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.

Numerical investigation on a transition prediction model

A new transition prediction model is introduced, which couples the intermittency effect into the turbulence transport equations and takes the characteristics of fluid transition into consideration to mimic the exact process of transition. Test cases include a two-dimensional incompressible plate and a two-dimensional NACA0012 airfoil. Performance of this transition model for incompressible flows is studied, with numerical results consistent to experimental data. The requirement of grid resolution for this transition model is also studied.

Laser action from 1,3,5,7-tetramethyl-2,6-diethyl-8-n-propyl pyrromethene-BF2

We measured spectroscopic and laser action properties of a novel 8-position substituted pyrromethene-BF2, namely 1,3,5,7-tetramethyl-2,6-diethyl-8-n-propyl pyrromethene-BF2 complex. The laser action was performed with the corresponding dye solution in ethanol, which was placed in a Littman-type laser cavity pumped by the second harmonic of a Q-switched Nd:YAG laser. The spectroscopic measurements clearly indicated that the corresponding dye solution in ethanol exhibited intense absorption in the visible spectral region with large fluorescence quantum yield. It possesses rather low triplet-triplet absorption in the spectral region 460-550 nm and almost negligible triplet-triplet absorption in the lasing spectral region. As a consequence, it lases nearly as efficiently as commercially available benchmark laser dyes such as Rhodamine-6G and outperformed them in wavelength tunability in our laser cavity and pump geometry. (C) 2002 Optical Society of America.

Stormsmart coasts in action: Two case studies of local level climate change adaptation

Coastal communities throughout the United States have dealt with the devastating effects of storms for centuries, however today’s threats are greater due to three factors. First, the population along the coastline has grown, and is projected to increase.i Additionally, past land use management decisions in the coastal zone have rarely led to the greatest protection from threats. Finally, climate change is predicted to affect coastal areas by accelerating current sea level rise rates and possibly increasing storm intensity.ii These factors compounded together mean that coastal communities are facing a very dangerous situation that threatens economies and human life. (PDF contains 4 pages)

Molecular mechanisms of interleukin-2 gene inducibility: developmental control and combinatorial action of transcription factors

Interleukin-2 is one of the lymphokines secreted by T helper type 1 cells upon activation mediated by T-cell receptor (TCR) and accessory molecules. The ability to express IL-2 is correlated with T-lineage commitment and is regulated during T cell development and differentiation. Understanding the molecular mechanism of how IL-2 gene inducibility is controlled at each transition and each differentiation process of T-cell development is to understand one aspect of T-cell development. In the present study, we first attempted to elucidate the molecular basis for the developmental changes of IL-2 gene inducibility. We showed that IL-2 gene inducibility is acquired early in immature CD4- CD8-TCR- thymocytes prior to TCR gene rearrangement. Similar to mature T cells, a complete set of transcription factors can be induced at this early stage to activate IL-2 gene expression. The progression of these cells to cortical CD4^+CD8^+TCR^(1o) cells is accompanied by the loss of IL-2 gene inducibility. We demonstrated that DNA binding activities of two transcription factors AP-1 and NF-AT are reduced in cells at this stage. Further, the loss of factor binding, especially AP-1, is attributable to the reduced ability to activate expression of three potential components of AP-1 and NF-AT, including c-Fos, FosB, and Fra-2. We next examined the interaction of transcription factors and the IL-2 promoter in vivo by using the EL4 T cell line and two non-T cell lines. We showed an all-or-none phenomenon regarding the factor-DNA interaction, i.e., in activated T cells, the IL-2 promoter is occupied by sequence-specific transcription factors when all the transcription factors are available; in resting T cells or non-T cells, no specific protein-DNA interaction is observed when only a subset of factors are present in the nuclei. Purposefully reducing a particular set of factor binding activities in stimulated T cells using pharmacological agents cyclosporin A or forskolin also abolished all interactions. The results suggest that a combinatorial and coordinated protein-DNA interaction is required for IL-2 gene activation. The thymocyte experiments clearly illustrated that multiple transcription factors are regulated during intrathymic T-cell development, and this regulation in tum controls the inducibility of the lineage-specific IL-2 gene. The in vivo study of protein-DNA interaction stressed the combinatorial action of transcription factors to stably occupy the IL-2 promoter and to initiate its transcription, and provided a molecular mechanism for changes in IL-2 gene inducibility in T cells undergoing integration of multiple environmental signals.

Dirac spectra, summation formulae, and the spectral action

Noncommutative geometry is a source of particle physics models with matter Lagrangians coupled to gravity. One may associate to any noncommutative space (A, H, D) its spectral action, which is defined in terms of the Dirac spectrum of its Dirac operator D. When viewing a spin manifold as a noncommutative space, D is the usual Dirac operator. In this paper, we give nonperturbative computations of the spectral action for quotients of SU(2), Bieberbach manifolds, and SU(3) equipped with a variety of geometries. Along the way we will compute several Dirac spectra and refer to applications of this computation.

Concerted action for successful coastal communities in Tanzania: Lessons from the Tanzania Coastal Management Partnership (TCMP) 2006-2009

The Tanzania Coastal Management Partnership (TCMP) works to implement the National Integrated Coastal Environmental Management Strategy (ICEMS) in Tanzania’s coastal landscapes and seascapes, funded in large measure by the U.S. Agency for International Development. The overarching goal of the Sustainable Coastal Communities and Ecosystems in Tanzania (SUCCESS Tanzania) initiative is to conserve coastal and marine biodiversity while improving the well being of coastal residents through implementation of the Tanzania ICEMS and related ICM policies and strategies. It does this by focusing on three key results: -Policies and Laws that Integrate Conservation and Development Applied -Participatory Landscape Scale Conservation Practiced -Conservation Enterprises Generate Increased and Equitable Benefits from Sustainable Use An additional result sought in the program is gender equity and HIV/AIDS preventive behaviors promoted through communicating HIV/AIDS, environment, and equity messages. (PDF contains 3 pages)