cssi/SciSciGPT-SciSciNet huggingface dataset:
Romiplostim as a treatment for immune thrombocytopenia: a review.

“Immune thrombocytopenia” (ITP) is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk. Our understanding of the pathophysiology of ITP has evolved immensely, especially over the last 60 years. The discovery of the platelet-production stimulator, thrombopoietin (TPO), lent clarity to an earlier hypothesis that inhibition of platelet production at the level of the megakaryocyte, at least in part, accounts for thrombocytopenia in adults with ITP. This facilitated the development of TPO-based therapies to treat ITP. Thrombopoietin receptor agonists are one of the most recent treatments to enter the landscape. Original production of a recombinant human TPO was halted after clinical trials revealed the untoward effect of autoantibodies to the recombinant human TPO with cross-reactivity to endogenous TPO. Next-step development focused on stimulation of the TPO receptor with fewer immunogenic agents. Currently, two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are licensed in the USA to treat thrombocytopenia in adults with persistent or chronic ITP. Ongoing research will assess their efficacy in other immune-mediated and nonimmune-mediated primary and secondary thrombocytopenias.
Torsional vibration of a moving band

Abstract The problem of the torsional vibrations of a thin strip moving with constant speed in a longitudinal direction is formulated and solved. The effect of a point load acting on one of the thin edges is included. Some results of a parametric study show the effects of various parameters on the torsional frequency, and the occurrence of torsional buckling is predicted. In addition, an interesting behavior is shown in the case where the torsional wave propagation speed in the region “up-stream” from the point load is greater than in the “downstream” region.
Effects of awareness of prior-year testing strategies and engagement risk on audit decisions

Purpose – The purpose of the study is to examine how awareness of the prior year fraud detection testing strategy impacts auditor judgments at differing levels of engagement risk. Design/methodology/approach – A 2 × 2 between-subject experiment was conducted using 64 practicing auditors as participants. The independent variables are manipulated at two levels – awareness of prior-year testing strategy (aware versus unaware) and engagement risk (high versus low). The dependent measures are identified risk factors, targeted areas of auditors’ risk assessments, proposed audit procedures and the desire to consult with a forensic specialist. Findings – Although continuing auditors anchor on prior-year audit strategies, new auditors (who are unaware of prior-year testing strategies) focus on generally known high-risk areas and firm standard procedures while planning the audit. Practical implications – This paper contributes to the ongoing debate regarding how auditor tenure impacts auditors’ decision-making at a...
Effect of toluene on fathead minnow (Pimephales promelas Rafinesque) development

The environmental levels of aromatic hydrocarbons present in freshwater systems have been poorly characterized. This study examines the effect of toluene, a major water-soluble component of petroleum fuels on teleost development under controlled conditions. The fathead minnowPimephales promelas Rafinesque, was chosen as a model teleost for this study. Live embryos as well as serial sections of paraffin-embedded embryos were examined to determine effects of the toxicant. The toluene concentrations utilized ranged from 30 to 45 mg/L. Abnormalities noted under these conditions included distorted embryonic axis, abnormal heart and circulatory system development, hydration and swelling of the pericardial coelom, hemorrhaging, an overall stunted appearance, microphthalmia, and a unique migration of the ventrally located yolk syncytial layer and its associated nuclei.
Synthesis and evaluation of novel α-heteroaryl-phenylpropanoic acid derivatives as PPARα/γ dual agonists

Abstract The synthesis of a new series of phenylpropanoic acid derivatives incorporating an heteroaryl group at the α-position and their evaluation for binding and activation of PPARα and PPARγ are presented in this report. Among the new compounds, (S)-3-{4-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-phenyl}-2-1,2,3-triazol-2-yl-propionic acid (17j), was identified as a potent human PPARα/γ dual agonist (EC50 = 0.013 and 0.061 μM, respectively) with demonstrated oral bioavailability in rat and dog. 17j was shown to decrease insulin levels, plasma glucose, and triglycerides in the ZDF female rat model. In the human apolipoprotein A-1/CETP transgenic mouse model 17j produced increases in hApoA1 and HDL-C and decreases in plasma triglycerides. The increased potency for binding and activation of both PPAR subtypes observed with 17j when compared to previous analogs in this series was explained based on results derived from crystallographic and modeling studies.
Geological and geochemical legacy of a cold early Mars

[1] We consider the hypothesis that Mars never experienced an early warm, wet period and the implications of a continuously cold Martian climate for the hydrology and geochemistry of the planet. Geomorphic evidence previously interpreted to indicate a more temperate early climate can be explained by cold climate processes and the transient flow of liquid water at the surface rather than a terrestrial-like hydrological cycle. In this scenario, freezing and confinement of crustal aquifers lead to the eruption of water or brines to the surface: Hesperian events formed massive ice sheets, and triggered floods that carved the outflow channels, while smaller, present-day aqueous eruptions are responsible for the seepage and gully-like landforms identified in high-resolution imaging. This process may have fluxed a significant volume of groundwater to the surface and the polar caps. A primordial source of groundwater reconciles the present D/H isotopic ratio of the atmosphere with fractionating atmospheric escape and a primordial Martian D/H inferred from hydrous phases of SNC meteorites. A cold early climate and a thin CO2 atmosphere are consistent with the ubiquity of primary igneous minerals and the apparent absence of secondary minerals and copious carbonates on the surface. Aqueous eruptions introduced soluble chloride and sulfate salts into Martian soils, leaving clays and carbonates within the crust. If the Martian crust hosts a “deep biosphere,” aqueous eruptions can bring organisms or their chemical signature to the surface. The biotic component of any recent eruptions may be preserved in transient ice in cold traps on the surface.
Gyrotron travelling wave amplifier: II. Effects of velocity spread and wall resistivity

The small signal gain and bandwidth of the gyrotron travelling-wave amplifier (gyro-TWA) operating at the fundamental cyclotron harmonic are examined. The analytical and numerical studies focus on the effects of velocity spread in the electron beam and of a distributed wall resistivity in the waveguide. It is found that wall resistivity reduces the forward gain of the amplifier only by an amount approximately equal to 1/3 of the corresponding cold tube loss. Significant increase in bandwidth may result, under certain conditions, from the presence of wall resistivity. A moderate amount (5–10%) of velocity spread does not reduce the peak gain significantly in general, but may reduce the bandwidth by an amount depending on the applied magnetic field. Based on considerations of such factors as power, stability, gain, bandwidth, and efficiency, operating parameters for the gyro-TWA are suggested.
Mitotane (o, p‘-DDD) treatment in a cat with hyperadrenocorticism

An 11-year-old male castrated Persian cat with spontaneous hyperadrenocorticism was presented. Both adrenals were grossly enlarged and calcified. A diagnosis of pituitary-dependent hyperadrenocorticism was made. Signs of hyperadrenocorticism resolved with long-term mitotane treatment. Concurrent diabetes mellitus resolved after 220 days of therapy. No severe adverse drug reactions were noted.
Decolonizing Consultation: Advocacy as the Strategy, Diversity as the Context

The following is a reflection on the clinical practice of consultation in the context of human diversity with particular attention to developing theories falling under the headings of decolonization and multicontextuality. Related to descriptions of these theoretical perspectives, I make reference to the small yet promising literature of advocacy consultation as one methodology that can support action toward realizing progress in the application of theory. My perspective is necessarily limited to my experiences and understandings as (among other things) an educated woman raised White in the southern United States by children of the Depression Era. Given this limitation and because our collective discussion in these areas is new, I offer introduction to the terms decolonization and multicontextuality as potentially useful to ongoing development of consultation responsive to diversity in schools and communities.
Optimal-Algorithms for Multipacket Routing Problems on Rings

We study multipacket routing problems on rings of processors. We prove a new lower bound of 2n/3 routing steps for the case that k, the number of packets per processor, is at most 2. We also give an algorithm that tightens this lower bound. For the case where k > 2, the lower bound is kn/4. The trivial algorithm needs in the worst case k?n/2? steps to terminate. An algorithm that completes the routing in kn/4 + 2.5n routing steps is given.
Betty Tillman: a remembrance

I first met Betty Tillman when it was really a great time for me to meet her. I was at the Southern Economic Association’s meeting in New Orleans in November 1977, and excited about the possibility of spending the 1978–1979 academic year at the Public Choice Center at Virginia Tech. I had met Jim Buchanan only once when he visited the University of Colorado, Boulder where I was teaching, and I had never met Gordon Tullock or Betty. So my excitement was coupled with a dose of anxiety when I was invited to have dinner with Jim, Gordon, and Betty at Commander’s Palace. It was later that I learned that Jim enjoyed letting his hair down, so to speak, and enjoy a good joke in a social setting, but at the time I didn’t feel that engaging him in light-hearted banter was the right approach. With Gordon, I quickly became unsure if he was engaging in light-hearted banter or if he really did think I was a moron. Fortunately, Betty was there. Anyone who had the privilege of knowing Betty, even briefly, can understand what a comfort she was to me. Her charming comments, friendly smile and a couple of glasses of the milk punch she recommended neutralized the effects of Gordon’s comments on my self-confidence. Before dinner was over I was talking to Jim and Gordon about how an article of theirs had inspired me to write one of my own and telling Betty how beautiful her ankles were. I was completely serious about the ankles. People liked Betty because it was obvious that Betty sincerely liked them. The old joke that sincerity is important, and once you learn how to fake it you have it made, simply doesn’t apply to Betty. No one can fake the pleasure in the company of others that she conveyed with her smile, exuberance and kindness. One could know Betty a long time before knowing she suffered from frequent migraine headaches. I was unaware of these painful episodes for quite a while, and I learned of them because someone told me about them. There was nothing more natural than to think you were one of Betty’s favorites—that she must have liked you at least as much, and probably more, than she liked most others. J.R. Clark and I have has a long-time disagreement that is only superficially in jest.
Mercuric Chloride as a Preservative for Milk Samples Held for the Determination of Lactic Acid

Summary Milk samples can be preserved satisfactorily for lactic acid determination up to one month when treated as follows: Add not less than 0.5 per cent of mercuric chloride, then heat the sample to 80° C, for 5 minutes, cool and hold at 20° C., or lower, preferably in the dark. The possibility of the use of small amounts of mercuric chloride as a preservative for studying the proteolytic action of milk is discussed.
Soils and Environmental Quality, 3rd Edition

This book is intended for use as a text in upper-level undergraduate courses on environmental soil science. It was originally published in May 2005 and has already been the subject of several published book reviews ([Parkinson, 2006][1]; [Coyne, 2007][2]; [Lilly, 2007][3]). Taken together, these
Comparison and clinical application of frequency domain methods in analysis of neonatal heart rate time series.

The frequency content of the heart rate (HR) series contains information regarding the state of the autonomic nervous system. Of particular importance is respiratory sinus arrhythmia (RSA), the high-frequency fluctuation in HR attributable to respiration. The unevenly sampled nature of heart rate data, however, presents a problem for the discrete Fourier transform. Interpolation of the HR series allows even sampling, but filters high-frequency content. The Lomb periodogram (LP) is a regression-based method that addresses these issues. To evaluate the efficacy of the LP and Fourier techniques in detecting RSA, we compared the spectrum of intervals, the spectrum of HR samples, and the LP of simulated and clinical neonatal time series. We found the LP was superior to the spectrum of intervals and the spectrum of HR samples in analysis near the critical frequency of one half the average sampling rate. Applying the LP to clinical data, we found (1) evidence of stochastic resonance, an enhancement of periodicity with the addition of small amounts of noise, and (2) reduced power at all frequencies prior to clinical diagnosis of neonatal sepsis. © 2001 Biomedical Engineering Society. PAC01: 8719Hh, 8719La, 0260Ed, 0230Lt, 0545Tp, 0250-r, 0230Nw, 0230Uu
Plausible Transition States for glycosylation reactions.

The Transition State (TS) for any chemical glycosylation reaction is not known with certainty. Both experimental and computational approaches have been limited due to the complexity of the problem. This work describes a preliminary computational ionization approach using density functional theory calculations to arrive at hypothetical TSs. The new TSs contain the glycosyl donor as anomeric triflates, the acceptor as methanol, some CH(2)Cl(2) molecules, and a Li(+) ion promoter. In this computational approach all glycosylations are disassociative in that the C-1-O(Tf) bond length is greater then 2 A before any nucleophilic attack. All nucleophilic attack requires some preassociation of the nucleophile with examples of the pre-attack complexation to donor oxygens. These hypothetical models are intended to guide both experimental and computational approaches to finding TSs for glycosylation reactions that can be used to optimize stereoselectivity of glycosylation.
Synthesis and Characterization of L-Lysine Conjugated Silver Nanoparticles Smaller Than 10 nM

A rapid and convenient batch method for synthesizing lysine-conjugated silver nanoparticles of approximately 5 nm of size was developed. Nanoparticles of size less than 100 nm exhibit significant medical potential. L-Lysine demonstrates potential for therapeutic applications and silver nanoparticles are an optimal choice for drug delivery because of its intrinsic anti-platelet, anti-bacterial and anti-inflammatory capabilities. Current synthesis protocols for Lysine-capped particles under 10 nm are time consuming and tedious and allow only for the sythesis of small quantities of particles. The synthesis of Lysin-capped silver nanoparticles was based on the reaction in which AgNO3 was reduced by excess NaBH4. L-Lysine, a known essential amino acid, served as the capping agent to minimize initial aggregation. The particles were then separated by size chromatography. Capping occurred through the amide bond on L-Lysine as determined by FT-IR. The conjugation of the particle to the amide bond is important, since this leaves the amino group of Lysine open to further modifications. The particles were further characterized in regards to their shape, size and stability. Finally we demonstrated that the synthesized particles exhibit limited to no toxicity in cells, using HEK 293 cell line as a model system. Our sythesis protocol can be successfully used for scale-up and synthesis of high quantities of nanoparticles.
Veratridine actions on two types of fast Na+ channels in human uterine leiomyosarcoma cells

In human uterine leiomyosarcoma cell line (SK-UT-1B), we previously demonstrated two types of fast Na+ current (INa(f)) induced by serum, based on different time course of current decay: fast-inactivating and slow-inactivating. To further clarify the properties of these currents, we studied the effects of veratridine, which is known to modify the inactivation process of INa(f), using whole-cell voltage clamp. Bath application of veratridine (100 microM) produced a decrease in peak INa(f) (Ipeak), simultaneous with increase in the steady-state current (Iss) and tail current (Itail). These effects of veratridine were observed in only slow-inactivating INa(f). The induction of Iss and Itail was completely reversed by washout of veratridine within 5 min, whereas the decreased Ipeak did not recover even after 15 min of washout. These findings suggest that the fast Na+ channels in this cell line may have two binding sites for veratridine: a high-affinity site, involved in the decrease in Ipeak (possibly due to a decrease in conductance), and a low-affinity site, related to the appearance of Iss and Itail (due to a long opening of the channels). It is concluded that the two types of INa(f) in this cell line have different sensitivity to veratridine and the fast Na+ channels may have two binding sites for veratridine.
Simple rationality? The law of healthcare resource allocation in England

This paper examines the law relating to healthcare resource allocation in England. The National Health Service (NHS) Act 1977 does not impose an absolute duty to provide specified healthcare services. The courts will only interfere with a resource allocation decision made by an NHS body if that decision is frankly irrational (or where the decision infringes the principle of proportionality when a right under the European Convention on Human Rights (ECHR) is engaged). Such irrationality is very difficult to establish. The ECHR has made no significant contribution to domestic English law in the arena of healthcare provision. The decision of the European Court in the Yvonne Watts case establishes that, in relation to the question of entitlement to seek treatment abroad at the expense of the NHS, a clinical judgment about the urgency of treatment trumps an administrative decision about waiting list targets. That decision goes against the grain of domestic law about healthcare allocation, but is not likely to have wide ramifications in domestic law.
Prolongation of insulin removal by perfused liver from spontaneously obese rats.

The t1/2 of insulin removal by perfused liver from hyperinsulinaemic ob/ob mice has previously been shown to be prolonged as compared to livers from nonobese mice. Since this defect improved when insulin levels were lowered in vivo, it appeared that the abnormality might be secondary to hyperinsulinaemia. To test this hypothesis further, insulin removal by perfused liver from one year and 6 week old Sprague-Dawley rats has been compared. Older rats were both obese and hyperinsulinaemic, and their t1/2 of insulin removal (mean ± SEM) was significantly prolonged (11.0±0.56 min vs 7.6±0.29 min). In addition, the induction of severe streptozotocin-induced hypoinsulinaemia in young rats led to a shortening of the t1/2 (5.56±0.72 min). However, the t1/2 also fell comparably when weight gain of young control rats was limited to that of young hypoinsulinaemic rats by caloric restriction (5.89±0.81 min). Furthermore, t1/2 was not increased when young rats were made hyperinsulinaemic by administration of NPH insulin for 12–14 days, nor was it decreased when older rats were made moderately hypoinsulinaemic by the administration of streptozotocin. These results demonstrate that the defect in hepatic insulin removal observed in the ob/ob mouse is not unique to this genetic variant, but is also observed in normal obese rats. Although the mechanism responsible for this phenomenon remains to be defined, it does not seem to be a simple function of relatively short-term (1–2 weeks) changes in plasma insulin concentration. On the other hand, it is still possible that the prolongation of insulin removal in both the ob/ob mouse and the obese rat is secondary to more chronic elevations in plasma insulin, or, alternatively is related to the obese state itself. In either event, the defect in hepatic insulin removal may be a general feature of obesity and, as such, contribute to the maintenance of hyperinsulinaemia in a variety of states characterized by obesity.
Vorticity-Based Detection of Tropical Cyclogenesis

Abstract Ocean wind vectors from the SeaWinds scatterometer aboard the Quick Scatterometer (QuikSCAT) satellite and Geostationary Operational Environmental Satellite (GOES) imagery are used to develop an objective technique that can detect and monitor tropical disturbances associated with the early stages of tropical cyclogenesis in the Atlantic basin. The technique is based on identification of surface vorticity and wind speed signatures that exceed certain threshold magnitudes, with vorticity averaged over an appropriate spatial scale. The threshold values applied herein are determined from the precursors of 15 tropical cyclones during the 1999–2004 Atlantic Ocean hurricane seasons using research-quality QuikSCAT data. The choice of these thresholds is complicated by the lack of suitable validation data. The combination of GOES and QuikSCAT data is used to track the tropical disturbances that are precursors to the 15 tropical cyclones. This combination of data can be used to test detection but is not as...
Gangliogliomas in adults

BACKGROUND Gangliogliomas are rare tumors occurring in both children and adults that are characterized by the presence of neoplastic cells resembling both neurons and glia. METHODS The authors reviewed 18 adult patients with intracranial gangliogliomas treated at the study institutions between October 1987 and November 1995. RESULTS The median age at diagnosis was 33.7 years, with a range of 21 to 55 years. Median follow-up was 37.7 months, with a range of 4 months to 13 years. Clinical manifestations among the patients included seizures (13), headache (2), ataxia (1), and hemiparesis and paresthesias (1 patient each). Tumors were located in the temporal lobe (6 patients), temporal lobe and thalamus (1 patient), frontal lobe (5 patients), cerebellum (4 patients), and insula or thalamus (1 patient each). Thirteen patients underwent gross total resection, 4 underwent incomplete resection, and 1 underwent only a stereotactic biopsy. Treatment modalities included surgery only, surgery plus radiation, and surgery plus radiation and chemotherapy. Median survival was 90.3 months, with a range of 14 months to 13 years. Three patients were dead at follow-up with a mean survival of 32.3 months. These patients showed anaplastic features in their pathology at initial surgery or surgery for recurrence. CONCLUSIONS In adults, gangliogliomas have a relatively favorable prognosis; however, the presence of anaplastic features predicts a worse outcome. Cancer 1997; 79:127-31. © 1997 American Cancer Society.
Osteon pullout in the equine third metacarpal bone: effects of ex vivo fatigue

An important concept in bone mechanics is that osteons influence mechanical properties in several ways, including contributing to toughness and fatigue strength by debonding from the interstitial matrix so as to "bridge" developing cracks. Observations of "pulled out" osteons on fracture surfaces are thought to be indicative of such behavior. We tested the hypothesis that osteon pullout varies with mode of loading (fatigue vs. monotonic), cortical region, elastic modulus, and fatigue life. Mid-diaphseal beams from the dorsal, medial, and lateral regions of the equine third metacarpal bone were fractured in four point bending by monotonic loading to failure under deflection control, with or without 10(5) cycles of previous fatigue loading producing 5000 microstrain (15-20% of the expected failure strain) on the first cycle; or sinusoidal fatigue loading to failure, under load or deflection control, with the initial cycle producing 10,000 microstrain (30-40% of the expected failure strain). Using scanning electron microscopy, percent fracture surface area exhibiting osteon pullout (%OP.Ar) was measured. Monotonically loaded specimens and the compression side of fatigue fracture surfaces exhibited no osteon pullout. In load-controlled fatigue, pullout was present on the tension side of fracture surfaces, was regionally dependent (occurring to a greater amount dorsally), and was correlated negatively with elastic modulus and positively with fatigue life. Regional variation in %OP.Ar was also significant for the pooled (load and deflection controlled) fatigue specimens. %OP.Ar was nearly significantly greater in deflection controlled fatigue specimens than in load-controlled specimens (p=0.059). The data suggest that tensile fatigue loading of cortical bone eventually introduces damage that results in osteonal debonding and pullout, which is also associated with increased fatigue life via mechanisms that are not yet clear.
What is the available evidence to support immediate adjuvant intravesical chemotherapy after transurethral resection of superficial transitional cell carcinoma of the bladder

The endpoints chosen for analysis of outcome following intravesical therapy can be quite varied. Precise definitions of endpoints are mandatory to permit any comparative assessment between agents or treatment regimens. Although the recurrence endpoint favorably impacts on quality of life by reducing the number of biopsies and resections, the endpoint of greatest importance is progression. Progression of disease is an indication for cystectomy. Unfortunately, the majority of trials testing intravesical agents have not shown significant reduction in disease progression or have been too small or followed for too short an interval to be able to adequately measure this endpoint. Tumor recurrence after initial tumor resection may be explained by a number of factors; one is tumor cell implantation. A number of small trials have suggested a reduction in tumor recurrences by instillation of chemotherapy immediately after resection. Based on these preliminary data, large prospective multicenter trials have been conducted and have confirmed the benefit of immediate adjuvant intravesical chemotherapy. Bacillus Calmette-Guerin (BCG) cannot be administered immediately postresection because of the potential for systemic dissemination via the recently resected tumor bed. Therefore, combination strategies using immediate instillation of a cytotoxic agent followed by BCG induction and maintenance presents an attractive strategy that is currently under study and one that may be more commonly employed in the future treatment of patients with superficial transitional cell carcinoma of the bladder.
Zeolite A-supported Ru catalysts

Abstract A series of zeolite A-supported Ru catalysts was investigated to determine the catalytic possibilities when Ru is supported on such small-pore, low Si/Al ratio zeolites. Catalysts prepared by adding a Ru precursor to the zeolite A synthesis gel, designated [ZS], had metal dispersed intrazeolitically, although not uniformly. By comparison, catalysts prepared by surface deposition of Ru on zeolite A, designated [SD], had metal particles primarily on the external surfaces of the zeolite crystallites. All metal sites were accessible for ethane hydrogenolysis; however, molecular sieving strongly influenced cyclopropane hydrogenation. With the exception of the strong molecular sieving effect on the reaction of cyclopropane found for RuNaA[ZS], the most important effect on the catalytic properties was Ru particle size. There was no obvious effect of the method of preparation or the electrostatic field of the zeolite on Ru site activity. The synthesis preparation method was found to offer a viable means for preparing highly dispersed, catalytically active metal particles inside a small-pore zeolite such as A, where other methods are not successful.
Prevalence and predictors of left ventricular diastolic dysfunction in a Hispanic patient population.

Left ventricular (LV) diastolic dysfunction refers to an abnormality of diastolic distensibility, filling, or relaxation of the left ventricle, regardless of whether the ejection fraction is normal or abnormal and whether the patient is symptomatic or asymptomatic.1 Diastolic dysfunction can be either a result of myocardial ischemia/hypoxia2 that slows ventricular relaxation due to change in myocardial energy availability or could be a result of increase in passive stiffness as a result of metabolic derangements and structural remodeling in several conditions, for example, diabetes mellitus and hypertension.3 Furthermore, it has been shown that besides other existing risk factors for diastolic dysfunction such as hypertension, age, coronary artery disease, and others, the presence of diabetes itself is an independent factor for the development of diastolic dysfunction regardless of concomitant coronary artery disease.4 The pathogenetic mechanism is mainly explained by the interstitial accumulation of advanced-glycated end products, which include collagen, elastin, and other proteins, as well as fibrosis in the myocardium that have been reported in diabetes hearts, which can increase end-diastolic stiffness as well as LV mass.5 Furthermore, diastolic dysfunction reflects an early sign in the temporal sequence of ischemic events in coronary heart disease. The ischemic cascade, beginning with an oxygen demand supply imbalance and metabolic alterations, identifies diastolic disorders of the left ventricle as an early phenomenon; sometimes before systolic dysfunction, electrocardiographic changes, or chest pain occur.6 Finally, it has been documented in previous studies that the prevalence of diastolic dysfunction increases with age, even among healthy adults and can be higher if comorbidities such as diabetes, hypertension, or coronary artery disease are present. This can range from 2.8 to 27.3% depending on the population studied.7 8 9 However, minimal data exist on prevalence of diastolic dysfunction in the Hispanic patient population. Thus, it was our goal to investigate the prevalence and predictors of diastolic dysfunction in a Hispanic patient population.
On the equivalence of cancellative extensions of commutative cancellative semigroups by groups

In [1] D. W. Miller and the author established necessary and sufficient conditions for the existence of a cancellative (ideal) extension of a commutative cancellative semigroup by a cyclic group with zero. The purpose of this paper is to extend these results to cancellative extensions by any finitely generated Abelian group with zero and to establish in this general case conditions under which two such extensions are equivalent.
E-cigarette knowledge, attitudes, and use in opioid dependent smokers.

Abstract Individuals in treatment for opioid dependence have smoking rates 3–5 times greater than the U.S. prevalence rate. Traditional smoking cessation strategies have been ineffective in this population. Novel approaches are needed as well as harm reduction avenues. E-cigarettes (e-cigs) may provide such a novel harm reduction and cessation opportunity, but little is known about the knowledge of, attitudes about, and usage of e-cigs in opioid dependent smokers. The current study enrolled 315 opioid dependent smokers (164 methadone, 151 buprenorphine), treated in the same health system in Fall River, Massachusetts. The sample was 49.7% male and 85.1% non-Latino White. Overall 98.7% had heard of e-cigs, 73.0% had ever tried e-cigs, and 33.8% had used e-cigs in the past 30days. The most common reasons for use were curiosity (41.4%) and to quit all nicotine (26.0%). The proportion of opioid dependent smokers that had ever tried e-cigs and used them in the past month was substantially greater than that found in recent general population surveys. While e-cigs have been used to quit smoking, how to optimize their utility as a cessation tool remains undefined. E-cigs should be a part of smoking cessation discussions with this vulnerable, difficult-to-treat population.
Human Development Index (HDI) Predicts Infant and Childhood Mortality: An Analysis Of 22 Countries. 146

Per capita gross domestic product (pc GDP) has been shown to be a good predictor of infant mortality rate. In 1990, the United Nations Development Programme devised HDI which measures a country's level of human development using a composite index for literacy, life expectancy and pc GDP. We assessed how well HDI and its individual components predict infant and childhood mortality. Mortality data for the final analysis corresponded to the 22 countries which reported all five measures of infant (neonatal and postneonatal) and childhood (1-4 and 5-, 9 years) mortality in the period 1985-1990. Table
Plasticity in visual perception and physiology

Abstract Many factors influence our perception of local features. What we see is not strictly a reflection of the physical characteristics of a scene, but instead is highly dependent on the processes by which our brain attempts to interpret the scene. As a result, our percepts are shaped by the context within which local features are presented, by our previous visual experiences (operating over a wide range of time scales), and by our expectations of what is likely to be before us. The subsrate for these influences is found in the lateral interactions operating within individual areas of the cerebral cortex and in the feedback from higher to lower order cortical areas.
REVIEW OF HIV MODELS: THE ROLE OF THE NATURAL IMMUNE RESPONSE AND IMPLICATIONS FOR TREATMENT

We present a review and comparison of several recent differential equations models of treatment of HIV-1 infection. We seek to clarify the role of the natural anti-HIV immune response and determine its effect upon optimal treatment schemes. In this paper, we consider systems in which treatment is expressed as a forcing function, as well as those in which we determine optimal treatment via control theoretic techniques. The primary goal of this study is to compare treatment schemes for systems in which a natural nonconstant immune response of the patient is considered explicitly with those that consider implicitly a constant non-specific immune response. We find that when the natural immune response can be boosted sufficiently, drug levels may not need to be as high as previously supposed. This implies that a treatment scenario in which intervals of drug treatment are alternated with some form of immune-boosting therapy may be highly beneficial in terms of reducing toxicity to the patient. Additionally, in developing countries where HIV infection is widespread and sufficient funds are not available to supply rigourous drug regimens, the implications of these models are profound, as they suggest methods of treating HIV at a minimal cost.
Fever in subarachnoid hemorrhage: Relationship to vasospasm and outcome

Objective: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. Background: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. Methods: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt–Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 °C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 °C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. Results: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). Conclusion: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.
Bayesian detection and classification for space-augmented space situational awareness under intermittent communications

This paper examines the problem of detecting and classifying objects in Earth orbit using a space-augmented space surveillance network (SA-SSN). A SA-SSN uses a combination of ground- and space-based sensors to monitor activities over a range of space orbits from low earth orbits up to an altitude higher than the geosynchronous orbit. We develop a cost-aware Bayesian risk analysis approach for object detection and classification, using range-angle sensors with intermittent information-sharing between the sensors. The problem is formulated in a simplified two-dimensional setting where the SA-SSN is composed of four ground-based sensor and a space-based orbiting sensor satellite. This is done in order to reduce computational complexity while retaining the basic nontrivial elements of the problem. We will demonstrate that objects in geosynchronous orbits can be detected and perfectly classified (under appropriate sensor models) if they intermittently cross the field of view of some sensor in the SA-SSN, and that performance degrades for objects located in non-geosynchronous orbits. We will conclude the paper with future research directions on how to address the detection and classification of objects in non-geosynchronous orbits.
Picosecond X-ray Absorption Spectroscopy of a Photoinduced Iron(II) Spin Crossover Reaction in Solution

In this study, we perform steady-state and time-resolved X-ray absorption spectroscopy (XAS) on the iron K-edge of [Fe(tren(py)3)](PF6)2 dissolved in acetonitrile solution. Static XAS measurements on the low-spin parent compound and its high-spin analogue, [Fe(tren(6-Me-py)3)](PF6)2, reveal distinct spectroscopic signatures for the two spin states in the X-ray absorption near-edge structure (XANES) and in the X-ray absorption fine structure (EXAFS). For the time-resolved studies, 100 fs, 400 nm pump pulses initiate a charge-transfer transition in the low-spin complex. The subsequent electronic and geometric changes associated with the formation of the high-spin excited state are probed with 70 ps, 7.1 keV, tunable X-ray pulses derived from the Advanced Light Source (ALS). Modeling of the transient XAS data reveals that the average iron−nitrogen (Fe−N) bond is lengthened by 0.21 ± 0.03 A in the high-spin excited state relative to the ground state within 70 ps. This structural modification causes a change i...
ATR Inhibition Broadly Sensitizes Ovarian Cancer Cells to Chemotherapy Independent of BRCA Status

Replication stress and DNA damage activate the ATR-CHK1 checkpoint signaling pathway that licenses repair and cell survival processes. In this study, we examined the respective roles of the ATR and CHK1 kinases in ovarian cancer cells using genetic and pharmacological inhibitors of in combination with cisplatin, topotecan, gemcitabine and the poly(ADP-ribose)-polymerase (PARP) inhibitor veliparib (ABT-888), four agents with clinical activity in ovarian cancer. RNAi-mediated depletion or inhibition of ATR sensitized ovarian cancer cells to all four agents. In contrast, while cisplatin, topotecan and gemcitabine each activated CHK1, RNAi-mediated depletion or inhibition of this kinase in cells sensitized them only to gemcitabine. Unexpectedly, we found that neither the ATR kinase inhibitor VE-821 or the CHK1 inhibitor MK-8776 blocked ATR-mediated CHK1 phosphorylation or autophosphorylation, two commonly used readouts for inhibition of the ATR-CHK1 pathway. Instead, their ability to sensitize cells correlated with enhanced CDC25A levels. Additionally, we also found that VE-821 could further sensitize BRCA1-depleted cells to cisplatin, topotecan and veliparib beyond the potent sensitization already caused by their deficiency in homologous recombination. Taken together, our results established that ATR and CHK1 inhibitors differentially sensitize ovarian cancer cells to commonly used chemotherapy agents, and that CHK1 phosphorylation status may not offer a reliable marker for inhibition of the ATR-CHK1 pathway. A key implication of our work is the clinical rationale it provides to evaluate ATR inhibitors in combination with PARP inhibitors in BRCA1/2-deficient cells.
Region‐specific expression of scutate scale type beta keratins in the developing chick beak

This study shows that different patterns of scutate scale type beta keratins are accumulated in the three adjacent structures of the embryonic chick beak: periderm, egg tooth, and cornified beak. The cornified beak accumulates all of the beta keratins of scutate scale except pp2,3. The periderm, which is the outermost, multilayered covering of the whole embryonic beak, accumulates only beta keratins 2,3, and p2,3 of the scutate scale pattern. The egg tooth, which is the rounded elevation on the dorsal surface of the upper beak, and the embryonic claw accumulate greatly reduced levels of 2,3 and p2,3 compared to scutate scale. Like cornified beak, the claw does not accumulate pp2,3, but both tissues express a potentially new beta keratin, beta keratin 8. Neither the histidine rich “fast” proteins (HRPs), which are expressed in embryonic scutate scales and feathers, nor the avian cytokeratin associated proteins (cap-1 and cap-2), which are expressed in scutate and reticulate scales, are expressed in any of the embryonic beak structures or in the claw. The implications of these findings with regard to regulation of terminal differentiation of avian skin are discussed.
Real time implementation of a symbol timing recovery algorithm for a narrowband wireless modem

This paper examines some of the complexity issues arising in the real time implementation of the symbol timing subsystem of a narrowband wireless modem. The modem prototype has been designed for 4 kHz channels in the 220-222 MHz land mobile band. In an effort to achieve high bandwidth efficiency, the modem architecture employs transmitter diversity, pilot symbol assisted modulation, and trellis coded modulation. An experimental, non-real time system has been implemented and extensively field tested demonstrating bandwidth efficiencies in excess of 3 bits per second per Hz. The work on this project is focused on the real-time implementation of the baseband receiver functions using the Texas Instruments C54/spl times/ fixed point digital signal processor. Here we report on some of the performance/complexity tradeoffs present in the design of a DSP implementation of the digital filter and square symbol timing recovery algorithm.
Association of African American race with elevated pulmonary artery diastolic pressure: data from the Heart and Soul Study.

Background Whether increased severity of heart failure in African Americans is a result of differences in cardiac physiology is uncertain. The end-diastolic pulmonary regurgitation (EDPR) gradient is associated with abnormal cardiac physiology. We hypothesized that African American race is associated with an elevated EDPR gradient that may partially predispose African Americans to heart failure. Methods The Heart and Soul Study prospectively assessed the EDPR gradient in 480 patients with coronary disease. We used multivariable linear regression to investigate the independent association of African American race with EDPR gradient. Results Compared with 393 non-African Americans, the 87 African Americans had similar indices of left ventricular systolic and diastolic function, left ventricular mass index, mitral regurgitation, peak tricuspid regurgitation gradient, and pulmonary velocity time integral. However, the EDPR gradient was significantly higher in African Americans (4.2 ± 3.3 mm Hg) than in Caucasians (3.1 ± 2.5 mm Hg) or other racial groups (3.5 ± 2.7 mm Hg) ( P = .008). In a multivariable model, African American race was a significant predictor of elevated EDPR gradient (β coefficient 0.75, P = .03). Conclusion African American race is independently associated with an elevated EDPR gradient in patients with coronary artery disease.
Tn 7 inserts in both orientations at a single chromosomal location and apparently forms cointegrates in Pasteurella multocida

Summary Pasteurella multocida transconjugants isolated after mating with Escherichia coli strains that carry one or the other of two Tn7-containing suicide plasmids, pRKTV5 and pUW964 (pRKTV5::Tn5), were analysed. These plasmids have the C0IEI replication origin and were thus expected to deliver transposons but not be maintained as free replicons in Pasteurella. Five out of six transconjugants selected for acquisition of Tn7 from E. coli (pRKTV5) had simple insertions of the transposon, in either orientation, at a single chromosomal location, while the sixth had pFtKTV5 integrated at the same location. By contrast, all of 27 transconjugants selected for acquisition of either Tn7 or Tn5 from E. coli (pUW964) maintained pUW964. Of seven subsequently examined at the molecular level, all had pUW964 (in one case, a deletion derivative) integrated at the same location as the Tn 7 insertions obtained with pRKTV5. A copy of Tn7 was present at each boundary between the integrated plasmids (pRKTV5 or pUW964) and the chromosome in each strain. The two copies of Tn7 at either end of an integrated plasmid were either in the same (six cases) or in opposite (two cases) orientations with respect to each other. These seem to be products of replicative transposition by Tn7but can also derive from conservative mechanisms.
Statistical design considerations for pilot studies transitioning therapies from the bench to the bedside

Pilot studies are often used to transition therapies developed using animal models to a clinical setting. Frequently, the focus of such trials is on estimating the safety in terms of the occurrence of certain adverse events. With relatively small sample sizes, the probability of observing even relatively common events is low; however, inference on the true underlying event rate is still necessary even when no events of interest are observed. The exact upper limit to the event rate is derived and illustrated graphically. In addition, the simple algebraic expression for the confidence bound is seen to be useful in the context of planning studies.