cssi/SciSciGPT-SciSciNet huggingface dataset:
What determines the van der Waals coefficient beta in the LIE (linear interaction energy) method to estimate binding free energies using molecular dynamics simulations

Recently a semiempirical method has been proposed by Aqvist et al. to calculate absolute and relative binding free energies. In this method, the absolute binding free energy of a ligand is estimated as deltaGbind = alpha + beta , where Vel(bound) and Vvdw(bound) are the electrostatic and van der Waals interaction energies between the ligand and the solvated protein from an molecular dynamics (MD) trajectory with ligand bound to protein and Vel(free) and Vel(free) and Vvdw(free) are the electrostatic and van der Waals interaction energies between the ligand and the water from an MD trajectory with the ligand in water. A set of values, alpha = 0.5 and beta = 0.16, was found to give results in good agreement with experimental data. Later, however, different optimal values of beta were found in studies of compounds binding to P450cam and avidin. The present work investigates how the optimal value of beta depends on the nature of binding sites for different protein-ligand interactions. By examining seven ligands interacting with five proteins, we have discovered a linear correlation between the value of beta and the weighted non-polar desolvation ratio (WNDR), with a correlation coefficient of 0.96. We have also examined the ability of this correlation to predict optimal values of beta for different ligands binding to a single protein. We studied twelve neutral compounds bound to avidin. In this case, the WNDR approach gave a better estimate of the absolute binding free energies than results obtained using the fixed value of beta found for biotin-avidin. In terms of reproducing the relative binding free energy to biotin, the fixed-beta value gave better results for compounds similar to biotin, but for compounds less similar to biotin, the WNDR approach led to better relative binding free energies.
Structural differences between precommercially thinned and unthinned conifer stands

Effects of precommercial thinning (PCT) in young, high-density forest stands on the growth and yield of crop trees has been well-studied, but information about the response of habitat characteristics and structural attributes that are related to abundance and diversity of wildlife populations is deficient. We examined changes in habitat characteristics and forest structure that occurred with PCT and stand development in commercial spruce-fir stands within the Acadian forest of northern Maine. We selected 30 regenerating, herbicide-treated conifer stands (17 treated with PCT) of three development classes (1, 6, or 11 years post-PCT) and measured 27 variables that described the characteristics and structure of the understory, overstory, woody debris, or ground cover within these stands. The application of PCT accelerated some characteristics of stand development, resulting in a reduction of understory structure and complexity, which conflicts with previous studies of non-herbicide-treated forest that reported increases in understory complexity after thinning. Near-ground cover, overstory cover, and understory structure described >80% of the variation in vegetation structure between thinned and unthinned stands. Horizontal cover, an overstory to understory contrast, and a gradient of herbaceous vegetation described >75% of the variation that occurred as regenerating stands (thinned and unthinned) developed through time. The forest structure in regenerating stands treated with PCT may have negative effects on wildlife that are dependent on the structure of early successional forest, but may positively affect species that use more mature forest.
Optical duobinary spectral efficiency versus transmission performance: is there a tradeoff?

Tradeoffs between optical spectral efficiency, ASE noise-tolerance, and dispersion tolerance are investigated experimentally for three modulation formats - RZ, NRZ, and duobinary. Duobinary does not follow conventional wisdom - achieving excellent performance with the narrowest bandwidth.
Attention Deficit Disorder With Hyperactivity: a Review and Implications for the Classroom

One of the most common problems experienced by elementary school children is attention deficit disorder with hyperactivity (ADD-H). Although this syndrome is defined by the American Psychiatric Association in the Diagnostic and Statistical Manual (3rd ed.) (DSM III), much of the research regarding its validity as a diagnostic category has been generated after publication of DSM II1. This article reviews the research findings related to the various forms of intervention or treatment commonly employed in work with ADD-H children. Among the topics addressed are direct observation studies, drug treatment, drug effects on academic achievement, diet interventions, behavior modification, cognitive behavior modification, and metacognition and executive control. Practical implications of the research data are suggested for educators and school psychologists who do their work in school environments.
Transcript abundance supercedes editing efficiency as a factor in developmental variation of chloroplast gene expression.

In maize plastids, transcripts are known to be modified at 27 C-to-U RNA editing sites, affecting the expression of 15 different genes. The relative contribution of editing efficiency versus transcript abundance in regulation of chloroplast gene expression has previously been analyzed for only a few genes. We undertook a comprehensive analysis of the editing efficiency of each of the 27 maize editing sites in 10 different maize tissues, which contain a range of plastid types including chloroplasts, etioplasts, and amyloplasts. Using a reproducible poisoned primer extension assay, we detected variation between RNA editing extent of different sites in the same transcript in the same tissue, and between the same site in different tissues. The most striking editing deficiency is in an editing site in ndhB that is edited at only 8% and 1% in roots and callus plastids respectively, whereas green leaf chloroplasts edit this site at 100%. Editing efficiencies of some sites are not affected by the developmental stages we examined and are always edited close to 80–100%. The relative amounts of transcripts of each of the 10 genes that exhibited variable editing extents were determined by real-time PCR. Seven genes exhibited over 100 times lower transcript abundance in either roots or tissue-cultured cells relative to green leaf tissue. The quantitative analysis indicates that a particular editing site can be efficiently edited over a large range of transcript abundance, resulting in no general correlation of transcript abundance and editing extent. The independent variation of editing efficiency of different sites within the same transcript fits with a model that postulates individual trans-acting factors specific to each editing site. Because tissues where editing efficiency at certain sites is low invariably also exhibited greatly decreased abundance of the transcripts carrying those sites, decrease in the amounts of particular RNAs rather than a lack of editing is predicted to have the most significant impact on gene expression under steady-state conditions. Our data is consistent with the hypothesis that the role of editing in angiosperm plastids is to correct otherwise detrimental mutations rather than to generate significant protein diversity.
Why CIBERs matter to the competitiveness of U.S. businesses in the 21st century

Abstract Centers for International Business Education and Research (CIBERs)—located at 33 institutions of higher education across the U.S. and administered by the U.S. Department of Education under Title VI of the Higher Education Act—serve as regional and national resource centers for the business community, and as conduits for major initiatives to support and strengthen the international components of curricula in K-12 schools and institutions of higher education. This article argues that CIBERs are well-positioned to not only address current needs, but also drive innovative thinking and leading-edge activities toward longer-term challenges. Herein, exemplary activities from CIBERs serve as examples to support this claim, and Indiana University's CIBER strategic trajectory for the 2010-2014 grant cycle is explored within the context of the current global situation.
Dependence of estuarine productivity on anomalies in mean sea level

Abstract- The annual aboveground productiv- ity of Spartina alternijlora in a South Carolina salt marsh varies by a factor of two and correlates positively (r2 = 0.99, P < 0.001) with anomalies in mean sea level during the growing season. The effect of sea-level anomalies on the salinity of intertidal sediments probably accounts for the observed changes in primary production. We also show thzt commercial landings of shrimp and menhaden from the southeastern U.S. Atlantic and central Gulf of Mexico are positively cor- related with sea-level anomalies. These species use salt-marsh habitats as juveniles, and we at- tribute this correlation to effects of sea-level anomalies on habitat availability or food pro- duction. Macrophyte production in salt marshes of the east coast of North America is dom- inated by the cord grass Spartina alterni- flora, which is found in monospecific stands within the intertidal zone above mean sea level (msl) (McKee and Patrick 1 988). The major area of Spartina vegetation in marsh- es at North Inlet, South Carolina, occurs near the mean high tide (MHW) elevation (70 cm above msl) where the sediment is flooded an average of 14% of the time at a frequency of 1.4 d-I. The magnitude of in- terannual variation in aboveground pro-
Built to rebuild: in search of organizing principles in plant regeneration

Plants are under constant attack from insects, microbes, and other physical assaults that damage or remove body parts. Regeneration is one common strategy among plants to repair their body plan. How do organisms that are proficient at regeneration adapt their developmental programs for repatterning tissues? A new body of research employing high-resolution imaging together with cell-fate markers has led to new insights into the tissues competent to regenerate and the mechanisms that re-establish pattern. In parallel to new findings in metazoan systems, recent work in plants shows that regeneration programs commonly thought to rely on dedifferentiated cells do not need to reprogram to a ground state. Imaging studies that track the expression of regulators of the plant's proliferative centers, meristems, in conjunction with mutant analysis have shed new light on the earliest organizational cues during regenerative organ formation. One promise of plant regeneration studies is to reveal the common design attributes of programs that pattern similar organs in different developmental contexts.
Data-adaptive estimation of the treatment-specific mean

An important problem in epidemiology and medical research is the estimation of the causal effect of a treatment action at a single point in time on the mean of an outcome, possibly within strata of the target population defined by a subset of the baseline covariates. Current approaches to this problem are based on marginal structural models, i.e. parametric models for the marginal distribution of counterfactual outcomes as a function of treatment and effect modifiers. The various estimators developed in this context furthermore each depend on a high-dimensional nuisance parameter whose estimation currently also relies on parametric models. Since misspecification of any of these models can lead to severely biased estimates of causal effects, the dependence of current methods on such parametric models represents a major limitation. In this article, we introduce estimators that allow the marginal structural model as well as the parametric model for the relevant nuisance parameter to be selected data-adaptively. Our methodology is based on the unified loss-based estimation approach recently developed by van der Laan and Dudoit [2003. Unified cross-validation methodology for selection among estimators and a general cross-validated adaptive epsilonnet estimator: finite sample oracle inequalities and examples. Technical Report 130, Division of Biostatistics, University of California, Berkeley, November 2003] that in particular extends loss-based estimation to missing data problems. We study the practical performance of our proposed estimators in an extensive simulation study and also apply them to a data set derived from an epidemiologic study to assess the causal effect of forced expiratory volume on mortality in the elderly. All of the estimators presented in this article are made publicly available in the R package cvDSA.
The tides of Mercury and possible implications for its interior structure

The combination of the radio tracking of the MErcury Surface, Space ENvironment, GEochemistry, and Ranging spacecraft and Earth-based radar measurements of the planet's spin state gives three fundamental quantities for the determination of the interior structure of Mercury: mean density �� , moment of inertia C, and moment of inertia of the outer solid shell C m . This work focuses on the additional information that can be gained by a determination of the change in gravitational potential due to planetary tides, as parameterized by the tidal potential Love number k2. We investigate the tidal response for sets of interior models that are compatible with the available constraints (�� , C, and Cm). We show that the tidal response correlates with the size of the liquid core and the mean density of material below the outer solid shell and that it is affected by the rheology of the outer solid shell of the planet, which depends on its temperature and mineralogy. For a mantle grain size of 1 cm, we calculate that the tidal k2 of Mercury is in the range 0.45 to 0.52. Some of the current models for the interior structure of Mercury are compatible with the existence of a solid FeS layer at the top of the core. Such a layer, if present, would increase the tidal response of the planet.
Chapter 5 – Measurement

This chapter provides an overview of measurement, focusing on length measurements using the metric system and the US customary system: mass, weight, capacity of liquid, time, and temperature measurements. In addition, the chapter shows how to derive the units.
A Molecular Examination of Archontan and Chiropteran Monophyly

Comparative morphological and paleontological data have provided valuable information on higher-level eutherian mammal relationships, and several phylogenetic hypotheses are well supported by these comparative data (Wyss et al., 1987; Novacek et al., 1988). Nevertheless, many aspects of eutherian mammal relationships have not been resolved, and considerable conflicts between branching patterns diagnosed by different types of characters exist (Goodman et al., 1982; Miyamoto and Goodman, 1986; Novacek and Wyss, 1986; Shoshani, 1986; McKenna, 1987; Wyss et al., 1987; Novacek et al., 1988; Novacek, 1992; Stanhope et al., this volume).
Anastomosing hemangiomas: locations of occurrence, imaging features, and diagnosis with percutaneous biopsy

To describe a series of anastomosing hemangiomas and report its locations, imaging features, and the use of image-guided percutaneous biopsy to establish the diagnosis. In this institutional review board-approved, HIPAA compliant, retrospective study, an electronic pathology database was searched for all cases of anastomosing hemangioma from January 2009 to January 2015, yielding 32 cases (18 men, mean age 62 years). Tumor locations were recorded, and in a subgroup of patients with imaging, image characteristics (contour, attenuation, enhancement after intravenous contrast injection, the presence of hemorrhage or fat attenuation, and non-enhancing component) were evaluated. The number of cases diagnosed using percutaneous biopsy specimen was determined, and in a subgroup of these patients, biopsy technique and complications were assessed. Anastomosing hemangioma occurred in different locations, more commonly in the retroperitoneum (15/32, 47%), including the kidney (7/32, 22%), and more rarely in the ovary (4/32, 13%) and liver (2/32, 6%). Of the 5 cases with imaging available, four anastomosing hemangiomas were in the retroperitoneum (one in retroperitoneal fat, one para-aortic, one renal and one adrenal) and the fifth was mesenteric. Most tumors were well circumscribed (4/5, 80%), and on non-contrast CT, they appeared as mildly hyperdense (4/5, 80%) with avid contrast enhancement and heterogeneous attenuation (4/5, 80%) due to the presence of fat (2/5, 40%) or non-enhancing components (2/5, 40%). Diagnosis was rendered solely based on percutaneous biopsy in 7/32 (22%), all of which were core biopsy specimens. Fine-needle aspiration biopsy was performed in 1 case, which was non-diagnostic. Anastomosing hemangioma, a rare benign vascular tumor, is most commonly seen in the retroperitoneal fat and kidneys. On imaging, they are usually circumscribed, hyperdense, and heterogeneous due to fatty or non-enhancing hypodense areas and show avid post-contrast enhancement. Percutaneous biopsy can yield the diagnosis, potentially avoiding surgery.
Compressible Navier-Stokes equations with temperature dependent heat conductivity

Abstract. We prove the existence and uniqueness of global strong solutions to the one dimensional, compressible Navier-Stokes system for the viscous and heat conducting ideal polytropic gas flow, when heat conductivity depends on temperature in power law of Chapman-Enskog. The results reported in this article is valid for initial boundary value problem with non-slip and heat insulated boundary along with smooth initial data with positive temperature and density without smallness assumption.
Error Source Studies of Direct Measurement Skin Friction Sensors

An experimental study has been performed to further understand the potential error sources found in nonnulling, direct-measuring, skin friction sensors. Two different skin friction sensors were constructed and systematically tested to evaluate the introduction of extraneous forces due to misalignment. Design space parameters were varied and include the use of a protective collar component as well as geometric variations in the floating element including diameter, gap size, lip size, and thickness. The influences these variables have on the friction-, lip-, and normal-forces and ultimately the total-force output were extensively analyzed. The test series was conducted at the Virginia Tech Supersonic Tunnel under a nominal Mach 2.4 flow and unit Reynolds number of 34.6 ×10 per m (10.5 ×10 per ft). The boundary layer thickness at the skin friction sensor location was 11.3 mm (0.444 in.). At zero misalignment, the baseline wall shear was measured at 127.5 Pa (2.66 psf) with a resulting skin friction coefficient of 0.00144. It was concluded that a protective collar component surrounding the floating element significantly mitigates the effects associated with the sensor unit misalignment during facility installation. By itself however, floating element misalignment has a strong effect on the totalforce measurement and large misalignments cannot be tolerated without serious error. In addition, a larger gap size surrounding the floating element will help alleviate misalignment error. Good qualitative agreement was found with historical misalignment studies. As the driving error source in the current generation of skin friction sensors, the need to further understand misalignment error lead to the premise of this current study. This paper aims to provide practical guidance in successful skin friction sensor design and application.
Development of a fluorescence assay for the characterization of brevenal binding to rat brain synaptosomes.

The marine dinoflagellate Karenia brevis produces a family of neurotoxins known as brevetoxins. Brevetoxins elicit their effects by binding to and activating voltage-sensitive sodium channels (VSSCs) in cell membranes. K. brevis also produces brevenal, a brevetoxin antagonist, which is able to inhibit and/or negate many of the detrimental effects of brevetoxins. Brevenal binding to VSSCs has yet to be fully characterized, in part due to the difficulty and expense of current techniques. In this study, we have developed a novel fluorescence binding assay for the brevenal binding site. Several fluorescent compounds were conjugated to brevenal to assess their effects on brevenal binding. The assay was validated against the radioligand assay for the brevenal binding site and yielded comparable equilibrium inhibition constants. The fluorescence-based assay was shown to be quicker and far less expensive and did not generate radioactive waste or need facilities for handling radioactive materials. In-depth studies...
Breeding Behavior of the Andean Condor (Vultur Gryphus)

Lies and Behle (Condor 68:287, 1966) report that data are lacking in 1964 for the White Pelican (Pelecanus erythrorhynchos) colony at Stum Lake, British Columbia. This colony was visited by D. Lorne Frost on 22 June 1964 and the following notes were recorded. The pelican colony at Stum Lake is confined to two small sandy islands. Because of inclement weather only one island was inspected. This island was low, about two feet in height, and about 200 feet long and 75 feet wide at the widest point. The nests were shallow depressions in the sand, no nesting materials being used. A count showed 57 nests with one to three young each. The nestlings were naked, about 8 to 10 inches long, and incapable of walking. Another 25 nests contained one to two eggs, some of which were pipping. No dead young or adults were observed. This count indicates a breeding population of 164 adults for this island, a slight increase over 1963 data.
Al Jazeera English’s Networked Journalism during the 2011 Egyptian Uprising

Al Jazeera English (AJE) is the global English-language news service of the Al jazeera media conglomerate headquartered in Doha. Qatar. Founded in 2006, it is part of the network that began with the prominent Arabic news channel Al Jazeera. The Qatarl emir finances the company, though it derives some revenue income. AJE set out to challenge the BBC and CNN for international news audiences around the world, in its marketing and public outreach, it claims to offer a new perspective on global affairs, one that gives voice to the voiceless and emphasises global south perspectives long under-reported by the main Western news titans (Youmans, 2012). AJE has slowly built its audience around the world and is now available in more than 250 million households and is easily accessible online (except in the United States). In its short time on air, it has managed to win wide accolades and garner great attention for its close coverage of the popular uprisings that shook the Middle East and North Africa in 2011.
Transmission (“ABCD”) matrix representation of network elements in the security-constrained optimal power flow

This paper focuses on the preventive security constrained optimal power flow problems (PSCOPF), comparing full nonlinear AC models to linearized model. Generator participation factors (droop coefficients) are introduced to account for active power imbalance created by component outages under contingencies. Moreover, we propose a novel representation of network elements' electrical behavior, employing transmission (“ABCD”) matrices for lines and transformers. We demonstrate that this allows straightforward representation of breaker action and controllable transformers compared to standard approaches based on the admittance matrix Ybus. The proposed technique is tested on the RTS-96 test system and our results demonstrate that differences between the linear and nonlinear representation become particularly critical in the context of security analysis.
“We Only Speak English Here”: English Dominance in Language Diverse, Immigrant After-School Programs

Past research suggests that community after-school programs (ASPs) are crucial sites for culturally relevant programming for minority and immigrant youth; yet, we know little about how ASPs address language in their programming. Using an ethnographic fieldwork approach, we examine the goals and practices of ASP workers serving immigrant youth with diverse ethnic and language backgrounds in San Francisco, California. We find that, despite the best intentions regarding culturally relevant programming, ASP workers faced funding mandates, capacity issues, and increasingly diverse youth populations, and they adopted English-only policies or simply placed little priority on native-language usage. Ultimately, we observed competing processes related to English dominance: a lack of support for English language learners (ELLs) and bilingual youth, and the use of English as a bridge language across racial and ethnic lines. While staff sought to support and empower immigrant youth, ELL youth were often left on the si...
Routine Use of Distal Arterial Perfusion in Pediatric Femoral Venoarterial Extracorporeal Membrane Oxygenation

Lower-extremity ischemia is a significant complication in children on femoral venoarterial extracorporeal membrane oxygenation (VA ECMO). Our institution currently routinely uses distal perfusion catheters (DPCs) in all femoral arterial cannulations in attempts to reduce ischemia. We performed a single-center, retrospective review of pediatric patients supported with femoral VA ECMO from January 2005 to November 2015. The outcomes of patients with prophylactic DPC placement at cannulation (prophylactic DPC) were compared to a historical group with DPCs placed in response only to clinically evident ischemic changes (reactive DPC). Ischemic complication requiring invasive intervention (fasciotomy or amputation) was the primary outcome. Twenty-nine patients underwent a total of 31 femoral arterial cannulations, 17 with prophylactic DPC and 14 with reactive DPC. Ischemic complications requiring invasive intervention developed in 2 of 17 (12%) prophylactic DPC patients versus 4 of 14 (29%) reactive DPC. In the reactive DPC group, 7 of 14 (50%) had ischemic changes postcannulation, six underwent DPC placement, and three out of six of these patients still required invasive intervention. One of the seven patients had ischemic changes, did not undergo DPC, and required amputation. While a greater percentage of patients in the prophylactic group was cannulated during extracorporeal cardiopulmonary resuscitation (ECPR), statistical significance was not otherwise demonstrated. We demonstrate feasibility of superficial femoral artery (SFA) access in pediatric patients. We note fewer ischemic complications with prophylactic DPC placement, and observe that salvaging a limb with a reactive DPC was only successful 50% of the time. Although there was no statistical difference in the primary outcome between the two groups, limitations and confounding factors include small sample size and a greater percentage of patients in the prophylactic DPC group cannulated with ECPR in progress.
Properties of the Related Transposable Phage VcA1 and Defective Prophage dVcA1 in El Tor and Classical Biotypes of Vibrio Cholerae

Parker et al. (13) demonstrated that most classical strains of Vibrio cholerae produced defective phage structures after induction with mitomycin C, whereas pathogenic El Tor strains produced morphologically intact phage. Morphologically intact phage were also produced by an exceptional classical strain, NIH 41, which was subsequently shown by C. Parker to produce two different phages, both of which could infect or lysogenize the El Tor indicator strain, RJ1. These two phages, called VcAl and VcA2, were heteroimmune, and VcA2 has been shown (4) to belong to the “Kappa type” phage group described by Takeya (18). Several biological properties of phage VcAl have been described (21).
Environmental Agents in Lung and Pleural Neoplasms

A number of chemical and other environmental pollutants, including noxious gases and metals, infectious agents, insoluble agents such as asbestos and wood dusts, and dietary factors, induce or promote lung cancers. Many of these agents are classified as “known” or “reasonably anticipated” carcinogens, including polycyclic aromatic hydrocarbons, metals such as cadmium, hexavalent chromium, and nickel compounds, and mineral fibers such as asbestos and erionite.1 Others are “suspect” carcinogens based on inconclusive data from epidemiologic, animal, and mechanistic studies. The use of mechanistic studies to predict carcinogenicity of environmental and occupational agents in humans has been advocated recently as a critical component of risk analysis.2 With the evolution and vast potential of new technologies such as microarray analysis and proteomics, our knowledge of the mechanisms of lung carcinogenesis has increased.
The Role of Percutaneous Image-Guided Thermal Ablation for the Treatment of Pulmonary Malignancies.

OBJECTIVE. Image-guided thermal ablation is a minimally invasive treatment option for patients with primary and secondary pulmonary malignancies. Modalities include radiofrequency ablation, microwave ablation, and cryoablation. CONCLUSION. Although no large randomized studies exist comparing ablation to surgery or radiotherapy, numerous studies have reported safety and efficacy for the treatment of both primary and metastatic disease in select patients. Future studies will refine patient selection, procedural technique, and assessment for local recurrence and will evaluate long-term survival.
“Porque tenían sangre de ‘NEGROS’”: The Exclusion of Mexican Children from a Louisiana School, 1915-1916

This article examines the exclusion of Mexican children from a Louisiana public school in 1915-1916. A school board trustee threw the children out of the school because he saw them as racially mixed and used the socially recognized argument that they had “negro blood.” Although school officials did not see Mexican children as Black or White, their mestizo appearance became a racial marker. Given this time and location—where legal segregation was understood in Black and White terms—Mexicans posed a dilemma because they did not fit into the binary racial system. Although the Mexican consul conducted an investigation and the Mexican Ambassador filed a complaint to the U.S. Department of State, the case was never resolved. We want to broaden the conversation about the racialization of Mexicans in public schools by highlighting the complexities of race and segregation in the deep South.
Ethnic differences in psychosocial factors in methadone maintenance: Hmong versus non-Hmong.

Little is known about the characteristics of U.S.-based Asian populations undergoing methadone maintenance treatment for opioid use disorders. We evaluated psychosocial factors in 76 Hmong and 130 non-Hmong on methadone maintenance for at least two months in a single urban methadone maintenance clinic. Assessments included the Addiction Severity Index 5th Edition, the Symptom Checklist-90, and the Structured Clinical Interview for DSM-IV Axis I Disorders. The Hmong were older, predominately male, and on lower doses of methadone than the non-Hmong. Hmong had significantly lower ASI composite scores across all dimensions except employment and legal. While the SCL-90 Global Severity Index (GSI) score did not differ between groups, the Hmong had lower scores in the interpersonal sensitivity, depression, anxiety, hostility, and paranoid ideation dimensions. Sixty-seven percent of Hmong and 29% of non-Hmong were without Axis I diagnoses (p < .001). There was no difference between the groups in DSM-IV substance use diagnoses. The extent to which these psychosocial differences impact methadone dose requirements and treatment outcomes in Hmong and non-Hmong remains unknown.
A New Alcohol Environment: Trends in alcohol consumption, harms and policy: Finland 1990–2010

■ AIMSThis article reports developments in the Finnish alcohol field from 1990 to 2010, focusing on changes and trends in alcohol consumption, drinking habits and alcohol-related harm. We pay speci...
Abstract WP123: Neuroprotective Efficacy of P7C3-A20 After Ischemic Stroke

Ischemic stroke is a devastating condition with few therapeutics available. The recently identified neuroprotective compound P7C3-A20 (A20) inhibits mature neuronal apoptosis while increasing the n...
Hematologic safety data of single-agent ponatinib from a phase I and phase II trial in Philadelphia chromosome-positive (Ph+) CML/ALL patients.

e18021 Background: Ponatinib is a tyrosine kinase inhibitor (TKI) indicated for the treatment of Ph+ chronic myeloid leukemia (CML) or acute lymphocytic leukemia (ALL) in the absence of other appropriate TKI therapies or presence of the T315I BCR-ABL mutation. Hematologic toxicity can result in dose reductions, interruptions and discontinuation of drug therapy. In the following analysis, we summarize the hematologic safety profile of single agent ponatinib reported in 468 patients from 2 trials. The primary objective is to evaluate the number and percent of patients with hematologic toxicities based on previously published data. Methods: Data reported from patients treated with ponatinib in trials 10-201 and 07-101 was included in the analysis. Ponatinib was dosed at 45 mg orally once daily. Hematologic adverse effects analyzed included thrombocytopenia, neutropenia, anemia and arterial thrombotic events. Results: See Table below for summary of events. Thrombocytopenia, neutropenia and anemia were more fr...
A family of random and random type projections for radar STAP

In radar space time adaptive processing (STAP), training data from neighboring range cells is limited. This precludes implementation of the full-dimension adaptive detectors, i.e. the minimum variance distortionless response (MVDR) filter. In this paper we reduce the dimension of the problem by random sampling, i.e. by projecting the data into a random d-dimensional subspace. This offers two advantages, first, it permits implementation of classical detectors in the limited sample size regime. Second, it offers significant computational savings permitting possible real time solutions. Both these advantages are however at the cost of reducing the output SINR for radar STAP. In STAP, the cell under test is assumed to have known desired spatial and temporal responses. To ameliorate over this SINR loss from random projections, we propose other techniques where the lower dimension subspace is not entirely random, but is decomposed into both random and deterministic parts. The family of random and random type projections we develop here, are either l 2 norm preserving or contraction mappings in statistical expectation.
The Metasystem Paradigm: Applications

The metasystem paradigm is used to study problems afflicting five complex systems: employment of the disabled, environmental pollution control in Japan, the U.S. income tax system, the reproductive health-care system, and the U.S. nuclear power industry. In each section, the authors identify the problems within the system, discuss the application of the metasystem paradigm, and determine the flow of rationalities and the system’s failures. The wide range of topics discussed herein vouches for the versatility of the methodology presented in this text.
Héloïse (1100–1163)

Heloise’s life story as revealed in her letters to Abelard is as instructive to us as are her philosophical arguments.1 The vitality of the story is so compelling, that it has been retold through the centuries in novels, poems, songs, motion pictures, and art.2 Intimately connected to her philosophy the life of Heloise questions principles about love and its obligations, the relation of man and God and its consequences on human action and feeling, and the relation of women and men in regard to human and divine law, to personal ethics, to fate. How we live our lives when the fulfillment of love is impossible or unethical or imprudent is a dilemma of the human condition, as much a part of our life today as it was in Heloise’s Middle Ages.
Abstract B45: Studying the interactome of breast cancer: The cancer cell map initiative

Recent progress in genome sequencing has revealed numerous mutations in cancer genomes, but how many of these alterations result in changes in normal cellular processes is poorly understood. In addition, the biologic functions of the majority of genes (e.g., BRCA1/2) with cancer-associated mutations have not been fully characterized, despite their expression and/or activity being highly correlated with cancer. Through years of study, it is becoming clear that cancer is a disease that arises not only because of defects in individual genes and proteins, but also because of the action of hallmark cellular processes and biologic pathways. Therefore, what is urgently needed is to put the cancer genomic information into biologic context by mapping mutated genes onto the complexes and pathways in which they function. The goal of this study is to uncover the comprehensive protein-protein interaction networks and pathways in various breast cancer subtypes to better understand how mutated cancer genes and genomes hijack and rewire pathways and complexes during the course of breast tumorigenesis. Here we catalog protein-protein interactions for more than 40 genes recurrently mutated in breast cancer, using affinity purification and mass spectrometry (AP-MS). Our interaction network reveals subtype and mutation-specific protein-protein interactions, most of which are not previously reported. We anticipate the breast cancer interactome study will uncover many previously unidentified aberrant pathways and protein complexes uniquely operating in breast cancer cells, and thus pinpoint proteins central in these pathways and complexes that may potentially serve as distinct biomarkers or therapeutic targets for tumors having the same or similar subtypes and/or genomic mutations. Citation Format: Minkyu Kim, Kyumin Kim, Margaret Soucheray, Danielle Swaney, Nevan Krogan. Studying the interactome of breast cancer: The cancer cell map initiative [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B45.
Paradoxical Bronchoconstriction with Short-Acting Beta Agonist.

Patient: Male, 25 Final Diagnosis: Paradoxical bronchospasm Symptoms: Dyspnea on exertion • shortness of breath Medication: Albuterol • levalbuterol Clinical Procedure: Pulmonary function testing Specialty: General and Internal Medicine Objective: Unusual clinical course
Abstract WP23: Off-Hour Presentation and Outcomes in Patients With Large Vessel Occlusion After Endovascular Therapy: a Matched Case-Control Study

Background: Patients who are admitted during off-hours (nights and weekends) are thought to have worse outcomes. This might be explained by delayed times to treatment. We sought to determine the ef...
Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy

Objectives Malignant pleural mesothelioma and malignant pleural effusions are a major therapeutic challenge, and are associated with impairment in quality of life and increased mortality. Advances in systemic therapies of malignant pleural mesothelioma have demonstrated limited clinical benefit and there is ongoing interest in intrapleural immunotherapies which have been demonstrated to be well tolerated overall with variable clinical responses. We have reviewed the literature to provide a comprehensive summary of novel intrapleural immunotherapeutic paradigms, including oncolytic virus therapy, gene-mediated cytotoxic immunotherapy, direct cytokine-mediated immunotherapies, innate immunomodulators and adoptive transfer of intrapleural chimeric antigen receptor T-cell therapy. Data sources A review of PubMed for original manuscripts and conference reports published between 1998 and 2018 pertaining to intrapleural immunotherapy, as well as examination of reference lists from reviewed manuscripts. Study selection Human clinical trials on intrapleural immunotherapies in subjects with malignant pleural mesothelioma or malignant pleural effusion were included in this review, including some relevant preclinical studies and anticipated ongoing trials reported on Clinicaltrials.gov. Results Twenty-six clinical trials were identified, in addition to three trials currently in progress. Conclusion Intrapleural immunotherapies for pleural malignancy have demonstrated promise with regard to generating durable tumor-specific immune responses with possible clinical benefits which merit further investigation as part of multimodal chemotherapeutic and immunotherapeutic regimens.
Clinical Features and Outcomes of Patients with Sarcoidosis-associated Pulmonary Hypertension.

The presence of pulmonary hypertension (PH) significantly worsens outcomes in patients with advanced sarcoidosis, but its optimal management is unknown. We aimed to characterize a large sarcoidosis-associated pulmonary hypertension (SAPH) cohort to better understand patient characteristics, clinical outcomes, and management strategies including treatment with PH therapies. Patients at Duke University Medical Center with biopsy-proven sarcoidosis and SAPH confirmed by right heart catheterization (RHC) were identified from 1990–2010. Subjects were followed for up to 11 years and assessed for differences by treatment strategy for their SAPH, including those who were not treated with PH-specific therapies. Our primary outcomes of interest were change in 6-minute walk distance (6MWD) and change in N-terminal pro-brain natriuretic peptide (NT-proBNP) by after therapy. We included 95 patients (76% women, 86% African American) with SAPH. Overall, 70% of patients had stage IV pulmonary sarcoidosis, and 77% had functional class III/IV symptoms. Median NT-proBNP value was elevated (910 pg/mL), and right ventricular dysfunction was moderate/severe in 55% of patients. Median values for mean pulmonary artery pressure (49 mmHg) and pulmonary vascular resistance (8.5 Woods units) were consistent with severe pulmonary hypertension. The mortality rate over median 3-year follow-up was 32%. Those who experienced a clinical event and those who did not had similar overall echocardiographic findings, hemodynamics, 6MWD and NT-proBNP at baseline, and unadjusted analysis showed that only follow-up NT-proBNP was associated with all-cause hospitalization or mortality. A sign test to evaluate the difference between NT-Pro-BNP before and after PH therapy produced evidence that a significant difference existed between the median pre- and post-NT-Pro-BNP (−387.0 (IQR: −1373.0-109), p = 0.0495). Use of PH-specific therapy may be helpful in selected patients with SAPH and pre-capillary pulmonary vascular disease. Prospective trials are needed to characterize responses to PH-specific therapy in this subset of patients with SAPH.
Paroxysmal ventricular tachycardia and fibrillation without complete heart block: Report of a case treated with a permanent internal cardiac pacemaker

Abstract Recurrent paroxysmal ventricular tachycardia and fibrillation in a patient without evidence of atrioventricular block were successfully controlled by a permanently implanted internal pacemaker with the pacing rate set at 100/min. The rationale for the choice of the pacemaker rate is discussed. It is suggested that, should other conventional forms of therapy such as cardiac depressant drugs be ineffective, implantation of a permanent cardiac pacemaker may be useful in the control of this serious tachyarrhythmia.
How Aristotle and Husserl Differ on First Philosophy

Many of Rudolf Bernet’s essays juxtapose Husserl’s thought with that of other contemporary writers. Such juxtaposition enables us to better understand each of the parties, but it also brings us more adequately to the things themselves, to the topic that is at issue in both of them. If we successfully put two such things together, we get a third that is distinct from each but sheds light on both. For my contribution to this volume, I would like to follow Bernet’s example and put Husserl in contact, not with a contemporary thinker, but with Aristotle, and to do so on the topic of first philosophy.
Misannotations of the Genes Encoding Sugar N‐formyltransferases

Tens of thousands of bacterial genome sequences are now known due to the development of rapid and inexpensive sequencing technologies. An important key in utilizing these vast amounts of data in a biologically meaningful way is to infer the function of the proteins encoded in the genomes via bioinformatics techniques. Whereas these approaches are absolutely critical to the annotation of gene function, there are still issues of misidentifications, which must be experimentally corrected. For example, many of the bacterial DNA sequences encoding sugar N-formyltransferases have been annotated as l-methionyl-tRNA transferases in the databases. These mistakes may be due in part to the fact that until recently the structures and functions of these enzymes were not well known. Herein we describe the misannotation of two genes, WP_088211966.1 and WP_096244125.1, from Shewanella spp. and Pseudomonas congelans, respectively. Although the proteins encoded by these genes were originally suggested to function as l-methionyl-tRNA transferases, we demonstrate that they actually catalyze the conversion of dTDP-4-amino-4,6-dideoxy-d-glucose to dTDP-4-formamido-4,6-dideoxy-d-glucose utilizing N10 -formyltetrahydrofolate as the carbon source. For this analysis, the genes encoding these enzymes were cloned and the corresponding proteins purified. X-ray structures of the two proteins were determined to high resolution and kinetic analyses were conducted. Both enzymes display classical Michaelis-Menten kinetics and adopt the characteristic three-dimensional structural fold previously observed for other sugar N-formyltransferases. The results presented herein will aid in the future annotation of these fascinating enzymes.
Occupational and dietary differences in hydroxylated and methoxylated PBDEs and metals in plasma from Puget Sound, Washington, USA region volunteers.

Abstract Electronic waste (E-waste) recycling is a rapidly growing occupation in the USA with the potential for elevated exposure to flame retardants and metals associated with electronic devices. We previously measured polybrominated diphenyl ethers (PBDEs) in plasma from E-waste workers and found them similar to non-E-waste workers. This study focused on structurally related PBDE derivatives, the hydroxylated (OH-PBDEs) and methoxylated (MeO-PBDEs) forms along with metals known to occur in E-waste. Humans can metabolize PBDEs and some MeO-PBDEs into OH-PBDEs, which is a concern due to greater health risks associated with OH-PBDEs. We measured 32 different OH-PBDEs and MeO-PBDEs in plasma samples provided by 113 volunteers living in the greater Puget Sound region of Washington State, USA. We measured 14 metals in a subset of 10 E-waste and 10 non-E-waste volunteers. Volunteers were selected based on occupational and dietary habits: work outdoors and consume above average amounts of seafood (outdoor), electronic waste recycling (E-waste) or non-specific indoor occupations (indoor). A two-week food consumption diary was obtained from each volunteer prior to blood sampling. OH-PBDEs were detected in all volunteers varying between 0.27 and 102 ng/g/g-lipid. The MeO-PBDEs were detected in most, but not all volunteers varying between n.d. – 60.4 ng/g/g-lipid. E-waste recyclers had OH-PBDE and MeO-PBDE plasma levels that were similar to the indoor group. The outdoor group had significantly higher levels of MeO-PBDEs, but not OH-PBDEs. Comparison of plasma concentrations of BDE-47 with its known hydroxylated metabolites suggested OH-PBDE levels were likely determined by biotransformation and at least two subpopulations identified differing in their apparent rates of OH-PBDE formation. The metals analysis indicated no significant differences between E-waste workers and non-E-waste workers. Our results indicate E-waste workers do not have elevated plasma levels of these contaminants relative to non-E-waste workers.