First measurement of the T-violating muon polarization in the decay K^+ --> mu^+ nu gamma

We present the result of the first measurement of the T-violating muon polarization P_T in the decay K^+ --> mu^+ nu gamma. This polarization is sensitive to new sources of CP-violation in the Higgs sector. Using data accumulated in the period 1996-98 we have obtained P_T = (-0.64 +- 1.85(stat) +- 0.10(syst))x10^{-2} which is consistent with no T-violation in this decay.Comment: 11 pages, 8 figure

Predicting Physical Time Series Using Dynamic Ridge Polynomial Neural Networks

Forecasting naturally occurring phenomena is a common problem in many domains of science, and this has been addressed and investigated by many scientists. The importance of time series prediction stems from the fact that it has wide range of applications, including control systems, engineering processes, environmental systems and economics. From the knowledge of some aspects of the previous behaviour of the system, the aim of the prediction process is to determine or predict its future behaviour. In this paper, we consider a novel application of a higher order polynomial neural network architecture called Dynamic Ridge Polynomial Neural Network that combines the properties of higher order and recurrent neural networks for the prediction of physical time series. In this study, four types of signals have been used, which are; The Lorenz attractor, mean value of the AE index, sunspot number, and heat wave temperature. The simulation results showed good improvements in terms of the signal to noise ratio in comparison to a number of higher order and feedforward neural networks in comparison to the benchmarked techniques

Treatment of congenital extrahepatic portosystemic shunts in dogs : a systematic review and meta‐analysis

Background Several options have been proposed for the treatment of congenital extrahepatic portosystemic shunts (cEHPSS) in dogs, but formal comparisons among different treatment options are currently unavailable. A previous evidence-based review (2012) found low quality of evidence for papers assessing the treatment of cEHPSS in dogs. Objectives To assess the quality of evidence available in the treatment of cEHPSS, summarize the current state of knowledge with respect to outcome after cEHPSS management, and compare different treatment techniques. Animals Not used. Methods A bibliographic search was performed without date or language restrictions. Studies were assessed for quality of evidence (study design, study group sizes, subject enrollment quality, and overall risk of bias) and outcome measures reported (perioperative outcome, clinical outcome, and surgical or interventional outcome), all reported with 95% confidence intervals. A network meta-analysis was performed. Results Forty-eight studies were included. Six retrospective studies (grade 4b) compared 2 techniques and 7 were abstracts (grade 5). The quality of evidence was low and risk of bias high. Regarding surgical outcome, statistically significant superiority of ameroid constrictor over thin film band was observed (P = .003). No other comparisons were statistically significant. Conclusions and Clinical Importance The evidence base of choice of treatment of cEHPSS in dogs remains weak despite recent publications on the subject. Ameroid is superior to thin film band in causing EHPSS closure. Blinded randomized studies comparing different treatment modalities, which routinely include postoperative imaging to assess cEHPSS closure and acquired portosystemic shunt development are essential

Activation and modulation of recombinant glycine and GABAA receptors by 4-halogenated analogues of propofol

BACKGROUND AND PURPOSE: Glycine receptors are important players in pain perception and movement disorders, and therefore an important therapeutic target. Glycine receptors can be modulated by the intravenous anesthetic propofol (2,6-diisopropylphenol); however, the drug is more potent, by at least one order of magnitude, on GABAA receptors. It has been proposed that halogenation of the propofol molecule generates compounds with selective enhancement of glycinergic modulatory properties. EXPERIMENTAL APPROACH: We synthesized 4-bromopropofol, 4-chloropropofol, and 4-fluoropropofol. The direct activating and modulatory effects of these drugs and propofol were compared on recombinant rat glycine and human GABAA receptors expressed in oocytes. Behavioral effects of the compounds were compared in the tadpole loss-of-righting assay. KEY RESULTS: The concentration-response curves for potentiation of homomeric α1, α2, and α3 glycine receptors were shifted to lower drug concentrations by 2-10-fold for the halogenated compounds. Direct activation by all compounds was minimal with all subtypes of the glycine receptor. The four compounds were essentially equally potent modulators of the α1β3γ2L GABAA receptor with EC50 s between 4 and 7 μM. The EC50 s for loss-of-righting in Xenopus tadpoles, a proxy for loss of consciousness and considered to be mediated by actions on GABAA receptors, ranged from 0.35 to 0.87 μM. Conclusions and Implications We confirm that halogenation of propofol more strongly affects modulation of homomeric glycine receptors than α1β3γ2L GABAA receptors. However, the effective concentrations of all tested halogenated compounds remained lower for GABAA receptors. We infer that 4-bromo-, 4-chloro, or 4-fluoropropofol are not selective homomeric glycine receptor modulators

Long-term follow up of factual knowledge after a single, randomised problem-based learning course

BACKGROUND: The long-term effect of problem-based learning (PBL) on factual knowledge is poorly investigated. We took advantage of a previous randomised comparison between PBL and traditional teaching in a 3(rd )year course to follow up factual knowledge of the students during their 4(th )and 5(th )year of medical school training. METHODS: 3(rd )year medical students were initially randomized to participate in a problem-based (PBL, n = 55), or a lecture-based (LBL, n = 57) course in basic pharmacology. Summative exam results were monitored 18 months later (after finishing a lecture-based course in clinical pharmacology). Additional results of an unscheduled, formative exam were obtained 27 months after completion of the first course. RESULTS: Of the initial sample of 112 students, 90 participated in the second course and exam (n = 45, 45). 32 (n = 17 PBL, n = 15 LBL) could be exposed to the third, formative exam. Mean scores (± SD) were 22.4 ± 6.0, 27.4 ± 4.9 and 20.1 ± 5.0 (PBL), or 22.2 ± 6.0, 28.4 ± 5.1 and 19.0 ± 4.7 (LBL) in the first, second and third test, respectively (maximum score: 40). No significant differences were found between the two groups. CONCLUSION: A small-scale exposure to PBL, applied under randomized conditions but in the context of a traditional curriculum, does not sizeably change long-term presence of factual knowledge within the same discipline

Functional consequences of Kir2.1/Kir2.2 subunit heteromerization

Kir2 subunits form channels that underlie classical strongly inwardly rectifying potassium currents. While homomeric Kir2 channels display a number of distinct and physiologically important properties, the functional properties of heteromeric Kir2 assemblies, as well as the stoichiometries and the arrangements of Kir2 subunits in native channels, remain largely unknown. Therefore, we have implemented a concatemeric approach, whereby all four cloned Kir2 subunits were linked in tandem, in order to study the effects of Kir2.1 and Kir2.2 heteromerization on properties of the resulting channels. Kir2.2 subunits contributed stronger to single-channel conductance than Kir2.1 subunits, and channels containing two or more Kir2.2 subunits displayed conductances indistinguishable from that of a Kir2.2 homomeric channel. In contrast, single-channel kinetics was a more discriminating property. The open times were significantly shorter in Kir2.2 channels compared with Kir2.1 channels and decreased nearly proportionally to the number of Kir2.2 subunits in the heteromeric channel. Similarly, the sensitivity to block by barium also depended on the proportions of Kir2.1 to Kir2.2 subunits. Overall, the results showed that Kir2.1 and Kir2.2 subunits exert neither a dominant nor an anomalous effect on any of the properties of heteromeric channels. The data highlight opportunities and challenges of using differential properties of Kir2 channels in deciphering the subunit composition of native inwardly rectifying potassium currents

Regulation of Axonal HCN1 Trafficking in Perforant Path Involves Expression of Specific TRIP8b Isoforms

The functions of HCN channels in neurons depend critically on their subcellular localization, requiring fine-tuned machinery that regulates subcellular channel trafficking. Here we provide evidence that regulatory mechanisms governing axonal HCN channel trafficking involve association of the channels with specific isoforms of the auxiliary subunit TRIP8b. In the medial perforant path, which normally contains HCN1 channels in axon terminals in immature but not in adult rodents, we found axonal HCN1 significantly increased in adult mice lacking TRIP8b (TRIP8b−/−). Interestingly, adult mice harboring a mutation that results in expression of only the two most abundant TRIP8b isoforms (TRIP8b[1b/2]−/−) exhibited an HCN1 expression pattern similar to wildtype mice, suggesting that presence of one or both of these isoforms (TRIP8b(1a), TRIP8b(1a-4)) prevents HCN1 from being transported to medial perforant path axons in adult mice. Concordantly, expression analyses demonstrated a strong increase of expression of both TRIP8b isoforms in rat entorhinal cortex with age. However, when overexpressed in cultured entorhinal neurons of rats, TRIP8b(1a), but not TRIP8b(1a-4), altered substantially the subcellular distribution of HCN1 by promoting somatodendritic and reducing axonal expression of the channels. Taken together, we conclude that TRIP8b isoforms are important regulators of HCN1 trafficking in entorhinal neurons and that the alternatively-spliced isoform TRIP8b(1a) could be responsible for the age-dependent redistribution of HCN channels out of perforant path axon terminals

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

Modulation of Sn concentration in ZnO nanorod array: intensification on the conductivity and humidity sensing properties

Tin (Sn)-doped zinc oxide (ZnO) nanorod arrays (TZO) were synthesized onto aluminum-doped ZnO-coated glass substrate via a facile sonicated sol–gel immersion method for humidity sensor applications. These nanorod arrays were grown at different Sn concentrations ranging from 0.6 to 3 at.%. X-ray diffraction patterns showed that the deposited TZO arrays exhibited a wurtzite structure. The stress/strain condition of the ZnO film metamorphosed from tensile strain/compressive stress to compressive strain/tensile stress when the Sn concentrations increased. Results indicated that 1 at.% Sn doping of TZO, which has the lowest tensile stress of 0.14 GPa, generated the highest conductivity of 1.31 S cm− 1. In addition, 1 at.% Sn doping of TZO possessed superior sensitivity to a humidity of 3.36. These results revealed that the optimum performance of a humidity-sensing device can be obtained mainly by controlling the amount of extrinsic element in a ZnO film