cssi/SciSciGPT-SciSciNet huggingface dataset:
Does Aspirin Attenuate the Effect of Angiotensin‐Converting Enzyme Inhibitors on Health Outcomes of Very Old Patients with Heart Failure?

OBJECTIVES: Concomitant ischemic heart disease (IHD) is common in older individuals with heart failure (HF). We estimated the effect of aspirin use on the rate of mortality, morbidity, and decline in physical functioning in nursing home residents with HF taking angiotensin-converting enzyme (ACE) inhibitors. DESIGN: We conducted a retrospective cohort study using a nursing home database linking resident information collected via the Minimum Data Set (MDS) with drug utilization data. SETTING: Nursing homes in four states (1992–1995). PARTICIPANTS: Of 49,779 residents with HF admitted to these homes, 12,703 residents were taking an ACE inhibitor; 2,046 of these took aspirin. MEASUREMENTS: Medicare enrollment files provided the date of death, and we used the Part A Medicare files to identify hospital admissions. The activity of daily living scale from repeat MDS assessments allowed us to evaluate decline in physical function. Cox proportional hazards models provided adjusted estimates of the aspirin effect, with nonusers as the reference group. RESULTS: The overall mortality rate, hospitalization rate, and rate of decline in physical function of aspirin users were not different from those of nonusers (e.g., hospitalization rate ratio = 0.99, 95% confidence interval = 0.92–1.07). This effect did not vary by presence of concomitant IHD or by dose or type of ACE inhibitor. CONCLUSION: In a cohort of older HF residents receiving ACE inhibitors in nursing homes, we found that treatment with aspirin did not appear to affect outcomes negatively.
On steady vortex flow in two dimensions. I

(1983). On steady vortex flow in two dimensios, II. Communications in Partial Differential Equations: Vol. 8, No. 9, pp. 1031-1071.
Some Probability Inequalities of Multivariate Normal and Multivariate t

Abstract Applying the result of expectations of non-negative random variables, inequalities for the one-sided and two-sided rectangular probabilities of higher-dimensional multivariate normal and multivariate t distributions are obtained. It is shown that their k-dimensional rectangular probabilities is lower bounded by the (k/m)th power of their m-dimensional rectangular probabilities for every k≥ m ≥ 1, and this bound is quite good when k/m is close to one. Applications to multiple decision problems are considered.
Embryonic Stem Cells Express Neuronal Properties in Vitro

Mouse embryonic stem (ES) cells cultured as aggregates and exposed to retinoic acid are induced to express multiple phenotypes normally associated with neurons. A large percentage of treated aggregates produce a rich neuritic outgrowth. Dissociating the induced aggregates with trypsin and plating the cells as a monolayer results in cultures in which a sizable percentage of the cells have a neuronal appearance. These neuron-like cells express class III beta-tubulin and the neurofilament M subunit. Induced cultures express transcripts for neural-associated genes including the neurofilament L subunit, glutamate receptor subunits, the transcription factor Brn-3, and GFAP. Levels of neurofilament L and GAD67 and GAD65 transcripts rise dramatically upon induction. Physiological studies show that the neuron-like cells generate action potentials and express TTX-sensitive sodium channels, as well as voltage-gated potassium channels and calcium channels. We conclude that a complex system of neuronal gene expression can be activated in cultured ES cells. This system should be favorable for investigating some of the mechanisms that regulate neuronal differentiation.
Bandwagon Influences And Installed-Base Conversion In U.S. Telecommunications

The idea that firms are subject to bandwagon or imitation influences occupies a key position as an explanatory variable in the literature on technology adoption and diffusion. This study examines whether bandwagon influences help to explain differences in the patterns of conversion to a new technology, electronic switching, across firms in the U.S. telecommunications industry. The sample analyzed consists of 40 of the largest firms in the local operating sector of the industry, and firm-level data collected for the years 1973, 1978, 1981, 1984, and 1987 are used to undertake the analysis. The results strongly support the bandwagon hypothesis as a key influence on firm's technology adoption or conversion decisions.
A Comparison of the Active Stiffness of Fetal and Adult Cardiac Muscle

This report described the in vitro analysis of the series elasticity of ventricular myocardium isolated from five fetal lambs and six adult sheep. Active compliance measurements were obtained by quick releases utilizing a closed loop servosystem and electromagnetic positioning device to control cardiac muscle length or tension. Right ventricular moderator bands were obtained from five fetuses (average 139 days of gestation, term=147 days), and compared with two adult moderator bands and four adult right ventricular trabeculae carneae. After correction for equipment coupling the experimental load extension data were fit to an exponential expression by a least squares technique: strain=1/b ln (1 + stress/a). When fetal and adult data were compared, no age-related differences in the constants were observed (a=0.185 +/- 0.062 SE (fetal) and 0.159 +/- 0.03 g/mm2 (adult); b=40.4 +/- 5.2 (fetal) and 43.1 +/- 5.2 (adult); and ab=7.39 +/-2.34 (fetal) and 5.27 +/- .99 (adult). However, significant variation existed in the histologically determined amount of contractile tissue present in muscle samples from both fetus (57-85%, average=74.0 +/- 4.9) and adult (64-94%, average=82.3 +/- 5.3). Wihtout regard to age, a signficant correlation was found between the b stiffness constant and the amount of contractile mass present in cardiac muscle. Thus, it is concluded that there is no age-related difference in the stiffness of fetal and adult ventricular muscle. However, there is a significant relationship between active compliance and true muscle mass.
T Lymphocytes in Sjögren’s Syndrome: Contributors to and Regulators of Pathophysiology

Sjogren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. This multigenic and multifunctional disease can present as primary Sjogren's syndrome or secondary to an underlying connective tissue disease. Immune activation subsequent to activation or apoptosis of glandular epithelial cells in genetically predisposed individuals may expose autoantigens, which engage self-perpetuating T cell dependent autoimmune sequelae. The cellular and molecular context of this immune response may drive proinflammatory (Th1 and Th17) and restrain inhibitory (Treg) pathways. Inability to suppress the immune response results in persistent tissue damage and compromised function of salivary and lacrimal glands. Defining the contributions of participating T cells may unravel strategies for therapeutic intervention.
Energy and Carbon Costs of Selected Cow-Calf Systems

Abstract Fossil fuel-derived inputs can increase cow-calf production per unit of land or labor but can raise financial and environmental concerns. Eleven US cow-calf systems from nine ecological regions in Iowa, South Dakota, Tennessee, and Texas were analyzed to determine quantities of energy used and carbon (C) emitted due to fossil fuel use (excluding emissions from soils and biota) and to determine how management and environment influenced those quantities. Total energy and C cost, calculated cow −1 or ha −1 , were highly correlated (0.99). Energy use cow −1 and ha −1 varied greatly across systems, ranging from 3 000 to 12 600 megajoules (MJ) · cow −1 · yr −1 and from 260 to 20 800 MJ · ha −1 · yr −1 . As stocking rate increased, MJ · cow −1 increased at an increasing rate. Differences in quantity of fertilizer accounted for most variation in energy use. Fertilizer allowed higher stocking rates but reduced energy efficiency of liveweight marketed. Compared to intensive, higher stocking rate systems, rangeland systems based on native or naturalized forages used little or no fertilizer, but used more energy cow −1 for crude protein (CP) supplementation, fencing, and pickup trucks. Across all systems, energy used to produce winter feed ranged from 0% to 46% of total energy. Northern systems used higher percentages of total energy for winter feed and fed for more days year −1 , but southern systems that included large amounts of bermudagrass ( Cynodon dactylon L.) hay used the most MJ · cow −1 for winter feed. Systems with high MJ · cow −1 were vulnerable to shocks in energy prices. Reducing energy use and C emissions from cow-calf operations is possible, especially by reducing fertilizer and hay use, but would likely reduce productivity ha −1 . Forages with high nitrogen use efficiency, locally adapted plants and animals, and replacement of hay with unfertilized dormant forage and CP supplementation could reduce energy use.
Resonance ionization spectroscopy: How a new field expands

A scientometric study of communication and growth of a new development of physics, resonance ionization spectroscopy, has been made. Formal (journal publications) and informal (talks, lecures) communication patterns have been studied. Self citation dominates in early publications, but drops off as the field expands. Informal communication leads formal only by about a year in time, but is much larger in number.
Doping Effect on Chloroindium Phthalocyanine (ClInPc)/C60 Solar Cells

For inorganic semiconductor solar cells, controlled doping is important because it can cause Fermi level shift of the inorganic semiconductor and achieve ohmic contact at the metal-semiconductor interface. In this paper we show that doping can also be used to shift Fermi level in organic semiconductors and cause changes in solar cell performance. We have made chloroindium phthalocyanine (ClInPc)/C60 heterojunction solar cells, where tetrafluoro-teracyano-quinodimethane (F4-TCNQ) is used to dope ClInPc layer. Ultraviolet photoemission spectroscopy (UPS) is used to investigate the ITO/ClInPc interfaces. The result shows that doping causes a Fermi level shift at the ITO/ClInPc interface as it does for inorganic semiconductors. As the doping increases, dark saturation current J0 of the solar cell increases, while open-circuit voltage Voc, short-circuit current Jsc and fill factor decreases. As a result, the efficiency of the solar cell decreases as doping increases. More UPS studies on ClInPc (doped with F4TCNQ)/C60 junction are needed to correlate the energy band diagram of the whole solar cell structure with the J-V characteristics.
Characteristics of M spikes in cat motoneurons and their significance for the measurement of small composite la EPSPs

Some characteristics of intracellularly recorded M spikes in cat motoneurons have been determined in order to evaluate techniques for subtracting this spike from recordings of homonymous monosynaptic composite Ia EPSPs.
An Athenian Tradition of Dactylic Paeans to Apollo and Asclepius: Choral Degeneration or a Flexible System of Non-Strophic Dactyls?

The different epigraphic versions of the so-called Erythraean Paean date from the early fourth century BCE to the mid-second century CE and are generally thought to trace the degeneration of an original monostrophic lyric poem attested in the eponymous late-classical version. I argue that such an approach is inadequate and that the later versions of this poem are witnesses to a hitherto unappreciated genre of paean to Apollo and Asclepius composed almost entirely in dactyls and organized into segments of varying length, which generally begin with a dactylic tetrameter and end with a version of the traditional paeonic cry (the so-called epiphthegma): Παιν or Παιν. The space between the opening tetrameter and the closing cry can, however, accommodate between four to eight additional dactylic feet. The late Hellenistic paean composed in Athens by Macedonicus of Amphipolis is yet another witness to this tradition, which probably dates back at least as early as a famous—albeit almost entirely lost—paean of Sophocles and is reflected in the first two strophes of the parodos of his Oedipus Rex.
Carbocyanine dyes with long alkyl side-chains: broad spectrum inhibitors of mitochondrial electron transport chain activity.

Abstract Certain indocarbocyanine, thiacarbocyanine, and oxacarbocyanine dyes possessing short alkyl side-chains (one to five carbons) are potent inhibitors of mammalian mitochondrial NADH-ubiquinone reductase (EC 1.6.99.3) activity (Anderson et al., Biochem Pharmacol41: 677–684, 1991; Anderson et al., Biochem Pharmacol45: 691–696, 1993; Anderson et al., Biochem Pharmacol45: 2115–2122, 1993), and act similarly to rotenone. This study examines the inhibitory capacities of twelve other carbocyanine dyes (six indocarbocyanines, four oxacarbocyanines, and two thiacarbocyanines) possessing long alkyl side-chains (seven to eighteen carbons with both saturated and unsaturated side-chains) on mitochondrial NADH, succinate and cytochrome c oxidase activities. Three of the indocarbocyanines inhibited electron transport chain activity, while three were non-inhibitory. Two of the oxacarbocyanines also inhibited electron transport chain activity, while the other two were without effect. Both the thiacarbocyanines were non-inhibitory. In contrast to previous studies, the long alkyl side-chain carbocyanines exhibited a broad spectrum of inhibition of respiratory chain activity, affecting either oxidation of all three substrates or of NADH and cytochrome c, rather than specific inhibition of mitochondrial NADH-ubiquinone reductase activity, indicating that there could be multiple binding sites for these compounds. The five inhibitory long side-chain carbocyanines also inhibited reduction of ferricyanide and coenzyme Q1 by NADH, using submitochondrial particles, but not when tested with purified complex I, indicating that the mitochondrial inner membrane was an integral component in their inhibitory capacity. No general correlation of side-chain length or degree of unsaturation and inhibitory capacity was discernible.
Unexpected long-term survival without evidence of disease after salvage chemotherapy for recurrent metastatic cervical cancer: a case series.

Abstract Background. The prognosis of recurrent metastatic cervical cancer is extremely poor. Platinum-based palliative chemotherapy constitutes the mainstay of treatment. Cure is extremely rare. Case. We present 3 cases of recurrent metastatic cervical cancer in which the patients remain disease-free many years after completing salvage chemotherapy and surgery. The patients remain with no evidence of disease at 6, 7, and 13 years, respectively, following recurrence. Conclusion. In rare cases, an unexpected complete clinical remission and long-term survival without evidence of disease may be achieved in patients with recurrent metastatic cervical cancer treated with multimodal therapy.
Physiologic stability and physiologic state.

Several disease states (e.g., disseminated inflammation) demonstrate physiologic stability : they resolve only slowly and are resistant to both specific and symptomatic therapies. The existence of multiple stable physiologic states, including both health and disease states, is not anticipated by classical, linear descriptions of physiologic control mechanisms. Multiple stable states are, however, predicted by a simple nonlinear model in which the resistance to perturbation derives from interconnections among the model's elements. If the stability of selected disease states derives from nonlinear interactions among cells, tissues, and organs, then some therapies aimed at supporting or normalizing performance of specific organs may be misdirected.
T cell activation by clustered tyrosine kinases

Many cellular recognition events in the immune system are initiated by aggregation of cell surface receptors that lack intrinsic protein-tyrosine kinase activity. Receptor-associated kinases related to the src protooncogene product have been found to be essential for cellular activation and may interact with the cytoplasmic domains of the antigen receptor chains. We show here that anti-CD16 antibody-mediated clustering of chimeric transmembrane proteins bearing a CD16 extracellular domain and a Src family kinase intracellular domain is not sufficient to initiate a cellular activation signal in T cells, whereas clustering of similar chimeras bearing Syk or ZAP-70 kinase sequences triggers calcium mobilization. Aggregation of the Syk chimera alone, or coaggregation of chimeras bearing Fyn and ZAP-70 kinases, suffices to initiate cytolytic effector function. The pattern of tyrosine phosphorylation induced by clustering of the Syk chimera is similar to the pattern induced by aggregation of T cell receptor.
A generalization of a theorem of Hans Lewy

Let p be a real-valued Coo function defined in a neighborhood of the origin 0 in Cn, such that p(O) =O, dp(O) #0. Then, near zero, M= {z; p(z)=O} is a real submanifold of Cn of dimension 2n-1. If 30p(O) 5O, then M has a holomorphic hull which contains an open set. We shall prove an L2 version of this fact. Let 0b represent the tangential Cauchy-Riemann operator on M introduced by Kohn [1]. By L2 on M, we mean the space of functions which are square integrable with respect to surface area.
A Potent and Selective Inhibitor of KIAA1363/AADACL1 that Impairs Prostate Cancer Pathogenesis

Cancer cells show alterations in metabolism that support malignancy and disease progression. Prominent among these metabolic changes is elevations in neutral ether lipids (NELs). We have previously shown that the hydrolytic enzyme KIAA1363 (or AADACL1) is highly elevated in aggressive cancer cells, where it plays a key role in generating the monoalkylglycerol ether (MAGE) class of NELs. Here, we use activity-based protein profiling-guided medicinal chemistry to discover a highly potent and selective inhibitor of KIAA1363, the carbamate JW480. We show that JW480, and an shRNA probe that targets KIAA1363, reduce MAGEs and impair the migration, invasion, survival, and in vivo tumor growth of human prostate cancer cell lines. These findings indicate that the KIAA1363-MAGE pathway is important for prostate cancer pathogenesis and designate JW480 as a versatile pharmacological probe for disrupting this pro-tumorigenic metabolic pathway.
End-systolic regional wall stress-length and stress-shortening relations in an experimental model of normal, ischemic and reperfused myocardium☆

Assessment of left ventricular function is influenced by a number of hemodynamic factors. The purpose of this study was to evaluate the end-systolic regional wall stress-dimension relation in a series of 25 mongrel dogs. In Group A (n = 18) the regional wall stress-velocity of circumferential fiber shortening relation was measured before and after three interventions: volume infusion, metoprolol infusion and dobutamine infusion. The electrocardiogram, left ventricular pressure and its first derivative (dp/dt), arterial pressure and echocardiograms were recorded at baseline and after phenylephrine administration (to increase afterload). For each dog values for regional wall stress were plotted against the velocity of circumferential fiber shortening. For all dogs the relations were inversely linear (r = −0.65 to −0.98). Volume infusion increased end-diastolic volume (p < 0.05) without shifting the slope or intercept of the relation, indicating its independence from preload. Dobutamine caused a shift in the intercept to the right but no change in slope and metoprolol shifted the relation to the left without altering the slope. The effect of ischemia and reperfusion on the end-systolic regional wall stress-length relation was examined in Group B (n =7) at baseline, after 5 min of mid-left anterior descending coronary artery occlusion and after 10 min of reperfusion. Afterload was increased by hydraulic aortic occlusion. Regional wall stress was lowest at baseline, highest during ischemia and intermediate after reperfusion (100.2 ± 32.1, 193.5 ± 81.5, 141.9 ± 67.6 kdyn/cm2, respectively, p < 0.001). The end-systolic regional wall stress-length relation was linear during baseline, ischemia and reperfusion (r = 0.96, 0.95, 0.98, respectively, p < 0.05). Ischemia caused an increase in the slope and a shift in the intercept to the right compared with baseline. Reperfusion represented an incomplete return toward baseline. This study demonstrates that the regional wall stress-velocity of circumferential fiber shortening relation is linear, independent of preload, incorporates afterload and is sensitive to changes in contractility. In addition, the regional wall stress-length relation can be measured in a nonhomogeneously contracting left ventricle and is predictably altered by ischemia and reperfusion. This relation may prove useful to determine whether alterations in regional systolic function result from changes in local load or contractility in the left ventricle with a regional wall motion abnormality.
American Pediatric Society 2013 presidential address: 125th anniversary of the American Pediatric Society—lessons from the past to guide the future

This year is the 125th anniversary of the American Pediatric Society (APS), a time to reflect on the past 125 years of child health and child health research, a time to consider the health of America’s children in a social and global context, and a time to consider the future. This paper is a combination of pediatric and APS history and personal story.
Mathematical modeling to define optimum operating room staffing for pediatric patients in trauma centers.

Abstract Background Adult trauma centers (TCs) in the United States may be verified with an on-call operating room team if the performance improvement program shows no adverse outcome. Using queuing and simulation methodology, this study attempts to add a volume guideline for injured children. Methods Data from 63 verified TCs identified demographic factors including specific information regarding the first pediatric trauma-related operation done between 11 pm and 7 am each month for 1 year. Results The annual pediatric admits correlated with the number of operations (383) done from 11 pm to 7 am ( P Conclusion Trauma centers performing less than 6 pediatric trauma operations per year from 11 pm to 7 am could conserve resources by using an on-call operating room team.
Cell surface and intracellular expression of two Candida albicans antigens during in vitro and in vivo growth

Intracellular and cell surface expression of two antigenic determinants of Candida albicans was studied by reacting ultrathin sections of the fungus with monoclonal antibodies and locating the sites of antibody-antigen reactions by use of colloidal gold-coupled secondary antibody and electron microscopic techniques. Comparisons were made between fungal cells allowed to develop in vitro and cells (in vivo) recovered from infected mice. Differences between in vitro antigen expression and expression in vivo were particularly noted during early germination events. Antigen expression in vivo appears to be concentrated in deeper cell wall layers and beneath the plasmalemma especially on germ tubes. Cells which develop in vivo and in vitro have antigen associated with an outer flocculent layer and on the innermost cell wall layer of mother cells and hyphae. A middle electron transparent cell wall layer is usually devoid of antigen. Comparison of antigen expression during in vivo growth in early (intraperitoneal) infection versus late disseminated (kidney) disease suggests that both of the antigens are expressed in greater quantity on the surface of germ tubes than on mother cells in kidney tissue as compared to intraperitoneally-grown cells. Results also suggest that at least one of the antigens, which is a substituted mannan, can be found on a lamello-tubular intracellular structure.
A New Dimension of Sensory Dysfunction: Stereopsis Deficits in Schizophrenia

Background Schizophrenia is a neurocognitive disorder with a wide range of cognitive and sensory impairments. Early visual processing has been shown to be especially impaired. This article investigates the integrity of binocular depth perception (stereopsis) in schizophrenia. Methods Seventeen schizophrenia patients and 19 healthy control subjects were compared on the Graded Circles Stereo Test. Results of stereoacuity were compared between patients and control subjects using t test. Results Schizophrenia patients demonstrated significantly ( p = .006) reduced stereoacuity (mean = 142 arcseconds) versus control subjects (mean = 55 arcseconds). At the normative level for adults, patients performed below chance. Conclusions These findings demonstrate an impairment of binocular depth perception and further confirm deficits of early visual processing in schizophrenia. Findings are discussed in context of magnocellular/dorsal stream processing with implications for visual processing and cognitive deficits.
Video and image databases: who cares?

ABSTRACT In this paper I will not discuss the research frontiers of image and video databases but who will be the users of these systems.Questions that have not been adequately addressed by the research community is who are the users and what do they reallywant these systems to do? The purpose of this paper is to be controversial and to engage a debate within the researchcommunity as to where the real applications of our work lie. It should be noted that the author does not agree with everypoint made in this paper. 1. INTRODUCTION There has been a tremendous interest in recent years in the problem of how does one manage large amounts of image and video data. In particular, how does one acquire, store, query and display information in an image or video database. Applications often cited include digital libraries, medical images, geographic information systems (GIS), and consumerapplications.The purpose of this paper is to be controversial and to engage a debate within the research community. I feel that the image
A natureza do direito

Os juristas estao geralmente interessados na pergunta: o que e o direito em um caso particular? Essa e sempre uma pergunta local e as respostas tendem a diferir de acordo com a jurisdicao especifica na qual e formulada. Em contraste, a filosofia do direito e interessada na pergunta geral: o que e o direito? Essa pergunta geral sobre a natureza do direito pressupoe que o direito e um fenomeno socio-politico unico, com mais ou menos caracteristicas universais discerniveis por meio da analise filosofica. A Jurisprudencia Geral, como e chamada essa investigacao filosofica sobre a natureza do direito, pretende ser universal. Ela assume que o direito tem certas caracteristicas por sua propria natureza, ou essencia, enquanto direito, sempre que e em qualquer lugar que ele existe. Entretanto, mesmo se tais caracteristicas universais do direito existirem, as razoes para um interesse filosofico em elucida-las continuam precisando de explicacao. Primeiro, ha o puro interesse intelectual em entender esse fenomeno social complexo, que e, antes de tudo, um dos mais intricados aspectos da cultura humana. O direto, entretanto, tambem e uma pratica social normativa: pretende guiar o comportamento humano, dando origem a razoes para agir. Uma tentativa de explicar esse aspecto normativo fornecedor de razoes do direito e um dos desafios centrais da jurisprudencia geral. Essas duas fontes de interesse na natureza do direito estao estreitamente ligadas. O direito nao e o unico dominio normativo em nossa cultura. A moralidade, a religiao, as convencoes sociais, a etiqueta, e assim por diante, tambem guiam a conduta humana de muitas formas que sao similares ao direito. Logo, parte do que e envolvido no entendimento da natureza do direito consiste em uma explicacao de como o direito se difere desses dominios normativos similares, de como eles interagem com o direito, e se a sua inteligibilidade depende dessas outras ordens normativas, como a moralidade ou as convencoes sociais.
A Single Amino Acid Mutation Turns a P2X3 Antagonist into an Agonist

Purinergic P2X3 receptors (P2X3Rs) are ATP-gated cation channels expressed mainly in sensory neurons. Suramin inhibits P2X3R currents of several species and provides a useful tool for in vitro studies of P2X antagonism. A rhesus homolog of P2X3R was cloned, stably expressed, and pharmacologically characterized. Suramin was a more potent inhibitor of rhesus P2X3R (IC50: 0.4 μM) than of human P2X3R (IC50: 8.6 μM). Surprisingly, suramin activated rhesus P2X3R at higher concentrations (EC50: 4.7 μM). In contrast, suramin did not activate human P2X3R at similar concentrations. Other than differences in suramin agonism, the kinetic and pharmacological profile of rhesus and human P2X3Rs were similar. To investigate the molecular basis of suramin agonism with P2X3R, we generated single-point mutations in the P2X3R. Only four amino acid differences exist between rhesus and human P2X3Rs (S67F, L127F, L144F, and T162M). Mutant receptors were transiently expressed in HEK293 cells and their currents measured using an automated patch clamp instrument (PatchXpress, MDS Analytical Technologies, USA). A single amino acid mutation of human P2X3R (S67F) allowed suramin to act as an agonist and increased the potency of suramin. A corresponding mutation (F67S) in the rhesus P2X3R resulted in a loss of suramin agonism and a decrease of its inhibitory activity. This suggests that position 67 is critical for suramin modulation of P2X3R activity and that inhibition and activation by suramin may be mechanistically related.
Error Estimation Using Hybrid Methods

New formalisms are developed for robust calculation of the discretization errors in CFD applications. The new methods are based on the premise that the true error (i.e. the difference between the exact solution and the numerical solution) on a given mesh is similar to the approximate error (i.e. the difference between the fine grid solution and the coarse grid solution). The proportionality constant can be calculated theoretically for a given scheme and it is, to a first order approximation, only a function of the grid refinement ratio. This method is called Approximate Error Scaling (AES) method.Although AES is a viable method for error estimation it does not directly take into account the transport of error nor the error sources at the boundaries. To remedy this, a new method which is referred to, here and after, as the residual source in transport (REST-IC) method is formulated. This paper presents the theoretical details and the results from several test cases that are used for validation of the newly proposed methods.Application to the 1D and 2D steady scalar transport equation and 2D Navier-Stokes (N-S) equations has revealed excellent performance with a pressure based segregated N-S finite volume solver. Implementation of these methods into CFD commercial codes such as ANSYS-FLUENT can be done with the help of expert developers of the code who can handle residuals for the selected equation and the variable through user defined subroutines.Copyright © 2012 by ASME
Real-time molecular and cellular analysis: the new frontier of drug discovery.

Abstract The pharmaceutical industry is currently facing the challenge of maintaining increased efficiency and productivity while contending with a deluge of genomic and high-throughput screening data. To ease the bottlenecks at target validation and lead optimization, the industry must look to the living cell, the ultimate target of all drugs, as a source of new biological knowledge. This new ‘cell-centric’ perspective must integrate reagents that report on the state of molecular processes within the cell, automated detection and analysis of these processes, and cellular knowledge, building into a single platform.
TGFbeta signalling through Smad-independent mechanisms in human lens cells

Purpose Previous work has shown that TGFs can induce matrix contraction and is likely to be regulated by Smad-independent pathways. The present study investigated the role of the classical MAPK signalling and Rho kinase signalling pathways in TGFs mediated matrix contraction. Methods Cells from the human lens line FHL 124 were employed. Contraction was assessed using a patch assay, whereby the area covered by cells, was measured using imaging techniques. ERK activation was evaluated using western blot methods. To study SMAD2/3 distribution immunocytochemistry was used. Following a 24hr period of serum starvation, cells were maintained in the following conditions: Control medium +/– 10µM MEK inhibitor (U0126); 10ng/ml TGFs2 +/– U0126; Control medium +/– 10µM Rho kinase Inhibitor (Y–27632); 10ng/ml TGFs2 +/– Y–27632. The experimental duration for Smad2/3 staining was 2 hrs; western blots, 30mins & 24hr; patch contraction assays, 2-3 days. Results Addition of 10ng/ml TGFs2 lead to a significant elevation of P-ERK levels following both 30 min and 24hr periods of exposure. Addition of 10ng/ml TGFs2 to patch assays caused a significant contractile event to take place. Maintenance of cultures in the presence of 10µM U0126 or Y–27632 had no significant effect on patch area when added to control medium; however, when added in the presence of TGFs2, contraction was inhibited. With respect to cell population all groups were similar. Immunocytochemistry for SMAD2/3 showed clear nuclear translocation in response to 10ng/ml TGFs2; this signalling event was unaffected by U0126 and Y–27632. Conclusion MAPK and Rho kinase signalling play important roles in TGFs mediated matrix contraction of human lens cells. Commercial interest
The effects of an autologous transplant on patterns of regeneration in rat sciatic nerve.

Abstract Autologous transplants are often used in repair of peripheral nerve injury. Quantitative evaluation of the results of such a transplant is obviously desirable. In previous study, we determined numerical and cytologic parameters of the regeneration that followed transection of rat sciatic nerve, but no transplant was used. This work now serves as a basis for evaluating the use of an autologous transplant in the same transection paradigm. Our procedure is to remove 8 mm of sciatic nerve in the thigh. The removed segment is then put into the center of a silicone tube and the proximal and distal stumps of the severed nerve are placed into the ends of the tube. The data show: (1) a high percentage of successful regenerations; (2) a relatively large nerve in the gap; (3) a typical outer perineurium underlying the epineurium; (4) a well-developed fascicular perineurium; and (5) approxmately equal numbers of myelinated and unmyelinated axons in the gap and distal stump. If a transplant is not used there are: (1) a greater number of failures of regeneration; (2) a smaller nerve in the gap; (3) a less well-developed fascicular perineurium; (4) enequal numbers of axons in the gap as compared to the distal stump; and (5) no outer perineurium forms. The presence of a typical outer perineurium after a transplant and its absence if a transplant is not used is probably the most striking cytologic difference between the two paradigms. The equal numbers of axons in the gap and distal stump following regeneration after transplantation presumably indicate that all axons in the gap enter the distal stump without branching or ending blindly, a situation that is presumably beneficial and contrasts with the findings when a transplant is not used. Both paradigms show a remarkable increase in the density of blood vessels in the regenerated nerve in the gap between the two stumps. These findings will serve as a basis for further studies on the mechanisms of peripheral nerve regeneration.
Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis.

Abstract Purpose Pigment epithelium-derived factor (PEDF) has been demonstrated to suppress ocular angiogenesis in several animal models. In this study, we sought to measure the levels of PEDF and vascular endothelial growth factor (VEGF) in the vitreous of patients with and without ocular neovascular disorders. Design Case-control study of patients undergoing intraocular surgery for a variety of neovascular and nonneovascular conditions. Methods Vitreous samples were collected from 65 eyes of 65 patients with no neovascular disorder (n = 24), choroidal neovascularization (n = 9), active proliferative diabetic retinopathy (n = 16), and inactive proliferative diabetic retinopathy (n = 16). The levels of VEGF and PEDF in these vitreous samples were determined by enzyme-linked immunosorbent assay. Results The VEGF levels were at or below the level of detectability in the reference and choroidal neovascularization groups. The VEGF levels were significantly elevated in both the active and inactive PDR groups, and significantly higher in the active PDR group as compared with the inactive PDR group. The PEDF levels, which were present at relatively high concentrations in all groups, were higher in patients with active PDR compared with the control and choroidal neovascularization groups. Conclusions High levels of immunoreactive PEDF are present in the vitreous of individuals with or without ocular neovascularization, but PEDF levels are significantly higher in patients with active PDR compared with patients with choroidal neovascularization or nonneovascular retinal diseases. Although these results do not preclude the possibility that endogenous PEDF helps to modulate ocular neovascularization, they do not support ischemia-induced downregulation of PEDF as a mechanism for such modulation.
Analysis of Bread Bag Closures for Individuals with Rheumatoid Arthritis

The purpose of this study was to analyze four different plastic bag closure devices to determine if there was a difference in their ease of use for individuals with Rheumatoid Arthritis (RA) between closures currently on the market and an autoclave bag closure currently in use in medical laboratories. This was based on research into issues experienced by individuals with RA and their abilities to perform activities of daily living. This study evaluated the issues of opening and closing bread bags so that they are accessible to people with functional limitations due to the effects of RA. It was determined that the autoclave closure is not a preferred instrument for use by individuals with RA due to the difficulties in small object manipulation, the strength required to use the device and its unfamiliarity. However, closures currently available pose considerable frustration to the user and need to be re-evaluated.
THE MECHANISTIC DISSECTION OF THE PLUNGE IN ENZYMATIC ACTIVITY UPON TRANSITION FROM WATER TO ANHYDROUS SOLVENTS

Subtilisin Carlsberg dissolved in aqueous solution is several orders of magnitude more active than the enzyme suspended in anhydrous acetonitrile. In order to ascertain why, we employed crystalline subtilisin lightly cross-linked with glutaraldehyde as a catalyst in both aqueous and organic media. The structure of this crystalline enzyme in acetonitrile had been previously found to be virtually identical to that in water, thus ruling out solvent-induced conformational changes as the cause of the enzymatic activity drop. Titration of the competent active centers of subtilisin revealed that kcat/KM is solely responsible for this activity plunge. Quantitative mechanistic analysis of the 7-order-of-magnitude difference in kcat/KM values between subtilisin dissolved in water and cross-linked subtilisin crystals suspended in anhydrous acetonitrile allowed accounting for at least 5.6 orders of magnitude. This drastic decline is due to (i) a marked shift in the activity vs pH profile of the cross-linked crystalli...
Effects of biventricular pacing on left heart twist and strain in a porcine model of right heart failure.

Abstract Background Biventricular pacing (BiVP) improves cardiac output (CO) in selected cardiac surgery patients, but response remains variable, necessitating a better understanding of the mechanism. Accordingly, we used speckle tracking echocardiography (STE) to analyze BiVP during acute right ventricular pressure overload (RVPO). Materials and methods In nine pigs, the inferior vena cava (IVC) was snared to decrease CO and establish a control model. Heart block was induced, the pulmonary artery snared, and BiVP initiated. Echocardiograms of the left ventricular midpapillary level were taken at varying atrioventricular delay (AVD) and interventricular delay (VVD) for STE analysis of regional circumferential strain (CS) and radial strain (RS). Echocardiograms were taken of the left ventricular base, midpapillary, and apex during baseline, IVC occlusion, and each BiVP setting for STE analysis of twist, apical and basal rotations, CS, RS, and synchrony. Indices were correlated against CO with mixed linear models. Results During IVC occlusion, CO correlated with twist, apical rotation, RS, RS synchrony, and CS (P Conclusions In an open chest model, twist, RS, RS synchrony, and CS analyzed by STE may be noninvasive surrogates for changes in CO. During RVPO, changes in RS synchrony and CS with varying regional strain contributions may be the primary mechanism in which BiVP improves CO. Lack of correlation of remaining indices may reflect postsystolic function.
From Shakespeare on the Page to Shakespeare on the Stage: What I Learned about Teaching in Acting Class

This chapter is about both the difficulty and the usefulness of learning to see how differently our teaching might look—not to mention how our teaching might change—if we could get a view of it from the perspective of a totally different context than the one we are most used to. I was lucky enough to receive such an eye-opening view when I took an undergraduate Shakespeare acting class for theater majors at my home university. I did not do what any other busy faculty member with good sense might have done, which would have been to take just part of the course or merely hang around the fringes. No, in keeping with my full-bore approach to almost everything, I took all of the exercises and assignments. I will never forget the elocution exercise that entailed my being rolled back and forth on a gym mat by two undergraduate women while I recited my soliloquy from Hamlet using only vowels, no consonants.
Molecular cloning of a novel candidate G protein-coupled receptor from rat brain

A PCR cloning strategy using primers designed from sequences selectively conserved among a cannabinoid receptor and two orphan receptors, was used to isolate novel G protein-coupled receptors. rCNL3, a 1.75 kb cDNA encoding a 363 amino acid protein, was isolated from a rat cerebral cortex library. Sequence analysis showed that rCNL3 possesses a number of structural characteristics of G protein-coupled receptors and has 61% amino acid identity (from transmembrane region one through the carboxyl-terminus) with two other candidate G protein-coupled receptors. Therefore, these three receptors may comprise a receptor subfamily with identical or closely related endogenous ligands. Northern and in situ hybridization experiments demonstrated that rCNL3 mRNA is expressed in the rat brain, with a prominent distribution in striatum.
Neurological Surgery at New York University Medical Center

New york university Medical Center underwent a complex evolution in a rapidly growing and dynamic city. Care for the hospital-based poor resulted in international preeminence in surgical techniques. Neurosurgery at New York University has also evolved to meet the demands of the Medical Center and the community. Developments in high technology surgery and telecommunications will provide an international resource and trainees who are prepared to face the challenges of practice in the next century.
Synthesis and Characterization of Anionic Triazine Dendrimers with a Labile Disulfide Core

Anionic dendrimers based on melamine with disulfide bonds at the core were prepared to investigate the solubility of these architectures, the ability of these molecules to solubilize pyrene as a model drug, and the ability of these architectures to undergo thiol-disulfide exchange. The ability to solubilize pyrene is directly correlated with molecular weight of the dendrimer-aggregation of dendrons does not occur. Thiol-disulfide exchange occurs rapidly using dithiothreitol as the reductant to yield dendrimers with thiol cores that can undergo oxidation in air to yield the original dendrimer.
Age, manic psychopathology and treatment response

The authors describe relationships between age and ratings of signs and symptoms in 40 manic inpatients. Soon after admission, some psychopathologic features were less prominent in older patients. In older patients, after two weeks of treatment with lithium and neuroleptics, there was greater residual total psychopathology, higher ratings of some clinical features, and less change in total psychopathology and some clinical features. Older patients were hospitalized longer. Ageing may alter manic psychopathology and treatment response. The authors emphasize the need for prospective studies that include geriatric patients.
High-power proton linac for transmuting the long-lived fission products in nuclear waste

A high-power proton linac is being considered at Los Alamos as a driver for a high-flux spallation neutron source capable of transmuting the troublesome long-lived fission products in defense nuclear waste. The transmutation scheme under study provides a high flux (>10/sup 16//cm/sup 2/-s) of thermal neutrons which efficiently converts fission products to stable or short-lived isotopes. A transmuter based on a medium-energy proton linac generating 110 MW of beam power could burn accumulated /sup 99/Tc and /sup 129/I inventory at the US DOE's Hanford site within 30 years. Preliminary concepts for the accelerator are discussed. >
Appendectomy During Pregnancy: Follow-Up of Progeny

Background The incidence of appendicitis in pregnant patients is 0.04% to 0.20%, making it the most common nonobstetric surgical procedure in pregnancy. This study examines whether an appendectomy during any stage of pregnancy affects future development of motor, sensory, and social skills of the progeny. Study Design A prospective survey was administered to women who underwent an appendectomy during pregnancy at Mount Sinai Hospital from 2000 to 2009. The survey, which ranged from 1 to 9 years postpartum, consisted of questions about motor, sensory, and social development of their progeny, based on established pediatric milestones. Data were collected from the medical records of mother and child. Additional follow-up was gathered from outpatient and emergency room records. Results Fifty-two pregnant patients underwent an appendectomy during our study period. All pregnancies continued to full term with the exception of one fetal death due to extreme prematurity. Twenty-nine patients completed the follow-up survey, making the yield response rate 55.8%. There were 7 (26.9%), 14 (48.3%), and 8 (27.6%) appendectomies in the first, second, and third trimesters, respectively. Mean follow-up time was 47.2 months (range 13 to 117 months) after delivery. None of the children exhibited any developmental delay by their third year of life. Timing of the surgery (trimester) had no effect on child development. Conclusions Appendectomy during pregnancy is not associated with developmental delays in children, regardless of which trimester the procedure was performed. All children in this study had normal motor, sensory, and social development by 3 years of age.