Weizmann Institute of Science

About: Weizmann Institute of Science is a education organization based out in Rehovot, Israel. It is known for research contribution in the topics: Population & Gene. The organization has 21942 authors who have published 54561 publications receiving 3032812 citations. The organization is also known as: Bessie F. Lawrence International Summer Science Institute & Weitzman Institute.

How to conceptualize catalytic cycles? The energetic span model.

Abstract: A computational study of a catalytic cycle generates state energies (the E-representation), whereas experiments lead to rate constants (the k-representation). Based on transition state theory (TST), these are equivalent representations. Nevertheless, until recently, there has been no simple way to calculate the efficiency of a catalytic cycle, that is, its turnover frequency (TOF), from a theoretically obtained energy profile. In this Account, we introduce the energetic span model that enables one to evaluate TOFs in a straightforward manner and in affinity with the Curtin−Hammett principle. As shown herein, the model implies a change in our kinetic concepts.Analogous to Ohm’s law, the catalytic chemical current (the TOF) can be defined by a chemical potential (independent of the mechanism) divided by a chemical resistance (dependent on the mechanism and the nature of the catalyst). This formulation is based on Eyring’s TST and corresponds to a steady-state regime.In many catalytic cycles, only one transi...

Scaling Limits of Loop-Erased Random Walks and Uniform Spanning Trees

Abstract: The uniform spanning tree (UST) and the loop-erased random walk (LERW) are strongly related probabilistic processes. We consider the limits of these models on a fine grid in the plane, as the mesh goes to zero. Although the existence of scaling limits is still unproven, subsequential scaling limits can be defined in various ways, and do exist. We establish some basic a.s. properties of these subsequential scaling limits in the plane. It is proved that any LERW subsequential scaling limit is a simple path, and that the trunk of any UST subsequential scaling limit is a topological tree, which is dense in the plane.

Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity

Abstract: To design and direct at will the specificity of T cells in a non-major histocompatibility complex (MHC)-restricted manner, we have generated and expressed chimeric T-cell receptor (TcR) genes composed of the TcR constant (C) domains fused to the antibody's variable (V) domains. Genomic expression vectors have been constructed containing the rearranged gene segments coding for the V region domains of the heavy (VH) and light (VL) chains of an anti-2,4,6-trinitrophenyl (TNP) antibody (SP6) spliced to either one of the C-region gene segments of the alpha or beta TcR chains. Following transfection into a cytotoxic T-cell hybridoma, expression of a functional TcR was detected. The chimeric TcR exhibited the idiotope of the Sp6 anti-TNP antibody and endowed the T cells with a non-MHC-restricted response to the hapten TNP. The transfectants specifically killed and produced interleukin 2 in response to TNP-bearing target cells across strain and species barriers. Moreover, such transfectants responded to immobilized TNP-protein conjugates, bypassing the need for cellular processing and presentation. In the particular system employed, both the TNP-binding site and the Sp6 idiotope reside almost exclusively in the VH chain region. Hence, introduction into T cells of TcR genes containing only the VHSp6 fused to either the C alpha or C beta was sufficient for the expression of a functional surface receptor. Apparently, the VHC alpha or VHC beta chimeric chains can pair with the endogenous beta or alpha chains of the recipient T cell to form a functional alpha beta heterodimeric receptor. Thus, this chimeric receptor provides the T cell with an antibody-like specificity and is able to effectively transmit the signal for T-cell activation and execution of its effector function.

The DNA-encoded nucleosome organization of a eukaryotic genome

Abstract: The nucleosomes are the basic repeating units of eukaryotic chromatin, and nucleosome organization is critically important for gene regulation. Kaplan et al. tested the importance of the intrinsic DNA sequence preferences of nucleosomes by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map is remarkably similar to in vivo nucleosome maps, indicating that the organization of nucleosomes in vivo is largely governed by the underlying genomic DNA sequence. This study tests the importance of the intrinsic DNA sequence preferences of nucleosomes by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map is similar to in vivo nucleosome maps, indicating that the organization of nucleosomes in vivo is largely governed by the underlying genomic DNA sequence. Nucleosome organization is critical for gene regulation1. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers2, competition with site-specific DNA-binding proteins3, and the DNA sequence preferences of the nucleosomes themselves4,5,6,7,8. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo7,9,10,11, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for ∼40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.