Functional characterization of a minimal K+ channel expressed from a synthetic gene.

A gene for a slowly activating, voltage-dependent K(+) -selective channel was designed and synthesized on the basis of its known amino acid sequence. The synthetic gene was cloned into a transcription vector, and in vitro transcribed mRNA was injected into Xenopus oocytes for electrophysiological assay of the resulting ionic currents. The currents are voltage-dependent and highly selective for K+ over Na+. The selectivity among monovalent cations follows a familiar K(+)- channel sequence: K+ greater than Rb+ greater than NH4+ greater than Cs+ much greater than Na+, Li+. The currents are inhibited by Ba2+, Cs+, and tetraethylammonium (TEA), common pore blockers of K+ channels. Open-channel blockade by Cs+ (but not by Ba2+ or TEA) depends on applied voltage. The major inhibitory effect of Ba2+ is to alter channel gating by favoring the closed state; this effect is specific for Ba2+ and is relieved by external K+. The results argue that although the polypeptide expressed is very small for a eukaryotic ion channel, 130 amino acid residues in length, the ionic currents observed are indeed mediated by a genuine K(+) -channel protein. This synthetic gene is therefore well suited for a molecular analysis of the basic mechanisms of K(+) -channel function

Vacuum Ambiguity in de Sitter Space at Strong Coupling

It is well known that in the weak coupling regime, quantum field theories in de Sitter space do not have a unique vacuum, but a class of vacua parametrized by a complex parameter $\alpha$, i.e., the so-called $\alpha$-vacua. In this article, using gauge/gravity duality, we calculate the symmetric two-point function of strongly coupled ${\cal N}=4$ supersymmetric Yang-Mills theory on $dS_3$. We find that there is a class of de Sitter invariant vacua, parametrized by a set of complex parameters $\{\alpha_{\nu}\}$.Comment: 17 pages in JHEP style, references adde

Efficacy of theophylline in people with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis

Objectives: To determine the efficacy of oral theophylline compared with placebo in people with stable chronic obstructive pulmonary disease (COPD).Methods: Systematic review of randomized-controlled trials comparing oral Theophylline; with placebo for a minimum of 7 days in people with stable COPD.Results: Twenty randomized-controlled trials were included in this review. the Meta-analysis; following outcomes showed significant improvement with theophylline compared with placebo: FEV, and FVC both improved with theophylline (weighted mean difference [WMD] 0.10 L; 95% confidence interval [95% CI] 0.04-0.16 and WMD 0.21 L; 95% CI 0.10-0.32, respectively). VO2 max also improved with theophylline (WMD 195.27mL/ min; 95% Cl 112.71-277.83), as did PaO2 and PaCO2 (WMD 3.18mmHg;,95% Cl 1.23-5.13 and WMD -2.36mmHg; 95% Cl -3.52 to -1.21, respectively). Patients preferred theophylline over placebo (relative risk 2.27; 95% Cl 1.26-4.11). Theophylline increased the risk of nausea compared with placebo (RR 7.67; 95% Cl 1.47-39.94).Conclusion: This review has shown that theophylline still has a role in the management of stable COPD, and is preferred by patients over placebo. However, the benefits of theophylline in stable COPD have to be weighed against the risk of adverse effects. (C) 2004 Elsevier B.V. All rights reserved.Natl Collaborating Ctr Womens & Childrens Hlth, London, EnglandUniversidade Federal de São Paulo, Div Resp, São Paulo, BrazilEmergency Med Div, São Paulo, BrazilFed Univ Alagoas, Vasc Dis Div, São Paulo, BrazilUNIFESP, Div Resp, Pulm Rehabil Ctr, São Paulo, BrazilUniv Toronto, W Pk Healthcare Ctr, Toronto, ON, CanadaUniv Laval, Hop Laval, Ctr Pneumol, Inst Cardiol & Pneumol, Laval, PQ, CanadaUniversidade Federal de São Paulo, Div Internal Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Resp, São Paulo, BrazilUNIFESP, Div Resp, Pulm Rehabil Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Div Internal Med, São Paulo, BrazilWeb of Scienc

Black holes and black branes in Lifshitz spacetimes

We construct analytic solutions describing black holes and black branes in asymptotically Lifshitz spacetimes with arbitrary dynamical exponent z and for arbitrary number of dimensions. The model considered consists of Einstein gravity with negative cosmological constant, a scalar, and N U(1) gauge fields with dilatonic-like couplings. We study the phase diagrams and thermodynamic instabilities of the solution, and find qualitative differences between the cases with 12.Comment: 27 pages, 10 figures; v2 references added, minor comments adde

Clocking the Lyme Spirochete

In order to clear the body of infecting spirochetes, phagocytic cells must be able to get hold of them. In real-time phase-contrast videomicroscopy we were able to measure the speed of Borrelia burgdorferi (Bb), the Lyme spirochete, moving back and forth across a platelet to which it was tethered. Its mean crossing speed was 1,636 µm/min (N = 28), maximum, 2800 µm/min (N = 3). This is the fastest speed recorded for a spirochete, and upward of two orders of magnitude above the speed of a human neutrophil, the fastest cell in the body. This alacrity and its interpretation, in an organism with bidirectional motor capacity, may well contribute to difficulties in spirochete clearance by the host

Non-conformal Hydrodynamics in Einstein-dilaton Theory

In the Einestein-dilaton theory with a Liouville potential parameterized by $\eta$, we find a Schwarzschild-type black hole solution. This black hole solution, whose asymptotic geometry is described by the warped metric, is thermodynamically stable only for $0 \le \eta < 2$. Applying the gauge/gravity duality, we find that the dual gauge theory represents a non-conformal thermal system with the equation of state depending on $\eta$. After turning on the bulk vector fluctuations with and without a dilaton coupling, we calculate the charge diffusion constant, which indicates that the life time of the quasi normal mode decreases with $\eta$. Interestingly, the vector fluctuation with the dilaton coupling shows that the DC conductivity increases with temperature, a feature commonly found in electrolytes.Comment: 27 pages and 2 figures, published in JHE

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Laryngeal embryonal rhabdomyosarcoma in an adult - A case presentation in the eyes of geneticists and clinicians

<p>1. Abstract</p> <p>Background</p> <p>Rhabdomyosarcoma is a solid tumor, resulting from dysregulation of the skeletal myogenesis program. For rhabdomyosarcomas (RMS) with a predilection for the head and neck, genitourinary tract, extremities, trunk, retroperitoneum, the larynx is still an unusual site. Till now only several cases of this laryngeal tumor have been described in world literature in the adult population. The entire spectrum of genetic factors underlying RMS development and progression is unclear until today. Multiple signaling pathways seem to be involved in ERMS development and progression.</p> <p>Case presentation</p> <p>In this paper we report an interesting RMS case in which the disease was located within the glottic region. We report an embryonal rhabdomyosarcoma of the larynx in 33 year-old man. After unsuccessful chemotherapy hemilaryngectomy was performed. In follow up CT no signs of recurrence were found. Recently patient is recurrence free for 62 months.</p> <p>Conclusions</p> <p>Considering the histological diagnosis and the highly aggressive nature of the lesion for optimal diagnosis positron electron tomography (PET) and computerized tomography (CT) of the neck and thorax should be performed. At this time surgical treatment with adjuvant radiotherapy seems to be the treatment of choice for this disease. Rhabdomyosarcoma of the larynx has a better prognosis than elsewhere in the body, probably because of its earlier recognition and accessibility to radical surgery.</p