Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Interaction-induced Fermi surface deformations in quasi one-dimensional electronic systems

We consider serious conceptual problems with the application of standard perturbation theory, in its zero temperature version, to the computation of the dressed Fermi surface for an interacting electronic system. In order to overcome these difficulties, we set up a variational approach which is shown to be equivalent to the renormalized perturbation theory where the dressed Fermi surface is fixed by recursively computed counterterms. The physical picture that emerges is that couplings that are irrelevant tend to deform the Fermi surface in order to become more relevant (irrelevant couplings being those that do not exist at vanishing excitation energy because of kinematical constraints attached to the Fermi surface). These insights are incorporated in a renormalization group approach, which allows for a simple approximate computation of Fermi surface deformation in quasi one-dimensional electronic conductors. We also analyze flow equations for the effective couplings and quasiparticle weights. For systems away from half-filling, the flows show three regimes corresponding to a Luttinger liquid at high energies, a Fermi liquid, and a low-energy incommensurate spin-density wave. At half-filling Umklapp processes allow for a Mott insulator regime where the dressed Fermi surface is flat, implying a confined phase with vanishing effective transverse single-particle coherence. The boundary between the confined and Fermi liquid phases is found to occur for a bare transverse hopping amplitude of the order of the Mott charge gap of a single chain.Comment: 38 pages, 39 figures. Accepted for publication in Phys. Rev.

Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

BACKGROUND: There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. METHODS: To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. RESULTS: We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. CONCLUSION: We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

Conditional Gene Expression in Mycobacterium abscessus

Mycobacterium abscessus is an emerging human pathogen responsible for lung infections, skin and soft-tissue infections and disseminated infections in immunocompromised patients. It may exist either as a smooth (S) or rough (R) morphotype, the latter being associated with increased pathogenicity in various models. Genetic tools for homologous recombination and conditional gene expression are desperately needed to allow the study of M. abscessus virulence. However, descriptions of knock-out (KO) mutants in M. abscessus are rare, with only one KO mutant from an S strain described so far. Moreover, of the three major tools developed for homologous recombination in mycobacteria, only the one based on expression of phage recombinases is working. Several conditional gene expression tools have recently been engineered for Mycobacterium tuberculosis and Mycobacterium smegmatis, but none have been tested yet in M. abscessus. Based on previous experience with genetic tools allowing homologous recombination and their failure in M. abscessus, we evaluated the potential interest of a conditional gene expression approach using a system derived from the two repressors system, TetR/PipOFF. After several steps necessary to adapt TetR/PipOFF for M. abscessus, we have shown the efficiency of this system for conditional expression of an essential mycobacterial gene, fadD32. Inhibition of fadD32 was demonstrated for both the S and R isotypes, with marginally better efficiency for the R isotype. Conditional gene expression using the dedicated TetR/PipOFF system vectors developed here is effective in S and R M. abscessus, and may constitute an interesting approach for future genetic studies in this pathogen

The MBA as Careerist: An Analysis of Early-Career Job Change

This study examined the job changes of 680 early-career business school graduates. Although a number of anecdotal articles characterize MBAs as overly “careerist” and oriented toward job-hopping, little empirical research has focused on this issue. The research included a direct comparison of job-hopping behavior of MBAs with bachelor S degree graduates, taking into account a number of control variables, including demographic and economic variables. Results indicated that MBAs changed jobs less frequently than bachelor 5 degree graduates, even when a variety of other factors were controlled.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin