Voltage-independent SK-channel dysfunction causes neuronal hyperexcitability in the hippocampus of Fmr1 knock-out mice

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (

Dirac Neutrino Dark Matter

We investigate the possibility that dark matter is made of heavy Dirac neutrinos with mass in the range [O(1) GeV- a few TeV] and with suppressed but non-zero coupling to the Standard Model Z as well as a coupling to an additional Z' gauge boson. The first part of this paper provides a model-independent analysis for the relic density and direct detection in terms of four main parameters: the mass, the couplings to the Z, to the Z' and to the Higgs. These WIMP candidates arise naturally as Kaluza-Klein states in extra-dimensional models with extended electroweak gauge group SU(2)_L* SU(2)_R * U(1). They can be stable because of Kaluza-Klein parity or of other discrete symmetries related to baryon number for instance, or even, in the low mass and low coupling limits, just because of a phase-space-suppressed decay width. An interesting aspect of warped models is that the extra Z' typically couples only to the third generation, thus avoiding the usual experimental constraints. In the second part of the paper, we illustrate the situation in details in a warped GUT model.Comment: 35 pages, 25 figures; v2: JCAP version; presentation and plots improved, results unchange

High Energy Digestible Fiber-based Diets Improve Efficiency in Growing Heifers

An inherent challenge of long hauled, highly stressed calves is decreased feed intake upon destination arrival. Highly stressed, newly received stocker calves not consuming adequate amounts of energy are prone to a variety of disorders such as Bovine Respiratory Disease Complex and decreased performance throughout the feeding period. One mechanism that can be used to increase energy intake upon arrival is to make the diet more energy dense. Often times, this is accomplished by the addition of cereal grains high in fermentable carbohydrate including starch. Unfortunately, this has also been linked to increasing morbidity due to metabolic disorders. The goal of this study was to analyze the effects of limit-fed diets containing increasing amounts of energy from highly digestible fiber in by-product feeds on health and performance of newly received stocker calves

First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer: Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88

Background: In a phase III randomized trial, we compared the effectiveness and tolerability of fadrozole (CGS 16949A), a non-steroidal aromatase inhibitor, to tamoxifen as first-line endocrine therapy in postmenopausal women with advanced breast cancer. Patients and methods: Two hundred twelve eligible patients were randomized to receive tamoxifen 20 mg daily, or fadrozole 1 mg twice daily orally until disease progression or the advent of undue toxicity. The treatments were to be discontinued upon disease progression. Results: Prognostic factors were well balanced between the treatment groups, except for sites of metastatic disease. Fadrozole-treated patients had significantly more visceral, especially liver, involvement and less bone-dominant disease. Response rates for fadrozole and tamoxifen were similar, 20% and 27% (95% Confidence Limits (CL): 13%-29% and 21%-35%), respectively. Time to treatment failure was longer in patients randomized to tamoxifen (8.5 months for tamoxifen vs. 6.1 months for fadrozole), but did not reach statistical significance after adjustment for prognostic factors (P=0.09). Fadrozole, for which a significantly lower percentage of clinically relevant toxic effects (WHO toxicity gradeij2) was recorded (27% vs. 13% respectively; P=0.009), was better tolerated than tamoxifen. Severe cardiovascular events including 3 fatalities were seen only in patients treated with tamoxifen. Eighty-two patients crossed over to tamoxifen and 66 patients to fadrozole. Crossover endocrine therapy led to response or stable disease in 64% of the patients. The overall survival times of the two treatment groups were similar. Conclusions: Fadrozole and tamoxifen showed similar efficacy as first-line treatments in postmenopausal patients with advanced breast cancer. Fadrozole was significantly better tolerated and may therefore be an appropriate alternative to tamoxifen, especially for patients predisposed to thromboembolic event

The acheulean handaxe : More like a bird's song than a beatles' tune?

© 2016 Wiley Periodicals, Inc. KV is supported by the Netherlands Organization for Scientific Research. MC is supported by the Canada Research Chairs Program, the Social Sciences and Humanities Research of Canada, the Canada Foundation for Innovation, the British Columbia Knowledge Development Fund, and Simon Fraser UniversityPeer reviewedPublisher PD

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Size and composition measurements of background aerosol and new particle growth in a Finnish forest during QUEST 2 using an Aerodyne Aerosol Mass Spectrometer

International audienceThe study of the growth of nucleation-mode particles is important, as this prevents their loss through diffusion and allows them to reach sizes where they may become effective cloud condensation nuclei. Hyytiälä, a forested site in southern Finland, frequently experiences particle nucleation events during the spring and autumn, where particles first appear during the morning and continue to grow for several hours afterwards. As part of the QUEST 2 intensive field campaign during March and April 2003, an Aerodyne Aerosol Mass Spectrometer (AMS) was deployed alongside other aerosol instrumentation to study the particulate composition and dynamics of growth events and characterise the background aerosol. Despite the small mass concentrations, the AMS was able to distinguish the grown particles in the <100 nm regime several hours after an event and confirm that the particles were principally organic in composition. The AMS was also able to derive a mass spectral fingerprint for the organic species present, and found that it was consistent between events and independent of the mean particle diameter during non-polluted cases, implying the same species were also condensing onto the accumulation mode. The results were compared with those from offline analyses such as GC-MS and were consistent with the hypothesis that the main components were alkanes from plant waxes and the oxidation products of terpenes

Bremsstrahlung Suppression due to the LPM and Dielectric Effects in a Variety of Materials

The cross section for bremsstrahlung from highly relativistic particles is suppressed due to interference caused by multiple scattering in dense media, and due to photon interactions with the electrons in all materials. We present here a detailed study of bremsstrahlung production of 200 keV to 500 MeV photons from 8 and 25 GeV electrons traversing a variety of target materials. For most targets, we observe the expected suppressions to a good accuracy. We observe that finite thickness effects are important for thin targets.Comment: 52 pages, 13 figures (incorporated in the revtex LaTeX file

The Higgs Working Group: Summary Report (2001)

Report of the Higgs working group for the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001. It contains 7 separate sections: A. Theoretical Developments B. Higgs Searches at the Tevatron C. Experimental Observation of an invisible Higgs Boson at LHC D. Search for the Standard Model Higgs Boson using Vector Boson Fusion at the LHC E. Study of the MSSM channel $A/H \to \tau \tau$ at the LHC F. Searching for Higgs Bosons in $t\bar t H$ Production G. Studies of Charged Higgs Boson Signals for the Tevatron and the LHCComment: 120 pages, latex, many figures, proceedings of the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001, full Author list included in paper. Typos corrected, author list and acknowledgements completed. Convernors: D. Cavalli, A. Djouadi, K. Jakobs, A. Nikitenko, M. Spira, C.E.M. Wagner, W.-M. Ya