CRF1 Receptor Activation Increases the Response of Neurons in the Basolateral Nucleus of the Amygdala to Afferent Stimulation

The basolateral nucleus (BLA) of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF). Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatments for stress-related illnesses such as post-traumatic stress disorder

The flat phase of fixed-connectivity membranes

The statistical mechanics of flexible two-dimensional surfaces (membranes) appears in a wide variety of physical settings. In this talk we discuss the simplest case of fixed-connectivity surfaces. We first review the current theoretical understanding of the remarkable flat phase of such membranes. We then summarize the results of a recent large scale Monte Carlo simulation of the simplest conceivable discrete realization of this system \cite{BCFTA}. We verify the existence of long-range order, determine the associated critical exponents of the flat phase and compare the results to the predictions of various theoretical models.Comment: 7 pages, 5 figures, 3 tables. LaTeX w/epscrc2.sty, combined contribution of M. Falcioni and M. Bowick to LATTICE96(gravity), to appear in Nucl. Phys. B (proc. suppl.

An Investigation of the Steady-State Pharmacokinetics of Oral Valacyclovir in Immunocompromised Children

Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (±SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11±1.41 and 5.19±1.96 μg/mL, respectively. Corresponding single dose area-under-curve values were 12.14±6.60 and 14.49±4.69h×μg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discusse

Exact sampling from non-attractive distributions using summary states

Propp and Wilson's method of coupling from the past allows one to efficiently generate exact samples from attractive statistical distributions (e.g., the ferromagnetic Ising model). This method may be generalized to non-attractive distributions by the use of summary states, as first described by Huber. Using this method, we present exact samples from a frustrated antiferromagnetic triangular Ising model and the antiferromagnetic q=3 Potts model. We discuss the advantages and limitations of the method of summary states for practical sampling, paying particular attention to the slowing down of the algorithm at low temperature. In particular, we show that such a slowing down can occur in the absence of a physical phase transition.Comment: 5 pages, 6 EPS figures, REVTeX; additional information at http://wol.ra.phy.cam.ac.uk/mackay/exac

Heavy Quark Effective Theory beyond Perturbation Theory: Renormalons, the Pole Mass and the Residual Mass Term

We study the asymptotic behaviour of the perturbative series in the heavy quark effective theory (HQET) using the $1/N_f$ expansion. We find that this theory suffers from an {\it ultraviolet} renormalon problem, corresponding to a non-Borel-summable behaviour of perturbation series in large orders, and leading to a principal nonperturbative ambiguity in its definition. This ambiguity is related to an {\it infrared} renormalon in the pole mass and can be understood as the necessity to include the residual mass term $\delta m$ in the definition of HQET, which must be considered as ambiguous (and possibly complex), and is required to cancel the ultraviolet renormalon singularity generated by the perturbative expansion. The formal status of $\delta m$ is thus identical to that of condensates in the conventional short-distance expansion of correlation functions in QCD. The status of the pole mass of a heavy quark, the operator product expansion for inclusive decays, and QCD sum rules in the HQET are discussed in this context.Comment: LATEX, 43 pages, 6 figures appended as uu-encoded file, MPI-PhT/94-9, (Text as to appear in NPB, typing errors corrected [Eq.(3.24),(3.26)], some statements in Sect.5 more precise

Acute effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs

Funding: Silvia V. Conde declares that Galvani Bioelectronics provided funds to support their work associated with Type 2 diabetic project.New Findings: What is the central question of this study? What are the effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity in vivo and how do carotid body chemoreceptor stimulation-mediated cardiorespiratory responses in beagle dogs compare during euglycaemia and insulin-induced hypoglycaemia? What is the main finding and its importance? Intracarotid insulin administration leads to sustained increase in carotid body chemoreceptor activity and respiratory response with significant cardiovascular effects. Insulin-induced hypoglycaemia exacerbated NaCN-mediated carotid body chemoreceptor activity and respiratory response with enhanced cardiovascular reflex response. These findings suggest that insulin-induced hypoglycaemia augments the carotid body chemoreceptors to initiate the adaptive counter-regulatory responses to restore the normoglycaemic condition. Abstract: The carotid body chemoreceptors (CBC) play an important role in the adaptive counter-regulatory response to hypoglycaemia by evoking the CBC-mediated sympathetic neuronal system to restore normoglycaemia. Ex vivo studies have shown varied responses of insulin-induced hypoglycaemia on CBC function, and several in vivo studies have indirectly established the role of CBCs in restoring normoglycaemia in both animals and humans. However, a direct effect of insulin and/or insulin-induced hypoglycaemia on CBC activity is not established in animal models. Therefore, the aim of this study was to evaluate in vivo effects of insulin and insulin-induced hypoglycaemia on CBC activity and cardiorespiration in a preclinical large animal model. The carotid sinus nerve (CSN) activity and cardiorespiratory responses to sodium cyanide (NaCN; 25 µg/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5–100 µU/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation ((Formula presented.) E) with significant (P < 0.0001) effects on heart rate and blood pressure. Insulin-mediated effects on CSN and cardiorespiration were sustained and the change in (Formula presented.) E was driven by tidal volume only. Insulin significantly (P < 0.0001) lowered blood glucose level. NaCN-mediated CSN activity and (Formula presented.) E were significantly (P < 0.0001) augmented during insulin-induced hypoglycaemia. The augmented (Formula presented.) E was primarily driven by respiratory frequency and partially by tidal volume. The cardiovascular reflex response mediated through CBC stimulation was significantly (P < 0.0001) exacerbated during insulin-induced hypoglycaemia. Collectively, these results demonstrate direct effects of insulin and insulin-induced hypoglycaemia on CBC chemosensitivity to potentiate CBC-mediated neuroregulatory pathways to initiate adaptive neuroendocrine and cardiorespiratory counter-regulatory responses to restore normoglycaemia.publishersversionepub_ahead_of_prin

Frequency and patterns of early recanalization after vasectomy

BACKGROUND: Our understanding of early post-vasectomy recanalization is limited to histopathological studies. The objective of this study was to estimate the frequency and to describe semen analysis patterns of early recanalization after vasectomy. METHODS: Charts displaying serial post-vasectomy semen analyses were created using the semen analysis results from 826 and 389 men participating in a randomized trial of fascial interposition (FI) and an observational study of cautery, respectively. In the FI trial, participants were randomly allocated to vas occlusion by ligation and excision with or without FI. In the cautery study, sites used their usual cautery occlusion technique, two with and two without FI. Presumed early recanalization was based on the assessment of individual semen analysis charts by three independent reviewers. Discrepancies were resolved by consensus. RESULTS: Presumed early recanalization was characterized by a very low sperm concentration within two weeks after vasectomy followed by return to large numbers of sperm over the next few weeks. The overall proportion of men with presumed early recanalization was 13% (95% CI 12%–15%). The risk was highest with ligation and excision without FI (25%) and lowest for thermal cautery with FI (0%). The highest proportion of presumed early recanalization was observed among men classified as vasectomy failures. CONCLUSION: Early recanalization, occurring within the first weeks after vasectomy, is more common than generally recognized. Its frequency depends on the occlusion technique performed

High-Resolution Chandra X-Ray Imaging And Spectroscopy Of The Sigma Orionis Cluster

We present results of a 90 ks Chandra X-ray observation of the young sigma Orionis cluster ( age similar to 3 Myr) obtained with the HETGS. We use the high-resolution grating spectrum and moderate-resolution CCD spectrum of the massive central star sigma Ori AB (O9.5 V + B0.5 V) to test wind shock theories of X-ray emission and also analyze the high spatial resolution zero-order ACIS-S image of the central cluster region. Chandra detected 42 X-ray sources on the primary CCD (ACIS-S3). All but five have near-IR or optical counterparts and about one-fourth are variable. Notable high-mass stellar detections are sigma Ori AB, the magnetic B star sigma Ori E, and the B5 V binary HD 37525. Most of the other detections have properties consistent with lower mass K- or M-type stars. We present the first X-ray spectrum of the unusual infrared source IRS 1, located approximate to 3 \u27\u27 north of sigma Ori AB. Its X-ray properties and elongated mid-IR morphology suggest that it is an embedded low-mass T Tauri star whose disk/envelope is being photoevaporated by sigma Ori AB. We focus on the radiative wind shock interpretation of the soft luminous X-ray emission from sigma Ori AB, but also consider possible alternatives including magnetically confined wind shocks and colliding wind shocks. Its emission lines show no significant asymmetries or centroid shifts and are moderately broadened to HWHM approximate to 264 km s(-1), or one-fourth the terminal wind speed. Forbidden lines in He-like ions are formally undetected, implying strong UV suppression. The Mg XI triplet forms in the wind acceleration zone within one stellar radius above the surface. These X-ray properties are consistent in several respects with the predictions of radiative wind shock theory for an optically thin wind, but explaining the narrow line widths presents a challenge to the theory

Bayesian hierarchical clustering for studying cancer gene expression data with unknown statistics

Clustering analysis is an important tool in studying gene expression data. The Bayesian hierarchical clustering (BHC) algorithm can automatically infer the number of clusters and uses Bayesian model selection to improve clustering quality. In this paper, we present an extension of the BHC algorithm. Our Gaussian BHC (GBHC) algorithm represents data as a mixture of Gaussian distributions. It uses normal-gamma distribution as a conjugate prior on the mean and precision of each of the Gaussian components. We tested GBHC over 11 cancer and 3 synthetic datasets. The results on cancer datasets show that in sample clustering, GBHC on average produces a clustering partition that is more concordant with the ground truth than those obtained from other commonly used algorithms. Furthermore, GBHC frequently infers the number of clusters that is often close to the ground truth. In gene clustering, GBHC also produces a clustering partition that is more biologically plausible than several other state-of-the-art methods. This suggests GBHC as an alternative tool for studying gene expression data. The implementation of GBHC is available at https://sites. google.com/site/gaussianbhc

Therapeutic ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system

<p>Abstract</p> <p>Background</p> <p>Studies published in the 1970s by Mostafa S. Fahim and colleagues showed that a short treatment with ultrasound caused the depletion of germ cells and infertility. The goal of the current study was to determine if a commercially available therapeutic ultrasound generator and transducer could be used as the basis for a male contraceptive.</p> <p>Methods</p> <p>Sprague-Dawley rats were anesthetized and their testes were treated with 1 MHz or 3 MHz ultrasound while varying power, duration and temperature of treatment.</p> <p>Results</p> <p>We found that 3 MHz ultrasound delivered with 2.2 Watt per square cm power for fifteen minutes was necessary to deplete spermatocytes and spermatids from the testis and that this treatment significantly reduced epididymal sperm reserves. 3 MHz ultrasound treatment reduced total epididymal sperm count 10-fold lower than the wet-heat control and decreased motile sperm counts 1,000-fold lower than wet-heat alone. The current treatment regimen provided nominally more energy to the treatment chamber than Fahim's originally reported conditions of 1 MHz ultrasound delivered at 1 Watt per square cm for ten minutes. However, the true spatial average intensity, effective radiating area and power output of the transducers used by Fahim were not reported, making a direct comparison impossible. We found that germ cell depletion was most uniform and effective when we rotated the therapeutic transducer to mitigate non-uniformity of the beam field. The lowest sperm count was achieved when the coupling medium (3% saline) was held at 37 degrees C and two consecutive 15-minute treatments of 3 MHz ultrasound at 2.2 Watt per square cm were separated by 2 days.</p> <p>Conclusions</p> <p>The non-invasive nature of ultrasound and its efficacy in reducing sperm count make therapeutic ultrasound a promising candidate for a male contraceptive. However, further studies must be conducted to confirm its efficacy in providing a contraceptive effect, to test the result of repeated use, to verify that the contraceptive effect is reversible and to demonstrate that there are no detrimental, long-term effects from using ultrasound as a method of male contraception.</p