Fluorescence Resonance Energy Transfer (FRET) as a method to calculate the dimerization strength of basic Helix-Loop-Helix (bHLH) proteins

Post-translational modifications such as phosphorylation play a vital role in the regulation of protein function. In our study of the basic Helix-loop-Helix (bHLH) transcription factor HAND1, we show that HAND1 is phosphorylated during the trophoblast giant cell differentiation on residues residing in Helix I of the bHLH domain. Our hypothesis is that these modifications result in changes in HAND1 dimerization affinities with other bHLH factors. To test this idea, we employed FRET to measure the protein-protein interactions of HAND1 and HAND1 point mutants in HEK293 cells using YFP and CFP fusion proteins and laser scanning confocal microscopy

On the Refractive Index of Ageing Dispersions of Laponite

Aqueous dispersion of Laponite at low ionic concentration is of interest since it undergoes structural evolution with respect to time, which is usually termed as ageing. In this work we study the refractive index behavior as a function of ageing time, concentration and temperature. We observed that the extended Lorenz-Lorentz equation fitted the refractive index dependence on concentration and temperature very well. The refractive index did not show any dependence on ageing time. However, the dependence of refractive index on concentration showed a marked change as the system underwent transition from an isotropic to a biphasic state. The slope of the refractive index-density data is remarkably close to that of water at all Laponite concentrations. In the context of transport phenomena, optical measurements such as interferometry can exploit the water-like behavior of Laponite dispersions.Comment: 13 pages, 3 figures, to appear in Applied Clay Scienc

A Tale of Two Current Sheets

I outline a new model of particle acceleration in the current sheet separating the closed from the open field lines in the force-free model of pulsar magnetospheres, based on reconnection at the light cylinder and "auroral" acceleration occurring in the return current channel that connects the light cylinder to the neutron star surface. I discuss recent studies of Pulsar Wind Nebulae, which find that pair outflow rates in excess of those predicted by existing theories of pair creation occur, and use those results to point out that dissipation of the magnetic field in a pulsar's wind upstream of the termination shock is restored to life as a viable model for the solution of the "$\sigma$" problem as a consequence of the lower wind 4-velocity implied by the larger mass loading.Comment: 17 pages, 6 figures, Invited Review, Proceedings of the "ICREA Workshop on The High-Energy Emission from Pulsars and their Systems", Sant Cugat, Spain, April 12-16, 201

A review of the methodological features of systematic reviews in maternal medicine

Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine

The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins

TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-beta/TIR domain-containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines. The signalling involves TIR (Toll/interleukin-1 receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain. Here, the structural and functional characterization of the N-terminal domain of TRIF (TRIF-NTD) comprising residues 1-153 is reported. The 2.22 angstrom resolution crystal structure was solved by single-wavelength anomalous diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure consists of eight antiparallel helices that can be divided into two subdomains, and the overall fold shares similarity to the interferon-induced protein with tetratricopeptide repeats (IFIT) family of proteins, which are involved in both the recognition of viral RNA and modulation of innate immune signalling. Analysis of TRIF-NTD surface features and the mapping of sequence conservation onto the structure suggest several possible binding sites involved in either TRIF auto-regulation or interaction with other signalling molecules or ligands. TRIF-NTD suppresses TRIF-mediated activation of the interferon-beta promoter, as well as NF-kappa B-dependent reporter-gene activity. These findings thus identify opportunities for the selective targeting of TLR3- and TLR4-mediated inflammation

Clinical report of cervical arthroplasty in management of spondylotic myelopathy in Chinese

OBJECTIVES: To investigate clinical effects and manual operational point of Bryan cervical disc prosthesis in Chinese, to observe the stability and range of movement (ROM) post-operatively. METHODS AND MATERIALS: From 2003,12 to 2005,12, Bryan disc prosthesis replacement applied in 83 cases (102 levels) of cervical spondylotic myelopathy (CSM) after anterior decompression in our hospital. Clinical (JOA grade and Odom's scale) and radiological (X-ray of flexion, extension; left and right bending position) follow-up was performed. Systemic radiographic study about stability and ROM of replaced level post operationally were measured. CT or MRI scans were applied in all cases to evaluate the signs of the prosthesis deflexion and hetero-ossification in the replaced levels. RESULTS: At least 12 months follow-up were done in 65/83 of these paients. All of 83 patients were improved according to Odsm's scale. JOA score increased from average 8.7 to 15.5. There was no prosthesis subsidence. Replaced segment achieved stability and restored partial of normal ROM 4.73°(3.7°–5.9°) early postoperation and 8.12°(5.8°–13.6°) more than 12 months postoperation in flex and extension position. No obvious loss of lordosis was found. CT or MRI follow-up shows position deflexion of the prosthesis metal endplates (<1.5 mm) in 14/77 levels and (1.5~3 mm) in 4/77. heter-ossification was found in the replaced levels only in 2 cases. CONCLUSION: Byran cervical disc prosthesis restored motion to the level of the intact segment in flexion-extension and lateral bending in post-operative images. At the same time, it can achieve good anterior decompression treatment effect and immediate stability in replaced 1 or 2 levels, and which is a new choice for the treatment of CSM

Dalitz Plot Analysis of Ds to K+K-pi+

We perform a Dalitz plot analysis of the decay Ds to K+K-pi+ with the CLEO-c data set of 586/pb of e+e- collisions accumulated at sqrt(s) = 4.17 GeV. This corresponds to about 0.57 million D_s+D_s(*)- pairs from which we select 14400 candidates with a background of roughly 15%. In contrast to previous measurements we find good agreement with our data only by including an additional f_0(1370)pi+ contribution. We measure the magnitude, phase, and fit fraction of K*(892) K+, phi(1020)pi+, K0*(1430)K+, f_0(980)pi+, f_0(1710)pi+, and f_0(1370)pi+ contributions and limit the possible contributions of other KK and Kpi resonances that could appear in this decay.Comment: 21 Pages,available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR

Search for D0 to p e- and D0 to pbar e+

Using data recorded by CLEO-c detector at CESR, we search for simultaneous baryon and lepton number violating decays of the D^0 meson, specifically, D^0 --> p-bar e^+, D^0-bar --> p-bar e^+, D^0 --> p e^- and D^0-bar --> p e^-. We set the following branching fraction upper limits: D^0 --> p-bar e^+ (D^0-bar --> p-bar e^+) p e^- (D^0-bar --> p e^-) < 1.2 * 10^{-5}, both at 90% confidence level.Comment: 10 pages, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PRD. Comments: changed abstract, added reference for section 1, vertical axis in Fig.5 changed (starts from 1.5 rather than 2.0), fixed typo

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Precision Measurement of the Mass of the h_c(1P1) State of Charmonium

A precision measurement of the mass of the h_c(1P1) state of charmonium has been made using a sample of 24.5 million psi(2S) events produced in e+e- annihilation at CESR. The reaction used was psi(2S) -> pi0 h_c, pi0 -> gamma gamma, h_c -> gamma eta_c, and the reaction products were detected in the CLEO-c detector. Data have been analyzed both for the inclusive reaction and for the exclusive reactions in which eta_c decays are reconstructed in fifteen hadronic decay channels. Consistent results are obtained in the two analyses. The averaged results of the present measurements are M(h_c)=3525.28+-0.19 (stat)+-0.12(syst) MeV, and B(psi(2S) -> pi0 h_c)xB(h_c -> gamma eta_c)= (4.19+-0.32+-0.45)x10^-4. Using the 3PJ centroid mass, Delta M_hf(1P)= - M(h_c) = +0.02+-0.19+-0.13 MeV.Comment: 9 pages, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR