Simulated pathogenic conformational switch regions matched well with the biochemical findings

Pathogenic conformational conversion is a general causation of many disease, such as transmissible spon- giform encephalopathy (TSE) caused by misfolding of prion, sickle cell anemia, and etc. In such structural changes, misfolding occurs in regions important for the stability of native structure firstly. This destabi- lizes the normal conformation and leads to subsequent errors in folding pathway. Sites involved in the first stage can be deemed switch regions of the protein, and are vital for conformational conversion. Namely it could be a switch of disease at residue level. Here we report an algorithm that can identify such sites computationally with an accuracy of 93%, by calculating the probability of the native structure of a short segment jumping to a mistake one. Knowledge of such switch sites could be used to target clinical therapy, study physiological and pathologic mechanism of protein, and etc.

Switch Region for Pathogenic Structural Change in Conformational Disease and Its Prediction

Many diseases are believed to be related to abnormal protein folding. In the first step of such pathogenic structural changes, misfolding occurs in regions important for the stability of the native structure. This destabilizes the normal protein conformation, while exposing the previously hidden aggregation-prone regions, leading to subsequent errors in the folding pathway. Sites involved in this first stage can be deemed switch regions of the protein, and can represent perfect binding targets for drugs to block the abnormal folding pathway and prevent pathogenic conformational changes. In this study, a prediction algorithm for the switch regions responsible for the start of pathogenic structural changes is introduced. With an accuracy of 94%, this algorithm can successfully find short segments covering sites significant in triggering conformational diseases (CDs) and is the first that can predict switch regions for various CDs. To illustrate its effectiveness in dealing with urgent public health problems, the reason of the increased pathogenicity of H5N1 influenza virus is analyzed; the mechanisms of the pandemic swine-origin 2009 A(H1N1) influenza virus in overcoming species barriers and in infecting large number of potential patients are also suggested. It is shown that the algorithm is a potential tool useful in the study of the pathology of CDs because: (1) it can identify the origin of pathogenic structural conversion with high sensitivity and specificity, and (2) it provides an ideal target for clinical treatment.

Quantum computation based on a quantum switch in cavity QED

A feasible scheme for constructing quantum logic gates is proposed on the basis of quantum switches in cavity QED. It is shown that the light field which is fed into the cavity due to the passage of an atom in a certain state can be used to manipulate the conditioned quantum logical gate. In our scheme, the quantum information is encoded in the states of Rydberg atoms and the cavity mode is not used as logical qubits or as a communicating "bus"; thus, the effect of atomic spontaneous emission can be neglected and the strict requirements for the cavity can be relaxed.

Polarization analysis and experimental implementation of PLZT electro-optical switch using fiber Sagnac interferometers

The polarization characteristics of electro-optical (EO) switches using fiber Sagnac interferometer (FSI) structures are theoretically investigated. Analytical solutions of output fields are presented when the twists and birefringence in a Sagnac loop are considered. Numerical calculations show that the twists of fiber, the orientation of the inserted phase retarder, and the splitting ratio of the coupler will influence both the output intensity and the output polarization properties of the proposed switch. A polarization-independent EO switch based on a Sagnac interferometer and a PUT bar was experimentally implemented, which showed good coincidence with the analytical results. The experiment showed a switch with 22 dB extinction ratio and less than 31.1 ns switching time. (c) 2006 Optical Society of America.

Laser ranging based on electro-optic switch

Based on electro-optic switch effect in crystal, a novel laser ranging method is proposed. CW-laser emitted by laser transmitter propagates forward to the measured target, after being reflected by the target, and then goes back to the transmitter. Close to the transmitter, a special mono-block LiNbO3 crystal is added into the round-trip light beams. High-voltage pulses with the sharp enough changes in rising edges are loaded on the crystal. Based on electro-optic effect, double refraction and internal double reflection effect in crystal, the crystal cuts off the round-trip light beams, and reflects a light pulse cut out by the crystal to a detector aside from the original beam path. The pulse width T is the period that laser propagates forward and back between the crystal and the target. The feasibility of the new idea is proved by our experiments and a brand-new way for the laser ranging is provided. (c) 2005 Elsevier GmbH. All rights reserved.

Focal switch in unapertured converging Hermite-cosh-Gaussian beams

Based on the Huygens-Fresnel diffraction integral, analytical representation of unapertured converging Hermite-cosh-Gaussian beams is derived. Focal switch of Hermite-cosh-Gaussian beams is studied detailedly with numerical calculation examples and a physical interpretation of focal switch is presented. It is found that decentered parameter is the dominant factor for the emergence of focal switch, and Fresnel number affects the amplitude of focal switch and the value of critical decentered parameter to determine emergence of focal switch. Physically, the emergence of focal switch of Hermite-cosh-Gaussian beams is resulted from competition between two major maximum intensities and switch of the absolute maximum intensity from a point to another when decentered parameter increases. (C) 2005 Elsevier Ltd. All rights reserved.

Autophagic Marker MAP1LC3B Expression Levels Are Associated with Carotid Atherosclerosis Symptomatology

Objectives: The mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques). Methods: 80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools. Results: Several genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5-fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system-related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients. Conclusions: Carotid atherosclerotic plaques in which MAP1LC3B is underexpressed would not be able to benefit from MAP1LC3B-associated autophagy. This may lead to accumulation of dead cells at lesion site with subsequent plaque destabilization leading to cerebrovascular events. Identified biomarkers and network interactions may represent novel targets for development of treatments against plaque destabilization and thus for the prevention of cerebrovascular events.

Gradient force pattern, focal shift, and focal switch in an apodized optical system

In this paper, the evolution of the gradient force pattern, focal shift, and focal switch induced by a three-portion pure phase-shifting apodizer is numerically investigated in detail. The results show that the proposed apodizer may induce tunable gradient force on the particles in the focal region, focal shift, and focal switch. By adjusting the geometrical parameters of the phase-shifting apodizer, multiple traps may occur with changeable distance between them, and the shape of the optical trap also evolves evidently. More interestingly, for certain geometrical parameters of the proposed apodizer, by changing the phase shift of inner annular portion, the considerable focal shift may occur with focal switch accompanying, which is discussed to show that this kind of apodizer may be a very promising method of transporting trapped particles. © 2005 Elsevier GmbH. All rights reserved.