cm3, corresponding to different density humanoid tissues. The slabs were used to form different single and multilayer geometries. Dose was calculated with AXB 11.0.31 for 6MV, 15MV flattened and 6FFF (flattening filter free) energies for field sizes of 2×2 cm2 and 5×5 cm2. The phantoms containing radiochromic EBT3 films were irradiated. Absolute dose profiles and 2D gamma analyses were performed for 96 dose planes. Results: For all single slab, multislab configurations and energies, absolute dose differences between the AXB calculation and film measurements remained <3% for both fields, with slightly poor disagreement in penumbra. The gamma index at 2% / 2mm averaged 98% in all combinations of fields, phantoms and photon energies. Conclusions: The transport based dose algorithm AXB is in good agreement with the experimental measurements for small field sizes using 6MV, 6FFF and 15MV beams adjacent to low density heterogeneous media. This work provides sufficient experimental ground to support the use of AXB for heterogeneous dose calculation purposes.
Equal work for unequal pay: the gender reimbursement gap for healthcare providers in the United States

Introduction Gender disparities in income continue to exist, and many studies have quantified the gap between male and female workers. These studies paint an incomplete picture of gender income disparity because of their reliance on notoriously inaccurate or incomplete surveys. We quantified gender reimbursement disparity between female and male healthcare providers using objective, non-self-reported data and attempted to adjust the disparity against commonly held beliefs as to why it exists. Methods We analysed over three million publicly available Medicare reimbursement claims for calendar year 2012 and compared the reimbursements received by male and female healthcare providers in 13 medical specialties. We adjusted these reimbursement totals against how hard providers worked, how productive each provider was, and their level of experience. We calculated a reimbursement differential between male and female providers by primary medical specialty. Results The overall adjusted reimbursement differential against female providers was −US$18 677.23 (95% CI −US$19 301.94 to −US$18 052.53). All 13 specialties displayed a negative reimbursement differential against female providers. Only two specialties had reimbursement differentials that were not statistically significant. Conclusions After adjustment for how hard a physician works, his/her years of experience and his/her productivity, female healthcare providers are still reimbursed less than male providers. Using objective, non-survey data will provide a more accurate understanding of this reimbursement inequity and perhaps lead the medical profession (as a whole) towards a solution that can reverse this decades-old injustice.
Incorporating Fringe Benefits in Loss Calculations

This chapter provides an overview of how a loss of employer-provided fringe benefits is valued. Employers offer benefits because of scale economies and tax advantages, and to attract and keep employees. The major fringes, health insurance and retirement plans are valued differently depending on the type of information available. For youngsters with no work experience, their value is based on statistics showing the average employer cost of benefits, or the average individual replacement cost of benefits. For employees, it is information on the costs incurred by the worker’s employer. The perspective in personal injury and wrongful termination cases differs from that in death cases where the focus shifts from the value the worker places on benefits to the value that dependents of the deceased worker place on them. The final section of the paper discusses court cases involving fringes.
Efficacy of two lipid-lowering treatments on quantitative coronary angiographic endpoints.

This study contrasts the sensitivity of four quantitative coronary angiography (QCA) measures (percent diameter stenosis [%S], minimum lumen diameter, average segment diameter, and percent involvement) in detecting 2-year treatment effects of two lipid-lowering therapies and reports on the longitudinal pattern after 4 years of treatment on the primary QCA trial endpoint (%S) for all, mild/moderate (<50%S), and severe lesions (≥50%S). Patient cohorts were followed up from two randomized, placebo-controlled clinical trials of lipid-lowering therapies—colestipol/niacin in the Cholesterol Lowering Atherosclerosis Study (CLAS) and lovastatin in the Monitored Atherosclerosis Regression Study (MARS). Identical QCA methodology was used. In CLAS, the largest 2-year treatment effect size (=0.60) was noted for %S. In MARS, equivalent 2-year effect sizes (=0.15) were noted for three QCA measures. The largest 2-year effect size in %S was found in CLAS for mild/moderate lesions (=0.55) and in MARS for severe lesions (=0.31). Treatment in CLAS led to regression of disease in the first 2 years; treatment in MARS slowed progression of disease in the first 2 years and led to regression of disease after 4 years. Colestipol/niacin reduced progression of mild/moderate and severe lesions over the first 2 years of therapy; lovastatin reduced the progression of severe lesions over the last 2 years of therapy. We conclude that reducing the progression of atherosclerosis is not a simple proposition; maximal therapy for reducing and stabilizing atherosclerosis most likely will result from the selection of agents targeted at specific lesions.
Assessment of Vertical Mesh Refinement in Concurrently Nested Large-Eddy Simulations Using the Weather Research and Forecasting Model

AbstractTo facilitate multiscale simulation using the Weather Research and Forecasting Model, vertical mesh refinement for one-way concurrent nested simulation was recently introduced. Grid refinement in the vertical dimension removes the requirement of different grid aspect ratios on the bounding versus the nested domain, such that results from refinement are in the horizontal directions only, and thereby can also reduce numerical errors on the bounding domain arising from large aspect ratios in the presence of complex terrain. Herein, the impacts of vertical grid refinement on the evolving downstream flow in nested large-eddy simulations are evaluated in relation to other model configuration choices, including turbulence subfilter-scale (SFS) stress models, mesh configuration, and alternative methods for calculating several near-surface flow parameters. Although vertical nesting requires coarsening of the vertical grid on the bounding domain, leading to a smaller range of resolved turbulence scales in t...
Whisker growth on Sn thin film accelerated under gamma-ray induced electric field

We report on the growth of tin metal whiskers significantly accelerated under non-destructive gamma-ray irradiation. Sn thin film, evaporated on glass substrate, was subjected to a total of 60 h of irradiation. The irradiated samples demonstrated enhanced whisker development, in both densities and lengths, resulting in an acceleration factor of ~50. We attribute the observed enhancement to gamma-ray induced electrostatic fields, affecting whisker kinetics. These fields are due to the substrate charging under gamma-rays. We propose that gamma-ray irradiation can be a much needed tool for accelerated testing of whisker propensity.
The Secret Life of Exosomes: What Bees Can Teach Us About Next-Generation Therapeutics.

Abstract Mechanistic exploration has pinpointed nanosized extracellular vesicles, known as exosomes, as key mediators of the benefits of cell therapy. Exosomes appear to recapitulate the benefits of cells and more. As durable azoic entities, exosomes have numerous practical and conceptual advantages over cells. Will cells end up just being used to manufacture exosomes, or will they find lasting value as primary therapeutic agents? Here, a venerable natural process—the generation of honey—serves as an instructive parable. Flowers make nectar, which bees collect and process into honey. Cells make conditioned medium, which laboratory workers collect and process into exosomes. Unlike flowers, honey is durable, compact, and nutritious, but these facts do not negate the value of flowers themselves. The parallels suggest new ways of thinking about next-generation therapeutics.
Orbital implant exposure after Acanthamoeba panophthalmitis.

Abstract Purpose Acanthamoeba is a protozoa that can lead to severe ocular disease and sequelae. Although intraocular Acanthamoeba infection is rare, the following case demonstrates an unusual presentation of recurrent Acanthamoeba infection in a 30 year old contact lens wearing male. Observations After presenting with recurrent Acanthamoeba keratitis and undergoing various treatments, the patient developed nodular scleritis, which evolved into panophthalmitis, and ultimately, required enucleation. Eight months post-operatively, the patient developed orbital implant exposure secondary to persistent Acanthamoeba infection and underwent removal of the implant and aggressive, systemic treatment involving a multispecialty care team. He then underwent placement of a dermis fat graft and had no signs of persistent infection at the time of last follow-up, which was 24 months after placement of the dermis fat graft. Conclusions and Importance: To the authors' knowledge, this is the first known case of Acanthamoeba infection causing orbital implant exposure. Persistent infection should be considered in Acanthamoeba patients who have undergone enucleation and have orbital implant exposure. Better knowledge regarding the pathogenesis and extracorneal complications of this challenging disease may improve patient care and outcomes.
The price of civil society

Most work in algorithmic game theory assumes that players ignore costs incurred by their fellow players. In this paper, we consider superimposing a social network over a game, where players are concerned with minimizing not only their own costs, but also the costs of their neighbors in the network. We aim to understand how properties of the underlying game are affected by this alteration to the standard model. The new social game has its own equilibria, and the price of civil society denotes the ratio of the social cost of the worst such equilibrium relative to the worst Nash equilibrium under standard selfish play. We initiate the study of the price of civil society in the context of a simple class of games. Counterintuitively, we show that when players become less selfish (optimizing over both themselves and their friends), the resulting outcomes may be worse than they would have been in the base game. We give tight bounds on this phenomenon in a simple class of load-balancing games, over arbitrary social networks, and present some extensions.
Leveraging chromatography based physicochemical properties for efficient drug design

Applications of chromatography derived lipophilicity, polarity, and 3D concepts such as conformational states, exposed polarity and intramolecular hydrogen bonds (IMHB), are discussed along with recently developed methods for incorporating these concepts into drug design strategies. In addition, the drug design process is described with examples and practices used at Pfizer, as well as experimental and computed parameters used for parallel optimization of properties leading to drug candidate nominations.
Loss of MST/Hippo Signaling in a Genetically Engineered Mouse Model of Fusion-Positive Rhabdomyosarcoma Accelerates Tumorigenesis.

A hallmark of fusion-positive alveolar rhabdomyosarcoma (aRMS) is the presence of a chromosomal translocation encoding the PAX3-FOXO1 fusion oncogene. Primary cell-based modeling experiments have shown that PAX3-FOXO1 is necessary, but not sufficient for aRMS tumorigenesis, indicating additional molecular alterations are required to initiate and sustain tumor growth. Previously, we showed that PAX3-FOXO1-positive aRMS is promoted by dysregulated Hippo pathway signaling, as demonstrated by increased YAP1 expression and decreased MST activity. We hypothesized that ablating MST/Hippo signaling in a genetically engineered mouse model (GEMM) of aRMS would accelerate tumorigenesis. To this end, MST1/2-floxed (Stk3F/F;Stk4F/F ) mice were crossed with a previously established aRMS GEMM driven by conditional expression of Pax3:Foxo1 from the endogenous Pax3 locus and conditional loss of Cdkn2a in Myf6 (myogenic factor 6)-expressing cells. Compared with Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ controls, Stk3F/F;Stk4F/F;Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ animals displayed accelerated tumorigenesis (P < 0.0001) and increased tumor penetrance (88% vs. 27%). GEMM tumors were histologically consistent with aRMS. GEMM tumor-derived cell lines showed increased proliferation and invasion and decreased senescence and myogenic differentiation. These data suggest that loss of MST/Hippo signaling acts with Pax3:Foxo1 expression and Cdkn2a loss to promote tumorigenesis. The rapid onset and increased penetrance of tumorigenesis in this model provide a powerful tool for interrogating aRMS biology and screening novel therapeutics.Significance: A novel mouse model sheds light on the critical role of Hippo/MST downregulation in PAX3-FOXO1-positive rhabdomyosarcoma tumorigenesis. Cancer Res; 78(19); 5513-20. ©2018 AACR.
Psychiatric and Interpersonal Correlates of Suicide Ideation in Military Sexual Trauma Survivors: The National Health and Resilience in Veterans Study.

BackgroundVeterans who experience military sexual trauma are at increased risk for experiencing suicidal ideation, suicide attempt, and suicide. Yet few studies have attempted to discern factors th...
The importance of cognitive diversity for sustaining the commons

Cognitive abilities underpin the capacity of individuals to build models of their environment and make decisions about how to govern resources. Here, we test the functional intelligences proposition that functionally diverse cognitive abilities within a group are critical to govern common pool resources. We assess the effect of two cognitive abilities, social and general intelligence, on group performance on a resource harvesting and management game involving either a negative or a positive disturbance to the resource base. Our results indicate that under improving conditions (positive disturbance) groups with higher general intelligence perform better. However, when conditions deteriorate (negative disturbance) groups with high competency in both general and social intelligence are less likely to deplete resources and harvest more. Thus, we propose that a functional diversity of cognitive abilities improves how effectively social groups govern common pool resources, especially when conditions deteriorate and groups need to re-evaluate and change their behaviors.
Use of dd-cfDNA in Multiorgan Transplantation

Purpose Gene expression profiling testing (GEP; AlloMap) and donor-derived cell free DNA (dd-cfDNA; AlloSure) each provide non-invasive means to detect possible heart allograft rejection, including acute cellular rejection (ACR). Use of dd-cfDNA in multiorgan transplantation has not previously been reported. This report describes the largest single center use of dd-cfDNA to date in this population. Methods Post heart transplant (HT) management is standardized at our center such that endomyocardial biopsy is used for rejection surveillance in the early period with crossover to GEP testing at day 56. Elevated GEP (≥34) prompts biopsy. dd-cfDNA was utilized in conjunction with biopsy or in lieu of biopsy (barrier to biopsy). A cohort of 26 HT patients underwent dd-cfDNA testing, including 3 multiorgan (same donor) and 5 retransplant patients. The dd-cfDNA (%, AlloSure) and GEP (AlloMap, score 0-40) results were correlated patient survival. Results Among 26 HT patients, there were 3 multiorgan transplant recipients (2 heart-kidney & 1 heart-lung). Mean dd-cfDNA was 0.9 ± 0.5%. Mean GEP score was 32.8 ± 4.0. dd-cfDNA usage was due to inability to biopsy (33.3%), anticoagulation (33.3%) & elevated Allomap (33.3%). Mean LVEF was 55 ± 1%. Mean day post transplant for first dd-cfDNA was 153 (IQR 119-347). There were no deaths. Of the heart-kidney recipients, mean ACR & AMR biopsy grade was 0.67 & 0, respectively. The heart-lung recipient underwent 2 lung biopsies with mean grade of 0. Conclusion In surveillance of heart allograft recipients for rejection, consideration of dd-cfDNA levels may improve patient management decisions particularly when endomyocardial biopsy may not be feasible. This is the first report of use of dd-cfDNA in multiorgan transplantation. Baseline levels of dd-cfDNA appear to be higher than that of heart-only recipients. Further study is warranted to assess the utilization of dd-cfDNA in multiorgan transplantation.
FAK and Pyk2 activity promote TNF-α and IL-1β-mediated pro-inflammatory gene expression and vascular inflammation.

Protein tyrosine kinase (PTK) activity has been implicated in pro-inflammatory gene expression following tumor necrosis factor-α (TNF-α) or interkeukin-1β (IL-1β) stimulation. However, the identity of responsible PTK(s) in cytokine signaling have not been elucidated. To evaluate which PTK is critical to promote the cytokine-induced inflammatory cell adhesion molecule (CAM) expression including VCAM-1, ICAM-1, and E-selectin in human aortic endothelial cells (HAoECs), we have tested pharmacological inhibitors of major PTKs: Src and the focal adhesion kinase (FAK) family kinases - FAK and proline-rich tyrosine kinase (Pyk2). We found that a dual inhibitor of FAK/Pyk2 (PF-271) most effectively reduced all three CAMs upon TNF-α or IL-1β stimulation compared to FAK or Src specific inhibitors (PF-228 or Dasatinib), which inhibited only VCAM-1 expression. In vitro inflammation assays showed PF-271 reduced monocyte attachment and transmigration on HAoECs. Furthermore, FAK/Pyk2 activity was not limited to CAM expression but was also required for expression of various pro-inflammatory molecules including MCP-1 and IP-10. Both TNF-α and IL-1β signaling requires FAK/Pyk2 activity to activate ERK and JNK MAPKs leading to inflammatory gene expression. Knockdown of either FAK or Pyk2 reduced TNF-α-stimulated ERK and JNK activation and CAM expression, suggesting that activation of ERK or JNK is specific through FAK and Pyk2. Finally, FAK/Pyk2 activity is required for VCAM-1 expression and macrophage recruitment to the vessel wall in a carotid ligation model in ApoE−/− mice. Our findings define critical roles of FAK/Pyk2 in mediating inflammatory cytokine signaling and implicate FAK/Pyk2 inhibitors as potential therapeutic agents to treat vascular inflammatory disease such as atherosclerosis.
ATLAS LAr calorimeter performance in LHC run 2 and electronics upgrades for next runs

Abstract Liquid argon (LAr) sampling calorimeters are employed by ATLAS for all electromagnetic calorimetry in the pseudo-rapidity region | η | 3 . 2 , and for hadronic and forward calorimetry in the region from | η | = 1 . 5 to | η | = 4 . 9 . In the LHC Run 2 about 150 fb−1 of data at a center-of-mass energy of 13 TeV have been recorded. The well calibrated and highly granular LAr Calorimeter reached its design values both in energy measurement as well as in direction resolution. Electronics developments are pursued for the trigger readout of the ATLAS LAr Calorimeter towards the Phase-I upgrade scheduled in the LHC shut-down period between December 2018 and early 2021. Trigger signals with finer spatial granularity and higher precision are needed in order to improve the identification efficiencies of electrons, photons, taus, jets and missing energy, at high background rejection rates, already at the Level-1 trigger. Following new TDAQ buffering requirements and high expected radiation doses in the pileup conditions of the high-luminosity LHC, the LAr Calorimeter electronics will be further upgraded (Phase-II) to readout the full 182,500 calorimeter cells at 40 MHz with 16 bit dynamic range. Developments of low-power preamplifiers and shapers to meet these requirements are ongoing in 130 nm CMOS. In order to digitize the analogue signals on two gains after shaping, radiation-hard, low-power 40 MHz 14-bit ADCs are developed using a SAR architecture in 65 nm CMOS. This contribution gives an overview of the detector operation, changes in the monitoring and data quality procedures, to cope with increased pileup, as well as the achieved performance. Results of ASIC developments including quality assurance and quality control (QA/QC) and radiation hardness evaluations, performances of the pre-production boards and results of the system integration tests, progress of QA/QC of final production boards are presented along with the overall system design for the Phase-I upgrade. Results of tests of the first prototypes of front-end components are presented, along with design studies on the performance of the off-detector readout system for the Phase-II upgrade.
Social franchising: A systematic review

Social franchising is starting to garner more interest among researchers and practitioners as a replication approach used to help address a growing array of societal issues in both developed countr...
Alcohol metabolism contributes to brain histone acetylation

Emerging evidence suggests that epigenetic regulation is dependent on metabolic state, and implicates specific metabolic factors in neural functions that drive behaviour1. In neurons, acetylation of histones relies on the metabolite acetyl-CoA, which is produced from acetate by chromatin-bound acetyl-CoA synthetase 2 (ACSS2)2. Notably, the breakdown of alcohol in the liver leads to a rapid increase in levels of blood acetate3, and alcohol is therefore a major source of acetate in the body. Histone acetylation in neurons may thus be under the influence of acetate that is derived from alcohol4, with potential effects on alcohol-induced gene expression in the brain, and on behaviour5. Here, using in vivo stable-isotope labelling in mice, we show that the metabolism of alcohol contributes to rapid acetylation of histones in the brain, and that this occurs in part through the direct deposition of acetyl groups that are derived from alcohol onto histones in an ACSS2-dependent manner. A similar direct deposition was observed when mice were injected with heavy-labelled acetate in vivo. In a pregnant mouse, exposure to labelled alcohol resulted in the incorporation of labelled acetyl groups into gestating fetal brains. In isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory, which were sensitive to ACSS2 inhibition. We show that alcohol-related associative learning requires ACSS2 in vivo. These findings suggest that there is a direct link between alcohol metabolism and gene regulation, through the ACSS2-dependent acetylation of histones in the brain. Acetate that is produced from the breakdown of alcohol contributes to histone acetylation in the brain, indicating that there is a direct link between alcohol metabolism and gene expression.
Impact of 21-Gene Expression Assay on Clinical Outcomes in Node-Negative ≤ T1b Breast Cancer.

Prior to the advent of Oncotype DX 21-gene recurrence score (oDX) assay, the National Comprehensive Cancer Network (NCCN) guideline supported omission of adjuvant chemotherapy in patients with ≤ 1 cm (T1b) hormone receptor-positive (HR +), human epidermal growth factor receptor 2 (HER2−) node tumors. However, around 30% of these patients would have an oDX recurrence score that warrants consideration of adjuvant chemotherapy. To clarify the potential benefit of oDX in these patients, we performed a retrospective analysis comparing clinical outcomes of women with T1a or T1b, N0 HR + HER2− according to performance of oDX. After receiving institutional review board (IRB) approval, an institutional database was queried to identify patients with HR + HER2− ≤ T1bN0 tumors (n = 2307) diagnosed between 2009 and 2018. Patients were further stratified by recurrence score (RS) defined as low ( 30). Log-rank, Kaplan–Meier, and inverse probability of treatment weighting (IPW) analyses were used to compare disease-free survival (DFS) and overall survival (OS) across groups. Performance of oDX (n = 1149, 49.8%) was associated with larger tumors, younger age, and White race. On univariate analysis, performance of oDX was associated with improved OS (P < 0.01). On multivariate IPW analysis, performance of oDX lengthened DFS by an average of 16.5 months, while OS was similar between groups (P < 0.01 and P = 0.73). The improved DFS was mainly driven by those with tumors ≥ T1b. Overall, outcomes were excellent regardless of oDX testing. Performance of oDX testing was associated with improved DFS in patients with tumors ≥ T1b. Our results support routine use of oDX testing in patients with tumors ≥ T1b.
Not All Lithium Filaments Are the Same in Solid-State Batteries

Lithium filaments can grow in solid electrolytes and cause short circuits and decreases in Coulombic efficiencies. In the April issue of Matter, Kazyak et al. demonstrate an operando technique that is capable of exploring the nature of lithium nucleation and growth at solid electrolyte interfaces. Optical techniques reveal the various growth pathways for lithium filaments and shed light on the electro-chemo-mechanical phenomena that govern Li-SE interfaces.
Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury

Introduction: Elevated levels of blood-based proinflammatory cytokines are linked to acute moderate to severe traumatic brain injuries (TBIs), yet less is known in acute mild (m)TBI cohorts. The current study examined whether blood-based cytokines can differentiate patients with mTBI, with and without neuroimaging findings (CT and MRI). Material and Methods: Within 24 h of a mTBI, determined by a Glasgow Coma Scale (GCS) between 13 and 15, participants (n = 250) underwent a computed tomography (CT) and magnetic resonance imaging (MRI) scan and provided a blood sample. Participants were classified into three groups according to imaging findings; (1) CT+, (2) MRI+ (CT-), (3) Controls (CT- MRI-). Plasma levels of circulating cytokines (IL-6, IL-10, TNFα), and vascular endothelial growth factor (VEGF) were measured using an ultra-sensitive immunoassay. Results: Concentrations of inflammatory cytokines (IL-6, TNFα) and VEGF were elevated in CT+, as well as MRI+ groups (p < 0.001), compared to controls, even after controlling for age, sex and cardiovascular disease (CVD)-related risk factors; hypertension, and hyperlipidemia. Post-concussive symptoms were associated with imaging groupings, but not inflammatory cytokines in this cohort. Levels of VEGF, IL-6, and TNFα differentiated patients with CT+ findings from controls, with the combined biomarker model (VEGF, IL-6, TNFα, and IL-10) showing good discriminatory power (AUC 0.92, 95% CI 0.87-0.97). IL-6 was a fair predictor of MRI+ findings compared to controls (AUC 0.70, 95% CI 0.60-0.78). Finally, the combined biomarker model discriminated patients with MRI+ from CT+ with an AUC of 0.71 (95% CI 0.62-0.80). Conclusions: When combined, IL-6, TNFα, and VEGF may provide a promising biomarker cytokine panel to differentiate mTBI patients with CT+ imaging vs. controls. Singularly, IL-6 was a fair discriminator between each of the imaging groups. Future research directions may help elucidate mechanisms related to injury severity and potentially, recovery following an mTBI.
Bone Morphogenetic Protein-2 in Development and Bone Homeostasis

Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to be characterized and has been well-studied. BMP-2 has important roles during embryonic development, as well as bone remodeling and homeostasis in adulthood. Some of its specific functions include digit formation and activating osteogenic genes, such as Runt-Related Transcription Factor 2 (RUNX2). Because of its diverse functions and osteogenic potential, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery, tibial shaft repair, and maxillary sinus reconstructive surgery. However, shortly after initial injections of rhBMP-2, several adverse complications were reported, and alternative therapeutics have been developed to limit these side-effects. As the clinical application of BMP-2 is largely implicated in bone, we focus primarily on its role in bone. However, we also describe briefly the role of BMP-2 in development. We then focus on the structure of BMP-2, its activation and regulation signaling pathways, BMP-2 clinical applications, and limitations of using BMP-2 as a therapeutic. Further, this review explores other potential treatments that may be useful in treating bone disorders.