Extreme ultraviolet and X-ray spectroheliograph for OSO-H

A complex scientific instrument was designed, fabricated, tested, and calibrated for launch onboard OSO-H. This instrument consisted of four spectroheliographs and an X-ray polarimeter. The instrument is designed to study solar radiation at selected wavelengths in the X-ray and the extreme ultraviolet ranges, make observations at the H-alpha wavelength, and measure the degree of polarization of X-ray emissions

Benchmarking total knee replacement constructs using noninferiority analysis:the New Zealand Joint Registry study

Abstract Background The aim of this study was to compare the relative performance of total knee replacement constructs and discern if there is variability in performance in currently commonly used prostheses in the New Zealand Joint Registry (NZJR) using a noninferiority analysis. Methods All patients who underwent a primary total knee replacement (TKR) registered in the NZJR between 1st January 1999 to June 2020 were identified. Using a noninferiority analysis, the performance of total knee replacement prostheses were compared with the best performing contemporary construct. Construct all-cause revision rate was estimated using the 1-Kaplan Meier survival function method to estimate net failure. The difference in all-cause revision rates between the contemporary benchmark and all other constructs was tested. Results In total 110 183 TKR were recorded and 25 constructs (102 717 procedures) had > 500 procedures at risk at 3 years post-primary of which 5 were inferior by at least 20 % relative risk of which, one was inferior by at least 100 % relative risk. 14 constructs were identified with > 500 procedures at risk at 10 years with 5 inferior by at least 20 %, of which 2 were inferior by > 100 % relative risk. Conclusions We discerned that there is great variability in construct performance and at all time points, greater than 25 % of constructs are inferior to the best performing construct by at least 20 %. These results can help inform patients, clinicians and health care funders when considering TKR surgery

Benchmarking total hip replacement constructs using noninferiority analysis:the New Zealand joint registry study

Abstract Background The aim of this study was to compare the relative performance of total hip replacement constructs and discern if there is substantial variability in performance in currently commonly used prostheses in the New Zealand Joint Registry (NZJR) using a noninferiority analysis. Methods All patients who underwent a primary total hip replacement (THR) registered in the NZJR between 1st January 1999 to June 2020 were identified. Using a noninferiority analysis, the performance of hip prostheses were compared with the best performing contemporary construct. Construct failure was estimated using the 1-Kaplan Meier survival function method to estimate net failure. The difference in failure between the contemporary benchmark and other constructs was examined. Results In total 135,432 THR were recorded comprising 1035 different THR constructs. Notably 328 constructs were used just once. Forty-eight constructs (62,251 THR) had > 500 procedures at risk at 3 years post-primary of which 28 were inferior by at least 20% relative risk of which, 10 were inferior by at least 100% relative risk. Sixteen constructs were identified with > 500 procedures at risk at 10 years with 9 inferior by at least 20%, of which one was inferior by > 100% relative risk. There were fewer constructs noninferior to the best practice benchmark when we performed analysis by gender. In females at 10 years, from 5 constructs with > 500 constructs at risk, 2 were inferior at the 20% margin. In males at 10 years, there were only 2 eligible constructs of which one was inferior at the 20% margin. Conclusions We discerned that there is substantial variability in construct performance and at most time points, just over half of constructs are inferior to the best performing construct by at least 20%. These results can facilitate informed decision-making when considering THR surgery

The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2

MtrAB is a highly conserved two-component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular Mycobacterium tuberculosis and links antibiotic production to sporulation in the filamentous Streptomyces venezuelae. Chloramphenicol biosynthesis is directly regulated by MtrA in S. venezuelae and deletion of mtrB constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in Streptomyces coelicolor, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster-situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of mtrB switches on the production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and can be used to upregulate antibiotic production in distantly related streptomycetes

Coronary artery bypass grafting: Part 2—optimizing outcomes and future prospects

Since first introduced in the mid-1960s, coronary artery bypass grafting (CABG) has become the standard of care for patients with coronary artery disease. Surprisingly, the fundamental surgical technique itself did not change much over time. Nevertheless, outcomes after CABG have dramatically improved over the first 50 years. Randomized trials comparing percutaneous coronary intervention (PCI) to CABG have shown converging outcomes for select patient populations, providing more evidence for wider use of PCI. It is increasingly important to focus on the optimization of the short- and long-term outcomes of CABG and to reduce the level of invasiveness of this procedure. This review provides an overview on how new techniques and widespread consideration of evolving strategies have the potential to optimize outcomes after CABG. Such developments include off-pump CABG, clampless/anaortic CABG, minimally invasive CABG with or without extending to hybrid procedures, arterial revascularization, endoscopic vein harvesting, intraprocedural epiaortic scanning, graft flow assessment, and improved secondary prevention measures. In addition, this review represents a framework for future studies by summarizing the areas that need more rigorous clinical (randomized) evaluatio

Complete genome sequence of Streptomyces formicae KY5, the formicamycin producer

Here we report the complete genome of the new species Streptomyces formicae KY5 isolated from Tetraponera fungus growing ants. S. formicae was sequenced using the PacBio and 454 platforms to generate a single linear chromosome with terminal inverted repeats. Illumina MiSeq sequencing was used to correct base changes resulting from the high error rate associated with PacBio. The genome is 9.6 Mbps, has a GC content of 71.38% and contains 8162 protein coding sequences. Predictive analysis shows this strain encodes at least 45 gene clusters for the biosynthesis of secondary metabolites, including a type 2 polyketide synthase encoding cluster for the antibacterial formicamycins. Streptomyces formicae KY5 is a new, taxonomically distinct Streptomyces species and this complete genome sequence provides an important marker in the genus of Streptomyces

Signal transduction, receptors, mediators and genes: younger than ever - the 13th meeting of the Signal Transduction Society focused on aging and immunology

The 13th meeting of the Signal Transduction Society was held in Weimar, from October 28 to 30, 2009. Special focus of the 2009 conference was "Aging and Senescence", which was co-organized by the SFB 728 "Environmentally-Induced Aging Processes" of the University of Düsseldorf and the study group 'Signal Transduction' of the German Society for Cell Biology (DGZ). In addition, several other areas of signal transduction research were covered and supported by different consortia associated with the Signal Transduction Society including the long-term associated study groups of the German Society for Immunology and the Society for Biochemistry and Molecular Biology, and for instance the SFB/Transregio 52 "Transcriptional Programming of Individual T Cell Subsets" located in Würzburg, Mainz and Berlin. The different research areas that were introduced by outstanding keynote speakers attracted more than 250 scientists, showing the timeliness and relevance of the interdisciplinary concept and exchange of knowledge during the three days of the scientific program. This report gives an overview of the presentations of the conference

Biosynthesis of the 15-membered ring depsipeptide neoantimycin

Antimycins are a family of natural products possessing outstanding biological activities and unique structures, which have intrigued chemists for over a half century. Of particular interest are the ring-expanded antimycins that show promising anti-cancer potential and whose biosynthesis remains uncharacterized. Specifically, neoantimycin and its analogs have been shown to be effective regulators of the oncogenic proteins GRP78/BiP and K-Ras. The neoantimycin structural skeleton is built on a 15-membered tetralactone ring containing one methyl, one hydroxy, one benzyl and three alkylmoieties, as well as an amide linkage to a conserved 3-formamidosalicylic acid moiety. Although the biosynthetic gene cluster for neoantimycins was recently identified, the enzymatic logic that governs the synthesis of neoantimycins has not yet been revealed. In this work, the neoantimycin gene cluster is identified and an updated sequence and annotation is provided delineating a non-ribosomal peptide synthetase/polyketide synthase (NRPS/PKS) hybrid scaffold. Using cosmid expression and CRISPR/Cas-based genome editing, several heterologous expression strains for neoantimycin production are constructed in two separate Streptomyces species. A combination of in vivo and in vitro analysis is further used to completely characterize the biosynthesis of neoantimycins including the megasynthases and trans-acting domains. This work establishes a set of highly tractable hosts for producing and engineering neoantimycins and their C11 oxidized analogs, paving the way for neoantimycin-based drug discovery and development

Crystal structures of the transpeptidase domain of the Mycobacterium tuberculosis penicillin‐binding protein PonA1 reveal potential mechanisms of antibiotic resistance

Mycobacterium tuberculosis is a human respiratory pathogen that causes the deadly disease tuberculosis. The rapid global spread of antibiotic‐resistant M. tuberculosis makes tuberculosis infections difficult to treat. To overcome this problem new effective antimicrobial strategies are urgently needed. One promising target for new therapeutic approaches is PonA1, a class A penicillin‐binding protein, which is required for maintaining physiological cell wall synthesis and cell shape during growth in mycobacteria. Here, crystal structures of the transpeptidase domain, the enzymatic domain responsible for penicillin binding, of PonA1 from M. tuberculosis in the inhibitor‐free form and in complex with penicillin V are reported. We used site‐directed mutagenesis, antibiotic profiling experiments, and fluorescence thermal shift assays to measure PonA1's sensitivity to different classes of β‐lactams. Structural comparison of the PonA1 apo‐form and the antibiotic‐bound form shows that binding of penicillin V induces conformational changes in the position of the loop β4′‐α3 surrounding the penicillin‐binding site. We have also found that binding of different antibiotics including penicillin V positively impacts protein stability, while other tested β‐lactams such as clavulanate or meropenem resulted in destabilization of PonA1. Our antibiotic profiling experiments indicate that the transpeptidase activity of PonA1 in both M. tuberculosis and M. smegmatis mediates tolerance to specific cell wall‐targeting antibiotics, particularly to penicillin V and meropenem. Because M. tuberculosis is an important human pathogen, these structural data provide a template to design novel transpeptidase inhibitors to treat tuberculosis infections. Database Structural data are available in the PDB database under the accession numbers 5CRF and 5CXW