820 research outputs found

    An Enantioselective Artificial Suzukiase Based on the Biotin–Streptavidin Technology

    Get PDF
    Introduction of a biotinylated monophosphine palladium complex within streptavidin affords an enantioselective artificial Suzukiase. Site-directed mutagenesis allowed the optimization of the activity and the enantioselectivity of this artificial metalloenzyme. A variety of atropisomeric biaryls were produced in good yields and up to 90% ee. The hybrid catalyst described herein shows comparable TOF to the previous aqueous-asymmetric Suzuki catalysts, and excellent stability under the reaction conditions to realize higher TON through longer reaction time

    Evaluation of Passive Force on Skewed Bridge Abutments with Large-Scale Tests

    Get PDF
    Accounting for seismic forces and thermal expansion in bridge design requires an accurate passive force versus backwall deflection relationship. Current design codes make no allowances for skew effects on the development of the passive force. However, small-scale experimental results and available numerical models indicate that there is a significant reduction in peak passive force as skew angle increases for plane-strain cases. To further explore this issue large-scale field tests were conducted at skew angles of 0°, 15°, and 30° with unconfined backfill geometry. The abutment backwall was 11 feet (3.35-m) wide by 5.5 feet (1.68-m) high, and backfill material consisted of dense compacted sand. The peak passive force for the 15° and 30° tests was found to be 73% and 58%, respectively, of the peak passive force for the 0° test which is in good agreement with the small-scale laboratory tests and numerical model results. However, the small differences may suggest that backfill properties (e.g. geometry and density) may have some slight effect on the reduction in peak passive force with respect to skew angle. Longitudinal displacement of the backfill at the peak passive force was found to be approximately 3% of the backfill height for all field tests and is consistent with previously reported values for large-scale passive force-deflection tests, though skew angle may slightly reduce the deflection necessary to reach backfill failure. The backfill failure mechanism appears to transition from a log spiral type failure mechanism where Prandtl and Rankine failure zones develop at low skew angles, to a failure mechanism where a Prandtl failure zone does not develop as skew angle increases

    Phase- Specific Changes in Rate of Force Development and Muscle Morphology throughout a Block Periodized Training Cycle in Weightlifters

    Get PDF
    The purpose of this study was to investigate the kinetic and morphological adaptations that occur during distinct phases of a block periodized training cycle in weightlifters. Athlete monitoring data from nine experienced collegiate weightlifters was used. Isometric mid-thigh pull (IMTP) and ultrasonography (US) results were compared to examine the effects of three specific phases of a training cycle leading up to a competition. During the high volume strength-endurance phase (SE) small depressions in rate of force development (RFD) but statistically significant (p ≤ 0.05) increases in vastus lateralis cross-sectional area (CSA), and body mass (BM) were observed. The lower volume higher intensity strength-power phase (SP) caused RFD to rebound above pre-training cycle values despite statistically significant reductions in CSA. Small to moderate increases only in the earlier RFD time bands (\u3c150 \u3ems) occurred during the peak/taper phase (PT) while CSA and BM were maintained. Changes in IMTP RFD and CSA from US reflected the expected adaptations of block periodized training phases. Changes in early (\u3c100 \u3ems) and late (≥150 ms) RFD time bands may not occur proportionally throughout different training phases. Small increases in RFD and CSA can be expected in well-trained weightlifters throughout a single block periodized training cycle

    Symmetryâ Directed Selfâ Assembly of a Tetrahedral Protein Cage Mediated by de Novoâ Designed Coiled Coils

    Full text link
    The organization of proteins into new hierarchical forms is an important challenge in synthetic biology. However, engineering new interactions between protein subunits is technically challenging and typically requires extensive redesign of proteinâ protein interfaces. We have developed a conceptually simple approach, based on symmetry principles, that uses short coiledâ coil domains to assemble proteins into higherâ order structures. Here, we demonstrate the assembly of a trimeric enzyme into a wellâ defined tetrahedral cage. This was achieved by genetically fusing a trimeric coiledâ coil domain to its C terminus through a flexible polyglycine linker sequence. The linker length and coiledâ coil strength were the only parameters that needed to be optimized to obtain a high yield of correctly assembled protein cages.Geometry lesson: A modular approach for assembling proteins into largeâ scale geometric structures was developed in which coiledâ coil domains acted as â twist tiesâ to facilitate assembly. The geometry of the cage was specified primarily by the rotational symmetries of the coiled coil and building block protein and was largely independent of protein structural details.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138862/1/cbic201700406_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138862/2/cbic201700406.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138862/3/cbic201700406-sup-0001-misc_information.pd

    Identification of a photoredox-active Pt(IV) complex that induces light-mediated cell death

    Get PDF
    We report the synthesis and characterisation of a series of fluorogenic Pt(IV) complexes – CarboBlue, OxaliBlue and CisBlue. These Pt(IV) complexes were identified as photoactive, oxidising biomolecules under light irradation to then undergo rapid intramolecular photoreduction to release the fluorescent reporter, Nap-OH and corresponding Pt(II) species. OxaliBlue and CisBlue displayed cytotoxicity regardless of light irradiation. In contrast, HCT116 cells treated with CarboBlue displayed a light-dependent increase in fluorescence emission along with selective light-induced toxicity

    Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer

    Get PDF
    INTRODUCTION: Mutations in known predisposition genes account for only about a third of all multiple-case breast cancer families. We hypothesized that germline mutations in FANCD2, BRIP1/BACH1, LMO4 and SFN may account for some of the unexplained multiple-case breast cancer families. METHODS: The families used in this study were ascertained through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Denaturing high performance liquid chromatography (DHPLC) analysis of the coding regions of these four genes was conducted in the youngest affected cases of 30 to 267 non-BRCA1/2 breast cancer families. In addition, a further 399 index cases were also screened for mutations in two functionally significant regions of the FANCD2 gene and 253 index cases were screened for two previously reported mutations in BACH1 (p. P47A and p. M299I). RESULTS: DHPLC analysis of FANCD2 identified six silent exonic variants, and a large number of intronic variants, which tagged two common haplotypes. One protein truncating variant was found in BRIP1/BACH1, as well as four missense variants, a silent change and a variant in the 3' untranslated region. No missense or splice site mutations were found in LMO4 or SFN. Analysis of the missense, silent and frameshift variants of FANCD2 and BACH1 in relatives of the index cases, and in a panel of controls, found no evidence suggestive of pathogenicity. CONCLUSION: There is no evidence that highly penetrant exonic or splice site mutations in FANCD2, BRIP1/BACH1, LMO4 or SFN contribute to familial breast cancer. Large scale association studies will be necessary to determine whether any of the polymorphisms or haplotypes identified in these genes contributes to breast cancer risk

    Diet and foraging of Round Goby (Neogobius melanostomus) in a contaminated harbour

    Get PDF
    Copyright © 2017 Crown Copyright. Anthropogenic pollution and the introduction of invasive species are two contributing factors to ecosystem degradation. Although Hamilton Harbour (Ontario, Canada), a highly impacted ecosystem, is well-studied, the diet, trophic position, and foraging behaviour of the invasive Round Goby (Neogobius melanostomus) in this area is not well understood. In this study, we compared digestive tract contents, foraging behaviour, and stable isotope values of Round Goby from sites of low and high sediment contamination in Hamilton Harbour. We also assessed prey availability by conducting sediment invertebrate abundance analyses at these sites. Regardless of site, Chironomids, Cladocerans, Copepods and Dreissenids were the most common food items found in Round Goby digestive tracts, and females always had heavier gut contents compared to males. Fish from the high contamination site consumed fewer prey items, had lower gut fullness scores, and fed at a lower trophic level based on lower δ13C and δ15N values. Our results suggest that Round Goby living in highly contaminated areas are feeding less than Round Goby from areas of lower contamination, but that these diet differences do not reflect differences in prey availability. Fish from the high contamination site also typically moved more slowly while foraging. Taken together, these results provide an analysis of the main prey items of Round Goby in Hamilton Harbour, and demonstrate how polluted environments can impact diet, trophic position, and foraging of an introduced fish species
    corecore