cssi/SciSciGPT-SciSciNet huggingface dataset:
Oxyhemoglobin-Induced Suppression of Voltage-Dependent K+ Channels in Cerebral Arteries by Enhanced Tyrosine Kinase Activity

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences. Oxyhemoglobin (oxyhb) has been implicated in SAH-induced cerebral vasospasm as it causes cerebral artery constriction and increases tyrosine kinase activity. Voltage-dependent, Ca(2+)-selective and K(+)-selective ion channels play an important role in the regulation of cerebral artery diameter and represent potential targets of oxyhb. Here we provide novel evidence that oxyhb selectively decreases 4-aminopyridine sensitive, voltage-dependent K(+) channel (K(v)) currents by approximately 30% in myocytes isolated from rabbit cerebral arteries but did not directly alter the activity of voltage-dependent Ca(2+) channels or large conductance Ca(2+)-activated (BK) channels. A combination of tyrosine kinase inhibitors (tyrphostin AG1478, tyrphostin A23, tyrphostin A25, genistein) abolished both oxyhb-induced suppression of K(v) channel currents and oxyhb-induced constriction of isolated cerebral arteries. The K(v) channel blocker 4-aminopyridine also inhibited oxyhb-induced cerebral artery constriction. The observed oxyhb-induced decrease in K(v) channel activity could represent either channel block, or a decrease in K(v) channel density on the plasma membrane. To explore whether oxyhb altered trafficking of K(v) channels to the plasma membrane, we used an antibody generated against an extracellular epitope of K(v)1.5 channels. In the presence of oxyhb, staining of K(v)1.5 on the plasma membrane surface was markedly reduced. Furthermore, oxyhb caused a loss of spatial distinction between staining with K(v)1.5 and the general anti-phosphotyrosine antibody PY-102. We propose that oxyhb-induced suppression of K(v) currents occurs via a mechanism involving enhanced tyrosine kinase activity and channel endocytosis. This novel mechanism may contribute to oxyhb-induced cerebral artery constriction following SAH.
A generic biogeochemical module for Earth system models: Next Generation BioGeoChemical Module (NGBGC), version 1.0

Abstract. Physical and biogeochemical processes regulate soil carbon dynamics and CO2 flux to and from the atmosphere, influencing global climate changes. Integration of these processes into Earth system models (e.g., community land models (CLMs)), however, currently faces three major challenges: (1) extensive efforts are required to modify modeling structures and to rewrite computer programs to incorporate new or updated processes as new knowledge is being generated, (2) computational cost is prohibitively expensive to simulate biogeochemical processes in land models due to large variations in the rates of biogeochemical processes, and (3) various mathematical representations of biogeochemical processes exist to incorporate different aspects of fundamental mechanisms, but systematic evaluation of the different mathematical representations is difficult, if not impossible. To address these challenges, we propose a new computational framework to easily incorporate physical and biogeochemical processes into land models. The new framework consists of a new biogeochemical module, Next Generation BioGeoChemical Module (NGBGC), version 1.0, with a generic algorithm and reaction database so that new and updated processes can be incorporated into land models without the need to manually set up the ordinary differential equations to be solved numerically. The reaction database consists of processes of nutrient flow through the terrestrial ecosystems in plants, litter, and soil. This framework facilitates effective comparison studies of biogeochemical cycles in an ecosystem using different conceptual models under the same land modeling framework. The approach was first implemented in CLM and benchmarked against simulations from the original CLM-CN code. A case study was then provided to demonstrate the advantages of using the new approach to incorporate a phosphorus cycle into CLM. To our knowledge, the phosphorus-incorporated CLM is a new model that can be used to simulate phosphorus limitation on the productivity of terrestrial ecosystems. The method presented here could in theory be applied to simulate biogeochemical cycles in other Earth system models.
Thermal Expansion of Nb2O5

The high-temperature thermal expansion of monoclinic Nb2O5 was studied with X-ray and dilatometric techniques. The X-ray axial thermal expansion was anisotropic; the mean coefficients in the a, b, and c directions, respectively, were 5.3, 0, and 5.9×10−6°C-1 from room temperature to 1000°C. It is proposed that this anisotropy causes microcrack formation in sintered polycrystalline samples. The bulk linear thermal expansion of both sintered and hot-pressed samples was determined with a dilatometer from room temperature to 1200°C. A hysteresis effect between heating and cooling data observed for sintered samples was attributed to the occurrence and recombination of internal microcracks.
The Biology and Targeting of FLT3 in Pediatric Leukemia.

Despite remarkable improvement in treatment outcomes in pediatric leukemia over the past several decades, the prognosis for high risk groups of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), as well as for relapsed leukemia, remains poor. Intensified chemotherapy regimens have somewhat improved success rates, but at the cost of drastically increased morbidity and long term adverse effects. With the success of imatinib in Philadelphia-chromosome positive leukemia and all-trans retinoic acid in acute promyelocytic leukemia, the quest to find additional molecularly targeted therapies has generated much excitement over the past 15 years. Another such possible target in pediatric acute leukemia is FMS-like tyrosine kinase 3 (FLT3). FLT3 aberrations are among the most frequently identified transforming events in AML, and have significant clinical implications in both high risk pediatric AML and in certain high risk groups of pediatric ALL. Therefore, the successful targeting of FLT3 has tremendous potential to improve outcomes in these subsets of patients. This article will give an overview of the molecular function and signaling of the FLT3 receptor, as well as its pathogenic role in leukemia. We review the discovery of targeting FLT3, discuss currently available FLT3 inhibitors in pediatric leukemia and results of clinical trials to date, and finally, consider the future promise and challenges of FLT3 inhibitor therapy.
Intergranular Phases in Polycrystalline Ceramics

The majority of polycrystalline ceramics contain phases, often noncrystalline, along their grain boundaries. These intergranular phases affect the overall electrical and high temperature mechanical properties of the ceramics. This tutorial describes the microstructure, the conditions for wetting, and dewetting, of the boundaries by the phase and the factors affecting the equilibrium thickness of the phase. Finally, how the connectivity of the intergranular phase may be exploited in post-fabrication processing is described.
Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications

Trop2 is a transmembrane glycoprotein encoded by the Tacstd2 gene. It is an intracellular calcium signal transducer that is differentially expressed in many cancers. It signals cells for self-renewal, proliferation, invasion, and survival. It has stem cell-like qualities. Trop2 is expressed in many normal tissues, though in contrast, it is overexpressed in many cancers and the overexpression of Trop2 is of prognostic significance. Several ligands have been proposed that interact with Trop2. Trop2 signals the cells via different pathways and it is transcriptionally regulated by a complex network of several transcription factors. Trop2 expression in cancer cells has been correlated with drug resistance. Several strategies target Trop2 on cancer cells that include antibodies, antibody fusion proteins, chemical inhibitors, nanoparticles, etc. The in vitro studies and pre-clinical studies, using these various therapeutic treatments, have resulted in significant inhibition of tumor cell growth both in vitro and in vivo in mice. A clinical study is underway using IMMU-132 (hrS7 linked to SN38) in patients with epithelial cancers. This review describes briefly the various characteristics of cancer cells overexpressing Trop2 and the potential application of Trop2 as both a prognostic biomarker and as a therapeutic target to reverse resistance.
Interleukin-12 Preserves the Graft-Versus-Leukemia Effect of Allogeneic CD8 T Cells While Inhibiting CD4-Dependent Graft-Versus-Host Disease in Mice

We have recently demonstrated that a single injection of 4,900 IU of interleukin-12 (IL-12) on the day of bone marrow transplantation (BMT) markedly inhibits acute graft-versus-host disease (GVHD) in a fully major histocompatibility complex plus minor antigen-mismatched BMT model (A/J → B10, H-2a → H-2b), in which donor CD4+ T cells are required for the induction of acute GVHD. We show here that donor CD8-dependent graft-versus-leukemia (GVL) effects against EL4 (H-2b) leukemia/lymphoma can be preserved while GVHD is inhibited by IL-12 in this model. In mice in which IL-12 mediated a significant protective effect against GVHD, marked GVL effects of allogeneic T cells against EL4 were observed. GVL effects against EL4 depended on CD8-mediated alloreactivity, protection was not observed in recipients of either syngeneic (B10) or CD8-depleted allogeneic spleen cells. Furthermore, we analyzed IL-12–treated recipients of EL4 and A/J spleen cells which survived for more than 100 days. No EL4 cells were detected in these mice by flow cytometry, tissue culture, adoptive transfer, necropsies, or histologic examination. Both GVL effects and the inhibitory effect of IL-12 on GVHD were diminished by neutralizing anti–interferon-γ (IFN-γ) monoclonal antibody. This study demonstrates that IL-12–induced IFN-γ production plays a role in the protective effect of IL-12 against GVHD. Furthermore, IFN-γ is involved in the GVL effect against EL4 leukemia, demonstrating that protection from CD4-mediated GVHD and CD8-dependent anti-leukemic activity can be provided by a single cytokine, IFN-γ. These observations may provide the basis for a new approach to inhibiting GVHD while preserving GVL effects of alloreactivity.
Important Differences Between a Triage Pedigree and Risk Assessment

TO THE EDITOR: We would like to compliment Lu et al on their work tackling the complicated topic of triaging for inherited cancer predisposition and setting baseline recommendations for family history collection. However, we would like to emphasize that collecting the family history of only firstand second-degree relatives may be appropriate for triage, but it is not sufficient for a full cancer risk assessment. The gold standard for cancer risk assessment is a threeto four-generation pedigree with collection of health information on first-, second-, and third-degree relatives. The recommendations made by Lu et al may help with identifying many families who would benefit from a referral for genetic counseling and potentially genetic testing. However, as with any triage mechanism, some families will be missed, the percentage of which is unknown. The triage guidelines in this article may have limitations for individuals with a paternal family history of breast cancer or families with limited family structure. Physicians who identify families with a concerning family history or rare tumors or patients concerned about risk may enhance the care of their patient by referring to a provider with expertise in genetics, such as a genetic counselor. One of the barriers reported to obtaining a family history in a busy oncology clinic was time. The genetic testing landscape is changing rapidly, which makes it a challenge for health care providers to stay abreast of the data. Genetic counselors are uniquely positioned to assist oncologists in the collection of appropriate family histories and risk assessment. A list of genetic counselors may be found at www.nsgc.org.
Regional glycosaminoglycan coverage of healthy rabbit menisci

The meniscus is an important load-bearing structure in the knee, as it provides load distribution and cushioning properties during weight-bearing activities. The compressive modulus and permeability of the meniscus is attributed to the tissue’s glycosaminoglycan (GAG) content, as charged proteoglycan side chains allow for tissue swelling and resistance to compression [1]. The distribution of sulphated GAGs throughout the meniscus has not been thoroughly documented. Although load differs across the knee joint, few researchers have investigated medial/lateral and coronal differences in meniscal architecture and GAG distribution [2, 3]. It is hypothesized that the distribution of positive histological staining for sulfated GAGs will differ across spatial regions of rabbit menisci. Primarily, it is hypothesized that regions of the menisci that likely see higher loading will demonstrate an increase in sulfated GAG-positive staining area.© 2009 ASME
Death associated with bronchography. Question role of heating the contrast agent.

A young woman died following bronchography. The bilateral bronchogram done under general anesthesia without fluoroscopic control was associated with extensive small airway filling or “alveolarization” of the contrast medium. The oily Dionosil used had been heated in an autoclave. Experiments showed that the viscosity of oily Dionosil decreases with heating. The lowered viscosity could have contributed to the increased “alveolarization” of the contrast agent and death of the patient.
Research on Electric Power Communication Operation and Maintenance Management Risk Assessment and Its Application

In order to improve the risk management level of electric communication operation and maintenance,and to guarantee the safe and stable operation of the electric power communication network,based on the established communication operation and maintenace risk rating and evaluation matrix,this paper designs a risk assessment system and develops a corresponding risk assessment software system,which has the capacities of operation monitoring,overhaul management,troubleshooting and on-site inspection.The successful application of research achievements in Zhenjiang electric power communication operation and management system shows that the proposed risk assessment system can not only improve the operability of the risk assessment process and the scientificalness of risk results,but also achieve good management benefits.
Neutron radiation therapy for advanced thyroid cancers.

Abstract Purpose The aim of this study was to review institutional outcomes for advanced thyroid cancers treated with fast neutron radiation therapy (FNRT) and photon radiation therapy (RT). Methods and materials In all, 62 consecutive patients were analyzed. Fifty-nine had stage IV disease. Twenty-three were treated with FNRT and 39 with photon RT. Median follow-up was 14 months. The primary endpoint was overall survival (OS). Results There was no significant difference in median OS between FNRT and photon RT (26 vs 16 months; P = .49). Patients with well-differentiated histologies had superior median OS with photon RT (17 vs 69 months; P = .04). There was a nonsignificant trend toward improved OS with FNRT for medullary and anaplastic histologies. Conclusions Outcomes in this study are in line with historical results. There is an apparent detriment in OS with FNRT for well-differentiated histologies and a trend toward improved OS with medullary and anaplastic histologies that warrants further investigation.
Laryngology: from Galen to Garcia.

A brief cultural survey of the major highlights in the evolution of laryngology and voice science from Claudius Galen (c 130–200 AD) to Manuel Garcia (1805–1906) is presented.
Need for Status as a Motive for the Conspicuous Consumption of Cause-Related Goods

In other words, humans perceive their possessions to be a representation of their identity or self. Display in the form of possessions, attire, or actions represent a person’s perceived or actual place in society, be it related to character traits, religious affiliations, professional associations, or even wealth and social standing. One of the recognized phenomenon of display as a representation is conspicuous consumption, defined as the intentional display of expensive goods by the nouveau-riche to indicate financial status (Veblen 1899). The concept has been inextricably linked with luxury goods, but conspicuous displays, whether of wealth or other affiliations, are a way of signaling belonging to any social group (Ashforth and Mael 1989) or possessing certain individual qualities (Connelly et al. 2011). Corporations and consumers are driven by a desire to be seen as responsible members of society and hope to thus command social respect. In essence, companies and consumers engaging in prosocial behavior may not be doing so for purely altruistic reasons (Basil and Weber 2006). It is possible that the purchase of visible luxury items and of items visibly associated with a social cause are both motivated by similar mechanisms of an attempt to be seen as belonging to a desirable social group.
O15-3 Reality and aetiology: target parameters in occupational epidemiology

The determination of appropriate standards for workplace exposure requires accurate estimation of the health effects. This will sometimes require adjustment for the Healthy Worker Survivor Effect (HWSE) using g-methods, which can adjust for the time-varying confounding on the causal pathway that characterises this bias. These methods allow the estimation of a target parameter corresponding to an intervention on the data generating distribution. These target parameters generally capture the disease experience of workers under a fixed regimen of exposure at a constant level. However, any exposure regimen must acknowledge that terminated workers will no longer experience any occupational exposure. We consider two contrasting target parameters – the etiologic and the realistic – that both recognise this fact. An etiologic parameter corresponds to a hypothetical intervention that fixes exposure levels and keeps all workers employed throughout follow-up. A realistic parameters corresponds to an intervention that fixes exposure levels as long as workers are employed, but allows them to leave work. An etiologic parameter provides a better estimate of the biological effect of the exposure of interest. However, it requires information and assumptions about the process of leaving work. In addition, it corresponds to an infeasible intervention which may be of limited interest to policy makers. Realistic parameters, on the other hand, allow some of the processes that characterise the HWSE to affect the true parameter value. The true value of the realistic parameter could even be null when in fact exposure causes disease; interventions setting exposure at higher limits may induce earlier termination and less cumulative exposure accrual than lower limit interventions. We use directed acyclic graphs as our theoretical framework to define both types of target parameters in two contrasting types of occupational cohort designs. We discuss the rationale for each type and the ramifications of the choice.
Bacterial nanowires: electrically conductive filaments and their implications for energy transformation and distribution in natural and engineered systems

Bacteria, ranging from oxygenic photosynthetic cyanobacteria to heterotrophic sulfate reducing bacteria, produce electrically-conductive appendages referred to as bacterial nanowires. Dissimilatory metal reducing bacteria, including Shewanella oneidensis and Geobacter sulfurreducens, produce electrically conductive nanowires in direct response to electron acceptor limitation and facilitate electron transfer to solid phase iron oxides. Nanowires produced by S. oneidensis strain MR-1, which served as our primary model organism, are functionalized by decaheme cytochromes MtrC and OmcA that are distributed along the length of the nanowires. Mutants deficient in MtrC and OmcA produce nanowires that were poorly conductive. These mutants also differ from wild type cells in their ability to reduce solid phase iron oxides, to produce electrical current in a mediator less microbial fuel cell, and to form complex biofilms at air liquid interfaces. Although currently less completely characterized, conductive nanowires produced by other organisms reveal a strategy of energy/electron distribution that is conserved across a broad metabolic spectrum. This presentation will target the implications of bacterial nanowire for energy distribution and communication in biofilms and other natural microbial communities, bioelectrical coupling of electron donors with poorly accessible electron acceptors, and applications for alternative energy (microbial fuel cells) and nanoelectronic technologies
Effective Combination Therapies for B-cell Lymphoma Predicted by a Virtual Disease Model

The complexity of cancer signaling networks limits the efficacy of most single-agent treatments and brings about challenges in identifying effective combinatorial therapies. In this study, we used chronic active B-cell receptor (BCR) signaling in diffuse large B-cell lymphoma as a model system to establish a computational framework to optimize combinatorial therapy in silico We constructed a detailed kinetic model of the BCR signaling network, which captured the known complex cross-talk between the NFκB, ERK, and AKT pathways and multiple feedback loops. Combining this signaling model with a data-derived tumor growth model, we predicted viability responses of many single drug and drug combinations in agreement with experimental data. Under this framework, we exhaustively predicted and ranked the efficacy and synergism of all possible combinatorial inhibitions of eleven currently targetable kinases in the BCR signaling network. Ultimately, our work establishes a detailed kinetic model of the core BCR signaling network and provides the means to explore the large space of possible drug combinations. Cancer Res; 77(8); 1818-30. ©2017 AACR.
Modeling Distillers Dried Grains with Solubles (DDGS) Mass Flow Rate as Affected by Drying and Storage Conditions

Ethanol production in 2015 was over 15 million gallons in the United States, and it is projected to increase in the next few years to meet market demands. With the continued growth in the ethanol industry, there has been enormous expansion in distillers grains production. Because the local market for distillers dried grains with solubles (DDGS) is often saturated, it is essential to transport DDGS long distances, across the United States and to international markets. Caking and agglomeration of DDGS particles in hoppers and other storage structures are typical during transportation. The current study deals with DDGS prepared by combining condensed distillers solubles (CDS) with distillers wet grains and then drying at varying temperatures. DDGS was stored in conical hoppers under varying ambient temperature, consolidation pressure, and time conditions. We investigated the effects of CDS (10, 15, and 20% wb), drying temperature (100, 200, and 300°C), drying time (20, 40, and 60 min), cooling temperature (0...
DNA methylation changes in leukemia patients treated with 5-aza-2′-deoxycytidine (decitabine)

1599 5-aza-2′-deoxycytidine (decitabine) is a cytosine analog that has the unique ability to inhibit DNA methylation. Decitabine has been used in numerous clinical trials and has shown consistent activity in myeloid leukemias. We wished to investigate whether decitabine has activity in leukemia via its ability to inhibit DNA methylation. We therefore studied samples from leukemia patients who were treated in two clinical trials using decitabine. The first trial used a “high” dose of decitabine at 50-90mg/m 2 twice daily for 5 days. A second clinical trial used a “low” dose strategy of 5-20mg/m 2 once daily for 10 days in order to take advantage of the demethylating properties of decitabine. We analyzed DNA methylation of p15, H19, HoxA5 and Alu repetitive elements in peripheral blood samples of patients before, during and after treatment to examine methylation changes induced by decitabine. The p15 gene is a tumor suppressor gene that is normally unmethylated, but becomes aberrantly methylated in cancer. H19 is an imprinted locus that is only methylated on the paternal allele, and HoxA5 is a gene that is normally heavily methylated. Alu elements were studied as a surrogate marker for global genome methylation. We found that decitabine treatment could decrease DNA methylation in all the genes studied, but Alu methylation gave the most consistent results probably because Alu elements are more abundant and heavily methylated in the genome. Overall most patients (88%) showed a decrease in Alu methylation with decitabine treatment. However, the mean decrease in Alu methylation was only 7.7% with a range of –10.3 to 31.5% (SD=8.2%). We found a dose dependent decrease in methylation after decitabine treatment with a plateau at high doses. We examined patients treated at six doses (5, 10, 15, 20, 100 and 180mg/m 2 /day). Demethylation averaged 2.8%, 1.1%, 7.3%, 11.6%, 10.9%, and 8.5% at these six doses, respectively. Thus there did not appear to be a significant increase in demethylation beyond 20mg/m 2 /day. However, the number of patients studied at some doses was limited. There was a statistically significant correlation between inhibition of methylation and response to decitabine in the “low” dose strategy. Low dose study patients whose leukemia did not respond showed a mean decrease of only 3.3%, while those patients whose leukemia responded to decitabine showed a mean decrease of 11.5% (p=0.02). Remarkably, this dose-response relationship was not seen at high doses of decitabine, which in vitro induces primarily cytotoxic cell death. These data are consistent with previous in vitro studies that show that low doses of decitabine are optimal for inducing differentiation, and suggest that hypomethylation rather than cytotoxicity is critical for response to this agent.
On the diurnal cycle of surface energy fluxes in the North American monsoon region using the WRF-Hydro modeling system

The diurnal cycles of surface energy fluxes are important drivers of atmospheric boundary layer development and convective precipitation, particularly in regions with heterogeneous land surface conditions such as those under the influence of the North American monsoon (NAM). Characterization of diurnal surface fluxes and their controls has not been well constrained due to the paucity of observations in the NAM region. In this study, we evaluate the performance of the uncoupled WRF-Hydro modeling system in its ability to represent soil moisture, turbulent heat fluxes and surface temperature observations and compare these to operational analyses from other commonly-used land surface models (LSMs). After a rigorous model evaluation, we quantify how the diurnal cycles of surface energy fluxes vary during the warm-season for the major ecosystems in a regional basin. We find that the diurnal cycle of latent heat flux is more sensitive to ecosystem type than sensible heat flux due to the response of plant transpiration to variations in soil water content. Furthermore, the peak timing of precipitation affects the shape and magnitude of the diurnal cycle of plant transpiration in water-stressed ecosystems, inducing mesoscale heterogeneity in land surface conditions between the major ecosystems within the basin. Comparisons to other LSMs indicate that ecosystem differences in the diurnal cycle of turbulent fluxes are underestimated in these products. While this study shows how land surface heterogeneity affects the simulated diurnal cycle of turbulent fluxes, additional coupled modeling efforts are needed to identify the potential impacts of these spatial differences on convective precipitation.
Wealth-Associated Disparities in Death and Disability in the United States and England

Importance Low income has been associated with poor health outcomes. Owing to retirement, wealth may be a better marker of financial resources among older adults. Objective To determine the association of wealth with mortality and disability among older adults in the United States and England. Design, Setting, and Participants The US Health and Retirement Study (HRS) and English Longitudinal Study of Aging (ELSA) are nationally representative cohorts of community-dwelling older adults. We examined 12 173 participants enrolled in HRS and 7599 enrolled in ELSA in 2002. Analyses were stratified by age (54-64 years vs 66-76 years) because many safety-net programs commence around age 65 years. Participants were followed until 2012 for mortality and disability. Exposures Wealth quintile, based on total net worth in 2002. Main Outcomes and Measures Mortality and disability, defined as difficulty performing an activity of daily living. Results A total of 6233 US respondents and 4325 English respondents aged 54 to 64 years (younger cohort) and 5940 US respondents and 3274 English respondents aged 66 to 76 years (older cohort) were analyzed for the mortality outcome. Slightly over half of respondents were women (HRS: 6570, 54%; ELSA: 3974, 52%). A higher proportion of respondents from HRS were nonwhite compared with ELSA in both the younger (14% vs 3%) and the older (13% vs 3%) age cohorts. We found increased risk of death and disability as wealth decreased. In the United States, participants aged 54 to 64 years in the lowest wealth quintile (Q1) (≤$39 000) had a 17% mortality risk and 48% disability risk over 10 years, whereas in the highest wealth quintile (Q5) (>$560 000) participants had a 5% mortality risk and 15% disability risk (mortality hazard ratio [HR], 3.3; 95% CI, 2.0-5.6;P £310,550) had a 4% mortality risk and 17% disability risk (mortality HR, 4.4; 95% CI, 2.7-7.0;P Conclusions and Relevance Low wealth was associated with death and disability in both the United States and England. This relationship was apparent from age 54 years and continued into later life. Access to health care may not attenuate wealth-associated disparities in older adults.
Parasite Ecology of Invasive Species: Conceptual Framework and New Hypotheses

Biological invasions have the potential to influence parasite dynamics by altering ecological interactions. Similarly, parasitism can influence invasion by aiding or limiting expansion. While many parasite–invasion relationships have been evaluated, many have not been described. Here, we present a conceptual framework of potential interactions, and introduce two new concepts. The first, disease facilitation, nested within the parasite spillback hypothesis, is when invasive species facilitate parasite transmission through habitat alteration or physical transfer. The second, suppressive spillover, is when the deleterious effects of parasitic infection limit the expansion of an introduced species (and hence invasion success). Taken together, the proposed framework may aide in our understanding of ecological drivers of invasion and parasite ecology and can be used to improve mitigation strategies.
Comparison of Bayesian nonparametric density estimation methods

In this paper, we propose a nonparametric Bayesian approach for Lindsey and penalized Gaussian mixtures methods. We compare these methods with the Dirichlet process mixture model. Our approach is a...
Commercial spaceflight: Progress and challenges in expanding human access to space

Abstract Commercial access to space travel for private individuals is a near-term reality. Compared to the few professional astronauts, cosmonauts, and taikonauts who have flown in space through government programs in the past six decades, the number of these new spaceflight participants (SFPs) will rapidly expand. The SFP cohort will have a much greater age range than traditional astronauts and may also have a much greater prevalence of medical problems. To date, regulation regarding medical screening, certification, or guidelines for suborbital and orbital SFPs has been relegated to the commercial space companies. However, many organizations, ranging from space advocacy groups to academic institutions to the Federal Aviation Administration (FAA), have offered input and recommendations for medical screening of SFPs for the industry’s consideration. Simultaneously, governmental space agencies have made progress in defining appropriate preflight medical testing and medical standards and for those commercial providers that plan to provide access to the International Space Station (ISS). There is limited information available with regard to the effect of spaceflight-related stressors like acceleration, microgravity, and altered atmospheric pressure and breathing gas mixtures on individuals with medical conditions. To date, most research on humans exposed to challenging or extreme environments has focused on a healthy, young, and predominately male population. However, recent studies funded in part by the FAA and conducted by university programs have examined the effect of certain medical problems like cardiovascular disease, diabetes, and back problems in the acceleration environment. While the numbers are small, the early data from these studies examining the effects of acceleration are reassuring. There is still much for space medicine providers to learn from this new cohort of individuals that will soon be participating in commercial space activities. With appropriate training and treatment or stabilization of medical liabilities, most of those who desire to fly in space will be able to safely accomplish their dream.
Clinical genomic testing of anaplastic thyroid carcinoma (ATC) and need for integration into future prospective clinical trials.

6085Background: ATC is an aggressive disease requiring rapid diagnosis. Targeted therapeutics provide ATC patients (pts) with previously unavailable treatment options. Development of high throughpu...
Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim

Apoptosis of CD8 T cells is an essential mechanism that maintains immune system homeostasis, prevents autoimmunity, and reduces immunopathology. CD8 T cell death also occurs early during the response to both inflammation and costimulation blockade (CoB). In this article, we studied the effects of a combined deficiency of Fas (extrinsic pathway) and Bim (intrinsic pathway) on early T cell attrition in response to lymphocytic choriomeningitis virus infection and during CoB during transplantation. Loss of Fas and Bim function in Bcl2l11 −/− Fas lpr/lpr mice inhibited apoptosis of T cells and prevented the early T cell attrition resulting from lymphocytic choriomeningitis virus infection. Bcl2l11 −/− Fas lpr/lpr mice were also resistant to prolonged allograft survival induced by CoB targeting the CD40-CD154 pathway. These results demonstrate that both extrinsic and intrinsic apoptosis pathways function concurrently to regulate T cell homeostasis during the early stages of immune responses and allograft survival during CoB.
Some promises in the pitfalls of automated and autonomous vehicles: A response to commentators

AbstractMy interlocutors have offered numerous and important responses to my target article. Here, I endeavour to respond to the issues raised. Despite some contentions over specifics, the overall ...
Sleep and Self-Rated Health in an Aging Workforce:

The labor force participation rate for adults aged 55 years and older has increased nearly 10% over the past two and a half decades. As workers age, they frequently experience increased chronic health conditions and impaired sleep, which may negatively influence their self-rated health (SRH) and work performance. This study aimed to examine the associations between nonrestorative sleep (NRS) and work performance (i.e., difficulty concentrating or having lower productivity at work) and associations between demographic and sleep characteristics with SRH in middle-aged workers. We conducted a secondary data analysis among working middle-aged adults 50 to 65 years of age ( N = 392) from the 2008 Sleep in America Poll. Respondents frequently reported impaired sleep such as frequent insomnia symptoms, NRS, and short sleep duration. Nonrestorative sleep was associated with decreased work performance such as trouble organizing work, doing work over due to mistakes, and lower productivity. Nonrestorative sleep and short sleep duration were significantly associated with lower SRH. Strategies for the early detection of impaired sleep and implementation of interventions to improve sleep may improve SRH and work performance in working middle-aged adults.
Nickel-Catalyzed Preparation of Bicyclic Heterocycles: Total Synthesis of (+)-Allopumiliotoxin 267A, (+)-Allopumiliotoxin 339A, and (+)-Allopumiliotoxin 339B

A new method for the reductive cyclization of ynals involving a Ni(COD)2/PBu3 catalyst system to produce allylic alcohols was developed. The triethylsilane-mediated procedure allows preparation of ...
Perovskites with a Twist: Strong In1+ Off-Centering in the Mixed-Valent CsInX3 (X = Cl, Br)

The search for new halide perovskites has recently expanded to the double perovskites A2M+M3+X6, which form in the 3D elpasolite structure with alternating M+ and M3+ octahedra. Here, we report the...
UNTYING THE GORGIANIC ‘NOT’: ARGUMENTATIVE STRUCTURE IN ON NOT-BEING

Gorgias’ On Not-Being survives only in two divergent summaries. Diels–Kranz's classic edition prints the better-preserved version that appears in Sextus’ Aduersus Mathematicos. Yet, in recent years there has been rising interest in a second summary that survives as part of the anonymous De Melisso, Xenophane, Gorgia (= MXG). The text of MXG is more difficult; it contains substantial lacunae that often make it much harder to make grammatical let alone philosophical sense of. As Alexander Mourelatos reports, one manuscript has a scribal note that reads: ‘The original contains many errors; no one should blame me; I just copy what I see.’2 The treatise's state of preservation has aptly prompted Michael Gagarin to liken it to a black hole: ‘something we cannot see directly but know must exist because of certain effects it has on other objects.’3
Wise Ancestors and Current Social Issues as Guides to the Design of Contemporary Programs of Teacher Education.

I slowly developed the belief that sharing much of educational research with novice teachers was an error. To me, novice teachers appeared to have too little experience to adopt and adapt research ...
Risk of acute respiratory failure among hospitalized patients with various admission serum albumin levels: A cohort study.

Serum albumin is a marker of nutritional and frailty status. This study aimed to assess the association between serum albumin at the time of admission and the risk of acute respiratory failure (ARF) in hospitalized patientsThis cohort study, performed at a tertiary referral hospital, included all hospitalized adult patients from January 2009 to December 2013 who had serum albumin measurement and were not on mechanical ventilation within 24 hours of hospital admission. Serum albumin was stratified into 2.4, 2.5 to 2.9, 3.0 to 3.4, 3.5 to 3.9, 4.0 to 4.4, and ≥4.5 g/dL. Multivariate logistic regression analysis was performed to obtain adjusted odds ratio (OR) of risk of ARF requiring mechanical ventilation based on various admission serum albumin levels.Of 12,719 patients, ARF requiring mechanical ventilation occurred in 1128 (8.9%) during hospitalization. Hypoalbuminemia was associated with increased risk of ARF, in particular when serum albumin was ≤2.4 g/dL. Compared with serum albumin of 4.0-4.4 g/dL, serum albumin ≤2.4 g/dL at admission was associated with 2.38-time higher odds of ARF during hospitalization (OR 2.38, 95% confidence interval [CI] 1.84-3.07). In contrast, elevated serum albumin ≥4.5 g/dL was associated with lower odds of ARF (OR 0.68, 95% CI 0.48-0.97).Admission serum albumin level lower than 3.5 g/dL was associated with a higher risk of ARF requiring mechanical ventilation, whereas elevated serum albumin level at least 4.5 g/dL was associated with a lower risk of ARF. Therefore, admission albumin level at admission might be useful in the prediction of ARF during hospitalization.
Spectral 3D reconstruction of impressionist oil painting based on macroscopic OCT imaging

We present a hybrid scanning platform combined with effective algorithm for real-time sampling and artifact removal to achieve macroscopic OCT (macro-OCT) imaging and spectral 3D reconstruction of impressionist style oil painting.
Office of Medical Education, University of Kansas School of Medicine, Kansas City, Kansas, USA

After more than 28 years in medical student education, I can think of no role more demanding and complex than that of the medical student clerkship director. Luckily, the Alliance for Clinical Educ...
Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA.

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by a mutation or deletion of the maternally inherited UBE3A allele. In neurons, the paternally inherited UBE3A allele is silenced in cis by a long non-coding RNA called UBE3A-ATS. Here, as part of a systematic screen, we found that Cas9 can be used to activate ('unsilence') paternal Ube3a in cultured mouse and human neurons when targeted to Snord115 genes, which are small nucleolar RNAs that are clustered in the 3′ region of Ube3a-ATS. A short Cas9 variant and guide RNA that target about 75 Snord115 genes were packaged into an adeno-associated virus and administered to a mouse model of AS during the embryonic and early postnatal stages, when the therapeutic benefit of restoring Ube3a is predicted to be greatest1,2. This early treatment unsilenced paternal Ube3a throughout the brain for at least 17 months and rescued anatomical and behavioural phenotypes in AS mice. Genomic integration of the adeno-associated virus vector into Cas9 target sites caused premature termination of Ube3a-ATS at the vector-derived polyA cassette, or when integrated in the reverse orientation, by transcriptional collision with the vector-derived Cas9 transcript. Our study shows that targeted genomic integration of a gene therapy vector can restore the function of paternally inherited UBE3A throughout life, providing a path towards a disease-modifying treatment for a syndromic neurodevelopmental disorder. Genomic integration of an adeno-associated virus vector in a mouse model of Angelman syndrome unsilences paternal Ube3a and rescues anatomical and behavioural phenotypes, suggesting a pathway towards the treatment of this neurodevelopmental disorder.
Resistance to the wheat curl mite and mite-transmitted viruses: challenges and future directions

Wheat curl mite (WCM) is the only known arthropod vector of four wheat viruses, the most important of which is Wheat streak mosaic virus (WSMV). Host resistance to WCM and WSMV is limited to a small number of loci, most of which are introgressed from wild relatives and are often associated with linkage drag and temperature sensitivity. Reports of virulent WCM populations and potential resistance-breaking WSMV isolates highlight the need for more diverse sources of resistance. Genome sequencing will be critical to fully characterize the genetic diversity in WCM and WSMV populations to better understand the incidence of WCM-transmitted viruses and to evaluate the potential stability of resistance genes. Characterizing host resistance genes will help build a mechanistic understanding of wheat-WCM-WSMV interactions and inform strategies to identify and engineer more durable resistance sources.
I Came, I Saw, I... Adapted: An Empirical Study of Chinese Business Expansion in the United States and its Legal and Policy Implications

China’s economic expansion into the United States has generated intense debates and controversies. Some view it as posing a critical challenge to extant U.S. institutions; others see China as a stakeholder of the extant system and that the Chinese investors are by and large “playing our game.” However, theories and hypotheses on the subject abounding, little is yet known how exactly Chinese investors interact with U.S. institutions and the legal implications of such interactions. Relying on the first comprehensive survey of Chinese companies investing in the United States, this Article fills the gap with an interdisciplinary study of the adaptation of Chinese investors to the U.S. legal and regulatory systems. Under a novel analytic frame, the study finds evidence that Chinese investors are largely commercially driven and adaptive to the host country environment. The article further evaluates this general finding with a case study, i.e., Chinese companies’ adaptation to U.S. institutions governing employment discrimination, and finds confirming evidence. It then moves on to the discussion of two often-debated threats from China’s business expansion in the United States: the threat to U.S. national security and the threat to free market capitalism. The empirical evidence suggests that Chinese investors are unlikely to pose major threats to extant U.S. institutions in the near future. In light of the findings, policymakers should resist the temptation to hastily erect overly protective measures in response to the sharp rise of Chinese investments. Regulated properly, Chinese investors may become major stakeholders of the U.S. institutions and contribute to their long-term resilience. Associate Professor, Rutgers Law School, J.D. 2007, Yale Law School; Ph.D. 2012, Northwestern University. Email: jli@kinoy.rutgers.edu. For valuable comments, the author thanks Susan RoseAckerman, Weitseng Chen, Jerome Cohen, Hualing Fu, Yunsong Ge, Shaowei Mao, Jing Leng, Robin Huang, Christopher Gane, Haitian Lu, Shitong Qiao, Benjamin Liebman, Li Guo, Curtis Milhaupt, Gary Francione, John Leubsdorf, Douglas Eakeley, Alan Hyde, Sabrina Safrin, Taja-Nia Y. Henderson, Yingmao Tang, Wei Zhang, Wentong Zheng and other participants in workshops and seminars hosted by the National University of Singapore Faculty of Law, University of Hong Kong Faculty of Law, the Chinese University of Hong Kong Faculty of Law, Peking University Law School, Peking University School of Transnational Law, University of California-Irvine Law School, and Rutgers Law School. For excellent assistance in editing this article, the author thanks Kara Cooper, William Carpenter, and the JILB Staff. The views expressed in this article do not reflect the official views of the Association or any of its members. All errors are mine. 36_1_3_LI SUPERFINAL.DOCX (DO NOT DELETE) 2/10/16 3:28 PM Northwestern Journal of International Law & Business 36:143 (2016) 144 TABLE OF CONTENTS
Electronic Bypass for Diabetes: Optimization of Stimulation Parameters and Mechanisms of Glucagon-Like Peptide-1.

Objectives Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats. Materials and methods Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia. Results The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p 0.05, IES + Exendin 9-39 vs. sham-IES, N = 8). Conclusion IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.