cssi/SciSciGPT-SciSciNet huggingface dataset:
Locomotive Crash Energy Management Coupling Tests

Research to develop new technologies for increasing the safety of passengers and crew in rail equipment is being directed by the Federal Railroad Administration’s (FRA’s) Office of Research, Development, and Technology. Crash energy management (CEM) components which can be integrated into the end structure of a locomotive have been developed: a push-back coupler and a deformable anti-climber. These components are designed to inhibit override in the event of a collision. The results of vehicle-to-vehicle override, where the strong underframe of one vehicle, typically a locomotive, impacts the weaker superstructure of the other vehicle, can be devastating. These components are designed to improve crashworthiness for equipped locomotives in a wide range of potential collisions, including collisions with conventional locomotives, conventional cab cars, and freight equipment.Concerns have been raised in discussions with industry that push-back couplers may trigger prematurely, and may require replacement due to unintentional activation as a result of service loads. Push-back couplers are designed with trigger loads meant to exceed the expected maximum service loads experienced by conventional couplers. Analytical models are typically used to determine these required trigger loads. Two sets of coupling tests are planned to demonstrate this, one with a conventional locomotive equipped with conventional draft gear and coupler, and another with a conventional locomotive retrofit with a push-back coupler. These tests will allow a performance comparison of a conventional locomotive with a CEM-equipped locomotive during coupling. In addition to the two sets of coupling tests, car-to-car compatibility tests of CEM-equipped locomotives, as well as a train-to-train test are also planned. This arrangement of tests allows for evaluation of the CEM-equipped locomotive performance, as well as comparison of measured with simulated locomotive performance in the car-to-car and train-to-train tests.The coupling tests of a conventional locomotive have been conducted, the results of which compared favorably with pre-test predictions. In the coupling tests of a CEM-equipped locomotive, the coupling speed for which the push-back coupler (PBC) triggers will be measured. A moving, CEM-equipped locomotive will be coupled to a standing cab car. The coupling speed for the first test will be low, approximately 2 mph. The test will then be repeated with the speed increasing incrementally until the PBC triggers.This paper describes the fabrication, retrofit, test requirements, and analysis predictions for the CEM coupling tests. The equipment to be tested, track conditions, test procedures, and measurements to be made are described. A model for predicting the longitudinal forces acting on the equipment and couplers has been developed, along with preliminary predictions for the CEM coupling tests.
Comparing the Federal Arbitration Act and the UNCITRAL Model Law on International Commercial Arbitration

The United States (U.S.) Federal Arbitration Act (the “FAA”) and the United Nations Commission on International Trade Law (UNCITRAL) Model Law on International Commercial Arbitration (the “Model Law”) are two of the main sources of legislative guidance on international arbitration procedure and the enforcement of arbitral awards in the U.S. State arbitration statutes represent a third category of arbitration legislation that may apply to international commercial arbitrations seated or enforced in the U.S. The FAA always applies and the UNCITRAL Model Law may apply to arbitrations seated in the U.S., depending on the location of the seat of arbitration or the place of enforcement of the arbitral award. This book chapter compares the key elements of the FAA and the Model Law.
Tree-level gluon amplitudes on the celestial sphere

Abstract Pasterski, Shao and Strominger have recently proposed that massless scattering amplitudes can be mapped to correlators on the celestial sphere at infinity via a Mellin transform. We apply this prescription to arbitrary n-point tree-level gluon amplitudes. The Mellin transforms of MHV amplitudes are given by generalized hypergeometric functions on the Grassmannian G r ( 4 , n ) , while generic non-MHV amplitudes are given by more complicated Gelfand A-hypergeometric functions.
Robotic-Assisted Laparoscopic Partial Nephrectomy

The incidence of renal cell carcinoma (RCC) continues to increase in the USA in part due to earlier detection with prevalent imaging (Potretzke et al. in J Kidney Cancer VHL 2:30, [1], AUA guidelines [4]).
In-hospital outcomes of transcarotid artery revascularization and carotid endarterectomy in the Society for Vascular Surgery Vascular Quality Initiative

Abstract Objective Transcarotid artery revascularization (TCAR) with flow reversal offers a less invasive option for carotid revascularization in high-risk patients and has the lowest reported overall stroke rate for any prospective trial of carotid artery stenting. However, outcome comparisons between TCAR and carotid endarterectomy (CEA) are needed to confirm the safety of TCAR outside of highly selected patients and providers. Methods We compared in-hospital outcomes of patients undergoing TCAR and CEA from January 2016 to March 2018 using the Society for Vascular Surgery Vascular Quality Initiative TCAR Surveillance Project registry and the Society for Vascular Surgery Vascular Quality Initiative CEA database, respectively. The primary outcome was a composite of in-hospital stroke and death. Results A total of 1182 patients underwent TCAR compared with 10,797 patients who underwent CEA. Patients undergoing TCAR were older (median age, 74 vs 71 years; P 1 day (27% vs 30%; P = .046). On adjusted analysis, there was no difference in terms of stroke/death (odds ratio, 1.3; 95% confidence interval, 0.8-2.2; P = .28), stroke/death/MI (odds ratio, 1.4; 95% confidence interval, 0.9-2.1, P = .18), or the individual outcomes. Conclusions Despite a substantially higher medical risk in patients undergoing TCAR, in-hospital stroke/death rates were similar between TCAR and CEA. Further comparative studies with larger samples sizes and longer follow-up will be needed to establish the role of TCAR in extracranial carotid disease management.
Primary orbital melanoma without ocular involvement in a Balinese cat

A 6.5-year-old spayed female Balinese cat was diagnosed with a large and locally invasive primary orbital melanoma, without ocular involvement or detectable metastatic disease. Advanced imaging and immunohistochemical studies helped in obtaining the diagnosis. Because of advanced unresectable disease and ensuing poor quality of life, the cat was euthanized.
Untold Tales of the Self: the Ineffable in Early-Modern Jain Poetry

Jain ādhyātmik (spiritual, mystical) poets from the 17th to 19th centuries (e.g., Banārasīdās, Ānandghan, Cidānanda) elaborated a category of ineffability to discuss the pure experience of the soul or self (ātma-anubhava). These early-modern Jain poets mobilized a very specific understanding of the ineffable, one that resists language and logocentrism as sources of delusion and conflict. The focus on the ineffable in this poetry is always attended by a set of terms that qualify the ādhyātmik view. These are a privileging of the neutral (samatā), experience (anubhava), and on the other hand, a demotion of opinion, partisanship, doctrinarism, and bigotry (matawālā, mata-arthi, mata-jaṅgī). This paper will show that a shared constellation of terms, intertextuality, and a rejection of partisanship and logocentrism bound a group of Jain poets from the 17th to 19th centuries to a particular endorsement and understanding of ineffability; one which was authorized and emboldened by an engagement with Jain philosophical plurality and non-absolutism. The poetry exhibits a frequent co-occurrence of ādhyātmik anubhava with the Jain the epistemological system known as saptabhaṅgī (Jain seven-valued predications), of which avaktavya (sometimes translated as ineffable or non-assertable) is a prominent aspect. The association philosophically grounds ādhyātmik positions and reinforces their assertion that some aspects of reality, namely ātma-anubhava, are ineffable and beyond the realm of phenomenal predication.
Response to fire by a forest specialist in isolated montane forest

Abstract Fire events have increased in scale and severity due to hotter, drier conditions brought on by climate change and fire suppression. Extreme fire events can be detrimental to forest specialists, especially populations at the edge of the species range, where conditions can vary from those within the core of the range. The San Bernardino flying squirrel (Glaucomys oregonensis californicus) is the southernmost subspecies of Humboldt’s flying squirrel and occurs only in the San Bernardino Mountains of southern California after apparent extirpation from the nearby San Jacinto Mountains. We used non-invasive methods to assess how fire affects flying squirrel occupancy. We surveyed for flying squirrels in burned and unburned areas of the San Bernardino Mountains, and measured habitat features to construct occupancy models. Our top models indicated that flying squirrels occupy lower burn severities but could still occur at higher burn severities if canopy cover remained intact, forest duff remained deep, and tree mortality remained low, especially on steeper slopes. Our study illustrates the ability of San Bernardino flying squirrels, and the potential for other flying squirrels, to survive major fire events and maintain their role in the forest ecosystem. Such results are especially important for species management and understanding how parts of an ecosystem can react as fire frequency and severity increases.
How Do Factor Specificity and Emigration Make Income Inequality Worse in Developing Countries

Immigration policies in most developed countries are increasingly tilted toward skilled labor. Whether such policies hurt the sending countries is somewhat controversial. In this paper, we emphasize one aspect of skilled migrants’ effect, namely whether income inequality increases with migrants’ level of education in sending countries. Using pooled Gini coefficient from 1980 to 2010 data for 110 developing countries, the analysis finds that an emigration of unskilled labor produces an unfavorable effect on the wage inequality. That is, inequality increases with an increase in unskilled labor emigration from the country. However, there appears to be no effect of skilled emigration on inequality. A clearer understanding of the channels through which low-skilled migration will be detrimental for income inequality in developing countries may assist policymakers to craft appropriate policies to curtail low-skilled migration that would serve to improve equality. To the extent that inequality depresses (promotes) economic development, then emigration of low-skilled workers could impede (facilitate) economic growth.
Differences in outcome for patients with cholangiocarcinoma: Racial/ethnic disparity or socioeconomic factors?

Abstract Background Inequities in cancer survival are well documented. Whether disparities in overall survival (OS) result from inherent racial differences in underlying disease biology or socioeconomic factors (SEF) is not known. Our aim was to define the association of race/ethnicity and SEF with OS in pts with cholangiocarcinoma (CCA). Methods Patients with CCA of all sites and stages in the National Cancer Data Base (2004-13) were included. Racial/ethnic groups were defined as non-Hispanic White (NH-W), non-Hispanic Black (NH-B), Asian, and Hispanic. Income and education were based on census data for patients’ zip code. Income was defined as high (≥$63,000) vs low ( Results 27,151 patients were included with a mean age of 68 yrs; 51% were male. 78% were NH-W, 8% NH-B, 8% Hispanic, and 6% Asian. 56% had Medicare, 33% private insurance, 7% Medicaid, and 4% were uninsured. 67% had low income. 19% lived in an area where >20% of adults did not finish high school. NH-B and Hispanic patients had more unfavorable SEF including uninsured status, low income, and less formal education than NH-W and Asian pts (all p Conclusions Disparities in survival exist in CCA, however they are not driven by race/ethnicity. Non-privately insured and low-income patients had decreased OS, as did patients treated at non-academic centers and outside the Northeast. This suggests that decreased ability to access and afford care results in worse outcomes, rather than biological differences amongst racial/ethnic groups.
Palliative and end-of-life care in patients with ESRD

Abstract This chapter argues for the need for expansion of palliative nephrology and end-of-life care. It reviews the excess mortality, morbidity, and substantial symptom burden associated with end-stage renal disease. It outlines principles and guidelines for conservative kidney management with a discussion of advanced care directives. The chapter seeks to raise attention to the complex end-of-life issues experienced in renal palliative care with the goal of stimulating improved evidence-based and algorithmic treatments that will lead to improvements in patient-centered outcomes.
Educational attainment causally impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study in ~ 780,000 study participants

Background: Observational studies suggest that lower educational attainment may be associated with risky alcohol consumption behaviors. However, these findings may be biased by confounding and reverse causality. Using two-sample Mendelian randomization (MR), we can determine whether education is causally related to alcohol consumption behaviors and alcohol dependence (AD). Methods: We performed two-sample MR using summary statistics from recent genome-wide association studies (GWAS) in 784,726 study participants to assess the causal effects of educational attainment on alcohol consumption behaviors, including intake frequency, total weekly drinks, beverage preferences, whether alcohol is consumed with meals, as well as AD risk. Of 53 independent (linkage disequilibrium R2=0.001, kb distance<10,000) nucleotide polymorphisms (SNPs) that predict educational attainment, and after removal of palindromes with intermediate allele frequency, 51 were present in the alcohol consumption behaviors, and 44 were present in the AD GWAS. Complementary MR techniques accommodating different assumptions about genetic pleiotropy (inverse variance weighted (IVW), Egger, weighted median, and weighted mode MR) tested the sensitivity of our results. Results: We found strong evidence of a causal effect between years of education and alcohol consumption behaviors generally. Higher educational attainment decreased alcohol intake frequency (IVW odds ratio (ORIVW), 0.718, 95% CI, 0.673-0.765, PIVW=4.62E-24), as well as weekly distilled spirits intake (ORIVW, 0.874, 95% CI, 0.833-0.917, PIVW=3.91E-08), and weekly beer plus cider intake (ORIVW, 0.837, 95% CI, 0.805-0.869, P=5.58E-20), but increased weekly white wine (ORIVW, 1.220, 95% CI, 1.172-1.269, PIVW=7.96E-23), red wine (ORIVW, 1.227, 95% CI, 1.174-1.282, PIVW=6.67E-20), and fortified wine intake (ORIVW, 1.051, 95% CI, 1.027-1.075, PIVW ]=1.87E-07). We also found evidence educational attainment reduced AD risk (ORIVW .508, 95% CI, .315-.819, PIVW=5.51E-03). We found no evidence for total weekly consumption (ORIVW .508, 95% CI, .315-.819, PIVW=5.51E-03). Consistency of results across complementary MR methods strengthens our causal inferences. Conclusions: Our findings show low educational attainment is causally associated with increased alcohol consumption frequency, increased preference for beer, cider, and spirits, and AD risk, indicating a potential mechanism explaining reported associations between educational attainment and adverse health outcomes, including cardiovascular disease. These findings suggest increased educational attainment might be a useful prevention strategy to reduce risky alcohol behaviors and AD.
Processing implicatures in English as a Lingua Franca communication

Abstract The paper argues that cognitive mechanisms responsible for implicatures are the same no matter what language someone uses. However, linguistic knowledge, conceptual knowledge, encyclopedic knowledge and contextual effect that are all needed for producing and comprehending implicatures vary significantly in ELF users. They cannot be expected to act in accordance with the conventions and norms of the societal culture of native English-speaking communities. It is claimed that in ELF discourse participants must create their own temporary norms and conventions with implicatures among them. Consequently, it seems mistaken to test L2 users or ELF speakers on the use of L1-based conversational and/or frozen implicatures (functioning as idioms) as many studies have done. The paper offers a modified understanding of implicatures with the notion of “simplicature”, and a model to explain the relationship and interplay between factors that affect implicature processing: linguistic knowledge, conceptual knowledge, encyclopedic knowledge and contextual effect.
The response of prices, sales, and output to temporary changes in demand

We determine empirically how the Big Three automakers accommodate shocks to demand. They have the capability to change prices, alter labor inputs through temporary layoffs and overtime, or adjust inventories. These adjustments are interrelated, non-convex, and dynamic in nature. Combining weekly plant-level data on production schedules and output with monthly data on sales and transaction prices, we estimate a dynamic profit-maximization model of the firm. Using impulse response functions, we demonstrate that when an automaker is hit with a demand shock sales respond immediately, prices respond gradually, and production responds only after a delay. The size of the immediate sales response is linear in the size of the shock, but the delayed production response is non-convex in the size of the shock. For sufficiently large shocks the cumulative production response over the product cycle is an order of magnitude larger than the cumulative price response. We examine two recent demand shocks: the Ford Explorer/Firestone tire recall of 2000, and the September 11, 2001 terrorist attacks.
Imaging study of myringotomy in dairy calves

Otitis media is common in dairy calves. Antibiotic treatment alone does not always result in complete resolution. Based on human paediatric medicine experience, where myringotomy tubes are commonly placed to drain purulent accumulations from the ear, it has been suggested that a myringotomy can be performed in calves. We investigated whether performing a myringotomy using a straight rigid instrument (knitting needle) is anatomically feasible in calves. Two imaging techniques and direct visualization were used to observe the trajectory of the needle and its immediate effects on the tympanic membrane. Our study shows there is no anatomic impediment to performing a myringotomy in calves with a straight rigid instrument.
Linked fate among underrepresented groups: Investigating the relationships between Black college students’ perceptions of institutional diversity climate and mental health

Objective: Negative perceptions of institutional racial climate relate to worse mental health outcomes for Black college students. Yet, few scholars have considered how Black students’ perceptions ...
The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel

Hematopoietic stem cells (HSCs) are a rare stem cell population found primarily in the bone marrow and responsible for the production of the body's full complement of blood and immune cells. Used clinically to treat a range of hematopoietic disorders, there is a significant need to identify approaches to selectively expand their numbers ex vivo. Here we describe a methacrylamide-functionalized gelatin (GelMA) hydrogel for in vitro culture of primary murine HSCs. Stem cell factor (SCF) is a critical biomolecular component of native HSC niches in vivo and is used in large dosages in cell culture media for HSC expansion in vitro. We report a photochemistry based approach to covalently immobilize SCF within GelMA hydrogels via acrylate-functionalized polyethylene glycol (PEG) tethers. PEG-functionalized SCF retains the native bioactivity of SCF but can be stably incorporated and retained within the GelMA hydrogel over 7 days. Freshly-isolated murine HSCs cultured in GelMA hydrogels containing covalently-immobilized SCF showed reduced proliferation and improved selectivity for maintaining primitive HSCs. Comparatively, soluble SCF within the GelMA hydrogel network induced increased proliferation of differentiating hematopoietic cells. We used a microfluidic templating approach to create GelMA hydrogels containing gradients of immobilized SCF that locally direct HSC response. Together, we report a biomaterial platform to examine the effect of the local presentation of soluble vs. matrix-immobilized biomolecular signals on HSC expansion and lineage specification. This approach may be a critical component of a biomaterial-based artificial bone marrow to provide the correct sequence of niche signals to grow HSCs in the laboratory.
Evolutionary perspective on the structure and function of ribonuclease P, a ribozyme.

Ribonuclease P (RNase P) is a key enzyme in the biosynthesis of tRNA (for reviews, see references 3, 11, and 51). It is an RNA-processing endonuclease that specifically cleaves precursors of tRNA, releasing 59 precursor sequences and thereby forming the mature 59 ends of the tRNAs. RNase P is involved in processing all species of tRNA and is present in all cells and organelles that carry out tRNA synthesis. It is a particularly interesting enzyme because of its composition; it is a ribonucleoprotein (37). The nature of RNase P has been investigated for a broad diversity of organisms, including representatives of all the phylogenetic domains: Archaea, (eu)Bacteria, and Eucarya (see reference 72 for phylogenetic nomenclature). In the case of the enzyme from Bacteria, RNase P contains a catalytic RNA, or ribozyme (22, 62). The secondary structure of the bacterial RNase P RNA has now been determined, models for its three-dimensional structure have been proposed, and numerous correlations between catalytic function and structure are being discovered. The purpose of this minireview is to provide an overview of RNase P, with emphasis on the structure of the bacterial RNase P RNA and how it varies between different organisms. Any understanding of the function of this unusual type of enzyme will rest on knowledge of its structure and patterns of variation.
Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas: data from the SEER program, 1973-2001.

BACKGROUND Detailed population-based estimates of long-term survival as well as patterns of care for patients with low-grade gliomas examined by age at diagnosis, gender, and race have not been widely available. METHODS Time to death was examined among 2009 individuals diagnosed with a supratentorial low-grade glioma and reported to the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute from 1973–2001 using Kaplan–Meier estimation. A Cox proportional hazards model was used to assess the effect of age at diagnosis, race, gender, histology, anatomic location within the brain, first course of treatment, and year of diagnosis upon this risk. RESULTS The cumulative 5-, 10-, 15- and 20-year survival rates among all individuals initially diagnosed with a supratentorial low-grade glioma were 59.9% (95% confidence interval [95% CI], 57.6–62.2); 42.6% (95% CI, 39.9–45.2); 31.9% (95% CI, 29.0–34.8); and 26.0% (95% CI, 22.7–29.2), respectively. Improved survival was significantly associated with female gender (hazard ratio [HR], 0.84; 95% CI, 0.74–0.95), younger age, white race (HR, 0.70; 95% CI, 0.54–0.93), histology, and later year of diagnosis. Surgical treatment was associated with increased survival. The use of radiation therapy as a first course of treatment for these lesions has significantly decreased over time with the majority of patients receiving only surgery as a first course of treatment. CONCLUSIONS Data for patients diagnosed with low-grade gliomas revealed increasing survival times over the past 25 years with a subset of patients surviving for decades. Differences in survival by race, gender, histology, and first course of treatment were appreciated. These data suggested that the clinical course of low-grade glioma for some patients may be more encouraging than previously perceived and that the identification of this group of patients may allow refinement of current treatment protocols. Cancer 2006. © 2006 American Cancer Society.
Gadolinium inhibits group III but not group IV muscle afferent responses to dynamic exercise

Dynamic exercise has been shown to stimulate rapidly both group III and IV muscle afferents. The often rapid (i.e. 2 s) onset latencies of the group IV afferents is particularly surprising because these unmyelinated afferents are thought to respond to the gradual accumulation of metabolites signalling a mismatch between blood/oxygen demand and supply in exercising muscles. One explanation for the rapid onset to exercise by group IV afferents is that they are mechanosensitive, a concept that has been supported by the finding that these afferents were stimulated by vasodilatation induced by injection of vasoactive drugs. We therefore examined in decerebrated cats the effect of gadolinium, a blocker of mechanogated channels, on the responses of group III and IV muscle afferents to dynamic exercise induced by electrical stimulation of the mesencephalic locomotor region. We found that gadolinium (10 mm; 1 ml) injected into the abdominal aorta had no significant effect (P > 0.05) on the responses of 11 group IV afferents to dynamic exercise. In contrast, gadolinium markedly attenuated the responses of 11 group III afferents to exercise (P < 0.05). Our findings suggest that group IV afferents are not responding to a mechanical stimulus during exercise. Instead their rapid response to dynamic exercise might be caused by a chemical substance whose concentration is directly proportional to blood flow, which increases in the skeletal muscles when they are dynamically exercising.
Potential Responses of Landscape Boundaries to Global Environmental Change

Global change is likely to affect the location, size, shape, or composition of landscape boundaries. Neutral models were used to study two general mechanisms by which landscape boundaries may respond to global change: (1) disturbance regimes may change in response to climate, leading to rapid alterations in landscape structure, and (2) in the absence of disturbance, suitable habitat for different species may move gradually and directionally. The spread of disturbance was simulated as a function of the proportion of the landscape occupied by a disturbance-prone habitat and the frequency (probability of initiation) and intensity (probability of spread) of a habitat-specific disturbance. The effects of changing disturbance regimes on landscape boundaries were different in connected and fragmented landscapes. In connected landscapes, an increase in disturbance intensity caused landscape boundaries to decrease. In landscapes that were fragmented, an increase in disturbance frequency resulted in a decrease in landscape boundaries. The qualitative change in sensitivity to disturbance intensity and frequency occurred when the proportion of disturbance-susceptible habitat was near the critical threshold, pc, which is approximately 0.6 in random landscapes. Habitat displacement and species migration were simulated as a function of the proportion of available landscape occupied by a community, migration (probability of colonizing adjacent cells), extinction (probability of the community becoming locally extinct), and the rate at which potential habitat (i.e., climatic conditions suitable for establishment) is displaced. The simulated community could track the movement of habitat when the displacement rate was slow, the extinction probability was low, and the migration probability was at least moderate. Spatial lags (distance of remnants from main front) were greatest when extinction was low and the habitat moved quickly. Simulations such as these can be used to identify combinations of parameters which allow successful colonization and those for which community survival becomes critical. Neutral models can generate quantitative, testable hypotheses which can be used to better understand and predict landscape responses to global change.
Fault-based test generation for cause-effect graphs

The notion of cause-effect graphs (CEGs) has been used for the specification and test generation of a software system. In this paper, we present a fault-based approach to test generation for CEGs, called BOR (boolean operator) testing, which is based on the detection of boolean operator faults. We show how to generate a minimum BOR test set for a CEG and how to evaluate an existing test set for a CEG in order to determine whether additional tests are necessary for BOR testing. We have applied BOR testing to a CEG that specifies a real-time boiler control and monitoring system. The results of our empirical studies indicate that CEG-based BOR testing is very practical and effective.
IFN-γ-Inducible Protein-10 Is Essential for the Generation of a Protective Tumor-Specific CD8 T Cell Response Induced by Single-Chain IL-12 Gene Therapy

The successful induction of T cell-mediated protective immunity against poorly immunogenic malignancies remains a major challenge for cancer immunotherapy. Here, we demonstrate that the induction of tumor-protective immunity by IL-12 in a murine neuroblastoma model depends entirely on the CXC chemokine IFN-gamma-inducible protein 10 (IP-10). This was established by in vivo depletion of IP-10 with mAbs in mice vaccinated against NXS2 neuroblastoma by gene therapy with a linearized, single-chain (sc) version of the heterodimeric cytokine IL-12 (scIL-12). The efficacy of IP-10 depletion was indicated by the effective abrogation of scIL-12-mediated antiangiogenesis and T cell chemotaxis in mice receiving s.c. injections of scIL-12-producing NXS2 cells. These findings were extended by data demonstrating that IP-10 is directly involved in the generation of a tumor-protective CD8+ T cell-mediated immune response during the early immunization phase. Four lines of evidence support this contention: First, A/J mice vaccinated with NXS2 scIL-12 and depleted of IP-10 by two different anti-IP-10 mAbs revealed an abrogation of systemic-protective immunity against disseminated metastases. Second, CD8+ T cell-mediated MHC class I Ag-restricted tumor cell lysis was inhibited in such mice. Third, intracellular IFN-gamma expressed by proliferating CD8+ T cells was substantially inhibited in IP-10-depleted, scIL-12 NXS2-vaccinated mice. Fourth, systemic tumor protective immunity was completely abrogated in mice depleted of IP-10 in the early immunization phase, but not if IP-10 was depleted only in the effector phase. These findings suggest that IP-10 plays a crucial role during the early immunization phase in the induction of immunity against neuroblastoma by scIL-12 gene therapy.
Mucosal correlates of cross-protection for live-attenuated influenza virus vaccines in pigs (VET2P.1031)

Controlling swine influenza A virus (IAV) has become increasingly difficult with the emergence of novel reassorted strains and introduction of human seasonal IAV into pigs. In North American swine there are 6 antigenically distinct H1 subtypes currently circulating. Live-attenuated influenza vaccines (LAIV) provide broader cross-protection than whole-inactivated virus (WIV) vaccine making LAIV a candidate for next-generation swine IAV vaccines. However, there is no standardized assay to predict cross-protection following LAIV vaccination. Hemagglutination-inhibiting (HI) immunoglobulin (Ig) in serum has long been the gold standard correlate of protection following WIV vaccination; however, LAIV does not elicit a robust serum HI Ig titer. Oral fluids (OF) have become a rapidly developing diagnostic specimen for a variety of animal pathogens. We evaluated nasal wash (NW) and OF samples for measuring cross-reactive Ig responses to a panel of H1 viruses following vaccination. Both NW and OF had detectable levels of IAV-specific Ig when measured by ELISA. NW from LAIV vaccinated pigs had significant cross-reactive IgA titers, while NW from WIV vaccinated pigs did not have detectable IgA. Samples of OF from either LAIV or WIV vaccinated pigs had high titers of cross-reactive IAV-specific IgG and measurable IgA. OF samples also displayed IAV specific neutralization. These data suggest OF can serve as a sample for evaluating LAIV immunogenicity and predicting cross-protection.
Anesthetic-like Interactions of Nitric Oxide with Albumin and Hemeproteins A MECHANISM FOR CONTROL OF PROTEIN FUNCTION

Noncovalent bonding interactions of nitric oxide (NO) with human serum albumin (HSA), human hemoglobin A, bovine myoglobin, and bovine cytochrome c oxidase (CcO) have been explored. The anesthetic nitrous oxide (NNO) occupies multiple sites within each protein, but does not bind to heme iron. Infrared (IR) spectra of NNO molecules sequestered within albumin, with NO present, support the binding of NO and NNO to the same sites with comparable affinities. Perturbations of IR spectra of the Cys34 thiol of HSA indicate NO, NNO, halothane, and chloroform can induce similar changes in protein structure. Experiments evaluating the relative affinities of binding of NO and carbon monoxide (CO) to iron(II) sites of the hemeproteins led to evidence of NO binding to noniron, nonsulfur sites as well. With HbA, IR spectra of cysteine thiols and/or the iron(II) N-O stretching region denote changes in protein structure due to NO, NNO, or CO occupying noniron sites with an order of decreasing affinities of NO > NNO > CO. Loss of NO from some, not all, noniron sites in hemeproteins is very slow (t½∼ hours). These findings provide examples in which NO and anesthetics alter the structure and properties of protein similarly, and support the hypothesis that some physiological effects of NO (and possibly CO) result from anesthetic-like noncovalent bonding to sites within protein or other tissue components. Such bonding may be involved in mechanisms for control of oxygen transport, mitochondrial respiration, and activation of soluble guanylate cyclase by NO.
DIRECT OBSERVATION OF LONG‐RANGE MIGRATION OF SELF‐INTERSTITIAL ATOMS IN STAGE I OF IRRADIATED PLATINUM

The motion of single self‐interstitial atoms (SIA's) in stage I of irradiated platinum was observed directly by field ion microscopy. A specimen irradiated at a temperature of 10°K with 20‐keV Pt+ ions was found to contain immobile SIA's in the bulk at this temperature, as determined via pulse‐field evaporation experiments. Direct observation of specimens, irradiated with 20‐ or 30‐keV Pt+ ions, during warming experiments from 10 to 70°K showed that a flux of SIA's crossed the surface of the specimens between 13 and 25°K. Application of a diffusion model to the data yielded a value of ∼ 0.06 eV for the enthalpy change of migration and a diffusion coefficient of ∼ 0.5 exp(−0.06 eV/kT) cm2 sec−1 for the SIA.
Abstract 5535: Gcn5 modulates the cellular response to oxidative stress induced by histone deacetylase inhibitors

Aberrant histone post-translational modifications including acetylation are common in human cancers and result in dysregulation of gene expression. Our laboratory has focused on studying the effects of hydroxamic acid based HDAC inhibitors (HDACis) including TSA, SAHA and CG-1521. We have employed a whole genome yeast deletion library screen to gain insight into the mechanism of the HDAC inhibitor CG-1521 and identify potential combinatorial drug targets. Gene ontology enrichment analysis shows that sensitive strains are highly enriched in processes regulating chromatin remodeling and transcription. Deletions of components of the SAGA HAT complex are highly overrepresented in the sensitive strains, including the catalytic subunit Gcn5. The gcn5 deletion strain displays increased sensitivity to CG-1521 induced cell death compared to the wild type strain, suggesting that the SAGA complex is required to reduce the effect of CG-1521 on cell growth. Gene expression analysis indicates that CG-1521 elicits an oxidative stress response in both the wild type and the gcn5 deletion strain. Gcn5 deletion substantially increases the level of oxidative stress induced by CG-1521 as measured by flow cytometry. In the colorectal cancer cell line HT29, treatment with CG-1521 is accompanied by an increase in oxidative stress and co-treatment with the Gcn5 specific inhibitor MB-3 or RNAi-mediated knockdown of the human Gcn5 homologs, Gcn5 and PCAF, enhances the growth-inhibitory effect of CG-1521. These studies have shown that disruption of the SAGA HAT complex with MB-3 or RNAi-mediated knockdown sensitizes tumor cells to CG-1521. Taken together, our work suggests that the combination of selective HAT and HDAC inhibitors may be an effective treatment of cancer. Citation Format: Ann-Christin Gaupel, Thomas J. Begley, Martin P. Tenniswood. Gcn5 modulates the cellular response to oxidative stress induced by histone deacetylase inhibitors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5535. doi:10.1158/1538-7445.AM2014-5535
Devising Rule of Law Baselines: The Next Step in Quantitative Studies of Judging

Political scientists and law professors have lately taken to asserting that quantitative studies of judging reveal worrisome findings about the rule of law in the U.S. judicial system. The authors of Are Judges Political?, for example, declare: “We show that variations in panel composition lead to dramatically different outcomes, in a way that creates serious problems for the rule of law.” To evaluate such assertions, one must first know what the rule of law requires of judges; then one must identify or measure how much, or in what ways, judges are falling short of these requirements: there must be rule of law baselines or standards. None exist, however - a gap which allows researchers to draw misleading conclusions from the results of their studies. This essay demonstrates the need for rule of law baselines and offers several proposals for how they might be constructed (with due warnings about their limitations). Furthermore, it argues that the incorporation of such baselines into quantitative research on judging will enhance the value of the information produced in these studies. This brief essay was presented at a two-day colloquium at Duke Law School involving federal judges, legal theorists, and political scientists, which was convened to facilitate a productive exchange of ideas on the design and orientation of quantitative research on judging.
Iterative domain decomposition meshless method modeling of incompressible viscous flows and conjugate heat transfer

We develop an effective domain decomposition meshless methodology for conjugate heat transfer problems modeled by convecting fully viscous incompressible fluid interacting with conducting solids. The meshless formulation for fluid flow modeling is based on a radial basis function interpolation using Hardy inverse Multiquadrics and a time-progression decoupling of the equations using a Helmholtz potential. The domain decomposition approach effectively reduces the conditioning numbers of the resulting algebraic systems, arising from convective and conduction modeling, while increasing efficiency of the solution process and decreasing memory requirements. Moreover, the domain decomposition approach is ideally suited for parallel computation. Numerical examples are presented to validate the approach by comparing the meshless solutions to finite volume method (FVM) solutions provided by a commercial CFD solver.
Association of splenectomy with postoperative complications in patients with proximal gastric and gastroesophageal junction cancer.

Background: Splenectomy has been associated with increased morbidity after gastrectomy for gastric cancer. Resection of proximal versus distal tumors is associated with a higher morbidity. Because splenectomy is more commonly performed in resection of proximal tumors, these analyses may be biased. The aim of this study was to describe the association of splenectomy with complications in patients undergoing resection of proximal gastric and gastroesophageal junction (GEJ) cancers.
Some model‐based inference about global warming

The magnitude of the response of global temperature to changes in atmospheric composition depends on a parameter called temperature sensitivity. The value of this parameter is unknown. When temperature sensitivity is estimated by fitting the response of a climate model forced by historical changes in atmospheric composition to the historical trend in global temperature, the estimate is rather low. It has been suggested that this may be due to the suppression of warming by sulphate aerosols, an effect that is difficult to incorporate into model experiments. This paper presents an approach to estimating temperature sensitivity based on historical temperature variability, rather than trend, which circumvents this problem. The results are in close agreement with those based on fitting the trend.
Political Attitudes and the Local Community

Politicians and political scientists alike have long recognized the impact of the local political environment on the attitudes and behavior of community residents. V.O. Key demonstrated in a variety of contexts the striking persistence of distinctive community political traditions. The extensive discussion of the “suburban conversion” hypothesis has turned in part on the question of the influence of the local community on partisan attitudes. A number of studies of voting behavior have shown that majority views in a community have a disproportionate advantage in gaining and holding adherents. There is, in short, good reason to suspect that the local community has a significant influence on social attitudes and political behavior. Why is this so? How does the Republican “atmosphere” in Elmira affect the votes of individual Elmirans? How are community political traditions maintained through decades of changing community composition? Why does the minority party in a community fail to mobilize many of the voters who are predisposed toward it? What explanation of these sorts of community influence seems most adequate?—this is the question to be examined in this paper.
Origins of Rotational Barriers in Hydrogen Peroxide and Hydrazine

Compared with their isoelectronic system ethane, both hydrogen peroxide and hydrazine exhibit a double well torsional energy curve where skew conformers are favored over trans conformers and cis conformers are energy-maximum states. Clearly, the involvement of the lone oxygen and nitrogen pairs, or more specifically, the enhanced stabilizing n→σ* negative hyperconjugation effect and destabilizing repulsion among lone pairs, complicates the conformational analysis. In this work, the modern ab initio valence bond (VB) method is employed to quantitatively investigate the torsional energy curves of hydrogen peroxide and hydrazine in terms of hyperconjugative stabilization, steric repulsion, and structural and electronic relaxations. It is found that if the hyperconjugation effect is completely quenched, the trans conformers will be favored, while the cis conformers are the only transition state pertaining to the torsional motion in the potential energy surfaces of H2O2 and N2H4. Although usually the steric ef...
Nitrite Reductase Activity of Sol-Gel-encapsulated Deoxyhemoglobin INFLUENCE OF QUATERNARY AND TERTIARY STRUCTURE

Nitrite reductase activity of deoxyhemoglobin (HbA) in the red blood cell has been proposed as a non-nitric-oxide synthase source of deliverable nitric oxide (NO) within the vasculature. An essential element in this scheme is the dependence of this reaction on the quaternary/tertiary structure of HbA. In the present work sol-gel encapsulation is used to trap and stabilize deoxy-HbA in either the T or R quaternary state, thus allowing for the clear-cut monitoring of nitrite reductase activity as a function of quaternary state with and without effectors. The results indicate that reaction is not only R-T-dependent but also heterotropic effector-dependent within a given quaternary state. The use of the maximum entropy method to analyze carbon monoxide (CO) recombination kinetics from fully and partially liganded sol-gel-encapsulated T-state species provides a framework for understanding effector modulation of T-state reactivity by influencing the distribution of high and low reactivity T-state conformations.
Unintended consequences of child care regulations

Abstract The effects of regulations governing staff-child ratio, group size, and staff qualifications in child care centers are estimated, using data on a sample of centers. The data contain measures of staff characteristics and wages, price of the service, and the developmental quality of the child care provided. Regulations vary across states, but may be endogenous to these outcomes. Estimates with state fixed effects are feasible because regulations vary within states by age group of children and job title of staff. Estimates with state fixed effects show that tougher regulations have some impact on input use, but have little or no impact on price and quality. The most striking finding is that tougher regulations reduce staff wages, suggesting that the incidence of child care regulations is on employees of day care centers.
Experimental studies of forced, combined and natural convection of water in vertical nine-rod bundles with a square lattice

Experiments of upflow- and downflow-forced turbulent and laminar convection, natural convection and buoyancy-assisted combined convection of water are performed in uniformly heated, square arrayed, nine-rod bundles having P/D ratios of 1.25, 1.38 and 1.5. In the experiments, Re varies from 250 to 3 × 104, Pr from 3 to 9, Raq from 5 × 105 to 3 × 108 for natural convection and from 107 to 7 × 108 for combined convection, and Ri from 0.03 to 300. The heat transfer data are correlated in the respective convective regimes, where the heated equivalent diameter is used as the characteristic length in all dimensionless quantities and water properties are evaluated at the mean bulk temperature. The forced convection data fall into two distinct regimes: forced turbulent and forced laminar; the Reynolds number at the transition between these regimes is a linear function of P/D. In the forced convection experiments the flow is hydrodynamically developing, but thermally fully developed. The natural convection data are correlated to within ± 10% in terms of Raq and the combined convection data are correlated to within ± 15% by superimposing the Nusselt numbers, raised to the fourth power, of forced laminar and natural convection. For all P/D values, the transition from forced laminar to combined convection occurs at Ri = 2.0. A comparison with triangularly arrayed rod bundles shows that for the same flow area per rod, the rod arrangement negligibly affects Nu in both forced and natural convection regimes.
Tryptamine-4,5-dione: Properties and reaction with glutathione

Abstract At physiological pH tryptamine-4,5-dione (1), which might be an aberrant metabolite of 5-hydroxytryptamine involved in the etiology of Alzheimer's disease, reacts rapidly with glutathione to give 7-S-(glutathionyl)-tryptamine-4,5-dione (5). Procedures have been devised to isolate 5 and to elucidate its molecular structure using FAB-MS and 1H and 13C NMR spectroscopy. The redox characteristics of 1 and 5 have been elucidated using electrochemical methods.