cssi/SciSciGPT-SciSciNet huggingface dataset:
Immunization with temperature-sensitive mutants of Actinobacillus pleuropneumoniae induces protective hemolysin-neutralizing antibodies in mice.

The immunogenicity and protective potential of three temperature-sensitive mutants of Actinobacillus pleuropneumoniae were evaluated in mice with respect to antibodies against the capsular polysaccharide, lipopolysaccharide, outer membrane proteins, and hemolysin protein. Antibodies to the capsular polysaccharide and lipopolysaccharide could not be correlated with protection in the mice; there were no significant differences among the anti-capsular and anti-lipopolysaccharide antibody titers regardless of the severity of infection. Sera from mice immunized with the mutants and challenged with the wild type contained antibodies that reacted in immunoblots to four major outer membrane proteins (66, 39, 29, and 16 kDa) regardless of the severity of infection after challenge. Both the tight and coaster mutants synthesized and secreted the 105-kDa hemolysin protein exotoxin in vitro and in vivo; hemolysin protein neutralization titers and the blotting intensity of the sera, however, varied inversely with the severity of infection. Sera from mice surviving challenge with little to no lung involvement stained the hemolysin band more intensely and had significantly higher neutralization titers (P < 0.05) than sera from mice that either died or survived with severe pulmonary hemorrhage. These results confirm the importance of the hemolysin in pathogenesis and the need for including it in any vaccine preparation.
Intrinsic Luminescence of RbI and KI at 10°K

Emission and excitation spectra for the intrinsic luminescence of RbI and KI have been measured at 10\ifmmode^\circ\else\textdegree\fi{}K and compared with the exciton spectra of the two materials. Two emission bands appear at 3.31 and 4.15 eV for KI, and three for RbI at 2.64, 3.15, and 3.95 eV. Each band has a distinctive excitation spectrum. The high-energy band in each material appears to be connected either with interband transitions or excitation of the $n=2$ Wannier exciton line, while the low-energy emission is associated with absorption in or near the first exciton line. Evidence is given for the existence of a third component of the Wannier exciton series observed recently by Fischer and Hilsch.
Ecophysiological studies of Sonoran Desert plants : IV. Seasonal photosynthetic capacities of Acacia greggii and Cercidium microphyllum.

The gas exchange and water relations of two Sonoran Desert plants were measured throughout a 12 month period. Seasonal photosynthesis patterns of both species followed the seasonal variation in soil and plant water potential. Acacia greggii, a winter deciduous shrub, appears to be fall active since the day-long mean photosynthesis rate was maximum, i.e., 16 mg CO2 dm-2 h-1, at this time. Cercidium microphyllum, a drought deciduous and chlorophyllous-stemmed tree, also appears to be mainly fall active. For this species the day-long mean photosynthesis rate was not in excess of 14 mg CO2 dm-2 h-1. Both species initiate leaf production in the spring and neither experiences severe plant water stress. Seasonal minima of dawn plant water potential were-44 and-32 bars for the shrub and tree species, respectively. The two species differ slightly in their tolerance of heat and water stress, since foliated plants of Acacia greggii maintain summer gross photosynthesis.All of the aboveground organs for plants of C. microphyllum are capable of exogenous 14CO2 assimilation. This species appears to be unique in the magnitude of the photosynthetic production contributed by stems. Seasonal production by stems, leaves and flowers/fruits averaged 72, 24 and 4% of the total carbon gain per tree, respectively. Aboveground gross primary production was over 4.5-fold greater than aboveground net primary production. This difference between these two production estimates is likely due to the very small foliar biomass maintained throughout the year and the energy expenditure required to maintain the metabolically active cells of the chlorophyllous stems.
Jon Stewart Comes to Class: The Learning Effects of America (The Book) in Introduction to American Government Courses

This project posits that incorporating political humor into the classroom can have a positive effect on learning in higher education. Specifically, we present preliminary findings from a quasi-experiment in which a humorous, “mock” textbook titled America (The Book) (Stewart, Karlin, and Javerbaum 2004) was incorporated into Introduction to American Government curricula in conjunction with a standard textbook. Our hypothesis argues that humorous presentations of politics and government can enhance the learning process and increase test scores by way of Matthew Baum's (2003a) “gateway” or “incidental by-product” effects. Our empirical findings show no such learning effect. Our qualitative evidence, however, suggests that humor-based teaching is clearly more engaging and interesting for the students.
Diagnostic Approach to Infectious Respiratory Disorders

Infectious respiratory tract diseases in horses have been identified as one of the most common medical entities by veterinarians nationwide. Because of the contagious nature of certain pathogens involved in these diseases, early diagnosis is important to allow proper management and reduce the risk of exposure to other horses. The combination of general clinical signs, such as fever, anorexia, and depression, with specific respiratory signs such as tachypnea, nasal discharge, coughing, submandibular lymphadenopathy, and adventitial lung sounds should alert the veterinarian to a respiratory tract infection. The individual, herd, and farm histories are important in determining the contagious nature of the disease. Once the patient’s problems have been assessed and the differential diagnosis considered, a diagnostic workup is instituted. There are several diagnostic tools available to investigate a respiratory tract infection to achieve an accurate diagnosis in a timely manner. Generally, imaging techniques are performed at referral clinics, whereas samples of the respiratory tract can easily be collected in the field. Samples such as nasopharyngeal swab, transtracheal wash fluid, bronchoalveolar lavage fluid, or pleural fluid are routinely used for cytology and culture to detect the inciting pathogen(s). Molecular biological methods based on antigen (ELISA) or nucleic acid (PCR) detection have become more widespread in recent years, increasing the sensitivity and speed for detection of specific respiratory tract pathogens.
Does auditor tenure influence the reporting of conservative earnings

Abstract In this study, we examine the relation between auditor tenure and the reporting of conservative earnings. Using several measures of conservatism, we document a positive association between the conservatism in reported earnings and the length of the auditor–client relationship. We further document an increase in conservatism between short and medium tenure that does not deteriorate over long tenure. Collectively, the results imply lower conservatism for short auditor tenure, which suggests that mandating auditor rotation may have an adverse affect on the conservatism in reported earnings.
Reply [to “WIPP or is “how wet” the real question?”]

Spiegel and Anderson accept the hypothesis that the Salado Formation is saturated with brine. They go on to imply that brine in the WIPP underground will make disposing of wastes in the facility unwise. Groundwater hydrologists, when viewing Earth, start with two working hypotheses. First, all Earth materials within the crust to depths of at least 10 km have finite permeability, even though the permeability of some units might be quite low; i.e., no rocks are impermeable. Second, below the water table, all Earth materials are saturated with fluid, mostly groundwater, to a depth of at least 10 km.
Coronary artery calcium score and risk classification for coronary heart disease prediction.

Context The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. Objective To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. Design, Setting, and Participants CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1. Main Outcome Measures Incident CHD events. Results During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; P Conclusion In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.
Hall coefficient in brownian-like solutions

Abstract We calculate the Hall coefficient for an infinitely dilute electrolyte solution in which the ratio (solvent molecule mass/carrier particle mass) is small but finite. The first correction beyond the classical brownian motion result is found and shown to have a value identical to the brownian motion value.
Stability of functional partial differential equations

On etablit des conditions necessaires et suffisantes pour qu'une classe d'equations aux derivees partielles fonctionnelles soit asymptotiquement stable pour toutes les valeurs des retards
HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections

Abstract During the past three years, an epidemic of acquired immunodeficiency syndromes (AIDS) involving the presence of specific forms of cancer (notably Kaposi's sarcoma) and infection (e.g., pneumocystis carinii) ordinarily seen only in severely immunosupressed hosts has occurred among active homosexuals, Haitian immigrants, drug users, and hemophiliacs in large cities in the United States and elsewhere. An as yet unidentified viral agent is presumably the cause of the initial immunodeficiency and host genetic factors may influence the subsequent development of different clincial symptoms in different patients. We have previously reported that the HLA antigens DR5 and DR2 are associated with susceptibility to Kaposi's sarcoma (KS) in different Caucasian subpopulations. We now have also noted that AIDS patients with opportunistic infections have a normal frequency of DR2 and DR5 and a significantly increased frequency of DR3 and that the ultimate clinical expression of AIDS in patients with unexxplained lymphadenopathy may depend upon genetic factors associated with these particular DR types.
Therapists' orientation and defensive styles.

Summary.-A relationship was found bemeen therapists' orientations, defenses, and demographics. Three significant canonical variates were derived. The first was a group of men with doctoral degrees using reaction formation and projective style with little doubt or regression and oriented against marathons, physical contact, and expressive techniques. The second featured regression, displacement, doubt, projective sryle, regressive style, and repression. This group favored the therapeutic importance of therapist's personality and psychoanalytic orientation while minimizing feeling secure as a therapist and [he need for social adjustment. They had a relatively young, inexperienced, nondoctoral composition. The third variate emphasized rationalizing style and deemphasized doubt and projective sryle. A number of studies have suggested a relationship between the theoretical orientation and personality of psychotherapists (Angelos, 1977; Barton, 1978; Hart, 1982; Herron, 1978; Schwartz, 1978, Walton, 1978). The most recent study by Tremblay, Herron, and Schultz (1986) yielded a relationship between self-designated theoretical orientation and personality variables as measured on the Personal Orientation Inventory (Shostrom, 1964). The present study is an extension of the Tremblay, et al. work. Theoretical orientation was broadened to include therapists' orientation as measured by the Therapist Orientation Questionnaire (Sundland & Barker, 1962). A specific aspect of personality, defenses, was focused upon based on the finding of Singer and Luborsky (1978) that therapists' defense mechanisms significantly affect therapeutic behavior and that no attempt had been made previously to study the relationship between therapists' orientations and their defenses. This study hypothesized that there would be a significant relationship between therapists' orientation, defenses, and particular background variables. These variables included zge, sex, experience, degree, and license, variables that have been important in other investigations of therapists' attitudes and behavior (McDevitt, 1982; Parloff, Waskoff, & Wolfe, 1978; Strupp, 1978).
Glutamate is a cotransmitter in ventral midbrain dopamine neurons

Interactions between apparently separate dopaminergic and glutamatergic pathways figure prominently in the pathophysiology of Parkinson's Disease. So it is surprising that the ventral midbrain dopamine neurons, which give rise to the dopaminergic pathway, may themselves also be glutamatergic. We have addressed this idea in both rat and monkey brain and found that most ventral midbrain dopamine neurons exhibit glutamate immunoreactivity. We used postnatal cell culture to examine ventral midbrain dopamine neurons more closely. In vitro most dopamine neurons exhibit glutamate immunoreactivity, as well as immunoreactivity for phosphate-activated glutaminase, the enzyme principally responsible for the synthesis of neurotransmitter glutamate; inhibition of glutaminase reduces glutamate staining. In single cell microcultures, dopamine neurons make both dopaminergic and glutamatergic synaptic varicosities. Stimulation of individual dopamine neurons evokes a fast excitatory synaptic response mediated by glutamate; it also evokes dopamine release that inhibits the excitatory response via presynaptic D2 receptors. Thus, dopamine neurons appear to exert rapid synaptic actions via their glutamatergic synapses and slower modulatory actions via their dopaminergic synapses, including possibly inhibition of their own glutamatergic synapses. So, in the setting of dopamine neuron demise, there will be a loss of both dopaminergic and glutamatergic inputs to the striatum; furthermore, glutamate released by dopamine neurons may contribute to an excitotoxic cascade and the death of neighboring dopamine neurons.
Regional left ventricular wall thickening. Relation to regional uptake of 18fluorodeoxyglucose and 201Tl in patients with chronic coronary artery disease and left ventricular dysfunction.

BACKGROUNDIn previous studies comparing regional 201Tl (201Tl) and 18fluorodeoxyglucose (FDG) activity in patients with chronic coronary artery disease and left ventricular dysfunction, we hypothesized that regions with mild-to-moderate reduction in FDG activity and regions with mild-to-moderate irreversible 201Tl defects after 3- to 4-hour redistribution represent viable myocardium. In the present study, regional FDG and 201Tl activities were compared with regional systolic wall thickening by gated magnetic resonance imaging (MRI) to confirm the presence of viable myocardium in these territories.METHODS AND RESULTSTwenty-five patients with chronic stable coronary artery disease and left ventricular dysfunction (ejection fraction, 28 +/- 10) underwent exercise 201Tl tomographic imaging (SPECT), using a reinjection protocol, positron emission tomography (PET) with FDG and H2(15)O, and gated MRI. Matched SPECT, PET, and MRI tomograms were analyzed. From the PET data, 105 regions had matched reduction in FDG...
Changes in hemolymph properties accompanying heat death in the desert tenebrionid beetle Centrioptera muricata

Abstract 1. 1. Fifty minutes were required to kill an entire group of Centrioptera muricata at 47°C. 2. 2. Hemolymph osmotic pressure rose in heat-killed animals (controls, 350 m-osmoles/l.; treated, 475 m-osmoles/l.), while blood pH decreased (controls, 6·92; treated, 6·36). 3. 3. Both uric acid (controls, 12 mg/100 ml; treated, 21 mg/100 ml) and lactic acid controls, 7 mg/100 ml; treated, 45·5 mg/100 ml) increased significantly during heat death. 4. 4. Hemal sodium decreased (controls, 97 m-moles/l.; treated, 60 m-moles/l.) and potassium increased (controls, 21 m-moles/l.; treated, 105 m-moles/l.) in heat-killed beetles. 5. 5. Muscle tissue cation concentration changes were the inverse of those in the hemolymph.
Evaluation of Electronic Coupling in Transition-Metal Systems Using DFT: Application to the Hexa-Aquo Ferric−Ferrous Redox Couple

We present a density-functional theory (DFT) approach, with fractionally occupied orbitals, for studying the prototypical ferric-ferrous electron-transfer (ET) process in liquid water. We use a recently developed ab initio method to calculate the transfer integral (also named electronic-coupling or ET matrix element) between the solvated ions. The computed transfer integral is combined with previous ab initio values of the reorganization energy, within the framework of Marcus' theory, to estimate the rate of the electron self-exchange reaction. The self-interaction correction incorporated (through an appropriate treatment of the electronic correlation effects) into a Hubbard U extension to the DFT scheme leads to a theoretical value of the ET rate relatively close to an experimental estimate from kinetic measurements. The use of fractional occupation numbers (FON) turned out to be crucial for achieving convergence in most self-consistent calculations because of the open-shell d-multiplet electronic structure of each iron ion and the near degeneracy of the redox groups involved. We provide a theoretical justification for the FON approach, which allows a description of the chemical potential and orbital relaxation, and possible extension to other transition-metal redox systems. Accordingly, the methodology developed in this paper, which rests on a suitable combination of Hubbard U correction and a FON approach to DFT, seems to offer a fruitful approach for the quantitative description of ET reactions in biochemical systems.
Evaluation of policies to promote physical activity in afterschool programs: are we meeting current benchmarks?

Abstract Background Policies now recommend afterschool programs (ASP, 3–6 pm) provide children a minimum amount of physical activity daily. We examined the extent to which children attending ASPs meet existing national and state-level policies that specify expected levels of physical activity (PA). Methods Accelerometer-derived physical activity (light and moderate-to-vigorous, MVPA) of 253 children (5–13 years) was compared to policies that recommend varying amounts of PA children should achieve during an ASP. Results The proportion of children achieving a policy ranged from 0.0% (California 60 min MVPA and North Carolina 20% of daily program time devoted to MVPA), 1.2% (California 30 min MVPA), to 48.2% (National Afterschool Association 30 min light plus MVPA). Random effects logistic models indicated boys (odds ratio [OR] range 2.0 to 6.27) and children from a minority background (Black/Hispanic, OR range 1.87 to 3.98) were more likely to achieve a recommended level of physical activity, in comparison to girls and White children. Neither age nor BMI were related to achieving a policy. Conclusions The PA of children attending ASP falls below policy recommended levels; however, these policies were developed in absence of data on expected PA levels during ASPs. Thus, concerted effort towards building a stronger ASP evidence-base for policy refinement is required.
Impact of Experimental Factors in Soil Phosphorus Tests: Shaking Vessel, Filtration, and Centrifugation

In the analysis of Mehlich III, deionized water (DI), Bray, and Olsen soil phosphorus (P) extractions, variations in shaking vessel, centrifugation, and filter paper result in different soil test P (STP) values. Of these factors, centrifugation and type of filtration were found to have the greatest impact on the results of water‐extractable P (WEP), that is, extraction with DI. Further spectrophotometric experiments demonstrated that centrifugation removed fine soil particles from the extract. Without the commonly used 0.45‐µm filters or centrifugation, these particles scatter the radiation of the spectrometer. During colorimetric analysis, this scattering of radiation will be perceived as absorption. This misperception results in a falsely high STP. In WEP analysis with only qualitative filtration, the scattering is very significant and appears to be due to limited aggregation of soil particles in the low ionic strength extract.
Four-coordinate, planar Ru(II). A triplet state as a response to a 14-valence electron configuration

The ligand (tBu2PCH2SiMe2)2N1- (PNP) in [PNP]RuCl leads to an intermediate spin ground state, S = 1, which has been characterized by NMR and X-ray diffraction as having a planar structure. This spin state is attributed in part to N → Ru π donation. DFT calculations confirm that the singlet state lies higher in energy and is nonplanar. The molecule is converted to a diamagnetic product by addition of 2 mol of PhCN. The half-filled orbitals of the S = 1 state are suggested to be the reason agostic interactions do not compensate for the 14-valence electron count.
Quantifying and evaluating the space overhead for alternative C++ memory layouts

This paper develops a formalism that precisely characterizes when class tables are required for C++ memory layouts. A memory layout is a particular choice of data structures for implementing run-time support for object-oriented languages. We use this formalism to quantify and evaluate, on a set of benchmarks, the space overhead for a set of C++ memory layouts. In particular, this paper studies the space overhead due to three language features: virtual dispatch, virtual inheritance, and dynamic typing. To date, there has been no scientific quantification or evaluation of C++ memory layouts. Our approach can help C++ implementors. This work has already influenced the memory layout design choices in IBM's Visual Age C++ V5 compiler.Applying our approach to a set of five benchmarks, we demonstrate that the impact of object-oriented space overhead can vary dramatically between applications (ranging from 0.42% to 99.79% for our benchmarks). In particular, applications whose object space is dominated by instances of classes that heavily use object-oriented language features will be significantly impacted by the choice of a memory layout.
TIARA analysis of tritium inventory in Li2O

Abstract The TIARA code has been developed to predict tritium inventory in Li2O breeder ceramic and to predict purge exit flow rate and composition under steady-state operating conditions. Inventory predictions are based on models for bulk diffusion, surface desorption, solubility and precipitation. Parameters for these models are determined from the results of laboratory annealing studies on unirradiated and irradiated Li2O and from a limited number (2) of inventory data measured after in-reactor purge flow testing. The remaining inventory data points (18) are used for code validation. In the validation exercise, models and model parameters are fixed prior to running the validation cases to assess how well TIARA predictions agree with data. On average, the TIARA predictions are in excellent agreement with the inventory data from the following in-reactor tests: EXOTIC-2, SIBELIUS, VOM-15H, CRITIC-1, BEATRIX-II (Phase 1) thin ring, and BEATRIX-II (Phase 1) thick pellet. Thus, TIARA can be used with a reasonable degree of confidence for design analysis over a broad range of fabrication variables and steady-state operating conditions.
NMR demonstration of the rearrangement of 15N-labelled p-anisolediazonium ion

Abstract The conversion of p -CH 3 OC 6 H 4 N 2 + to the hydrazine and then to the benzaldehyde hydrazone gave a stable substance in which the proton NMR could be used to locate a 15 N label. In contrast to an earlier study on benzenediazonium ion by a similar method, this analysis showed that the α- 15 N label in the diazonium salt migrates during hydrolysis to the β position to about the extent indicated by a degradative method.
Asian Financial Integration: Trends and Interruptions

The paper compares trends in financial integration within Asia with those in industrialized countries and other regional groups. Declines in cross-country dispersion in equity returns and interest rates suggest increased Asian integration, with the process interrupted by crises and global volatility. Cross-border equity and bond holdings have also increased, but Asian countries remain considerably more financially integrated with major countries outside the region than with those within the region. The paper also discusses whether potential benefits of regional financial integration, such as increased risk-sharing and stability of the investor base, have materialized.
CC genotype donors for the interleukin-28B single nucleotide polymorphism are associated with better outcomes in hepatitis C after liver transplant.

Hepatitis C (HCV) is the most common indication for liver transplant (LT) in the United States. HCV recurrence is universal following transplantation and leads to allograft failure in about ten percent of recipients by the fifth postoperative year.(1) In the LT setting, the factors associated with the more aggressive disease progression are complex and multi-factorial, including recipient, donor and viral components. It is likely that host immune responses, both innate and adaptive, play a pivotal role in the clearance of viral infections, ongoing liver damage, and response to antiviral therapy. Therefore, defining the mechanisms of host immune system interaction with HCV after LT is critical for understanding HCV-related allograft injury and response to antiviral treatment. This knowledge is also vital to guide immunosuppression strategies that minimize HCV disease progression and increase the overall survival of the graft. Although multiple host factors have been implicated in HCV disease progression, interleukin-28B (IL-28B) single nucleotide polymorphism (SNP) on the chromosome 19, rs12979860, seems to be strongly associated with HCV clearance and treatment response.(2) So far, this SNP is the strongest predictor for sustained viral response (SVR) to interferon (IFN)-based therapy in the HCV population. The C allele is the most frequent allele in the white population associated with SVR. Patients with CC genotype have a two-fold chance of SVR compared to patients with T alleles.(3) In a recent study of IL-28B SNP in HCV LT recipients and donors, IL-28B genotypes predicted an SVR with 83% sensitivity and 82% specificity.(4) In addition, IL-28B recipient genotype was predictive of fibrosis, with the TT allele associated with more rapid fibrosis. Similar to interferon-based therapy in non-transplant patients, the CC genotype in either recipient or donor has been associated with increased rate of SVR.(5–7) Emerging evidence suggests that both donor and recipient IL-28B SNP background may play an important role in post-transplant HCV recurrence and its response to current therapy (8), but the available data is limited. Recently, others have reported that follow up liver biopsies may not be suitable for IL-28B determination.(9) Therefore, the objective of our study was to examine the role of IL-28B polymorphism of both donor and recipient livers in HCV disease progression after LT and its response to interferon-based therapy in a well characterized group of transplant patients.
The evolution of alternative biofilms in an opportunistic fungal pathogen: an explanation for how new signal transduction pathways may evolve

The evolution of two types of biofilms, one pathogenic and one sexual, is unique for Candidaalbicans, the most pervasive fungal pathogen in humans. When in the predominant a/α configuration, cells can form a traditional biofilm made up of a basal layer of yeast cells and an extensive upper layer of hyphae and dense matrix. This a/α biofilm is impermeable, impenetrable and drug-resistant. When in the a/a or α/α configuration, white cells form a biofilm of similar architecture, but which is permeable, penetrable and drug-susceptible. The latter biofilm facilitates mating between minority opaque a/a and α/α cells. The two biofilms are regulated by different signal transduction pathways that provide clues for deducing not only how the sexual a/a or α/α biofilms evolved, but how the pathogenic a/α biofilm evolved as well. In the deduced evolutionary models, regulatory molecules, including components of the signal transduction pathways and transcription factors, are recruited from conserved pathways. The evolution of the alternative biofilms of C. albicans provides a rare glimpse into how new regulatory pathways may evolve in general.
Where thiazolidinediones will fit.

Individuals with type 2 diabetes have two defects: insulin resistance, which occurs in the first stages of disease progression, and pancreatic beta-cell failure, which occurs later in the disease. Insulin resistance is the major pathological defect. During the course of the disease, insulin levels are initially elevated to compensate for the increased insulin resistance and then decline as the disease progresses and beta-cells become less responsive. It is necessary to change antidiabetic therapies to address this progression. Current management of type 2 diabetes follows a stepwise treatment program of diet and exercise, monotherapy with oral antidiabetic agents, combination oral therapy and, ultimately, combination therapy with insulin to control blood glucose levels. While control of blood glucose will reduce the risk of microvascular complications, such as microalbuminuria and retinopathy, the incidence of macrovascular complications is not significantly reduced. The introduction of the thiazolidinediones (TZDs) or 'glitazones', a class of agents that offer effective glycemic control and work through the reduction of insulin resistance, offers a new strategy in the management of this condition. These agents have beneficial effects on the pancreatic beta-cell and, in addition, may have potential benefits on the macrovascular complications that commonly occur in these patients.
Reduced biological effectiveness of orally administered L-thyroxine in the rat in the presence of blood plasma.

SummaryThe efficiency of absorption of an orally administered dose of L-thyroxine (L-T4) in saline was found to be 48% compared to subcutaneous administration using the thyroid secretion rate (TSR) as an index. The addition of rat blood plasma to the L-T4 before oral administration reduced its biological effectiveness to 34%, a significant reduction of 30% in comparison to oral L-T4. These data suggest that the reduced biological effectiveness of oral L-T4 may be due, in part, to a plasma-binding protein (TBP) in the intestines to which the L-T4 becomes bound and fails to be absorbed.
Gli1 regulates the proliferation and differentiation of HSCs and myeloid progenitors

The Hedgehog (Hh) pathway is essential for normal embryonic development and tissue repair. The role of Hh signaling in hematopoiesis has been studied primarily by modulating the activity of Patched and Smoothened, but results have been conflicting. Some studies demonstrate a requirement for pathway activity in hematopoiesis, whereas others report that it is dispensable. Hh activity converges on the Gli transcription factors, but the specific role of these downstream effectors in hematopoiesis has not been reported. We have analyzed hematopoietic stem cell (HSC) and progenitor function in mice with a homozygous deletion of Gli1 (Gli1(null)). Gli1(null) mice have more long-term HSCs that are more quiescent and show increased engraftment after transplantation. In contrast, myeloid development is adversely affected with decreased in vitro colony formation, decreased in vivo response to granulocyte colony-stimulating factor (G-CSF), and impaired leukocyte recovery after chemotherapy. Levels of the proto-oncogene Cyclin D1 are reduced in Gli1(null) mice and may explain the loss of proliferation seen in HSCs and progenitor cells. These data demonstrate that Gli1 regulates normal and stress hematopoiesis. Moreover, they suggest that Gli1 and Smoothened may not be functionally redundant, and direct GLI1 inhibitors may be needed to effectively block HH/GLI1 activity in human disease.
Neuropharmacologic investigations of the lower urinary tract

The urinary bladder is a smooth muscle organ whose function is to collect and store urine at low intravesical pressures, and then to periodically expel the urine via a highly coordinated sustained contraction. Classically, the control of bladder function is through the autonomic nervous system. During bladder filling (at least in animal models), the sympathetic nervous system is active and this produces an increase in tension of the bladder base and urethra via activation of alpha-adrenergic receptors; and the relaxation of the bladder body via activation of beta-adrenergic receptors. In addition, sympathetic activity inhibits parasympathetic ganglionic transmission via postsynaptic sympathetic fibers which act upon alpha-2 type receptors located in the ganglion. Bladder emptying is mediated via the parasympathetic system with the activation of primarily muscarinic cholinergic receptors (and purinergic receptors in various animal species). In general, bladder function is dependent on the state of the neuronal innervation, the structure of the organ as a whole, the contractile response of the smooth muscle elements. Experimentally, an alteration in one factor will induce substantial adaptive changes in the other two. In this review, we will present some current concepts of urophysiology, uropharmacology, and uropathology; and how some of this current information may be helpful in the development of specific pharmacological agents directed specifically at the urogenital system.
Cross-sensitization of histamine-independent itch in mouse primary sensory neurons

Abstract Overexpression of pruritogens and their precursors may contribute to the sensitization of histamine-dependent and –independent itch-signaling pathways in chronic itch. We presently investigated self- and cross-sensitization of scratching behavior elicited by various pruritogens, and their effects on primary sensory neurons. The MrgprC11 agonist BAM8-22 exhibited self- and reciprocal cross-sensitization of scratching evoked by the protease-activated receptor-2 (PAR-2) agonist SLIGRL. The MrgprA3 agonist chloroquine unidirectionally cross-sensitized BAM8-22-evoked scratching. Histamine unidirectionally cross-sensitized scratching evoked by chloroquine and BAM8-22. SLIGRL unidirectionally cross-sensitized scratching evoked by chloroquine. Dorsal root ganglion (DRG) cells responded to various combinations of pruritogens and algogens. Neither chloroquine, BAM8-22 nor histamine had any effect on responses of DRG cell responses to subsequently applied pruritogens, implying that their behavioral self- and cross-sensitization effects are mediated indirectly. SLIGRL unilaterally cross-sensitized responses of DRG cells to chloroquine and BAM8-22, consistent with the behavioral data. These results indicate that unidirectional cross-sensitization of histamine-independent itch-signaling pathways might occur at a peripheral site through PAR-2. PAR-2 expressed in pruriceptive nerve endings is a potential target to reduce sensitization associated with chronic itch.
Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury.

Abstract Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of such compounds is still limited. In this study ethylene-vinyl acetate copolymer matrices containing standard and modified heparin were placed adjacent to rat carotid arteries at the time of balloon dendothelialization. After 14 days arterial occlusion by smooth muscle cell proliferation was defined. Matrix delivery of both heparin compounds effectively diminished this proliferation in comparison to controls without producing systemic anticoagulation or side effects. In addition, this mode of therapy appeared more effective than the administration of the same agents by either intravenous pumps or heparin/polymer matrices placed in a subcutaneous site distant from the injured carotid artery. Thus, heparin's inhibition of smooth muscle cell proliferation after vascular injury might be most effective within the microenvironment of the injured vessel wall, and the accelerated atherosclerosis or restenosis that often follows angioplasty and other vascular interventions might best be treated with site-specific therapy.
Qualitative and quantitative risk assessment

Abstract Risk assessment and HACCP are related, but fundamentally different processes. Four major elements of risk assessment are commonly described (hazard identification; exposure assessment; dose-response assessment or hazard characterization; and risk characterization). Some similarities exist between the inputs for the first elements of risk assessment (hazard identification) and HACCP (hazard analysis). However, HACCP involves the identification of critical control points of a process for the purpose of producing a ‘safe’ product, and thus is essentially a risk management procedure that does not estimate risk with attendant uncertainty as in the formal structured procedure described for risk assessment. For quantitative models in microbial risk assessment, exposure assessment requires data for pathogen occurrence, density or level, and distribution in foods and live animals, parameters for growth and decline, and consumption information. A crucial difference between chemical and microbial risk assessment is that for the latter, exposure models must account for pathogen growth and deactivation, termed predictive microbiology. This field has emphasized prediction of the expected changes in a population of organisms and is extended by an example accounting for the stochastic or random variability of microbial growth in a given circumstance. Dose-response assessment, the third element of risk assessment, is the crucial link between exposure in food to adverse human health outcomes. Data, from controlled human studies with healthy adult volunteers to describe dose-response relationships, are limited. Differences between human sub-populations may be inferred from animal studies, based on a common mechanism, such as the observed pre-disposition of antibiotic-treated animals to subsequent challenges with enteric pathogens. Professional organizations, such as the Society for Risk Analysis, can greatly assist governments, industry, academia, and stakeholders in scrutinizing the risk analysis processes of risk assessment, risk management, and risk communication.
Timing of endoscopy in gastrointestinal bleeding

Background: In gastrointestinal bleeding, a physician often has to make a decision between two possible choices. Endoscopic management of the bleeding could be initiated immediately, or it could be delayed until the patient has become haemodynamically stable or the conditions for a successful endoscopy have otherwise improved. Objective: The present article serves to present such situations and highlights their characteristic features. Methods: The choice between immediate and delayed endoscopy is analysed in terms of a decision tree, comparing the expected results of the two management alternatives. The decision tree is applied to three different clinical scenarios associated with gastrointestinal bleeding, where performing endoscopy later rather than sooner represents the preferred management option. Results: The work up of chronic iron-deficient anaemia in patients with serious cardiac problems should be deferred until resolution of their reduced cardiovascular status. It is also recommended that, even in acute bleeding, endoscopy is deferred until the patient has become haemodynamically stable. Lastly, for nonemergency treatment of oesophageal varices bleeding, a long rather than short interval between consecutive banding sessions appears more beneficial. Conclusions: The results illustrate how to use threshold analysis as a simple bedside tool to solve seemingly complex decisions associated with management of gastrointestinal bleeding.
EFFECTS OF CHRONIC WASTING DISEASE ON REPRODUCTION AND FAWN HARVEST VULNERABILITY IN WISCONSIN WHITE-TAILED DEER

Chronic wasting disease (CWD) is a fatal, transmissible spongiform encephalopathy that affects free-ranging and captive North American cervids. Although the impacts of CWD on cervid survival have been documented, little is known about the disease impacts on reproduction and recruitment. We used genetic methods and harvest data (2002–04) to reconstruct parentage for a cohort of white-tailed deer (Odocoileus virginianus) fawns born in spring 2002 and evaluate the effects of CWD infection on reproduction and fawn harvest vulnerability. There was no difference between CWD-positive and CWD-negative male deer in the probability of being a parent. However, CWD-positive females were more likely to be parents than CWD-negative females. Because our results are based on harvested animals, we evaluated the hypothesis that higher parentage rates occurred because fawns with CWD-positive mothers were more vulnerable to harvest. Male fawns with CWD-positive mothers were harvested earlier (>1 mo relative to their mother’s...
Automatic Tractography Segmentation Using a High-Dimensional White Matter Atlas

We propose a new white matter atlas creation method that learns a model of the common white matter structures present in a group of subjects. We demonstrate that our atlas creation method, which is based on group spectral clustering of tractography, discovers structures corresponding to expected white matter anatomy such as the corpus callosum, uncinate fasciculus, cingulum bundles, arcuate fasciculus, and corona radiata. The white matter clusters are augmented with expert anatomical labels and stored in a new type of atlas that we call a high-dimensional white matter atlas. We then show how to perform automatic segmentation of tractography from novel subjects by extending the spectral clustering solution, stored in the atlas, using the Nystrom method. We present results regarding the stability of our method and parameter choices. Finally we give results from an atlas creation and automatic segmentation experiment. We demonstrate that our automatic tractography segmentation identifies corresponding white matter regions across hemispheres and across subjects, enabling group comparison of white matter anatomy.
Social power and communication in small groups

“Social Power” was defined and manipulated, in the context of 5-person interactim, as the conditional probability that a communicative act would succeed once it had been initiated. Five subjects sent content-free signals to each other, which they were instructed to accumulate for an eventual payoff of 1 cent per signal received. The only way a subject could control his receipts was by varying his own sending behavior. Unknown to the subjects, the probability (π) that their signals would reach their intended target was controlled by the experimenter. Ten different patterns of π values in five person groups were studied: .3.5.5.5.7, .3.4.5.6.7, .3.3.5.7.7, .1.5.5.5.9, .1.3.5.7.9, .1.1.1.1.5, .1.5.5.5.5, .5.5.5.5.9, 5.9.9.9.9. These patterns provided variations in average group power (π) and variance of group power (σπ2). The results showed that a subject's receipts depended in a simple linear manner in his own π value relative to π. If an individual's share of the receipts is designated P and there are N individuals in the group then the equation P = (1/N) + b(N - 2/N - 1) (π - π) provided a reasonable fit to the receipt data. This result follows from the more molecular assumption that each individual asymptotically sends signals to another with a probability that depends linearly on the other's relative power position among the possible targets. If Pij is the probability that i sends to j and πi is the mean power of subjects other than i in the group, then Pij = (1/N - 1) + b(πj - πi). The degree of differentiation in receipts in a group thus depends on the slope b; here b = .169 provided the best fit to the individual sending proportions. The value (N - 2/N - 1)b = .126 for receipt data was compared with a slope of .284 found in a previous study with three person groups, supporting a conjecture that differentiation would decline with size of the group.
Deflection performance of a bi-directional distributed polymeric piezoelectric micromotor

Distributed piezoelectric micromotor architectures have great potential because they combine the advantages of piezoelectric micromotors with the advantages of distributed architectures. However, to use a distributed architecture paradigm for piezoelectric micromotors, a basic motor building block is needed. To meet this need a piezoelectric micromotor building block, called a C-block, was developed. These C-blocks can be combined together in a variety of distributed architectures to expand their capabilities. This paper introduces a basic polymeric piezoelectric C-block micromotor design and a serial C-block micromotor architecture that demonstrates increased deflection capabilities. For both micromotor designs, simple manufacturing steps are described and analytical deflection models are presented. These micromotors were experimentally tested with prototypes ranging in size from a few millimeters to a few centimeters in scale. Results for an individual C-block micromotor and a serial C-block micromotor are presented. These results demonstrate the accuracy of the models and the feasibility of designing and fabricating polymeric piezoelectric micromotor architectures.
Network Connectivity of VANETs in Urban Areas

Modeling complicated vehicular traffic behavior and the associated network connectivity in urban areas has been a challenging task for the past several years. In this paper, we study how intersections and two-dimensional road topology affect the connectivity behavior of traffic in urban areas. To better understand this phenomenon, we investigate both static and dynamic aspects of network connectivity in urban areas and analyze several characteristics such as network connectivity, path redundancy, re-healing time, etc. Based on a comprehensive study, we make several key observations and provide insights into the behavior of network connectivity whereby critical routing problems are identified and suggestions are made for the key components of an appropriate routing protocol for different vehicular ad hoc network (VANET) applications in urban areas.