cssi/SciSciGPT-SciSciNet huggingface dataset:
Chapter 30. Reactions of Interest in Medicinal Chemistry

Publisher Summary This chapter discusses the various reactions and techniques in medicinal chemistry. Alkynes in ethereal solvents are stereospecifically reduced by LiAlH4 to trans-olefins. This result contrasts with the cis-products reported from LiAlH4 reduction of alkynes in hydrocarbon solvents. A homogeneous catalytic hydrogenation of unsaturated aldehydes to saturated aldehydes can be accomplished by use of a tris-(tripheny1phosphine)chlororhodium catalystz. The reaction is specific for carbon–carbon multiple bonds and other functional groups do not interfere. Aliphatic and alicyclic olefins are oxidized to ketones by a pertrifluoroacetic acid-BF3 reagent. For some carbocyclic systems ring contraction, expansion, or rearrangement may also occur, forming interesting compounds not otherwise readily preparable. Terminal acetylenic groups can be protected from participating in undesirable reactions with organometallic reagents by first forming the ethynyl Grignard reagent and treating it with trirnethylchlorosilane, forming a carbon–silicon bond at the primary acetylenic carbon. Iodine isocyanate reacts with olefins to form α-iodoisocyanates which can be converted to a variety of useful derivatives.
GP38-targeting monoclonal antibodies protect adult mice against lethal Crimean-Congo hemorrhagic fever virus infection.

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. Limited evidence suggests that antibodies can protect humans against lethal CCHFV disease but the protective efficacy of antibodies has never been evaluated in adult animal models. Here, we used adult mice to investigate the protection provided against CCHFV infection by glycoprotein-targeting neutralizing and non-neutralizing monoclonal antibodies (mAbs). We identified a single non-neutralizing antibody (mAb-13G8) that protected adult type I interferon–deficient mice >90% when treatment was initiated before virus exposure and >60% when administered after virus exposure. Neutralizing antibodies known to protect neonatal mice from lethal CCHFV infection failed to confer protection regardless of immunoglobulin G subclass. The target of mAb-13G8 was identified as GP38, one of multiple proteolytically cleaved glycoproteins derived from the CCHFV glycoprotein precursor polyprotein. This study reveals GP38 as an important antibody target for limiting CCHFV pathogenesis and lays the foundation to develop immunotherapeutics against CCHFV in humans.
The Costs of Autonomy: Decisional Autonomy Undermines Advisees' Judgements of Experts

Over the past several decades, the United States medical system has increasingly prioritized patient autonomy. Doctors routinely encourage patients to come to their own decisions about their medica...
Placement of Reveal LINQ Device in the Left Anterior Axillary Position.

Implantable loop recorders (ILR) are utilized for long-term rhythm monitoring. Typical placement of the Medtronic Reveal LINQ along the left parasternal border may compromise the quality and/or feasibility of future imaging studies. We sought to evaluate the utility of placing an ILR in the left anterior axillary position and the impact on the quality of cardiac imaging. We reviewed patients from May 2017 to June 2018 who had placement of a Reveal LINQ device in the left anterior axillary position. Demographic, procedural, and clinical data were collected via retrospective review. Cardiac magnetic resonance imaging (MRI) studies were reviewed for image quality after ILR placement. Eight patients met inclusion criteria for this study (median age 6 years, 50% female). Six patients (75%) had an ILR placed in the operating room, while all others were placed in the electrophysiology lab. All patients demonstrated acceptable R waves for diagnostic evaluation (median = 0.85 mV, range 0.24–1.7 mV). Cardiac MRI was obtained in 7 patients following ILR placement with diagnostic image quality and no adverse events. One device was explanted 28 days after placement due to concern for possible infection. No other devices required removal or revision (median follow up duration 11 months, IQR 8–13.5). ILR placement in the left anterior axillary position can record adequate signals in pediatric patients. In addition, axillary ILR device position may allow for completion of cardiac imaging, particularly cardiac MRI, without significant artifacts which is critical for patients with congenital heart disease.
MMPdb and MitoPredictor: Tools for facilitating comparative analysis of animal mitochondrial proteomes

Data on experimentally-characterized animal mitochondrial proteomes (mt-proteomes) are limited to a few model organisms and are scattered across multiple databases, impeding a comparative analysis. We developed two resources to address these problems. First, we re-analyzed proteomic data from six species with experimentally characterized mt-proteomes: animals (Homo sapiens, Mus musculus, Caenorhabditis elegans, and Drosophila melanogaster), and outgroups (Acanthamoeba castellanii and Saccharomyces cerevisiae) and created the Metazoan Mitochondrial Proteome Database (MMPdb) to host the results. Second, we developed a novel pipeline, "MitoPredictor" that uses a Random Forest classifier to infer mitochondrial localization of proteins based on orthology, mitochondrial targeting signal prediction, and protein domain analyses. Both tools generate an R Shiny applet that can be used to visualize and interact with the results and can be used on a personal computer. MMPdb is also available online at https://mmpdb.eeob.iastate.edu/.
Exercise-induced bronchoconstriction in elite or endurance athletes:: Pathogenesis and diagnostic considerations.

Abstract Objective To review the pathogenesis and evaluation of exercise-induced bronchoconstriction pertaining to the elite or endurance athlete, as well as propose a diagnostic algorithm based on the current literature. Data Sources Studies were identified using Ovid MEDLINE and reference lists of key articles. Study Selections Randomized controlled trials were selected when available. Systematic reviews and meta-analyses of peer-reviewed literature were included, as were retrospective studies and observational studies of clinical interest. Results Exercise-induced bronchoconstriction (EIB) is the physiologic entity in which exercise induces acute narrowing of the airways and occurs in patients both with and without asthma. It may present with or without respiratory symptoms, and the underlying cause is likely attributable to environment stressors to the airway encountered during exercise. These include the osmotic effects of inhaled dry air, temperature variations, autonomic nervous system dysregulation, sensory nerve reactivity, and airway epithelial injury. Deposition of allergens, particulate matter, and gaseous pollutants into the airway also contribute. Elite and endurance athletes are exposed to these stressors more frequently and in greater duration than the general population. Conclusion A greater awareness of EIB among elite and endurance athletes is needed, and a thorough evaluation should be performed if EIB is suspected in this population. We propose an algorithm to aid in this evaluation. Symptoms should not be solely relied on for diagnosis but should be taken into the context of bronchoprovocative challenges, which should replicate the competitive environment as closely as possible. Further research is needed to validate these tests' predictive values.
Surface Ki-67 Expression Improves Reproducibility of Dysplasia Diagnosis in Barrett's Esophagus.

OBJECTIVES Many studies have shown poor reproducibility among pathologists for diagnosing dysplasia in Barrett's esophagus (BE). Immunohistochemical stains (IHC) are not widely used due to overlapping expression patterns in reactive and dysplastic processes. We hypothesized that markers involved in cell-cycle (cyclin D1, Ki-67, P16), differentiation/cell-cell interaction (β-catenin, SATB2 CD44, OCT4) and senescence (γH2AX) would produce different results in reactive and dysplastic processes. METHODS A micrograph album of 40 H&E and matching IHCs depicting optimally oriented lesions were evaluated independently by 3 pathologists. Expression was scored separately in the surface, isthmus, and base regions of the glands. RESULTS Statistical analysis showed that surface Ki-67 expression showed the largest difference in expression and smallest P value (P < .001) for identifying dysplasia. At a cutoff level of 5% or less, negative predictive value (NPV) was 100%. κ correlation between pathologists improved from substantial to almost perfect (0.70-0.95) using ancillary surface Ki-67. CONCLUSION A case-control study with glass slides including all diagnostic categories using this parameter confirmed improved κ correlation among pathologists (0.29 vs 0.60), better correlation with outcomes (76% vs 69%), increased odd risks (15.3) for progression in positive cases, and an improvement in sensitivity (88% vs 64%) and NPV (88% vs 73%) compared to histology alone.
Clinical outcome and toxicity from taxanes in breast cancer patients with BRCA1 and BRCA2 pathogenic germline mutations

Germline variations in genes coding for proteins involved in the oxidative stress and DNA repair greatly influence drug response and toxicity. Because BRCA1 and BRCA2 proteins play a role in DNA damage repair, we postulated that taxane-related toxicity is potentially higher and clinical outcome in different in patients with BRCA pathogenic variants (PV). Seven hundred nineteen women who underwent BRCA genetic testing and were treated with taxane-containing chemotherapy for early-stage breast cancer between 1997 and 2018 were included in the study. Patients with BRCA variants of uncertain significance were excluded. The Kaplan-Meier product-limit method was used to estimate recurrence-free survival (RFS) and overall survival (OS) rates. Logistic regression models were used to assess the association between chemotherapy toxicity and factors of interest. Cox regression models were used to assess the association between RFS and OS and factors of interest. Ninety-four (13%) and 54 (7%) patients had BRCA1 and BRCA2-PVs, respectively. While anemia (P = .0025) and leukopenia (P = .001) were more frequently seen in BRCA noncarriers, there was no difference in regards to peripheral neuropathy or other toxicities between the groups. Increasing doses of taxane were associated with increased risk of neutropenia, stomatitis, nausea, vomiting, acne/rash, and peripheral neuropathy across all groups. In a multivariate logistic regression model, BRCA2 status remained as an independent significant predictor for decreased hematologic toxicity (HR: 0.36; 95% CI: 0.20-0.67; P = .001) and increased gastrointestinal toxicity (HR: 1.93; 95% CI: 1.02-3.67; P = .04). Being overweight, obese and African-American race were significant predictors for peripheral neuropathy (P = .04; P = .03; P = .06, respectively). Total taxane dose received did not have any impact on survival outcomes. Our study demonstrates that taxane-containing chemotherapy regimens do not increase risk of peripheral neuropathy or hematologic toxicity in patients with BRCA PVs. The mechanisms for this finding need to be further investigated as it may provide an opportunity to combine taxanes with other agents, such as platinum salts or PARP inhibitors, with less anticipated toxicity.
Exploring the Growth of Homeschooling and Unschooling

Homeschooling has grown exponentially in the past decade. Researchers estimate that almost two million students in the United States are home educated, accounting for over 3% of the school-aged population. Around 10–20% of those who homeschool define their philosophy of homeschooling as unschooling, and that number seems to be growing every day. This chapter provides a summary of the demographics of the homeschooling and unschooling movements, and discusses the tremendous growth seen in the number of diverse families choosing to unschool in the United States.
On the Kármán momentum-integral approach and the Pohlhausen paradox

This work explores simple relations that follow from the momentum-integral equation absent a pressure gradient. The resulting expressions enable us to relate the boundary-layer characteristics of a velocity profile, u(y), to an assumed flow function and its wall derivative relative to the wall-normal coordinate, y. Consequently, disturbance, displacement, and momentum thicknesses, as well as skin friction and drag coefficients, which are typically evaluated and tabulated in classical monographs, can be readily determined for a given profile, F(ξ) = u/U. Here, ξ = y/δ denotes the boundary-layer coordinate. These expressions are then employed to provide a rational explanation for the 1921 Pohlhausen polynomial paradox, namely, the reason why a quartic representation of the velocity leads to less accurate predictions of the disturbance, displacement, and momentum thicknesses than using cubic or quadratic polynomials. Not only do we identify the factors underlying this behavior but also we proceed to outline a procedure to overcome its manifestation at any order. This enables us to derive optimal piecewise approximations that do not suffer from the particular limitations affecting Pohlhausen’s F = 2ξ − 2ξ3 + ξ4. For example, our alternative profile, F = (5ξ − 3ξ3 + ξ4)/3, leads to an order-of-magnitude improvement in precision when incorporated into the Karman–Pohlhausen approach in both viscous and thermal analyses. Then, noting the significance of the Blasius constant, s¯≈1.630 398, this approach is extended to construct a set of uniformly valid solutions, including F=1−exp[−s¯ξ(1+12s¯ξ+ξ2)], which continues to hold beyond the boundary-layer edge as y → ∞. Given its substantially reduced error, the latter is shown, through comparisons to other models, to be practically equivalent to the Blasius solution.
Turn-on Switching Transition Control using a GaN-FET based Active Gate Drive

A switched resistor based active drive scheme is delineated in this paper. The active gate drive does switching transition control (STC) of a wide bandgap (WBG) SiC MOSFET. Contrary to prevalent active gate drive schemes which are validated on a double pulse (DP) testbed, this paper synthesizes an STC scheme for a WBG PES prototype to meet a system-level goal like efficiency increment. An HF Cuk PES operating at 50 kHz using Cree SiC MOSFET half-bridge module is fabricated for testing purpose of the STC framework. The switched resistor based STC uses HF GaN-FET based network, consisting of state-of-the-art EPC8004 GaN and LMG1020 Texas drivers. The design achieved transitions of 1 ns to create short pulse widths that can control the turn-on trajectory of the SiC device. The simple approach is realized only with the use of an industrial-scale F28379D processor.
Biomarkers for brain tumors - a feasibility study using mass spectrometric proteomic analysis (P4.229)

Objective: The aim of this pilot study is to optimize methodology for biomarker discovery in brain tumors. Protein expression patterns in limited number of tumor and control tissues were analyzed for biomarker signatures with a view to escalating to larger series. Background: Brain tumors constitute the most frequent solid malignancy in children. So far, no reliable biomarkers exist for most types. Rapid progress in molecular techniques has expanded the scope for improved biomarker discovery, early diagnosis, and better therapeutic choices. However, proteomic approaches have not been well explored. Design/Methods: Using mass spectrometry-based proteomics technologies, we investigated the proteome profile for normal brain tissues from four autopsy cases and pairs of surgically removed tumor and control tissues from medulloblastoma and oligodendroglioma. Tissue micro-dissection, protein extraction, and Orbitrap mass spectrometric methods were applied. Proteome data were analyzed with Scaffold 4.0. Results: Through stringent proteomic approaches, more than 1000 proteins were identified in each sample. A panel of 533 proteins was selected as a potential control set generated from three normal cerebellar tissues. There were also potential control sets identified for gray matter of the medulla, white matter of the medulla, and the midbrain, with 124, 57, and 495 proteins, respectively. A total of 207 proteins were found with more than 2-fold overexpression in oligodendroglioma compared to adjacent normal brain tissue. A total of 83 proteins were significantly associated with medulloblastoma comparing with normal controls. Using ingenuity pathway analysis (IPA) software, these datasets will be further explored to generate a short list of meaningful biomarkers. Conclusions: Mass spectrometric proteomic analysis represented a highly useful tool for the initial screening for potential biomarker candidates. Our methodology appeared robust and reproducible. Laboratory validation using more quantitative techniques is needed to establish clinical utility. Further evaluation in a larger group of patients is currently in progress. Disclosure: Dr. Liu has nothing to disclose. Dr. Sandberg has nothing to disclose. Dr. Herrmann has nothing to disclose. Dr. Raghavan has nothing to disclose.
Understanding the New Biology of Estrogen-Induced Apoptosis and Its Application in Patient Care

Aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs) are effectively used as treatments for breast cancer, but acquired resistance still occurs. Laboratory studies and clinical trials have demonstrated that after long-term estrogen deprivation, either by exhaustive anti-hormone therapy or years after menopause, estrogen is paradoxically able to kill breast cancer cells. Estrogen-induced apoptosis can be used as a potent strategy to treat anti-hormone-resistant breast cancer as well as prevent occult breast cancer from developing. This work outlines the background leading to the current understanding of estrogen-induced apoptosis and the clinical opportunities it presents both now and in the future.
Artificial insemination in pigs today

Use of artificial insemination (AI) for breeding pigs has been instrumental for facilitating global improvements in fertility, genetics, labor, and herd health. The establishment of AI centers for management of boars and production of semen has allowed for selection of boars for fertility and sperm production using in vitro and in vivo measures. Today, boars can be managed for production of 20 to 40 traditional AI doses containing 2.5 to 3.0 billion motile sperm in 75 to 100 mL of extender or 40 to 60 doses with 1.5 to 2.0 billion sperm in similar or reduced volumes for use in cervical or intrauterine AI. Regardless of the sperm dose, in liquid form, extenders are designed to sustain sperm fertility for 3 to 7 days. On farm, AI is the predominant form for commercial sow breeding and relies on manual detection of estrus with sows receiving two cervical or two intrauterine inseminations of the traditional or low sperm doses on each day detected in standing estrus. New approaches for increasing rates of genetic improvement through use of AI are aimed at methods to continue to lower the number of sperm in an AI dose and reducing the number of inseminations through use of a single, fixed-time AI after ovulation induction. Both approaches allow greater selection pressure for economically important swine traits in the sires and help extend the genetic advantages through AI on to more production farms.
Evaluation of biological response modifiers in the enhancement of tumor uptake of technetium-99m labeled macromolecules. A preliminary report.

Abstract Imaging tumors with radioactive monoclonal remains attractive but continu challenging. With the hypothesis that the use of biological response modifiers (BRMs) may augment the tumor uptake, technetium-99m(99mTc)-labeled tumor necrosis factor (TNF) and nuclear histone specific TNT-1-F(ab′)2 were evaluated in tumor bearing mice given a single dose of interferon (IFN), Ukrain or pokeweed mitogen as BRMs. As early as 1.5 h post injection (p.i.) of the radioactive macromolecules, the absolute tumor uptake (% administered dose/g) of each agent was enhanced (e.g., TNF, control = 1.8 ± 0.4, Ukrain = 3.2 ± 0.5, P= 0.006) and tumor to muscle ratios were elevated (e.g., TNF, control a 4.1 ± 2.2, interferon 8.3 ± 2.7, P = 0.01). The absolute tumor uptake remained practically unchanged at 4 h p.i. Generally with BRMs, the blood clearance was rapid and tumor/blood ratios and tumor/muscle ratios were higher than in the control group, increasing to greater than 200% for IFN as a BRM. The early enhancement in tumor uptake of macromolecules, leading to excellent delineation of tumors by scintigraphy is highly encouraging and warrants further studies to explore the full potential of BRMs.
Fibroblast Androgen Receptors in Patients with Genitourinary Anomalies

The etiology of certain disorders of sexual differentiation is unclear. The authors have examined the hypothesis that hypospadias and other disorders compatible with a defect in androgen action, such as cryptorchidism, micropenis, chordee/penile torsion, and ectopic testis, might be explained by androgen receptor abnormalities. Therefore, 25 subjects were studied who were selected only because they had one of these developmental defects, together with a predominantly male phenotype, and no readily ascertainable explanation for the defect. Four of these subjects had mixed gonadal dysgenesis with multiple genito-urinary anomalies. They were included for comparative purposes, since there is no evidence for androgen resistance in this disorder. Patients with testicular regression syndrome (gross testosterone deficiency), impaired testosterone biosynthesis (relative testosterone deficiency), 5α-reductase deficiency (altered T/DHT ratio), and a family history or endocrine profile suggestive of androgen resistance, were all excluded from evaluation. Androgen receptor content (Ro) and binding affinity (Kd) were measured in 26 genital or pubic skin fibroblast strains cultured from 25 affected patients using a dispersed, whole cell assay at 22 C. There was no difference in the mean androgen receptor content (approximately 10,000 sites/cell) or binding affinity (approximately 1 nM) between the patients' fibroblasts and those from 26 fibroblast strains established from 26 normal males. Moreover, there were no differences in the nuclear uptake of [3H]dihydrotestosterone into dispersed, intact fibroblasts incubated at 37 C when 11 patient and seven normal male fibroblast strains were compared. In conclusion: these disorders of sexual differentiation cannot be attributed to androgen resistance on the basis of decreased androgen receptor binding affinity or receptor number, as reflected in whole cells or nuclei of cultured skin fibroblasts.
The Testing Behind the Test Facility: The Acoustic Design of the NASA Glenn Research Center's World-Class Reverberant Acoustic Test Facility

The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is leading the design and build of the new world-class vibroacoustic test capabilities at the NASA GRC’s Plum Brook Station in Sandusky, Ohio, USA. Benham Companies, LLC is currently constructing modal, base-shake sine and reverberant acoustic test facilities to support the future testing needs of NASA’s space exploration program.
THE PERFORMANCE OF ALTERNATE FUELS IN GENERAL AVIATION AIRCRAFT

Abstract : This report describes the results of a study which measured the effects of pressure altitude on fuel weathering. In this study, samples of unleaded automobile gasoline were exposed to varying pressure altitudes, and the effects of this exposure on aircraft performance and volatility were measured. The composition of the fuel, aircraft configuration, and the initial temperature of the fuel when transferred to the tank were varied to determine the extent these variables affected the aircraft performance. Experiments were conducted which demonstrated that the use of 110-degree Fahrenheit fuel during aircraft certification will provide the greatest margin of safety. In addition, the suitability of methyl-tertiary-butyl ether as an acceptable fuel for use in general aviation aircraft was demonstrated. Keywords: Autogas, Alcohol fuels, Methyl-tertiary-butyl Ether (MTBE), Alternate fuels, Aircraft, Material compatibility, Vapor lock, Engines, Aircraft, Flight tests, Gasohol, Spark ignition engines.
Energy metabolism in human retinal Müller cells.

Purpose To measure selected parameters of energy metabolism and adenosine triphosphate (ATP) production in passaged monolayer cultures of human retinal glial (Muller) cells to assess the effects of varying substrate and oxygen availability on the biochemistry and histologic integrity of these cells. Methods Confluent Muller cell cultures were incubated for up to 4 hours at 37 degrees C in a modified minimal essential medium (no serum) under aerobic or mitochondrial-inhibited conditions in the presence and absence of 5 mM glucose or in the presence of lactate, pyruvate, glutamate, or glutamine. Cellular ATP levels, lactic acid production, and (14)CO(2) production from labeled glucose or glutamate were measured along with an examination of cellular morphology. Immunohistochemistry with antibodies to glial cell-specific proteins was also performed. Cells were positive for vimentin, but negative for glial fibrillary acidic protein and glutamine synthetase. Results Human Muller cells maintained ATP content aerobically at the same level for 4 hours in the presence and absence of glucose. ATP content was also maintained anaerobically at a value equal to that found aerobically, but only in the presence of glucose. ATP content in human Muller cells declined to a very low level when glycolysis was blocked by iodoacetate, and inclusion of lactate, pyruvate, glutamate, or glutamine did not restore the level of ATP. Aerobically, lactic acid production accounted for 99% of the total glucose used, whereas the oxidation of glucose by the mitochondria accounted for only 1%. When mitochondria were inhibited with antimycin A, there was only a modest (1.3-fold) increase in the rate of lactic acid production. No significant differences were found in the histologic appearance of the cells after mitochondrial blockade, but there was massive death of cells after inhibition of glycolysis with iodoacetate. Conclusions These results suggest that, in the presence of glucose and oxygen, cultured Muller cells obtain their ATP principally from glycolysis and have a low rate of oxygen consumption. This metabolic pattern may spare oxygen for retinal neurons, particularly in the inner nuclear and ganglion cell layers under normal physiological conditions. Furthermore, retinal Muller cells in culture are resistant to anoxia or absence of glucose, which provides a basis for understanding why Muller cells are less susceptible than neurons to ischemia or hypoglycemia.
Recent demographic change: implications for families planning for the future.

Because of dramatic reductions in mortality levels across the 20th century, most Americans today can anticipate living into old age. The predictability of a long-lived life today, however, is accompanied by increasingly diverse life oppurtunities and experiences. Partly as a result of reduced mortality, we have witnessed marked changes in marriage, divorce, fertility and employment patterns in recent decades. These demographic changes introduce both new chances and challenges for the life course of individuals. This chapter describes recent trends in morality, fertility, marriage, divorce and employment, and considers their implications for how individuals and their families plan and prepare for their later adult years.
Identification of a 70-base-pair cell cycle regulatory unit within the promoter of the human thymidine kinase gene and its interaction with cellular factors.

Abstract The promoter of the human thymidine kinase gene contains cis-regulatory elements responsible for its cell-cycle-regulated expression. We report here that a 70-bp region between -133 and -64 is sufficient to confer cell cycle regulation on a heterologous promoter. The 20-bp region between -64 and -83, which contains an inverted CCAAT motif, is important for transcriptional stimulation of this functional unit. The sequence of this CCAAT motif is nearly identical to the consensus sequence for the transcriptional factor CP1. We also examined the specificity and binding activities of cellular factors interacting with the 70-bp fragment. We showed that the cellular factors binding to the 70-bp region are similar during the G1, S, and G2 phases, suggesting that the cell cycle regulatory activity observed must involve processes other than factor binding to the DNA.
Model-Based Design of Time-Triggered Real-Time Embedded systems for industrial automation

This paper presents a novel Model-Based Design (MBD) approach and associated tool-chain for the Time-Triggered Real-time Embedded (TTRE)1 systems. Our tool-chain automatically synthesizes software for manufacturing TTRE systems. A Software-In-the-Loop Simulation (SILS) framework integrated into our tool-chain helps to reduce the design iterations. Using a manufacturing robot-arm use-case, we validate our tool-chain and demonstrate a 39× improvement in the Quality-of-Control (QoC) when compared to the state-of-the-art approach [3]. Our auto-generated scheduler meets all the hard real-time constraints (zero deadline misses) for a given TTRE system when compared to the scheduler (e.g., 145 deadline misses for a CPU utilization of 95%) presented in [1], [25]. Moreover, compared to the traditional MBD approach for the TTRE systems where many design iterations are required [4], our approach and tool-chain can generate high quality and accurate tasks with an associated scheduler in a single design iteration.
One- and two-electron reduction of 2-methyl-1,4-naphthoquinone bioreductive alkylating agents: kinetic studies, free-radical production, thiol oxidation and DNA-strand-break formation.

The one- and two-electron enzymic reduction of the bioreductive alkylating agents 2-methylmethoxynaphthoquinone (quinone I) and 2-chloromethylnaphthoquinone (quinone II) was studied with purified NADPH-cytochrome P-450 reductase and DT-diaphorase respectively, and characterized in terms of kinetic constants, oxyradical production, thiol oxidation and DNA-strand-break formation. The catalytic-centre activity values indicated that DT-diaphorase catalysed the reduction of quinone I far more efficiently than NADPH-cytochrome P-450 reductase, although the Km values of the two enzymes for this quinone were similar (1.2-3.0 microM). The one-electron-transfer flavoenzyme also catalysed the reduction of quinone II, but the behaviour of DT-diaphorase towards this quinone did not permit calculation of kinetic constants. A salient feature of the redox transitions caused by the one- and two-electron catalysis of these quinones was the different contributions of disproportionation and autoxidation reactions respectively. In the former case, about 26% of NADPH consumed was accounted for in terms of autoxidation (as H2O2 formation), whereas in the latter, the autoxidation component accounted for most (98%) of the NADPH consumed. This difference was abrogated by superoxide dismutase, which enhanced autoxidation during NADPH-cytochrome P-450 catalysis to a maximal value. E.s.r. analysis indicated the formation of superoxide radicals, the signal of which was suppressed by superoxide dismutase and unaffected by catalase. The one- and two-electron reduction of these quinones in the presence of GSH was accompanied by formation of thiyl radicals. Although superoxide dismutase suppressed the thiol radical e.s.r. signal in both instances, the enzyme enhanced GSSG accumulation during NADPH-cytochrome P-450 catalysis of quinone I, whereas it inhibited GSSG formation during reduction of the quinone by DT-diaphorase. One- and two-electron reduction of quinone I led to calf thymus DNA-strand-break formation, a process that (a) was substantially decreased in experiments performed with dialysed DNA and in the presence of desferal and (b) was partially sensitive to superoxide dismutase and/or catalase. These findings are rationalized in terms of the occurrence of metal ions ligated to DNA, protecting against the toxic effects of superoxide radicals generated during enzymic reduction of quinones.
Characteristics of asthmatic patients with and without repeat emergency department visits at an inner city hospital

AbstractObjective: The objective of this study was to document the frequency and clinical characteristics associated with repeat emergency department (ED) visits for asthma in an inner city population with a high burden of asthma. Methods: During an ED visit for asthma in an inner city hospital (‘index visit’), patients completed a valid survey addressing disease and behavioral factors. Hospital records were reviewed for information about ED visits and hospitalizations for asthma during the 12 months before and the 90 days after the index visit. Results: One hundred and ninety-two patients were enrolled; the mean age was 42 years, 69% were women, 36% were black, 54% were Latino, 69% had Medicaid, and 17% were uninsured. 100 patients (52%) were treated and released from the ED, 88 patients (46%) were hospitalized, and 4 patients (2%) left against medical advice. During the subsequent 90 days, 64 patients (33%) had at least one repeat ED visit for asthma and 27 (14%) were hospitalized for asthma. In a multi...
LC-MS analysis of carbonyl compounds and their occurrence in diesel emissions.

Liquid chromatography coupled with atmospheric pressure chemical ionization (APCI) ion trap mass spectrometry (ITMS) is applied to atmospheric aerosol relevant carbonyls. Characterization of positive and negative ion detection mass spectra are presented for 24 model compounds analyzed in their underivatized and O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) oxime forms. The addition of PFBHA derivatization enhanced the detection and sensitivity for many of the carbonyls investigated. For all but five of the carbonyls examined, a pseudomolecular (M + H)+ ion is the base peak in the APCI positive ion mass spectra of PFBHA oxime derivatives and is observed in four of the five exceptions. Application of the evaluated analysis methodology to heavy-duty diesel source emissions facilitated the quantification of 10 aliphatic carbonyls (5 C5−C9 ketones, 4 C6 unsaturated ketones, 1 C6 dicarbonyl) and 14 aromatic carbonyls (1 C9 aldehyde, 5 C8−C13 ketones, 8 C6−C14 quinones). Diesel truck engine emission facto...
An Optical Study of the Formation Stages of Spark Breakdown

With the electrooptical shutter described in the preceding paper a visual and photographic study has been made of the manner in which a static breakdown occurs in an air gap with an approximately homogeneous initial field. The study covered a range of pressures $P$ from 20 to 76 cm of Hg and gap lengths $\ensuremath{\delta}$ from 1.25 to 10 mm. The manner of breakdown for any condition can be told by the product (${P}^{\frac{1}{3}}\ensuremath{\delta}$): for values less than 11.9 the breakdown starts at the cathode; for values greater than 11.9 there are two initial breakdown regions, one at the cathode and one out in the gap. The exact manner in which the breakdown proceeds is shown and discussed in detail. The effect of space charges on the time required for the gap to completely breakdown is also shown and a possible arrangement of space charges is suggested which would explain the phenomena observed. Data on the rate of voltage fall of the gap are given.
Evaluating Readability of Domestic Violence Information Found on Domestic Violence State Coalitions' Websites

With the popularity of the Internet, more and more individuals are accessing health and mental health information from an array of websites. Yet, health literacy has emerged as barrier despite easier access to health information. The U.S. Department of Education (1986) stated that educational materials should be no higher than 8th grade reading level; yet, the reality is that often information written is above this level. This study examined the grade reading level and readability (as measured by the SMOG, Flesch-Kincaid Grade Level, and the Flesch Reading Ease) of domestic violence materials on the websites of domestic violence state coalitions. Findings indicated that the average grade reading level of the domestic violence materials were statistically significantly higher than the 8th grade standard. This was true regardless of the region where the domestic violence state coalitions were located. Implications for social service providers were discussed.
Operation of Steam Turbines to Minimize Shell Cracking

Some methods for reducing the tendencies toward cracking in steam-turbine shells are described. Involved are improved operating procedures, application of accessories, and improved mechanical design, all of which aid in properly controlling shell thermal distribution.
Infrared Radiometric Observations of the Solar Corona During the Total Solar Eclipse of 20 July 1963

Radiometric measurements of the solar corona have been made in the spectral region 1.15–5.1 μ during the total solar eclipse of 20 July 1963. A 78.7-cm diam, f/2 radiometer equipped with a thermistor bolometer detector was employed. Four wide band interference filters were used for spectral isolation, namely, 1.15–2.60 μ, 2.9–4.2 μ, 4.5–5.1 μ, and 7.6–13.4 μ. Coronal spectral intensities were measured as a function of radial position. The radial dependence of these intensities was calculated and compared with the van de Hulst model of the visible corona. Radiometric measurements were made during and after totality.
Materials development for precision segmented reflector applications

The requirements developed to guide the selection of current and future materials for precision segmented reflectors are presented along with a list of desirable properties. Some potential candidate materials including modified fiber reinforced organic matrix composites as well as carbon/carbon composites, graphite/glass composites, and metal matrix composites are identified. It is noted that in the near term, it is likely that modified fiber reinforced organic matrix composites have good applicability. In the longer term, materials such as carbon/carbon composites, graphite/glass composites and metal matrix composites may provide the best mix of properties.
Non-uniform electrical field effect caused by different concentrations of electrolyte in capillary zone electrophoresis

Abstract Capillary zone electrophoresis is usually performed with uniform electrolyte concentrations in the electrolyte reservoirs and the capillary and a resultant uniform electrical field. Thus, the sample species migrates as the algebraic sum of electroosmotic flow mobility and ionic mobilities. A non-uniform electrical field can be formed by filling the capillary and outlet reservoir with electrolyte at a given concentration (initial electrolyte) and the inlet reservoir with a different electrolyte concentration of the same chemical species (replacement electrolyte). Application of an electrical field causes continuous entrance of the replacement electrolyte changing the conductivity consequent to electrolyte concentration. Therefore, the electrical field strength is not uniform along the capillary. In this paper we will discuss the effect of this non-uniform electrical field on migration rates of different sample ions as well as its application to model samples.
Efficient Stereospecific Syntheses of Chiral Ruthenium Dimers

The stereospecific synthesis of three isomeric Ru dimers, Δ,Δ-[(phen)2Ru(tpphz)Ru(phen)2]4+ (Δ,Δ-4) (where tpphz = tetrapyrido[3,2-a:2‘,3‘-c:3‘‘,2‘‘-h:2‘‘,3‘‘-j]phenazine), Λ,Λ-4, and Λ,Δ-4, can be accomplished in high yield with retention of optical activity by the formation of a phenazine ring between appropriately functionalized chiral precursors.
Volatilidad y crisis: tres lecciones para países en desarrollo

La crisis internacional reciente no ha invalidado el conocimiento adquirido previamente sobre los origenes y las curas de las crisis economicas. Por el contrario, lo ha confirmado. En este articulo se describen tres lecciones de siempre, confirmadas por la ultima crisis internacional. Primero, las politicas e instituciones domesticas, y no la globalizacion, son los principales determinantes de la volatilidad excesiva y las crisis economicas. Segundo, los seguros gratuitos o subsidiados al riesgo y la practica de “rescates” a bancos y empresas deficientes estan en el origen de las peores crisis. Y tercero, la flexibilidad para ajustarse a nuevas condiciones, alentada por un marco regulatorio ligero y eficiente, es el mejor antidoto contra los descalabros macroeconomicos.
Transition radiation detector for relativistic particles at accelerator energies

Abstract Transition radiation (TR) has been investigated by using the arithmetic mean and the geometric mean of the pulses from 10 multiwire proportional chambers. The discrimination factor for different kinds of particles has been determined. Also the dependence of the intensity of TR on the Lorentz factor γ has been measured and compared with theoretical calculations.
Modelling of hollow-fibre ultrafiltration of skimmilk under mass-transfer limiting conditions

Abstract The performance of a commercial hollow-fibre ultrafiltration module processing skimmilk has been studied. The flux displayed a typical asymptotic behaviour with increasing transmembrane pressure, indicative of concentration polarization. In the polarized pressure-independent region, flux was significantly affected by velocity and feed concentration; temperature had a small positive effect. The Leveque and the Grober laminar flow models underpredicted the experimental flux. The model was mofified to include a concentration-dependent diffusivity term and to account for non-Newtonian rheological behaviour at high concentrations. The correlation which best fitted the data was Sh =0·087( Re ) 0·64 ( Sc ) 0·33
Superfluid vs Ferromagnetic Behavior in a Bose Gas of Spin-1/2 Atoms

We study the thermodynamic phases of a Bose gas of spin-1/2 atoms in the Hartree-Fock approximation. Our main result is that, for repulsive or weakly attractive inter-component interaction strength, the superfluid and ferromagnetic phase transitions occur at the same temperature. For strongly attractive inter-component interaction strength, however, the ferromagnetic phase transition occurs at a higher temperature than the superfluid phase transition. We also find that the presence of a condensate acts as an effective magnetic field that polarizes the normal cloud. We finally comment on the validity of the Hartree-Fock approximation in describing different phenomena in this system.
When is QT prolongation antiarrhythmic and when is it proarrhythmic

A large number of pathophysiologic conditions and pharmacologic interventions produce a significant lengthening of the QT interval. For many physicians a long QT interval continues to be associated with a propensity for polymorphic ventricular tachycardia to develop.’ This belief undoubtedly stems from an appreciation of the life-threatening arrhythmic complications of the congenital forms of the long QT-interval syndromes.2 The fear of an arrhythmogenic correlate of prolonged QT interval became entrenched in the early 1960s (about the time potent oral diuretics began to be introduced) when it was recognized that “quinidine syncope” was due to paroxysmal ventricular arrhythmia.3 This arrhythmia was called torsades de pointes.4 The features of this electrocardiographic and clinical entity are now clearly delineated.5 It occurs in the setting of long QT interval, and most cases are drug induced. The tendency for torsades de pointes to develop in the setting of prolonged QT interval is now known to be aggravated by the presence of bradycardia and severe electrolyte disturbances, especially hypokalemia.6 In recent years, a number of observations on the clinical significance of drug-induced lengthening of the QT interval have been made.7 First, we now know that there is not a linear relation between the degree of lengthening of the QT interval and the development of torsades de pointes. For example, a modest lengthening of the QT interval with quinidine may lead to the development of torsades de pointes, whereas with a profound increase, as with amiodarone, it rarely occurs. Second, for a given degree of QT lengthening produced by a variety of drugs, the incidence of torsades de pointes varies from one compound to the next. Third, there are several instances of QT prolongation in clinical situations (e.g., hypocalcemia and hypothyroidism) in which’ torsades de pointes or any other form of tachyarrhythmias is exceedingly uncommon. Finally, there is now compelling evidence7 that the lengthening of the QT interval induced by a number of cardioactive compounds (e.g., amiodarone, sotalol) constitutes a discrete antiarrhythmic and antifibrillatory mechanism as suggested 19 years ago. 8,g How does one reconcile these 2 seem-
Enhancement of compounded ultrasound images using spatial filtering

Compound ultrasound (US) images benefit from reduced speckle noise, at the expense of blurring. The purpose of this work was to evaluate several different methods for reducing the effects of blurring on compounded ultrasound images. We evaluated 3 different approaches: unsharp masking (USM), Gaussian deconvolution (GD), and system measured point-spread-function (PSF) deconvolution (PD). The compounded images are created from summation of approximately 300 B-Mode US images. We applied the different de-blurring methods to these images and examined the images subjectively as well as measured resolution with an autocorrelation metric. Overall, these methods improved resolution by 1.25 (USM), 1.09 (GD), and 1.27 (PD). Unsharp masking was the best trade-off between runtime performance and image quality.
An accurate numerical solution for mass diffusion-induced bubble growth in viscous liquids containing limited dissolved gas

Abstract A mathematical formulation based on potential theory is used to develop an accurate numerical technique to calculate the mass diffusion-induced growth of a spherical gas bubble surrounded by a viscous Newtonian liquid with a limited dissolved gas concentration under isothermal conditions. We solve for the complete concentration profile of the dissolved gas in the liquid enveloping the bubble to predict the bubble growth. These results are contrasted against the dynamics of bubble growth predicted by the widely used approach of employing polynomial profiles to describe the gas concentration. The influence of key dimensionless parameters on the differences in the bubble growth due to the choice of concentration profile is examined. The investigation reveals that the commonly used approximate solutions for the concentration profile not only underpredict the growth rate at the early stages of the growth but also overestimate the steady-state bubble radius due to the implicit assumption of an unlimited supply of dissolved gas in the liquid.
Poetry as play

During the Golden Age, poetry and drama entered into a dynamic intertextual and intergeneric exchange. The Comedia appropriated the different poetic currents prevalent during the Renaissance and also often enacted the controversies surrounding poetic language. Of particular interest is the influence of gongorismo on the comedia. Luis de Gongora himself experimented with dramatic form in his two little-known plays, Las firmezas de Isabela and El doctor Carlino . In his quest for effective dramatic language, Lope de Vega dramatized Gongorine language through both parody and respectful imitation. Calderon de la Barca, whose plays represent the culmination of Gongora's influence on Golden Age theater, transformed gongorismo into a rich, performative code that functions simultaneously as poetic discourse and dramatic convention.