cssi/SciSciGPT-SciSciNet huggingface dataset:
The Role of the Clinical Research Coordinator in Multicenter Clinical Trials

The clinical research coordinator plays a crucial role in organizing a site's participation in the expanding arena of multicenter medical and pharmacologic clinical trials. This summary clarifies the role of the clinical research coordinator for inexperienced staff members assuming these responsibilities and outlines planning procedures leading to successful implementation. Emphasis is placed on establishing an interdependent relationship with the principal investigator, careful protocol assessment, team building, and staff feedback. Useful tools such as study manuals and physicians' study orders are described.
Enzymatic synthesis and purification of l-pyrroline-5-carboxylic acid

Abstract Δ 1 -Pyrroline-5-carboxylic acid (P5C) is an intermediate in the metabolism of proline, ornithine, and glutamic acid. It has been obtainable by chemical synthesis only as a mixture of the d - and l -stereoisomers. We report a method for the enzymatic synthesis of P5C on a preparative scale. The P5C is formed from l -ornithine by purified ornithine aminotransferase and then isolated by Dowex-50W cation-exchange resin chromatography. The purified compound exists entirely as the biologically active l -stereoisomer. With [ 14 C]ornithine as precursor, high specific activity uniformly labeled [ 14 C]P5C can be obtained.
PREY PREFERENCES IN THE DESERT HORNED LIZARD: INFLUENCE OF PREY FORAGING METHOD AND AGGRESSIVE BEHAVIOR'

Desert horned lizards Phrynosoma platyrhinos consumed the solitary-foraging seed- harvester ant, Pogonomyrmex californicus, 10 to 100 times more often than expected based upon its relative abundance in the environment. The group-foraging seed-harvester ants, Pogonomyrmex ru- gosus and Veromessor pergandei, were correspondingly underrepresented in the horned lizard's natural diet. In a series of laboratory prey choice tests, where prey availabilities were held constant and equal, these preferences were confirmed: P. californicus was eaten more often than P. rugosus which was eaten more often than V. pergandei. These preferences correspond to differences in ant aggressive behavior which, in turn, correspond to differences in ant foraging-group size and foraging method. Colonies of solitary-foraging ants have small foraging groups and are generally incapable of mobbing a lizard, but they are also difficult to find. Colonies of group-foraging ants have large to massive foraging groups and vigorously mob lizards. Such aggressiveness is probably effective by increasing the risk of exposure of a lizard to predators of its own; the indirect costs of preying upon these ant species, normally assumed constant over all prey types for most predators, are variable here. Differences in experience with ant aggressive behavior probably account for differences in prey preferences found among adult lizards captured from the same area. Ant-species-specific predation by Phrynosoma may be an important ecological force structuring the Mohave Desert seed-harvesting ant community.
Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon

Abstract The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.
Concerning the structure of a high pressure phase in californium metal

Abstract Using a model based on a hexagonal lattice and on a structure reported for the high pressure distorted f.c.c. phase of praseodymium a structure has been suggested for one of the high pressure phases of californium metal that is labeled “distorted f.c.c.”. In the present work an alternative solution based on a triclinic cell is described. The application of either structure model to the reported d spacings of the high pressure phase of californium under consideration is discussed.
Pink herring & the fourth persona: J. Edgar Hoover's sex crime panic

During the 1930s, sexuality significantly shaped J. Edgar Hoover's public discourse. In response to a homosexual panic that plagued the nation's men and endangered his public persona, Hoover engaged in a passing performance. His masking rhetoric employed the pink herring, a tactic that manipulated a moral panic about sex crime to stabilize gender and sexual norms, divert attention from his private life, and silence an invisible audience that I term the fourth persona.
Combining Near-surface Seismic Reflection And Ground-penetrating Radar Data In the Depth Domain

Shallow seismic reflection (SSR) and ground-penetrating radar (GPR) data of approximately the same wavelength were collected over a coincident volume of geologic material in an effort to image the water table at a test site near Clay Center, KS. Although the top of the saturated zone was successfully imaged using both techniques, no significant reflectors were imaged above the water table using SSR or below the water table using GPR. The SSR and GPR data sets were depth converted and vertically stacked to provide a more complete image of the subsurface. Instead of having two different sections representing depths of ~0-5 m (GPR) and ~4-30 m (SSR), the combined section includes the near-surface stratigraphy, water table, and bedrock, among other geologic features. It is important to note, however, that this method of data combination is intended for qualitative purposes only because the two methods measure different physical properties of the subsurface and quantitative analysis of the vertically stacked section may lead to erroneous results.
The alanine racemase of Brucella abortus.

Wood and Gunsalus (1) have isolated, resolved, and partially purified an enzyme from Streptococcus jaecalis which racemizes alanine and which is specifically activated by pyridoxal phosphate. This enzyme is widely distributed among bacteria but absent in yeast, molds, and animal tissues. Alanine racemase is also present in high concentration in bacterial spores (2). Goodlow and his co-workers have identified alanine as a metabolic product of Brucellu abortus and have shown that the addition of n-alanine to cultures results in a shift in populaticn from smooth and virulent to nonsmooth and avirulent (3, 4). B. abortus was found to form alanine both by transamination between pyruvate and certain amino acids (5, 6) and possibly by direct amination (6), yet the mechanism of formation of the n-isomer was obscure. We have found that n-alanine is a product of the oxidation of glutamate by washed cells of B. abortus and that sonic extracts of these cells contain aporacemase. Several of the properties of this enzyme have been determined, and data are presented which indicate that alanine is not deaminated during racemization.
Global Transcriptome Profile of Cryptococcus neoformans during Exposure to Hydrogen Peroxide Induced Oxidative Stress

The ability of the opportunistic fungal pathogen Cryptococcus neoformans to resist oxidative stress is one of its most important virulence related traits. To cope with the deleterious effect of cellular damage caused by the oxidative burst inside the macrophages, C. neoformans has developed multilayered redundant molecular responses to neutralize the stress, to repair the damage and to eventually grow inside the hostile environment of the phagosome. We used microarray analysis of cells treated with hydrogen peroxide (H2O2) at multiple time points in a nutrient defined medium to identify a transcriptional signature associated with oxidative stress. We discovered that the composition of the medium in which fungal cells were grown and treated had a profound effect on their capacity to degrade exogenous H2O2. We determined the kinetics of H2O2 breakdown by growing yeast cells under different conditions and accordingly selected an appropriate media composition and range of time points for isolating RNA for hybridization. Microarray analysis revealed a robust transient transcriptional response and the intensity of the global response was consistent with the kinetics of H2O2 breakdown by treated cells. Gene ontology analysis of differentially expressed genes related to oxidation-reduction, metabolic process and protein catabolic processes identified potential roles of mitochondrial function and protein ubiquitination in oxidative stress resistance. Interestingly, the metabolic pathway adaptation of C. neoformans to H2O2 treatment was remarkably distinct from the response of other fungal organisms to oxidative stress. We also identified the induction of an antifungal drug resistance response upon the treatment of C. neoformans with H2O2. These results highlight the complexity of the oxidative stress response and offer possible new avenues for improving our understanding of mechanisms of oxidative stress resistance in C. neoformans.
Current trends in robot assisted surgery: a survey of gynecologic oncologists

Background To evaluate the perceptions of the importance and utility of robot assisted surgery in gynecologic oncology. Methods A 39 question web-based survey was sent to members of the Society of Gynecologic Oncologists. Results The survey response rate was 28%, with 277 surveys completed. Nearly 40% of respondents felt robotic surgical training was required as a part of their career goals, and 73% of respondents have performed a robotic hysterectomy. Among respondents, 39% felt that robotic surgery was as good as laparoscopic surgery but 23% thought robot assisted surgery should be the gold standard for the treatment of endometrial cancer. Conclusions Robot assisted surgery is gaining widespread acceptance and is perceived to be as good as laparoscopic surgery for the treatment of early stage endometrial and cervical cancers. Among respondents the greatest benefit of robot assisted surgery was its ease of use and perceived improvement in a patient's quality of life. Copyright © 2010 John Wiley & Sons, Ltd.
Evaluation of polymers for controlled‐release properties when incorporated with nitrogen fertilizer solutions

Abstract Three polymers (polyacrylate, vinyl‐alcohol, starch‐based) were evaluated for controlled‐release properties when expanded in urea, ammonium sulfate ((NH4)2SO4), and potassium nitrate (KNO3) solutions, at five nitrogen (N) concentrations (0,10,15, 20 g N/L, and saturation). The expansion capacity (mL solution absorbed/g dry polymer) of each polymer varied and was dependent on the type and concentration of fertilizer solution. On average, polymers incorporated with urea, (NH4)2SO4, and KNO3 fertilizer solutions had expansion capacities of 275, 24, and 30 mL/g, respectively. All three polymers reacted with ammonium ions in solution and resisted normal extraction procedures of ammonium with 2N KCl. To determine gel characteristics when applied to a soil medium, selected gel treatments were incubated in containers of loamy sand soil up to 28 days and then assessed for the quantity of gel recovered, N content, and N concentration. Although most gels released a large portion of N after only 7 days, some...
Integrating property value and local recreation models to value ecosystem services from regional parks

Abstract Multiple ecosystem services of parks may be capitalized into the property values of nearby houses. A joint hedonic housing price model and recreation demand model evaluates how park services are capitalized into property values for two regional parks in Portland, Oregon. The hedonic model suggests parks are an amenity of bundled positive and negative services. A non-linear variable for the percentage of park land surrounding a home explains how parks affect property values the best. The optimal percentage within a half-mile neighborhood is around 20%. An improvement in the quality of parks for recreation by 30% increases the property value of homes five to ten miles away by 0.04–0.06%. Thus, programs that improve recreation access to parks can increase the property values of a community.
Stellenwert von Nedocromil-Natrium in der Behandlung des kindlichen und jugendlichen Asthmas

Bei Nedocromil-Natrium (NN) und Dinatrium cromoglicicum (DNCG) handelt es sich um nicht-steroidale, antiinflammatorisch wirkende Substanzen zur Behandlung des Asthmas. Obwohl sie sich von ihrer chemischen Struktur her unterscheiden, weisen sie hinsichtlich ihrer Wirkungen viele Ahnlichkeiten auf. Wahrend sie in einigen Provokationsmodellen (Allergen, Anstrengung) eine vergleichbare Wirkung zeigen, ist in den sogenannten nicht-allergischen, neuronalen Modellen (z.B. SO2 ) Nedocromil-Natrium uberlegen. Die Zahl der direkten Vergleichsstudien beider Pharmaka ist gering. Eine Vergleichsstudie an Kindern zeigt, das 2× taglich verabreichtes Nedocromil-Natrium genauso wirksam wie 4× taglich gegebenes DNCG ist. Die Moglichkeit der 2-taglichen Anwendung kann als Vorteil fur Nedocromil-Natrium angesehen werden. Ein weiterer Vorteil fur Nedocromil-Natrium besteht darin, das fur diese Substanz im Gegensatz zum DNCG ein steroidsparender Effekt aufgezeigt werden konnte. Beide Pharmaka werden als Basistherapeutika zur Behandlung des leichten persistierenden Asthmas empfohlen.
Determination of the specific gravity of human pineal

Specific gravity values for the pineal gland in any species are lacking. These data are necessary for calculating and interrelating pineal weight and volume. This report deals with the specific gravity of human pineal gland. The specific gravity of fresh, unfixed human pineal has been determined to be 1.197 +/- 0.036 SEM at 20 degrees C (N = 11) using water as the measuring medium. By contrast, human brain has been reported in the literature to have a specific gravity of 1.036. Specific gravities of human pineals fixed in Bouin's fluid, Bouin's fluid followed by 80% ethanol, 80% ethanol, and embalming fluid were found to be 1.113 +/- 0.025 (N = 5), 0.941 +/- 0.009 (N = 5), 0.990 +/- 0.022 (N = 3), and 1.149 +/- 0.021 (N = 7), respectively. These are corrected values accounting for the specific gravities of the respective measuring fluids. It is shown that the specific gravity of human pineal as derived in this study is directly applicable to calculations of pineal volumes and weights not only in humans, but in other species as well.
Sheet Metal Joint Configurations and Their Variation Characteristics

In sheet metal assembly, joints are designed to facilitate welding the parts. The three basic joints used in sheet metal assemblies are lap (slip) joints, butt joints, and butt-lap (corner) joints. Each joint configuration has its own variation characteristics. However, the currently available variation analysis methods, such as worst case analysis, root sum squarely, etc., are not applicable to deformable sheet metal because they are based on rigid bodies. This paper analyzes the variation characteristics of simple assemblies constructed from the three basic joints, using Mechanistic Variation Simulation. Mechanistic Variation Simulation combines engineering structural models with statistical analysis in predicting deformable sheet metal assembly variation. Furthermore, the variation characteristics of the boxes constructed from the three basic joints are also evaluated. The developed models and analysis provide an improved understanding of sheet metal product design and process design.
Activation-induced T-cell death and immune dysfunction after implantation of left-ventricular assist de vice

Summary Background Cardiac transplantation is a limited option for end-stage heart failure because of the shortage of donor organs. Left-ventricular assist devices (LVADs) are currently under investigation as permanent therapy for end-stage heart failure, but long-term successful device implantation is limited because of a high rate of serious infections. To examine the relation between LVAD-related infection and host immunity, we investigated immune responses in LVAD recipients. Methods We compared the rate of candidal infection in 78 patients with New York Heart Association class IV heart failure who received either an LVAD (n=40) or medical management (controls, n=38). Fuorochrome-labelled monoclonal antibodies were used in analyses of T-cell phenotype. Analysis of T-cell function included intradermal responses to recall antigens and proliferative responses after stimulation by phytohaemagglutinin, monoclonal antibodies to CD3, and mixed lymphocyte culture. We measured T-cell apoptosis in vivo by annexin V binding, and confirmed the result by assessment of DNA fragmentation. Activation-induced T-cell death was measured after T-cell stimulation with antibodies to CD3. All immunological tests were done at least 1 month after LVAD implantation Between-group comparisons were by Kaplan-Meier actuarial analysis and Student's t test. Findings By 3 months after implantation of LVAD, the risk of developing candidal infection was 28% in LVAD recipients, compared with 3% in controls (p=0·003). LVAD recipients had cutaneous anergy to recall antigens and lower ( Interpretation LVAD implantation results in an aberrant state of T-cell activation, heightened susceptibility of CD4 T cells to activation-induced cell death, progressive defects in cellular immunity, and increased risk of opportunistic infection.
Effects of repeated administration of l-DOPA and apomorphine on circling behavior and striatal dopamine formation

Abstract We tested the circling response to l -DOPA and apomorphine administration in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Rats demonstrated a progressively diminished circling response when l -DOPA–carbidopa was repeatedly administered at 120 min intervals. This decreasing response was not present when apomorphine was administered under the same conditions. We also perfused l -DOPA directly into the striatum in vivo of rats with an ipsilateral 6-OHDA nigrotomy at 60 min intervals and monitored striatal dopamine levels with the technique of brain microdialysis. Dopamine formation increased from the first to the fifth trial. This may be secondary to the decrease in uptake sites which accompanies the loss of striatal dopamine nerve terminals. We postulate that the continued presence of dopamine at striatal receptor sites conditions a short-term loss of dopamine receptor sensitivity and a consequent decreased circling response. The observation that desensitization (as measured by decreasing circling) was not present following repeated apomorphine administration may be attributable to its shorter duration of action. We also perfused l -DOPA into the striatum of normal rats and noted a progressive decrease in striatal dopamine levels from the first to the fifth trial. Since this occurred following direct administration of l -DOPA into the striatum, the decrease could not be accounted for by peripheral pharmacodynamics or bioavailability of l -DOPA in the striatum. Since this decrease in dopamine formation was seen only in the normal striatum, its relevance to the diminished behavioral response is unclear.
Comparing Incremental Latent Semantic Analysis Algorithms for Efficient Retrieval from Software Libraries for Bug Localization

The problem of bug localization is to identify the source files related to a bug in a software repository. Information Retrieval (IR) based approaches create an index of the source files and learn a model which is then queried with a bug for the relevant files. In spite of the advances in these tools, the current approaches do not take into consideration the dynamic nature of software repositories. With the traditional IR based approaches to bug localization, the model parameters must be recalculated for each change to a repository. In contrast, this paper presents an incremental framework to update the model parameters of the Latent Semantic Analysis (LSA) model as the data evolves. We compare two state-of-the-art incremental SVD update techniques for LSA with respect to the retrieval accuracy and the time performance. The dataset we used in our validation experiments was created from mining 10 years of version history of AspectJ and JodaTime software libraries.
Defectors cannot be detected during"small talk" with strangers.

To account for the widespread human tendency to cooperate in one-shot social dilemmas, some theorists have proposed that cooperators can be reliably detected based on ethological displays that are difficult to fake. Experimental findings have supported the view that cooperators can be distinguished from defectors based on "thin slices" of behavior, but the relevant cues have remained elusive, and the role of the judge's perspective remains unclear. In this study, we followed triadic conversations among unacquainted same-sex college students with unannounced dyadic one-shot prisoner's dilemmas, and asked participants to guess the PD decisions made toward them and among the other two participants. Two other sets of participants guessed the PD decisions after viewing videotape of the conversations, either with foreknowledge (informed), or without foreknowledge (naive), of the post-conversation PD. Only naive video viewers approached better-than-chance prediction accuracy, and they were significantly accurate at predicting the PD decisions of only opposite-sexed conversation participants. Four ethological displays recently proposed to cue defection in one-shot social dilemmas (arms crossed, lean back, hand touch, and face touch) failed to predict either actual defection or guesses of defection by any category of observer. Our results cast doubt on the role of "greenbeard" signals in the evolution of human prosociality, although they suggest that eavesdropping may be more informative about others' cooperative propensities than direct interaction.
Grand cru versus generic: different approaches to altering the ratio of general internists to subspecialists.

In the last decade internal medicine has become a less popular career choice among medical school graduates. In addition, there has been an increase in the percentage of internal medicine residents...
Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl.

Abstract The c- Cbl protooncogene product is a prominent substrate of protein tyrosine kinases and is rapidly tyrosine-phosphorylated upon stimulation of a wide variety of cell-surface receptors. We have identified a novel c-Cbl-interacting protein termed CIN85 with a molecular mass of 85 kDa which shows similarity to adaptor proteins, CMS and CD2AP. CIN85 mRNA is expressed ubiquitously in normal human tissues and cancer cell lines analyzed. CIN85 was basally associated with c-Cbl. For interaction of CIN85 with c-Cbl, the second SH3 domain of CIN85 was shown to serve as a central player. The CIN85–c-Cbl association was enhanced shortly after stimulation of 293 cells with epidermal growth factor (EGF) and gradually diminished to a basal level, which correlated with a tyrosine phosphorylation level of c-Cbl. Our results suggest that CIN85 may play a specific role in the EGF receptor-mediated signaling cascade via its interaction with c-Cbl.
PROXIMAL EMBOLIC PROTECTION DECREASES CEREBRAL MICROEMBOLIZATION COMPARED TO DISTAL PROTECTION FOR CAROTID STENTING: A META-ANALYSIS

Embolic protection devices have become standard of care during carotid artery stenting (CAS) to reduce periprocedural stroke risk. Distal Protection Devices (DPD) were the first and are the most commonly used devices. Proximal protection devices (PPD) avoid lesion crossing and thus are potentially
Measuring geographic access to health care: raster and network-based methods

Inequalities in geographic access to health care result from the configuration of facilities, population distribution, and the transportation infrastructure. In recent accessibility studies, the traditional distance measure (Euclidean) has been replaced with more plausible measures such as travel distance or time. Both network and raster-based methods are often utilized for estimating travel time in a Geographic Information System. Therefore, exploring the differences in the underlying data models and associated methods and their impact on geographic accessibility estimates is warranted. We examine the assumptions present in population-based travel time models. Conceptual and practical differences between raster and network data models are reviewed, along with methodological implications for service area estimates. Our case study investigates Limited Access Areas defined by Michigan’s Certificate of Need (CON) Program. Geographic accessibility is calculated by identifying the number of people residing more than 30 minutes from an acute care hospital. Both network and raster-based methods are implemented and their results are compared. We also examine sensitivity to changes in travel speed settings and population assignment. In both methods, the areas identified as having limited accessibility were similar in their location, configuration, and shape. However, the number of people identified as having limited accessibility varied substantially between methods. Over all permutations, the raster-based method identified more area and people with limited accessibility. The raster-based method was more sensitive to travel speed settings, while the network-based method was more sensitive to the specific population assignment method employed in Michigan. Differences between the underlying data models help to explain the variation in results between raster and network-based methods. Considering that the choice of data model/method may substantially alter the outcomes of a geographic accessibility analysis, we advise researchers to use caution in model selection. For policy, we recommend that Michigan adopt the network-based method or reevaluate the travel speed assignment rule in the raster-based method. Additionally, we recommend that the state revisit the population assignment method.
Using genetic algorithms for the construction of a space mission automaton

Many interesting problems in numerical optimization are hybrid optimal control problems. Hybrid optimal control (HOC) problems include both continuous-valued variables and categorical variables in the problem formulation. For the types of problems envisioned here the categorical variables will specify the structure or sequence of events that qualitatively describes the trajectory or mission. Continuous variables are used in the modeling of the continuous dynamics. In this work, the mission planning problem is of interest. The problem is qualitatively different from the typical interception of multiple targets as the discrete variables now represent events like impulses, coast and thrust arcs that change the structure of the problem. In addition, the number of events in the categorical sequence is not fixed. For the dynamical assembly of events required for the solution of the mission planning problem, a scheme that defines events as modules consisting of parameters and constraints is presented. The method assembles the respective events one next to the other in time according to the given mission structure. For the generation of the initial guess, two new methods were developed that approximate optimal low-thrust trajectories. The first method, based on genetic algorithms (GA), handles the rendezvous constraints explicitly using a conditional penalty function. The second method, Feasible Region Analysis (FRA), is based on GA and nonlinear programming (NLP), which allows taking advantage of the GA capabilities in finding a global optimum and NLP ability in handling constraints. A rendezvous problem with known solution is solved.
Will Diabetes Save the Platelet Blockers

More than 30 000 patients have been enrolled in trials assessing the efficacy of glycoprotein (GP) IIb/IIIa inhibitors in unstable angina (UA) or non–ST-segment elevation MI (NSTEMI). The initial trials demonstrated that the use of a GP IIb/IIIa inhibitor resulted in a significant decrease in the rate of death or nonfatal myocardial infarction.1,2 More recently, however, the GP IIb/IIIa inhibitor with the best track record to date in the setting of percutaneous coronary intervention (PCI), abciximab, was tested in UA/NSTEMI in the Global Use of Strategies To Open occluded coronary arteries in Acute Coronary Syndromes (GUSTO IV–ACS) trial, which enrolled patients in whom PCI was not intended, and showed no benefit.3 These disappointing results may have been related to issues of dosing, patient selection, and trial design, but nevertheless, they have led to a reappraisal of the utility of GP IIb/IIIa inhibitors in UA/NSTEMI. See p 2767 In the present issue of Circulation , Roffi and colleagues4 revive enthusiasm for the use of GP IIb/IIIa inhibitors in acute coronary syndromes (ACS). They wished to determine whether patients presenting with UA/NSTEMI who had diabetes mellitus derived particular benefit from GP IIb/IIIa inhibition. To answer this question, they performed a meta-analysis of the 6 major, placebo-controlled, GP IIb/IIIa inhibitor trials to date. Stratifying by diabetic status, they found that assignment to active treatment with a GP IIb/IIIa inhibitor was associated with a significant 26% reduction in mortality among diabetic patients, whereas there was no effect among nondiabetics. These results were consistent across all 6 trials, despite the use of different GP IIb/IIIa inhibitors. There is a priori biologic plausibility to support these intriguing results. Not only is diabetes mellitus a well-established risk factor for the development of atherosclerotic coronary artery disease, but compared with their nondiabetic counterparts, diabetic patients …
Immune-mediated adverse events of anticytotoxic T lymphocyte-associated antigen 4 antibody therapy in metastatic melanoma.

Ipilimumab, an antibody that blocks cytotoxic T lymphocyte–associated antigen 4 (CTLA-4; CD152), was approved by the Food and Drug Administration in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti–CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies and specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma.
Usefulness of residual plasma fibrinogen after intravenous streptokinase for predicting delay or failure of reperfusion in acute myocardial infarction.

The relation between the level of residual plasma fibrinogen and coronary artery reperfusion after 750,000 IU of intravenous (i.v.) streptokinase (SK) was examined in 76 patients with acute myocardial infarction. Both the frequency and rapidity of reperfusion were greater in the 53 patients in whom the residual fibrinogen level was 50 mg/dl or less (low fibrinogen) than in the 23 patients in whom it was more than 50 mg/dl (high fibrinogen). Reperfusion occurred in all 53 patients in the low-fibrinogen group, compared with only 15 patients in the high-fibrinogen group (p less than 0.001). The interval from initiation of SK to clinical signs of reperfusion was 50 +/- 34 minutes in the low-fibrinogen group and 110 +/- 54 minutes in the high-fibrinogen group (p less than 0.001). A high fibrinogen level occurred in 58% of patients who weighed more than 85 kg and in 25% of patients who weighed 85 kg or less (p less than 0.05). No patient who weighed 60 kg or less had a high fibrinogen level. The high-fibrinogen group also had a greater incidence of a high anti-SK antibody titer: 8 of 13 patients (62%) tested, compared with none of the 8 patients tested in the low-fibrinogen group (p less than 0.01). Our data indicate that a high residual fibrinogen level after administration of i.v. SK identifies patients in whom SK is relatively ineffective, probably because of inadequate dosage of inactivation of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Furosemide Elicits Immediate Sympathoexcitation via a Renal Mechanism Independent of Angiotensin II

This investigation aimed at examing the hypothesis that furosemide elicits renal sympathoexcitation through stimulation of renal renin release, which in turn produces increased plasma angiotensin II levels, causing centrally mediated sympathoexcitation. In addition, direct central nervous actions of furosemide on central control of mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity were examined. Furosemide (300 mg/kg intravenously) was administered to four groups of rats: (1) control; (2) nephrectomized; (3) with intravenous losartan blockade (10 mumol/kg); and (4) with intracerebroventricular losartan blockade (10 nmol). In a fifth group of rats, furosemide was administered intracerebroventricularly (0, 2.5, 25 or 250 micrograms). To eliminate reflex control of mean arterial pressure, heart rate and efferent renal sympathetic nerve activity, all experiments were performed in rats with sinoaortic denervation and bilateral vagotomy. Experiments were performed during Saffan anaesthesia (0.9% alphaxalone/0.3% alphadolone), and rats were paralyzed with pancuronium and artifically ventilated. Furosemide produced an immediate 40% increase in efferent renal sympathetic nerve activity while the furosemide vehicle, 2 vol.% ethanolamine, did not affect efferent renal sympathetic nerve activity. The furosemide-induced increase in efferent renal sympathetic nerve activity was abolished in rats with bilateral nephrectomy but it was not affected by intravenous or intracerebroventricular losartan blockade. Intracerebroventricular angiotensin II produced an increase in mean arterial pressure and efferent renal sympathetic nerve activity whereas intravenous angiotensin II produced a pressor response in absence of increased efferent renal sympathetic nerve activity. Losartan effectively blocked responses to intravenous or intracerebroventricular angiotensin II. Intracerebroventricular administration of furosemide produced no changes in mean arterial pressure, heart rate or efferent renal sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)
An Investigation of Entrepreneurial Orientation, Perceived Environmental Hostility, and Strategy Application among Chinese SMEs

Little is known about how Chinese small and medium‐sized enterprises (SMEs) respond to their competitive environment. We predict that when industry competition is intense, entrepreneurial Chinese S...
Foliar nitrogen and phosphorus accumulation responses after fertilization: an example from nutrient-limited Hawaiian forests

How plants respond to long-term nutrient enrichment can provide insights into physiological and evolutionary constraints in various ecosystems. The present study examined foliar concentrations after fertilization—to determine if nutrient accumulation responses of the most abundant species in a plant community reflect differences in N and P uptake and storage. Using a chronosequence in the Hawaiian Islands that differs in N and P availability, it was shown that after fertilization, plants increase foliar P to a much greater degree than foliar N, as indicated by response ratios. In addition, foliar P responses after fertilization were more variable and largely driving the observed changes in N:P values. Across species, both inorganic and organic P increased but neither form of N increased significantly. This pattern of P accumulation was consistent across 13 species of varying life forms and occurred at both the N-limited and P-limited site, although its magnitude was larger at the P-limited site. Foliar P accumulation after nutrient enrichment may indicate nutrient storage and may have evolved to be a general strategy to deal with uncertainties in P availability. Storage of P complicates interpretations of N:P values and the determination of nutrient limitation.
Stability of One-Dimensional Spatially Invariant Arrays Perturbed by White Noise

For the one-dimensional spatially invariant array, a necessary and sufficient stability condition in terms of the Schur stability of a matrix over spatial frequency is obtained in this paper. Then based on the theorem on nonnegative pseudo-polynomial matrices, the frequency-dependent stability condition is converted to a finite dimensional linear matrix inequality (LMI) problem, the solution of which is easy to compute.
Residues from anabolic preparations after good veterinary practice.

The purpose of this study was to determine the endogenous concentrations of estrogens, particularly estradiol-17β (E2β), in edible tissues of beef cattle (females and intact and neutered males) and the concentrations of E2β, and trenbolone beta and alpha (βTb, αTb) after an E2β and/or trenbolone acetate (TA) ear implant. Radioimmunoassays were validated for quantitation of E2β (active isomer), E2α, estrone (E1), βTb and αTb for bovine muscle, liver, kidney and fat tissues. The criteria of accuracy, precision, specificity and sensitivity were applied according to the standards of the U.S. Food & Drug Administration. In steer tissues, endogenous E2β was <15 ppt, as was heifer muscle; but heifer liver and kidney were 3-fold greater. An E2β implant in steers had no effect on muscle E2β concentration, but increased E2β in liver and fat 4- and 3-fold, respectively, but by 24 h post-implant removal, E2β had fallen by half. Tissue E1 concentrations in cyclic females were similar to E2β, but rose many fold greater than did E2β during gestation; E2β rose 3-fold during gestation. After E2β/TA implant, steer tissues had E2β concentrations equal to (for muscle and fat) and one-half (for liver) the E2β measured in E2β implant only steers; βTb was in a low range (250–380 ppt) in muscle, liver and fat and αTb was even lower, except in liver (800–1500 ppt). An implant of TA only (no E2β) resulted in βTb and αTb concentrations 2–3-fold greater in liver, kidney and fat, but no greater in muscle than βTb in tissues of E2β/TA implant steers. In conclusion, anabolic implants in steers resulted in tissue E2β concentrations less than the FDA allowable increment and βTb in the lowest quartile (0.25) of a part per billion 30 days after implant.
Water soluble levan polysaccharide biopolymer electrospun fibers

Electrospinning has been used to prepare nanofibers from diverse biopolymers. Here we report on preparation of fibers by electrospinning of levan (a polysaccharide) from distilled water. A high concentration of levan was required for fiber formation. This suggests that higher concentrations enable the formation of chain entanglements required to maintain the jet strength. In general, fiber diameter decreased with increased voltage, distance between collector plate and needle and decreased pump flow rate. X-ray diffraction of the fibers showed a highly amorphous character in levan formed from solution compared to the levan powder.
A Galerkin solution for stochastic algebraic equations

Galerkin solutions are developed for linear stochastic algebraic equations, that is, linear algebraic equations with random coefficients. Two classes ofGalerkin solutions, referred to as optimal and sub-optimal Galerkin solutions, are constructed. It is shown that optimal Galerkin solutions for a linear stochastic algebraic equation are given by conditional expectations of the exact solution of this equation with respect to s-fields that are coarser than the σ-field relative to which the exact solution is measurable. The σ-fields needed to defined optimal Galerkin solutions can be constructed from, for example, σ-fields generated by measurable partitions of the sample space. Galerkin solutions that are not optimal are called sub-optimal. Optimal and sub-optimal Galerkin solutions are unbiased and biased approximations of the exact solution.
Cluster-dependent feature selection by multiple kernel self-organizing map

Motivated by the fact that data of each cluster are often well captured by distinct features, we propose a clustering approach called multiple kernel self-organizing map (MK-SOM) that integrates multiple kernel learning into the learning procedure of SOM, and carries out cluster-dependent feature selection simultaneously. MK-SOM is developed to reveal the intrinsic relation between features and clusters, and is derived with an efficient optimization procedure. The proposed approach is evaluated on two benchmark datasets, UCI and Caltech-101. The promising experimental results demonstrate its effectiveness.
Kluge's Auswege

If Alexander Kluge's prose and films are populated with figures looking for escape, his programmatic statements on the media are no less concerned with how various narrative strategies provide more or less possibility for a way out from dominant discursive practices. This idea of Auswege—at the level of both the experience as well as the representation and the conceptualization of historical events—is at the core of Kluge's multi-media project and is the focus of this article. Auswege describe processes of representation/depiction that serve as the reader's point of departure to re-imagine the present, and potentially, offer a Rettung from the repetition of catastrophe. The article traces the evolution of this concept in examples of Kluge's work from the 1970s (Luftangriff auf Halberstadt and Verschrottung durch Arbeit) and in prose texts composed in the context of the end of the GDR and the unification of Germany in 1989/90 (Verfallserscheinungen der Macht).
Social Network Sensors for Early Detection of Contagious Outbreaks

Current methods for the detection of contagious outbreaks give contemporaneous information about the course of an epidemic at best. It is known that individuals near the center of a social network are likely to be infected sooner during the course of an outbreak, on average, than those at the periphery. Unfortunately, mapping a whole network to identify central individuals who might be monitored for infection is typically very difficult. We propose an alternative strategy that does not require ascertainment of global network structure, namely, simply monitoring the friends of randomly selected individuals. Such individuals are known to be more central. To evaluate whether such a friend group could indeed provide early detection, we studied a flu outbreak at Harvard College in late 2009. We followed 744 students who were either members of a group of randomly chosen individuals or a group of their friends. Based on clinical diagnoses, the progression of the epidemic in the friend group occurred 13.9 days (95% C.I. 9.9-16.6) in advance of the randomly chosen group (i.e., the population as a whole). The friend group also showed a significant lead time (p<0.05) on day 16 of the epidemic, a full 46 days before the peak in daily incidence in the population as a whole. This sensor method could provide significant additional time to react to epidemics in small or large populations under surveillance. The amount of lead time will depend on features of the outbreak and the network at hand. The method could in principle be generalized to other biological, psychological, informational, or behavioral contagions that spread in networks.
An exploratory analysis of network characteristics and quality of interactions among public health collaboratives

While the benefits of collaboration have become widely accepted and the practice of collaboration is growing within the public health system, a paucity of research exists that examines factors and mechanisms related to effective collaboration between public health and their partner organizations. The purpose of this paper is to address this gap by exploring the structural and organizational characteristics of public health collaboratives. Design and Methods. Using both social network analysis and traditional statistical methods, we conduct an exploratory secondary data analysis of 11 public health collaboratives chosen from across the United States. All collaboratives are part of the PARTNER (www.partnertool.net) database. We analyze data to identify relational patterns by exploring the structure (the way that organizations connect and exchange relationships), in relation to perceptions of value and trust, explanations for varying reports of success, and factors related to outcomes. We describe the characteristics of the collaboratives, types of resource contributions, outcomes of the collaboratives, perceptions of success, and reasons for success. We found high variation and significant differences within and between these collaboratives including perceptions of success. There were significant relationships among various factors such as resource contributions, reasons cited for success, and trust and value perceived by organizations. We find that although the unique structure of each collaborative makes it challenging to identify a specific set of factors to determine when a collaborative will be successful, the organizational characteristics and interorganizational dynamics do appear to impact outcomes. We recommend a quality improvement process that suggests matching assessment to goals and developing action steps for performance improvement. Acknowledgements the authors would like to thank the Robert Wood Johnson Foundation’s Public Health Program for funding for this research.
Two Dissimilar N-Acyl-Homoserine Lactone Acylases of Pseudomonas syringae Influence Colony and Biofilm Morphology

Plant aerial surfaces comprise a complex habitat for microorganisms, and many plant-associated bacteria, such as the pathogen Pseudomonas syringae, exhibit density-dependent survival on leaves by utilizing quorum sensing (QS). QS is often mediated by diffusible signals called N-acyl-homoserine lactones (AHLs), and P. syringae utilizes N-3-oxo-hexanoyl-dl-homoserine lactone (3OC6HSL) to control traits influencing epiphytic fitness and virulence. The P. syringae pathovar syringae B728a genome sequence revealed two putative AHL acylases, termed HacA (Psyr_1971) and HacB (Psyr_4858), which are N-terminal nucleophile hydrolases that inactivate AHLs by cleaving their amide bonds. HacA is a secreted AHL acylase that degrades only long-chain (C > or = 8) AHLs, while HacB is not secreted and degrades all tested AHLs. Targeted disruptions of hacA, hacB, and hacA and hacB together do not alter endogenous 3OC6HSL levels under the tested conditions. Surprisingly, targeted disruptions of hacA alone and hacA and hacB together confer complementable phenotypes that are very similar to autoaggregative phenotypes seen in other species. While AHL acylases might enable P. syringae B728a to degrade signals of competing species and block expression of their QS-dependent traits, these enzymes also play fundamental roles in biofilm formation.