cssi/SciSciGPT-SciSciNet huggingface dataset:
Drug Resistance by Non-Tuberculous Mycobacteria

Non-tuberculous Mycobacterium species (NTM) cause disease in diverse animals as well as in susceptible humans. Antiretroviral therapy has decreased AIDS-associated NTM in many settings; however, the reported incidence of M. avium complex (MAC) infection of non-AIDS patients has increased in recent years, especially among women (1–4). Most NTMs are slowly growing mycobacteria like their close cousin, M. tuberculosis, with which they share many similarities in genomic composition, cellular physiology, and mechanisms of pathogenesis. Chemotherapeutic treatments, and mechanisms of resistance to these treatments, also bear many similarities to tuberculosis. However, there are critical distinctions, especially in the case of the most common NTM pathogen of humans, MAC. This chapter focuses on clinical aspects of NTM therapy and the biology of antimicrobial resistance by NTMs.
Potential Functions and the Simulation of Defects in Lattice Dynamical Defect Problems

The use of interatomic potential functions in the study of lattice dynamical defect problems has some differences from their use in other types of defect problems. In general, only the second derivatives of the potential function evaluated at the equilibrium separation between atoms in a crystal (the atomic force constants) are required. The latter can certainly be determined once an interatomic potential function is known, but can sometimes be determined indirectly without recourse to an assumed analytic expression for the potential function. For many substitutional impurities the potential of interaction between the atom or ion and the atoms of the host crystal is not known ab initio, and the atomic force constants have to be determined from experiment. In such cases the restrictions imposed on the force constants by the invariance and transformation properties of the force on an atom under infinitesimal, rigid-body translations and rotations of the crystal, as well as by the point symmetry of the defect site, can reduce considerably the number of independent, nonzero force constants that have to be determined. These conditions are described and their importance for a correct description of the dynamical properties of lattice defects is illustrated by applications drawn from the study of isolated point defects and of extended defects such as crystal surfaces. Finally, the results of attempts at first-principles calculations of the interactions between substitutional defects and the host crystal, in ionic crystals and in metals, are summarized and commented upon.
Opportunities for Early Intervention to Avoid Prolonged Work Disability: Introduction to the Special Section

Purpose The articles in this special section examine opportunities for early intervention that is intended to retain the jobs of workers who have medical conditions that could put them at risk of prolonged work disability. Methods The first three articles examine options for analyzing various types of disability claims data for targeting early intervention; the fourth article provides new information from 50 case studies on how employers decide to invest in the retention of individual workers. Results Together, the four articles demonstrate that there may be an opportunity to positively affect longer-term outcomes for workers with medical conditions. This would be accomplished by building and expanding on existing systems in order to efficiently identify, and provide timely support to, workers with medical conditions in a critical period during which the decisions and actions of various stakeholders, including the workers themselves, may have a major influence on these outcomes. Conclusions Forthcoming opportunities to develop, implement, and test evidence-based interventions to promote job retention can provide further insight into the value of the options described in the articles.
An unusual case of Toxic Leukoencephalopathy. (P1.152)

Objective: We describe an unusual case of Toxic leukoencephalopathy (TLE) with features combining both heroin-induced TLE and delayed post hypoxic leukoencephalopathy (DPHL). Background: Toxic leukoencephalopathy (TLE) represents a group of CNS white matter disorders with varying presentations that depend on the causative agent. Two TLEs that have been identified as having distinct characteristics are “chasing the dragon” heroin inhalation leukoencephalopathy and delayed posthypoxic leukoencephalopathy (DPHL). Design/Methods: 48 year old female with history of polysubstance abuse (alcohol, benzodiazepines and opiates) who presented with worsening mentation and bizarre behavior. Her history was positive for recent Morphine and Oxycodone ingestion. Initial exam was notable for disorientation, apraxia, aphasia, patellar hyper-reflexia, and wide based gait. She was treated initially with intravenous corticosteroids with no improvement. Her symptoms progressed and she developed significant rigidity, fever and hemodynamic instability. She was intubated, treated with Lorazepam, Acetaminophen and cooling blankets. She continued to decline and eventually became comatose. Results: An initial computed tomography of the head showed no acute intracranial abnormalities. Electroencephalogram (EEG) showed intermittent, generalized, reactive polymorphic delta slowing. Magnetic Resonance Imaging (MRI) of the brain revealed confluent supra-tentorial white matter signal changes with mild diffuse cortical swelling suggestive of diffuse encephalitis. CSF studies were normal. Repeat MRI brain showed similar findings. Cerebral angiogram was unrevealing. A brain biopsy was performed and was consistent with spongiform leukoencephalopathy. Conclusions: Here we report a case of spongiform leukoencephalopathy that has clinical, radiological and pathological features of both DPHL and heroin-induced TLE. As with DPHL, her clinical course was delayed and her MRI findings were more periventricular, sparing the U fibers and cerebellum. However, the brain biopsy findings of spongiform vacuolization without demyelination or axonal involvement were more suggestive of heroin-induced TLE. Her symptoms were unusual and combined both cortical and cerebellar deficits. We believe this may suggest an overlap between both entities. Disclosure: Dr. Alenzi has nothing to disclose. Dr. Kesari has nothing to disclose. Dr. Fleet has nothing to disclose. Dr. Goodman has nothing to disclose.
Astrocytes migrate from human neural stem cell grafts and functionally integrate into the injured rat spinal cord.

Abstract Neural stem cells (NSCs) can differentiate into both neurons and glia after transplantation into spinal cord injury (SCI) sites. The neuronal component of stem cell grafts has the potential to form functional synaptic relays across the lesion site. The glial component may reform a blood-spinal cord barrier, support neuronal function, and contribute to remyelination. We performed a long-term, 1.5-year time course study focused on astrocyte migration, differentiation, integration, and safety following human NSC transplantation into C5 hemisection sites in immunodeficient rats. NSCs that adopted a neuronal fate did not migrate from the lesion site. In contrast, transplanted cells that adopted astrocyte fates exhibited long distance migration from the lesion site through host white matter in rostrocaudal directions. These cells migrated slowly at a mean rate of 2–3 mm/month, divided as they migrated, and gradually differentiated into astrocytes. After 1.5 years, human astrocytes migrated nine spinal cord segments, caudally to the mid-thoracic level, and rostrally into the brainstem. The migrated human astrocytes joined the endogenous population of astrocytes in the host spinal cord, extended perivascular endfeet towards host pericytes and endothelium, formed interspecies and intraspecies perivascular astrocytic networks connected by gap junctions, and expressed glutamate transporter proteins in perisynaptic processes, suggesting structural and functional integration. No adverse consequences of this extended glial migration were detected. Adjacent to the lesion site, chronic host astrocytic upregulation was significantly attenuated by NSC grafts. Thus, human astrocytes can migrate long distances from sites of SCI and safely integrate into the host central nervous system. Significance statement Neural stem cell (NSC) grafts are a candidate therapy for spinal cord injury (SCI). Here we report an 18-month study of astrocyte survival and migration from sites of SCI in immunodeficient rats. NSC grafts significantly attenuate host astrocyte reactivity at the lesion/host interface. Intra-graft astrocytes integrate into the host blood-spinal cord barrier (BSCB) and widely express glutamate transporter proteins characteristic of neurotransmitter regulation. Notably, astrocytic components of NSC grafts exhibit gradual yet extensive migration after implantation into the mid-cervical injury site; neurons do not migrate at all. This extensive astrocyte migration is not detectably associated with adverse outcomes anatomically or behaviorally.
Diabetes-related events in adolescents and young adults: opportunities for psychosocial interventions

This study was conducted to evaluate predictive factors of diabetes-related emergency room (ER) visits and hospitalizations among adolescents and young adults (AYA) with type 1 diabetes (T1D). Base...
Overview and Understanding of Basic Circadian Physiology

The circadian system represents a complex, tightly coordinated structure, present in nearly all organisms. In mammals the circadian system is regulated by the suprachiasmatic nucleus, which coordinates the activity of peripheral clocks throughout the body. Central and peripheral circadian timing plays an important role in multiple physiological processes, including regulation of the immune response, which could explain the variability of severity of allergic symptoms across the day and night. The circadian clock is uniquely responsive to various timekeeping stimuli at different times of the day, including exposure to light, melatonin, feeding, and activity. This system provides opportunities for future clock-based interventions for allergic disease.
The Moderating Effect of Substance Abuse Treatment Engagement on the Connection Between Support From Program Participants and Substance-Related Recidivism for Justice-Involved Women:

This study examines the prediction of substance-related technical violations and arrests from (a) a three-dimensional measure of substance abuse treatment engagement-treatment satisfaction, treatment participation, and counselor rapport-and (b) support from peers in the treatment program. The study focuses on 204 women on probation or parole who attended a substance abuse treatment program in the first 9 months of supervision. Data were collected in face-to-face interviews and from official records of violations and arrests. Generalized linear mixed-effects modeling was used to assess the main effects and the interaction effect of within-program peer support and other indicators of engagement as predictors of substance-related technical violations and arrests. Peer support was positively related to violations/arrests when treatment engagement was low. Findings suggest that for women who do not score high in treatment engagement, support from peers is related to increased recidivism, and group treatment may be contraindicated.
Hurricane Risk Communication: Visualization and Behavioral Science Concepts

AbstractIncreasingly, the risk assessment community has recognized the social and cultural aspects of vulnerability to hurricanes and other hazards that impact planning and public communication. Ho...
Drug interactions with antimalarial medications in older travelers: a clinical guide.

Increasingly older adults are traveling to international destinations with malaria as a present risk. Surveillance systems indicate that older adults are more likely to suffer severe complications from malaria. The role of health care providers in selecting an appropriate medication for chemoprophylaxis or treatment of malaria in adults becomes more difficult as older adults undergo physiologic changes that alter the pharmacokinetic and pharmacodynamic nature of medications potentially causing increased drug interactions, adverse events and altered drug action. A comprehensive literature search from 1970 to present, with a focus on the past 10 years, was conducted on drug interactions, pharmacokinetic and pharmacodynamic effects on antimalarials in adults. It was determined that due to pharmacodynamic and pharmacokinetic changes in older adults, especially renal and cardiovascular, special attention should be given to this population of travelers in order to minimize the likelihood of adverse events or altered drug efficacy. Antimalarial drug-disease interactions in older adults can occur more often due to QT prolongation, exacerbation of hypoglycemia, decreased renal elimination and decreased hepatic metabolism. Older antimalarials have well-documented drug-drug interactions. Tafenoquine, a new antimalarial, requires glucose-6-phosphate dehydrogenase screening like primaquine and monitoring of new potential drug interaction with MATE1 and OCT2 substrates. While drug-drug interactions in older travelers may occur more often as a result of polypharmacy, data did not indicate adverse reactions or decreased drug efficacy is greater compared with younger adults. Overall, with the exception of recently approved tafenoquine, much is known about antimalarial drug and disease interactions, but new drugs are always being approved, requiring travel health providers to understand the pharmacokinetics and pharmacodynamics of antimalarial drugs to predict the impact on safety and efficacy in travelers. This guide provides travel health providers with valuable insights on potential outcomes associated with drug interactions in adults and recommended monitoring or drug regimen modification.
Grade III subcapsular liver hematoma secondary to HELLP syndrome: A case report of conservative management

Subcapsular liver hematoma (SLH) is a rare condition that is associated with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. A high level of suspicion, early diagnosis, and coordinated, intensive multidisciplinary management are necessary to monitor for serious complications and prevent death. Options include conservative management, hepatic resection, hepatic artery ligation and liver transplantation. This paper describes a 34-year-old woman with HELLP syndrome who developed a large grade III SLH that was managed conservatively.
Not Just Another Headache: Cerebral Venous Sinus Thrombosis in a Patient With Isolated Antithrombin III Deficiency.

Cerebral venous sinus thrombosis (CVST) is a rare condition. Symptoms and signs arise from a combination of thrombosis of cerebral veins and increased intracranial pressure. The most common presenting symptom is a non-descriptive headache, but presentation varies with underlying etiology. CVST requires a high index of suspicion to diagnose, particularly in those without apparent risk factors. Evaluation and diagnosis should include a combination of a thorough history, ophthalmoscopic examination, laboratory studies, and imaging. Management is multidimensional and aims to reverse the underlying causes, and prompt treatment with anticoagulation by heparin to decrease thrombotic burden, risk of permanent neurological deficits, and death. In the present study, we report the case of a 61-year-old man referred to the emergency department by an ophthalmologist for bilateral papilledema and eventually diagnosed with CVST secondary to isolated antithrombin III deficiency. Although CVST is uncommon, this case is worthwhile to report as the presentation is unique, and it requires a high index of clinical awareness for timely diagnosis and early therapeutic intervention.
Hierarchy to Self Management: How Unmoored Managers Cope with Transformation of Organizational Form

Self-management has become an attractive option in the range of available organizational structures for companies seeking innovative and entrepreneurial outcomes. Thus, some firms existing previous...
Novel assessment of intestinal anastomotic perfusion using ICG SPY in a continuous flow LVAD patient

HeartMate II left ventricular assist device (LVAD) assists heart failure patients by generating continuous flow via axial flow pump placed in the left ventricle. Little is known of the effect of continuous flow on intestinal anastomoses. This is the first case visually documenting altered perfusion patterns in patients with LVADs using indocyanine green (ICG). A 72-year-old male required a colon resection, for adenocarcinoma, following implantation of an LVAD. Perfusion of the anastomosis was evaluated using indocyanine. During the assessment, an unusual perfusion pattern was noticed. Normally, flow as measured by SPY is seen as an initial blush of contrast followed by a gradual, pulsatile increase in the progression of the indocyanine through the tissues. In this patient, instead of the usual initial blush, a continuous beam of ICG was seen to flow though the blood vessels. This novel perfusion pattern is consistent with flow generated from LVAD.
Adolescent and Adult Correlates of Prescription Opioid Use and Misuse in Adulthood: Associations Across Domains of Despair.

Objective: Given continued increases in “deaths of despair”, there is a need to examine associations of factors across multiple domains of despair (i.e. cognitive, emotional, behavioral, biological...
Rediscovering Political Friendship: Aristotle's Theory and Modern Identity, Community, and Equality

Aristotle argued that citizenship is like friendship, and this book applies his argument to modern society. Modern citizens may lack the concept of civic friendship, but they persist in many practices and passions that were once considered essential to it. Citizens share many similarities with friends: prejudices held in common, favoritism towards each other, and - despite disagreement on specifics - underlying agreement about what is important, such as freedom and equality. Aristotle's theory reminds us that civic friendship is a factual condition of healthy societies, not a pie-in-the-sky ideal. By recognizing when it occurs and understanding it, we can build on it to counteract societal polarization. Civic friendship offers an alternative to populism and nationalism by engaging some of the same passions. In an era increasingly marked by tribalism and identity politics, this timely study will be of interest to a wide range of readers in political science, classics, and philosophy.
Analysis of recurrently protected genomic regions in cell-free DNA found in urine

Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture is unknown. Here, we characterized fragmentation patterns in urine cfDNA using whole-genome sequencing. Size distribution of urine cfDNA fragments showed multiple strong peaks between 40 and 120 base pairs (bp) with a modal size of 81- and sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were robust to preanalytical perturbations, such as at-home collection and delay in processing. Genome-wide sequencing coverage of urine cfDNA fragments revealed recurrently protected regions (RPRs) conserved across individuals, with partial overlap with nucleosome positioning maps inferred from plasma cfDNA. The ends of cfDNA fragments clustered upstream and downstream of RPRs, and nucleotide frequencies of fragment ends indicated enzymatic digestion of urine cfDNA. Compared to plasma, fragmentation patterns in urine cfDNA showed greater correlation with gene expression and chromatin accessibility in epithelial cells of the urinary tract. We determined that tumor-derived urine cfDNA exhibits a higher frequency of aberrant fragments that end within RPRs. By comparing the fraction of aberrant fragments and nucleotide frequencies of fragment ends, we identified urine samples from cancer patients with an area under the curve of 0.89. Our results revealed nonrandom genomic positioning of urine cfDNA fragments and suggested that analysis of fragmentation patterns across recurrently protected genomic loci may serve as a cancer diagnostic.
The descriptive epidemiology of brand-specific gun ownership in the US: results from the 2019 National Lawful Use of Guns Survey.

No previous study has identified the specific brands of guns owned by gun owners. This study aimed to: (1) ascertain and describe patterns of brand- and model-specific gun ownership among US gun owners; and (2) investigate the relationship between gun owners’ brand and model preferences and their attitudes towards common firearm violence prevention policies. Using a national, pre-recruited internet panel of US adults in 2019, we surveyed gun owners (N = 2086) to ascertain their opinions regarding firearm violence prevention policies and to assess the brands and models of guns that they owned. Brand-specific gun ownership was highly concentrated and was dominated by three pistol brands, two revolver brands, three rifle brands, and three shotgun brands. There was wide variation in policy attitudes among owners of different gun brands, but little variation across owners of different gun types (i.e., pistols, rifles, revolvers, shotguns). We were able to identify the specific gun models owned by 1218 (59.4%) of the gun owners. Based on the classification of these gun models into three types we categorized the gun ownership pattern of the sample as 33.4% recreational, 45.5% self-defense, and 21.1% tactical. There were marked differences in support for firearm-related policies among the three groups, with support generally highest among the Recreation group and lowest among the Tactical group. We conclude that gun brands and models are strong predictors of a gun owner’s attitudes regarding firearm-related policies. This information could help public health practitioners develop segment-specific communications that will appeal to each group in order to more effectively engage gun owners in firearm violence prevention.
O Processamento Lexical de línguas tipologicamente próximas entre falantes trilíngues de Espanhol, Inglês e Português

Research shows (VAN HESTE, 1999; VAN HELL; DE GROOT, 1998; VAN HEUVEN, DIJSTRA; GRAINGER, 1998) that when bilinguals process words in one language, shared word features from both languages are also activated. Most lexical processing studies have examined word processing among bilinguals and a smaller subset of studies have focused on word processing among trilinguals. The present study investigates how native and heritage trilingual Spanish speakers process words in comparison to non-native trilingual Spanish speakers. A group of native and heritage trilingual Spanish speakers (n=26) (L1-Spanish, L2-English and L3-Portuguese) and a group of non-native trilingual Spanish speakers (n=40) (First Language (L1) English, Second Language (L2) Spanish and Third Language (L3) Portuguese) visually processed words in different languages (Spanish, Portuguese, German and Basque) and had to determine whether the words they saw were real Spanish words. Reaction times and accuracy were analyzed among both groups and across word type. The goal was to test whether the presence of a third language such as Portuguese would affect processing in a previous known language (first or second language-Spanish). All participants included in this study were at the beginning stages of learning Portuguese as a third language. Results show native/heritage trilingual speakers were able to process words in Spanish faster than nonnative trilingual speakers in addition to processing all word types (in Portuguese, Spanish, German and Basque) more accurately as well. The present findings are analyzed in light of Dijkstra and Van Heuven’s (2002) Bilingual Interactive Activation Plus model of word recognition (BIA+).
Abstract P178: Social Determinants Of Health And Preventable Hospitalization For Hypertension

Introduction: Social determinants of health (SDH) can have a significant impact on the risk of hypertension related hospitalization. Understanding the drivers of potentially preventable hospitaliza...
Clinical Approach to the Patient with Ocular Inflammation

Successful treatment of uveitis depends on establishing a diagnosis and understanding the predominant pathophysiologic mechanism responsible for the intraocular inflammation. Thus, it is essential to obtain a specific syndrome diagnosis. Because of the often elusive nature of uveitis, however, efforts to establish a diagnosis may be prolonged and difficult. It is not uncommon to establish a syndrome diagnosis months or even years after the onset of uveitis. Several authors have proposed systems of diagnosis that emphasize one or more of the clinical features of uveitis.1–8 For example, one method of diagnosis identifies patient age as the focal point for diagnosis. Other strategies have focused on the granulomatous or nongranulomatous nature of the disease, or whether the disease is acute or chronic.
Image Models (and their Speech Model Cousins)

Iterative reconstruction algorithms based on cross-entropy minimization.- Stop consonants discrimination and clustering using nonlinear transformations and wavelets.- Maximum a posteriori image reconstruction from projections.- Direct parsing of text.- Hierarchical modelling for microstructure of certain brittle materials.- Hidden Markov models estimation via the most informative stopping times for the Viterbi algorithm.- Constrained stochastic language models.- Recovering DNA sequences from electrophoresis data.- Image and speech and EM.- Non-stationary hidden Markov models for speech recognition.- Applications of the EM algorithm to linear inverse problems with positivity constraints.
Efficient parallel-by-line methods in CFD

Today's trend in Computational Science is characterized by quick shift from the yon Neumann computer architecture representing a sequential machine executed scalar data to MIMD computers where multiple instruction streams render multiple data. For implicit numerical methods, computations at each grid point are coupled to other grid points belonging to the same grid line in a fixed direction but can be done independently of the computations at grid points on all other lines in that direction. The coupling arises from solution of linear banded systems by Gaussian Elimination and leads to insertion of communications inside the computational sub-routines, idle stage of processors and large communication latency time. Traditional ADI methods, high-order compact schemes and methods of lines in multigrid solvers fall into the category of implicit numerical methods. This chapter proposes a novel methodology for efficient parallelization of implicit structured and block-structured codes. This method creates a parallel code driven by communication and computation schedule instead of usual “creative programming” approach. Using this schedule, processor idle and communication latency times are considerably reduced.
Single-strand breaks in deoxyribonucleic acid and viability loss during deoxyribonucleic acid synthesis inhibition in Escherichia coli.

Abstract The effects of deoxyribonucleic acid (DNA) synthesis inhibition brought about in four different ways—thymidine starvation, nalidixic acid, hydroxyurea, and dnaB mutation—were examined in isogenic strains of Escherichia coli K-12. Three parameters were examined to determine whether there are strict correlations among them: (i) the extent of DNA synthesis inhibition; (ii) cell survival; and (iii) the rate of breakage of DNA molecules. There was no significant correlation between the extent of DNA synthesis inhibition and the rate of viability loss caused by the four DNA synthesis inhibitors, nor was there a strict correlation between the rate of occurrence of single-strand breaks in DNA and loss of viability. During treatment with hydroxyurea (0.1 M), no viability loss was observed and little, if any, single-strand breakage of DNA occurred. Both thymidine starvation and nalidixic-acid (20 μg/ml) treatment resulted in viability loss and breakage of DNA. For these latter two inhibitors, the two events appeared to be associated because greater rates of both viability loss and DNA breakage were observed for nalidixic acid compared with thymidine starvation. However, viability loss need not be associated with extensive breakage of DNA as demonstrated with a temperature-sensitive DNA synthesis mutant; at 39 C, viability loss occurred at a high rate without significant DNA breakage. With the other agents, the amount of DNA breakage accumulated when a cell population has sustained an average of one lethal hit was estimated to be about 30 single-strand breaks per genome. Differences in chromosomal and episomal breakage rates were observed.
A Real-Time Deformable Model for Flexible Instruments Inserted into Tubular Structures

In this paper we present an approach to the problem of modelling long, flexible instruments, such as endoscopes or catheters. The idea is to recursively enumerate all possible shapes and subsequently filter them according to given mechanical and physical constraints. Although this brute-force approach has an exponential worst-case complexity, we show with a typical example that in case of tubular structures the empirical complexity is polynomial. We present two approximation methods that reduce this bound to a linear complexity. We have performed accuracy, runtime and robustness tests in preparation for first clinical studies.
Reaction of rat liver phenylalanine hydroxylase with fatty acid hydroperoxides. Characterization and mechanism.

Rat liver phenylalanine hydroxylase must be in a reduced form to be catalytically active (Marota, J.J. A., and Shiman, R. (1984) Biochemistry 23, 1303-1311). In this communication we show that a fatty acid hydroperoxide, 13-hydroperoxylinoleic acid (LOOH), can efficiently oxidize the reduced enzyme. In the process, the hydroperoxide is decomposed, oxygen consumed, and hydrogen peroxide formed. Enzyme reduction by the tetrahydropterin cofactor and reoxidation by LOOH can occur as two single steps or, when the enzyme concentration is low compared to that of the substrates, as part of a catalytic cycle. In this latter case, phenylalanine hydroxylase is a hydroperoxide-dependent tetrahydropterin oxidase. The reaction requires 1.0 mol of O2, 1.0 mol of tetrahydropterin, and 0.5 mol of LOOH to yield 1.0 mol of quinonoid dihydropterin, 0.4 mol of H2O2, and fatty acid products. Thus far, the catalytic and single-step reactions appear the same in all properties, consistent with the steady-state reaction following a ping-pong mechanism. Phenylalanine hydroxylase is an excellent catalyst for this reaction: the turnover number with LOOH is slightly greater than with phenylalanine; the Km(app) for LOOH is 11 +/- 4 microM; and the kcat/Km ratio for LOOH is about 25 times greater than for phenylalanine. LOOH and phenylalanine appear to react at different sites on phenylalanine appear to react at different sites on phenylalanine hydroxylase, and the reaction of LOOH is inhibited only slightly by phenylalanine and not at all by 5-deaza-6-methyltetrahydropterin, a competitive inhibitor of phenylalanine hydroxylation. The reaction of LOOH with phenylalanine hydroxylase strongly resembles the nonenzymatic reaction of LOOH with hematin, implying similar mechanisms for the two reactions and implicating the enzyme's non-heme iron as both the site of reaction of LOOH and of electron transfer during oxidation and reduction. The formation of hydrogen peroxide during a reaction of phenylalanine hydroxylase is unusual. Indirect evidence indicates a reduced oxygen species, formed on the enzyme during the reduction step, is (partially) released as H2O2 when the hydroperoxide reacts.
Citrus bitter principles—III ☆: Application of ORD and CD to stereochemical problems

Abstract A systematic CD and ORD study of limonoids is reported. The data obtained have been used to define completely the relative stereochemistry at the 13- and 17-positions and absolute stereochemistry of odoratin as well as that at C-17 in obacunone and congeners. The role of C-1 stereochemistry in the conversion of ichangin to limonin is discussed.
Aligning Auditor Materiality Choice and the Needs of a Reasonable Person

Materiality choice impacts the transparency, consistency and comparability of financial statements. Lack of prescriptive guidance, however, results in auditors often using a subjective heuristic to determine whether to waive or require correction of identified omissions or likely misstatements. This paper shows that if the auditor actually adheres to any one of the commonly-used heuristics, earnings per share may be misstated by potentially unacceptable amounts. As capital markets research indicates that the markets react to changes in earnings per share as small as one cent, it is recommended that a policy be promulgated defining an identified omission or likely misstatement to be material when, if corrected, primary earnings per share would change by one cent. Implementation of this policy will make financial statements more transparent, comparable and reliable by applying a uniform metric across industries, across entities of different sizes, and across time and will reduce the possibility of impaired auditor independence.
Multi-lingual and multi-modal speech processing and applications

Over the last decade voice technologies for telephony and embedded solutions became much more mature, resulting in applications providing mobile access to digital information from anywhere. Both a growing demand for voice driven applications in many languages and the need for improved usability and user experience now drives the exploration of multi-lingual speech processing techniques for recognition, synthesis and conversational dialog management. In this overview article we discuss our recent activities on multi-lingual voice technologies and describe the benefits of multi-lingual modeling for the creation of multi-modal mobile and telephony applications.
On the performance of optimum noncoherent amplify-and-forward reception for cooperative diversity

In this paper, we present receiver structures for maximum-likelihood (ML) noncoherent amplify-and-forward (AF) communication links when multiple relay nodes are employed. We consider both on-off keying (OOK) and binary frequency shift keying (BFSK) modulation schemes on Rayleigh fading relay channels with no channel state information. Even for the simple case of having only one relay node, the optimum noncoherent receiver is quite involved, and the ML metric computation requires certain integral evaluations. To lower hound the average bit error rate (BER), we assume that the link between the relay and the destination node is unfaded, a reasonable assumption when there is a strong line-of-sight path between the relay and the destination, and obtain simple closed-form expressions for the average BER with an arbitrary number of relays. Upper bounds on the average BER are also presented by numerically evaluating the Bhattacharyya distance between the likelihood functions. Further, simple suboptimum receiver structures are proposed, for both OOK and BFSK, along with an analytical performance evaluation, and an asymptotic diversity order analysis.
Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis and epithelial‑to‑mesenchymal transition in colon and breast cancers

The Nef-M1 peptide competes effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in colon cancer (CRC) and breast cancer (BC). Its role in tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) regulation, key steps involved in tumor growth and metastasis, are unknown. We evaluated the angioinhibitory effect of Nef-M1 peptide and examined its role in the inhibition of EMT in these cancers. Colon (HT29) and breast (MDA-MB231) cancer cells expressing CXCR4 were studied in vitro and in xenograft tumors propagated in severe combined immunodeficient mice. The mice were treated intraperitoneally with Nef-M1 or scrambled amino acid sequence of Nef-M1 (sNef-M1) peptide, a negative control, starting at the time of tumor implantation. Sections from tumors were evaluated for tumor angiogenesis, as measured by microvessel density (MVD) based on immunostaining of endothelial markers. In vitro tumor angiogenesis was assessed by treating human umbilical vein endothelial cells with conditioned media from the tumor cell lines. A BC cell line (MDA-MB 468) which does not express CXCR4 was used to study the actions of Nef-M1 peptide. Western blot and immunofluorescence analyses assessed the effect of Nef-M1 on tumor angiogenesis and EMT in both tumors and cancer cells. Metastatic lesions of CRC and BC expressed more CXCR4 than primary lesions. It was also found that tumors from mice treated with sNef-M1 had well established vascularity, while Nef-M1 treated tumors had very poor vascularization. Indeed, the mean MVD was lower in tumors from Nef-M1 treated mice than in sNef-M1 treated tumors. Nef-M1 treated tumor has poor morphology and loss of endothelial integrity. Although conditioned medium from CRC or BC cells supported HUVEC tube formation, the conditioned medium from Nef-M1 treated CRC or BC cells did not support tube formation. Western blot analyses revealed that Nef-M1 effectively suppressed the expression of VEGF-A in CRC and BC cells and tumors. This suggests that Nef-M1 treated CRC and BC cells are more consistent with E-cadherin signature, and thus appears more epithelial in nature. Our data indicate that Nef-M1 peptide inhibits tumor angiogenesis and the oncogenic EMT process. Targeting the chemokine receptor, CXCR4, mediated pathways using Nef-M1 may prove to be a novel therapeutic approach for CRC and BC.
SU‐E‐J‐162: Systematic Feasibility Analysis of a Quantitative Elasticity Estimation for Breast Anatomy Using Supine/prone Model Postures

Purpose: The purpose of this project is to estimate an elasticity distribution of breast tissue using supine/prone patient postures. Using biomechanical high-resolution breast models, a systematic assessment was performed in order to determine the feasibility of using patient standard clinical CT data. Methods: A GPU-based framework was used to generate a mass-spring model with a hemispherical geometry to represent a breast in the prone position. The model was anchored to the base of the hemisphere mimicking the chest-wall/breast tissue interface. The model then was deformed with several ground-truth elasticity distributions. Both isotropic and anisotropic elasticity distributions were used to demonstrate a tumor’s presence in the breast tissue. Solving the inverse elasticity problem was accomplished with a forward iterative approach by resetting the model to a non-deformed position and iteratively deforming it. A gradient-based iterative optimization scheme was used to update elasticity distribution in order to minimize the discrepancy between ground-truth and computed mechanical responses (displacement) for each voxel. For the purpose of our feasibility study, convergence was obtained when each voxel of tissue was within 1 mm of the ground-truth deformation. The model resolution was systematically varied to verify convergence at different volume representations. Results: For a simulated hemisphere running at 200 deformations per second (dps) with about 100,000 mass elements and 26 mass-spring connections, convergence occurred within minutes for each elastic distribution. Using apriori information about the underlying anatomy, these elasticity distribution were estimated in half the computation time with the accuracy improving from 89% to 93%. Though the effective elasticity estimation varied slightly from the ground-truth, displacement magnitude difference was well within 0.1 mm. Conclusion: By utilizing a forward iterative approach to solve the inverse elasticity problem, this work indicates the feasibility and potential of the fast reconstruction of breast tissue elasticity distribution using supine/prone postures.
Relationship of Some Cryptococcus neoformans Hypha-Forming Strains to Standard Strains and to Other Species of Yeasts as Determined by Deoxyribonucleic Acid Base Ratios and Homologies

The taxonomic relationship between some hypha-forming Cryptococcus neoformans strains and those that morphologically fit the standard description of this species was determined on the basis of DNA base ratios and DNA-DNA duplex formation. The average guanosine plus cytosine content, as estimated from melting temperature profiles, varied between 43.0 and 45.9% for all C. neoformans strains examined. The relative homology was at least 60% for all C. neoformans strains when the labeled DNA was from either a hyphal variant or a standard strain. The nonpathogenic cryptococci, C. laurentii and C. uniguttulatus, showed less than 10% relative homology with either the hyphal or standard C. neoformans strains. Thus, hyphal and standard strains of C. neoformans were sufficiently related to be considered members of the same species.
Ovaries secrete male hormone. V. A comparison of some synthetic androgens with the naturally occurring ovarian androgen in mice.

IN VIEW of the many recent studies (I-12) concerning androgenic substances which I derive from ovaries it becomes of increasing interest and importance to learn JL something of the identity of those materials. Hill and Strong (8) decided that ovarian and testicular androgens were similar physiologically but probably of a differ' ent chemical nature. Deanesly (II), from similar experiments with rats, likewise con' eludes that grafted ovaries do not produce an androgen chemically identical with that liberated by the testis. At present it seems that any amount of androgen which might be produced by mouse ovaries would be of quantities so minute as to preclude any chemical analysis. Until some means of making such a chemical analysis is available we must be content with a probably less accurate physiological test. We herewith present data which show some similarities and differences demonstrable in the action of ovarian and synthetic androgens.
A TPC detector for the study of high multiplicity heavy ion collisions

Abstract The design of a Time Projection Chamber (TPC) detector with complete pad coverage is presented. The TPC will allow the measurements of high multiplicity (~200 tracks), relativistic nucleus-nucleus collisions initiated with the heaviest, most energetic projectiles available at the LBL BEVALAC accelerator facility. The front end electronics, composed of over 15,000 time sampling channels, will be located on the chamber.
N-Way Video Communication over Enterprise Networks Based on Adaptive Bit Stream Extraction in Scalable Video Coding

In this paper, we explore real time N-way video communication over enterprise networks based on scalable video coding, SVC (Scalable extension of H.264/AVC). We present a bit stream extraction strategy based on GOP size prediction and perceptual importance of temporal and quality enhancements, and validate the strategy through initial subjective testing. We also compare it with extraction based on average bit rate of each constituent layer of the bit stream. Our extraction is adaptive with respect to variations in available bandwidth and is proxy driven, in that the decision process and the adaptation are preformed at proxy servers located at the edges of the backbone network. The main goals are to 1)maximize the user perceived quality even during deteriorating channel conditions, 2) maximize the reaction speed to changes in available bandwidth and 3) minimize the extraction delay. We report objective and subjective results for the N=2 case, with HD video clips encoded at 600 – 900 kbps. With a channel utilization of 92.7%, our extraction algorithm based on GOP size prediction shows an average increase in PSNR of about 2.2 dB over the extraction based on average bit rate. Initial subjective tests also prove that our layer extraction strategy is perceptually more efficient than other extraction schemes.
SIPs: Shift-and-invert parallel spectral transformations

SIPs is a new efficient and robust software package implementing multiple shift-and-invert spectral transformations on parallel computers. Built on top of SLEPc and PETSc, it can compute very large numbers of eigenpairs for sparse symmetric generalized eigenvalue problems. The development of SIPs is motivated by applications in nanoscale materials modeling, in which the growing size of the matrices and the pathological eigenvalue distribution challenge the efficiency and robustness of the solver. In this article, we present a parallel eigenvalue algorithm based on distributed spectrum slicing. We describe the object-oriented design and implementation techniques in SIPs, and demonstrate its numerical performance on an advanced distributed computer.
Florence Nightingale: The Evolution and Social Impact of Feminist Values in Nursing

Although generally recognized as the founder of modern nursing, Florence Nightingale has been criticized for her apparent lack of support of women's issues, including suffrage. This article examines the primary and supporting literature surrounding this topic. Findings indicate that Nightingale developed a complex set of beliefs that supported women as individuals rather than from a gender perspective. She did, in fact, support the concept of women's suffrage but did not give it priority. Victorian women suffered from lack of legal status, education, financial independence, and support from either the family or church as social institutions. Therefore, Nightingale's conception of nursing as a secular, educated profession cannot be overemphasized as a benchmark in the developing importance of women in the social system.
Immunocytochemical characterisation of proteins secreted by retinal pigment epithelium in retinas of normal and Royal College of Surgeons dystrophic rats.

In a previous study, an antigen consisting of proteins secreted by retinal pigment epithelial (RPE) cells was injected into a sheep and the specificity of the resulting antiserum was shown by Western blotting and its effects on retinal development were determined in vitro and in vivo. In the present study, the distribution of these secreted proteins was determined by light microscopy immunocytochemistry in cultured neonatal rat RPE cells and retinas of normal and Royal College of Surgeons (RCS) dystrophic rats and cerebrum of normal adult rats. Immunolabelling for these RPE-secreted proteins was detected in cytoplasmic vesicles surrounding nuclei and within processes of cultured normal and transformed rat RPE. In retinas of late postnatal and adult rats, dense immunostaining was found in the cytoplasm of RPE cells and ganglion cell bodies. In addition to RPE and ganglion cells, scattered photoreceptors within the thin outer nuclear layer and small structures within the debris zone were also densely immunoreactive in retinas of 2-mo-old RCS dystrophic rats. The numbers of immunostained ganglion cells appeared to decrease in retinas of older RCS rats, although the immunoreactivity within the RPE appeared to increase in density. No other neuron within the retina, i.e. bipolar, amacrine or horizontal, was immunoreactive for RPE-secreted proteins. In the cerebral cortex of adult rats, immunoreactivity for RPE-secreted proteins was primarily detected within large perikarya of pyramidal neurons and smaller granule neurons. In conclusion, we report an immunocytochemical analysis of an antiserum raised against secreted proteins of rat RPE. This antiserum recognised proteins within secretory-like vesicles of cultured neonatal normal and transformed rat RPE and showed a specificity for RPE and ganglion cells in normal rat retinas, that appeared to be developmentally regulated, and neuron perikarya in adult rat cerebrum.