Subtle pH differences trigger single residue motions for moderating conformations of calmodulin

This study reveals the essence of ligand recognition mechanisms by which calmodulin (CaM) controls a variety of Ca2+ signaling processes. We study eight forms of calcium-loaded CaM each with distinct conformational states. Reducing the structure to two degrees of freedom conveniently describes main features of the conformational changes of CaM via simultaneous twist-bend motions of the two lobes. We utilize perturbation-response scanning (PRS) technique, coupled with molecular dynamics simulations. PRS is based on linear response theory, comprising sequential application of directed forces on selected residues followed by recording the resulting protein coordinates. We analyze directional preferences of the perturbations and resulting conformational changes. Manipulation of a single residue reproduces the structural change more effectively than that of single/pairs/triplets of collective modes of motion. Our findings also give information on how the flexible linker acts as a transducer of binding information to distant parts of the protein. Furthermore, by perturbing residue E31 located in one of the EF hand motifs in a specific direction, it is possible to induce conformational change relevant to five target structures. Independently, using four different pKa calculation strategies, we find this particular residue to be the charged residue (out of a total of 52), whose ionization state is most sensitive to subtle pH variations in the physiological range. It is plausible that at relatively low pH, CaM structure is less flexible. By gaining charged states at specific sites at a pH value around 7, such as E31 found in the present study, local conformational changes in the protein will lead to shifts in the energy landscape, paving the way to other conformational states. These findings are in accordance with Fluorescence Resonance Energy Transfer (FRET) measured shifts in conformational distributions towards more compact forms with decreased pH. They also corroborate mutational studies and proteolysis results which point to the significant role of E31 in CaM dynamics

Centralized and Decentralized Optimal Control of Variable Speed Heat Pumps

Utility service providers are often challenged with the synchronization of thermostatically controlled loads. Load synchronization, as a result of naturally occurring and demand-response events, has the potential to damage power distribution equipment. Because thermostatically controlled loads constitute most of the power consumed by the grid at any given time, the proper control of such devices can lead to significant energy savings and improved grid stability. The contribution of this paper is the development of an optimal control algorithm for commonly used variable speed heat pumps. By means of selective peer-to-peer communication, our control architecture allows for the regulation of home temperatures while simultaneously minimizing aggregate power consumption, and aggregate load volatility. An optimal centralized controller is also explored and compared against its decentralized counterpart

Structural properties of cyclic polyelectrolytes in dilute good solvent

Cyclic polymers display unique physical behaviors in comparison to their linear counterparts. Theoretical, computational and experimental studies have revealed that some of their distinctive properties are also observed in charged variants of cyclic polymers, known as cyclic polyelectrolytes (PEs), especially in terms of their structural responses to variations in the strength of electrostatic interactions. In this study, we investigate the impact of cyclic topology on the conformations of PE chains in dilute good solvent using scaling analysis and coarse-grained bead-spring molecular dynamics simulations. Our observations indicate that, in contrast to linear PE chains, cyclic topology results in more compact conformations at low and intermediate Bjerrum lengths. Moreover, two structural metrics, asphericity and prolateness, which quantify deviations from spherical and flat molecular shapes, exhibit non-monotonic behaviors for cyclic PEs. This stands in contrast to linear PEs, where these shape characteristics exhibit a monotonic trend with increasing Bjerrum length. A feasible analytical theory, developed to account for ionic distributions around cyclic PE chains, suggests that the fundamental difference between linear and cyclic chain conformations may be attributed to topological effects influencing long-range electrostatic interactions

Saving Lives: The Principle of Distinction and the Realities of Modern War

WOS: 000332942700005PubMed ID: 24778561In this study, we assessed the feasibility of fetal RhD genotyping by analysis of cell-free fetal DNA(cffDNA) extracted from plasma samples of Rhesus (Rh) D-negative pregnant women by using real-time polymerase chain reaction (PCR). Fetal genotyping was performed on 30 RhD-negative women between 9 and 39 weeks of gestation who were referred to us for invasive testing [amniocentesis/chorionic villi sampling (CVS)]. The fetal RHD genotype was determined based on real-time PCR method. Exons 7 and 10 of the RHD and SRY genes were targeted. Among the pregnant women, 12 were carrying male and 17 were carrying female fetuses. Out of 29 pregnant women, 21 had RhD-positive and nine had RhD-negative fetuses. One sample) case 12, whose blood group was found to be AB Rh [+] (was excluded due to controversial results from repeated serological analyses. All prenatal results were in concordance with postnatal RhD status and fetal sex without false-positive or -negative results. Performing real-time PCR on cffDNA showed accurate, efficient and reliable results, allowing rapid and high throughput non invasive determination of fetal sex and RhD status in clinical samples

The 11 March 2011 Tohoku tsunami wavefront mapping across offshore Southern California

The 11 March 2011 (M_w = 9.0) Tohoku tsunami was recorded by a temporary array of seafloor pressure gauges deployed off the coast of Southern California, demonstrating how dense array data can illustrate and empirically validate predictions of linear tsunami wave propagation characteristics. A noise cross-correlation method was used to first correct for the pressure gauge instrument phase response. Phase and group travel times were then measured for the first arrival in the pressure gauge tsunami waveforms filtered in narrow bands around 30 periods between 200 and 3000 s. For each period, phase velocities were estimated across the pressure gauge array based on the phase travel time gradient using eikonal tomography. Clear correlation was observed between the phase velocity and long-wavelength bathymetry variations where fast and slow velocities occurred for deep and shallow water regions, respectively. In particular, velocity gradients are pronounced at the Patton Escarpment and near island plateaus due to the abrupt bathymetry change. In the deep open ocean area, clear phase velocity dispersion is observed. Comparison with numerically calculated tsunami waveforms validates the approach and provides an independent measure of the finite-frequency effect on phase velocities at long periods

500 KW Rüzgar Türbini İçin Ana Şaft Tasarımı Ve Analizi

Konferans Bildirisi -- Teorik ve Uygulamalı Mekanik Türk Milli Komitesi, 2013Conference Paper -- Theoretical and Applied Mechanical Turkish National Committee, 2013Bu çalışmada, 500 kW güç üreten bir rüzgar türbinin ana şaftının tasarımı ve yapısal analizleri yapılmıştır. Ana şaftın boyutlandırılmasında yorulma kriterlerinin esas alınması gerekmektedir. Ana şaftın yorulmaya ait yük durumu ise literatürde bulunan ampirik formüller kullanılarak hesaplanmıştır. Yorulma analizlerinde şaftı çevrimsel yüklerle zorlayan rotor ağırlığının yanında rüzgar kesmesi ve kule blokaj etkisi vb. sebeplerle ortaya çıkan değişken eğilme momenti ve tork değerleri de hesaba katılmıştır. Ana şaftın kritik kesitlerindeki çap hesabı, ASME Eliptik yorulma kriteri kullanılarak sonsuz ömre göre yapılmıştır. Ana şaftın tasarımındaki kritik bölgeler şaftın yataklandığı bölge ve şaftın dişli kutusuna bağlandığı bölgedir. Ayrıca, kontrol amaçlı olarak Uluslararası Elektroteknik Komisyonu’nun (International Electrotechnical Commision) yayınlamış olduğu IEC 64100-1 standardında belirtilen yükleme şartları için ana şaftın statik analizleri ANSYS 14.5 sonlu elemanlar yazılımı kullanılarak gerçekleştirilmiştir. Şaftın sonlu eleman modeli SOLID185 elemanlar kullanılarak oluşturulmuştur. Ayrıca, ana şaft - göbek bağlantı elemanlarının analizi de bu çalışma kapsamında yapılmıştır. Sayısal ve analitik yöntemler kullanılarak elde edilen deformasyon ve gerilme sonuçları karşılaştırılmış ve iyi bir uyum olduğu görülmüştür.In this paper, the main shaft which is one of the important structural parts for a 500 kW wind turbine has been designed. The fatigue criteria has been based on sizing the main shaft. The main shafts critic desing loads have been calculated by empirical formulas which are on the literatures. Oscillation moments of the torque and the flexural moments which is created by wind share, and effect of tower, etc. have been envisaged for analytical and numerical studies. In this study, the main shaft has been designed for infinite life using with ASME Elliptic criteria. There are two critic areas which are supported and connected to the gear box. In addition Iternational Electrotechnical Commision (IEC) 64100-1 standards have been based on the critic design load cases. The main shaft and the fasteners are modeled using the finite element method. The finite element model of the shaft is designed using with SOLID185 elements. Its static analysis have been achieved with using ANSYS 14.5 software. Also a comparison of two different approximations have been mentioned in this paper. The values of analitic and numerical of deplacement and stress are compared each