Enantiocontrol in radical coupling reactions : a catalytic [1,2]-rearrangement of allylic ammonium ylides

Funding: A.D.S. and K.K. thank the EPSRC Programme Grant “Boron: Beyond the Reagent” (EP/W007517) for support.The [1,2]-rearrangement of ammonium ylides is a fascinating reaction that has captivated the mechanistically inclined for almost a century. Allylic migration of these ylides is dominated by a thermally allowed concerted [2,3]-rearrangement, with the [1,2]-process usually absent or a minor pathway. As such, development of a [1,2]-selective reaction within allylic systems is an uphill battle. Decades of mechanistic insights have not settled the debate on the true pathway for [1,2]-rearrangement, with a C–N homolysis step followed by a radical coupling within a solvent cage commonly accepted. Herein, we describe our journey through the development of such a process and opine on the broader context in which this chemistry may currently rest.Peer reviewe

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Advanced optical imaging in living embryos

Developmental biology investigations have evolved from static studies of embryo anatomy and into dynamic studies of the genetic and cellular mechanisms responsible for shaping the embryo anatomy. With the advancement of fluorescent protein fusions, the ability to visualize and comprehend how thousands to millions of cells interact with one another to form tissues and organs in three dimensions (xyz) over time (t) is just beginning to be realized and exploited. In this review, we explore recent advances utilizing confocal and multi-photon time-lapse microscopy to capture gene expression, cell behavior, and embryo development. From choosing the appropriate fluorophore, to labeling strategy, to experimental set-up, and data pipeline handling, this review covers the various aspects related to acquiring and analyzing multi-dimensional data sets. These innovative techniques in multi-dimensional imaging and analysis can be applied across a number of fields in time and space including protein dynamics to cell biology to morphogenesis

Muon (g-2) Technical Design Report

The Muon (g-2) Experiment, E989 at Fermilab, will measure the muon anomalous magnetic moment a factor-of-four more precisely than was done in E821 at the Brookhaven National Laboratory AGS. The E821 result appears to be greater than the Standard-Model prediction by more than three standard deviations. When combined with expected improvement in the Standard-Model hadronic contributions, E989 should be able to determine definitively whether or not the E821 result is evidence for physics beyond the Standard Model. After a review of the physics motivation and the basic technique, which will use the muon storage ring built at BNL and now relocated to Fermilab, the design of the new experiment is presented. This document was created in partial fulfillment of the requirements necessary to obtain DOE CD-2/3 approval

Platelet-Rich Plasma Promotes the Proliferation of Human Muscle Derived Progenitor Cells and Maintains Their Stemness

Human muscle-derived progenitor cells (hMDPCs) offer great promise for muscle cell-based regenerative medicine; however, prolonged ex-vivo expansion using animal sera is necessary to acquire sufficient cells for transplantation. Due to the risks associated with the use of animal sera, the development of a strategy for the ex vivo expansion of hMDPCs is required. The purpose of this study was to investigate the efficacy of using platelet-rich plasma (PRP) for the ex-vivo expansion of hMDPCs. Pre-plated MDPCs, myoendothelial cells, and pericytes are three populations of hMDPCs that we isolated by the modified pre-plate technique and Fluorescence Activated Cell Sorting (FACS), respectively. Pooled allogeneic human PRP was obtained from a local blood bank, and the effect that thrombin-activated PRP-releasate supplemented media had on the ex-vivo expansion of the hMDPCs was tested against FBS supplemented media, both in vitro and in vivo. PRP significantly enhanced short and long-term cell proliferation, with or without FBS supplementation. Antibody-neutralization of PDGF significantly blocked the mitogenic/proliferative effects that PRP had on the hMDPCs. A more stable and sustained expression of markers associated with stemness, and a decreased expression of lineage specific markers was observed in the PRP-expanded cells when compared with the FBS-expanded cells. The in vitro osteogenic, chondrogenic, and myogenic differentiation capacities of the hMDPCs were not altered when expanded in media supplemented with PRP. All populations of hMDPCs that were expanded in PRP supplemented media retained their ability to regenerate myofibers in vivo. Our data demonstrated that PRP promoted the proliferation and maintained the multi-differentiation capacities of the hMDPCs during ex-vivo expansion by maintaining the cells in an undifferentiated state. Moreover, PDGF appears to be a key contributing factor to the beneficial effect that PRP has on the proliferation of hMDPCs. © 2013 Li et al

Recurrent abdominal pain in children and adolescents – a survey among paediatricians

Objective: Little is known about prevalence and usual treatment of childhood and adolescent recurrent abdominal pain (RAP) in outpatient paediatricians’ practice. This study’s primary objective was to acquire insights into the usual paediatricians’ treatment and their estimation of prevalence, age and gender of RAP patients. Further objectives were to assess to which extent family members of patients report similar symptoms, how paediatricians rate the strain of parents of affected children and adolescents and how paediatricians estimate the demand for psychological support

Recurrent abdominal pain in children and adolescents – a survey among paediatricians

Objective: Little is known about prevalence and usual treatment of childhood and adolescent recurrent abdominal pain (RAP) in outpatient paediatricians’ practice. This study’s primary objective was to acquire insights into the usual paediatricians’ treatment and their estimation of prevalence, age and gender of RAP patients. Further objectives were to assess to which extent family members of patients report similar symptoms, how paediatricians rate the strain of parents of affected children and adolescents and how paediatricians estimate the demand for psychological support

Comparative evaluation of pebble-bed and prismatic fueled high-temperature gas-cooled reactors

A comparative evaluation has been performed of the HTGR and the Federal Republic of Germany's Pebble Bed Reactor (PBR) for potential commercial applications in the US. The evaluation considered two reactor sizes (1000 and 3000 MW(t)) and three process applications (steam cycle, direct cycle, and process heat, with outlet coolant temperatures of 750, 850, and 950/sup 0/C, respectively). The primary criterion for the comparison was the levelized (15-year) cost of producing electricity or process heat. Emphasis was placed on the cost impact of differences between the prismatic-type HTGR core, which requires periodic refuelings during reactor shutdowns, and the pebble bed PBR core, which is refueled continuously during reactor operations. Detailed studies of key technical issues using reference HTGR and PBR designs revealed that two cost components contributing to the levelized power costs are higher for the PBR: capital costs and operation and maintenance costs. A third cost component, associated with nonavailability penalties, tended to be higher for the PBR except for the process heat application, for which there is a large uncertainty in the HTGR nonavailability penalty at the 950/sup 0/C outlet coolant temperature. A fourth cost component, fuel cycle costs, is lower for the PBR, but not sufficiently lower to offset the capital cost component. Thus the HTGR appears to be slightly superior to the PBR in economic performance. Because of the advanced development of the HTGR concept, large HTGRs could also be commercialized in the US with lower R and D costs and shorter lead times than could large PBRs. It is recommended that the US gas-cooled thermal reactor program continue giving primary support to the HTGR, while also maintaining its cooperative PBR program with FRG

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Citation: Shi, Z. Z., Chapes, S. K., Ben-Arieh, D., & Wu, C. H. (2016). An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. Plos One, 11(8), 39. doi:10.1371/journal.pone.0161131We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-a ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies