Dynamics of Alpha-Helix Formation in the CSAW Model

We study the folding dynamics of polyalanine (Ala$_{20}$), a protein fragment with 20 residues whose native state is a single alpha helix. We use the CSAW model (conditioned self-avoiding walk), which treats the protein molecule as a chain in Brownian motion, with interactions that include hydrophobic forces and internal hydrogen bonding. We find that large scale structures form before small scale structures, and obtain the relevant relaxation times. We find that helix nucleation occurs at two separate points on the protein chain. The evolution of small and large scale structures involve different mechanisms. While the former can be describe by rate equations governing the growth of helical content, the latter is akin to the relaxation of an elastic solid.Comment: 18 pages, 10 figure

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis : a subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.651); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68) and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Spectrum from the warped compactifications with the de Sitter universe

We discuss the spectrum of the tensor metric perturbations and the stability of warped compactifications with the de Sitter spacetime in the higher-dimensional gravity. The spacetime structure is given in terms of the warped product of the non-compact direction, the spherical internal dimensions and the four-dimensional de Sitter spacetime. To realize a finite bulk volume, we construct the brane world model, using the cut-copy-paste method. Then, we compactify the spherical directions on the brane. In any case, we show the existence of the massless zero mode and the mass gap of it with massive Kaluza-Klein modes. Although the brane involves the spherical dimensions, no light massive mode is excited. We also investigate the scalar perturbations, and show that the model is unstable due to the existence of a tachyonic bound state, which seems to have the universal negative mass square, irrespective of the number of spacetime dimensions.Comment: Journal version (JHEP

Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica

<p>Abstract</p> <p>Background</p> <p>The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO.</p> <p>Methods</p> <p>We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission.</p> <p>Results</p> <p>Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4⁺CD25⁺and CD4⁺CD45RO⁺was higher, while that of CD4⁺CC chemokine receptor (CCR)3⁺(T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4⁺CXC chemokine receptors (CXCR)3⁺/CD4⁺CCR3⁺(Th1/Th2) and CD8⁺CXCR3⁺/CD8⁺CCR4⁺(T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8⁺CXCR3⁺T cell (Tc1) and CD4⁺CXCR3⁺T cell (Th1) decreased significantly during remission in MS patients (<it>P <</it>0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC.</p> <p>Conclusions</p> <p>Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3⁺T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.</p

Natural extension of choice functions

International Conference on Information Processing and Management of Uncertainty in Knowledge-Based Systems, IPMU (17 th, 2018, Cádiz, Spain

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

Frequent allelic imbalances (AIs) including loss of heterozygosity and microsatellite instability on a specific chromosomal region have been identified in a variety of human malignancies. The objective of our study was to assess the possibility of prognostication and monitoring of oral squamous cell carcinoma (SCC) by microsatellite blood assay. DNA from normal and tumorous tissues and serum DNA obtained at three time points (preoperatively, postoperatively, and 4 weeks postoperatively) from 64 patients with oral SCC was examined at nine microsatellite loci. In all, 38 (59%) DNA samples from tumorous tissues and 52% from serum showed AIs in at least one locus. Patterns of AIs in the serum DNA were matched to those detected in tumour DNA. Of them, AIs were frequently detected preoperatively (44%, 28 of 64), and postoperatively (20%, 13 of 64). Moreover, among 12 cases with AIs during the postoperative period, six had no evidence of an AI 4 weeks postoperatively, and they had no recurrence and were disease free. In contrast, six patients with AI-positive DNA 4 weeks postoperatively have died with distant metastasis within 44 weeks. Thus, our results suggest that the assessment of microsatellite status in the serum DNA could be a useful predictive tool to monitor disease prognosis

Non-Markovian polymer reaction kinetics

Describing the kinetics of polymer reactions, such as the formation of loops and hairpins in nucleic acids or polypeptides, is complicated by the structural dynamics of their chains. Although both intramolecular reactions, such as cyclization, and intermolecular reactions have been studied extensively, both experimentally and theoretically, there is to date no exact explicit analytical treatment of transport-limited polymer reaction kinetics, even in the case of the simplest (Rouse) model of monomers connected by linear springs. We introduce a new analytical approach to calculate the mean reaction time of polymer reactions that encompasses the non-Markovian dynamics of monomer motion. This requires that the conformational statistics of the polymer at the very instant of reaction be determined, which provides, as a by-product, new information on the reaction path. We show that the typical reactive conformation of the polymer is more extended than the equilibrium conformation, which leads to reaction times significantly shorter than predicted by the existing classical Markovian theory.Comment: Main text (7 pages, 5 figures) + Supplemantary Information (13 pages, 2 figures

Excitation of Kaluza-Klein gravitational mode

We investigate excitation of Kaluza-Klein modes due to the parametric resonance caused by oscillation of radius of compactification. We consider a gravitational perturbation around a D-dimensional spacetime, which we compactify on a (D-4)-sphere to obtain a 4-dimensional theory. The perturbation includes the so-called Kaluza-Klein modes, which are massive in 4-dimension, as well as zero modes, which is massless in 4-dimension. These modes appear as scalar, vector and second-rank symmetric tensor fields in the 4-dimensional theory. Since Kaluza-Klein modes are troublesome in cosmology, quanta of these Kaluza-Klein modes should not be excited abundantly. However, if radius of compactification oscillates, then masses of Kaluza-Klein modes also oscillate and, thus, parametric resonance of Kaluza-Klein modes may occur to excite their quanta. In this paper we consider part of Kaluza-Klein modes which correspond to massive scalar fields in 4-dimension and investigate whether quanta of these modes are excited or not in the so called narrow resonance regime of the parametric resonance. We conclude that at least in the narrow resonance regime quanta of these modes are not excited so catastrophically.Comment: 15 pages LaTeX, submitted to Phys.Rev.

Brane World Effective Action at Low Energies and AdS/CFT Correspondence

A low energy iteration scheme to study nonlinear gravity in the brane world is developed. As a result, we obtain the brane world effective action at low energies. The relation between the geometrical approach and the approach using the AdS/CFT correspondence is also clarified. In particular, we find generalized dark radiation as homogeneous solutions in our iteration scheme. Moreover, the precise correspondence between the bulk geometry and the brane effective action is established, which gives a holographic view of the brane world.Comment: Revtex4, 12 pages, references added. Version accepted for publicaton in Phys. Rev.