Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair: A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair

RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for transcription resumption. One important type of hindrance consists of DNA lesions, which are removed by transcription-coupled repair (TC-NER), a specific sub-pathway of nucleotide excision repair. To improve our knowledge of transcription elongation and its coupling to TC-NER, we used the yeast library of non-essential knock-out mutations to screen for genes conferring resistance to the transcription-elongation inhibitor mycophenolic acid and the DNA-damaging agent 4-nitroquinoline-N-oxide. Our data provide evidence that subunits of the SAGA and Ccr4-Not complexes, Mediator, Bre1, Bur2, and Fun12 affect transcription elongation to different extents. Given the dependency of TC-NER on RNA Polymerase II transcription and the fact that the few proteins known to be involved in TC-NER are related to transcription, we performed an in-depth TC-NER analysis of a selection of mutants. We found that mutants of the PAF and Ccr4-Not complexes are impaired in TC-NER. This study provides evidence that PAF and Ccr4-Not are required for efficient TC-NER in yeast, unraveling a novel function for these transcription complexes and opening new perspectives for the understanding of TC-NER and its functional interconnection with transcription elongation

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Search for B → μ μ And B0 → μ+ μ- Decays

A search for the rare decays B → μ μ and B → μ μ is performed in pp collisions at ps = 7TeV, with a data sample corresponding to an integrated luminosity of 5 fb collected by the CMS experiment at the LHC. In both decays, the number of events observed after all selection requirements is consistent with the expectation from background plus standard model signal predictions. The resulting upper limits on the branching fractions are B(B → μ μ-) < 7:7 × 10 and B(B → μ μ ) < 1:8 × 10 at 95% confidence level

Global measures of distributive mixing and their behavior in chaotic flows

Two measures of distributive mixing are examined: the standard deviation sigma and the maximum error E, among average concentrations of finite-sized samples. Curves of E versus sample size L are easily interpreted in terms of the size and intensity of the worst flaw in the mixture. E(L) is sensitive to the size of this flaw, regardless of the overall size of the mixture. The measures are used to study distributive mixing for time-periodic flows in a rectangular cavity, using the mapping method. Globally chaotic flows display a well-defined asymptotic behavior: E and sigma decrease exponentially with time, and the curves of E(L) and sigmaL) achieve a self-similar shape. This behavior is independent of the initial configuration of the fluids. Flows with large islands do not show self-similarity, and the final mixing result is strongly dependent on the initial fluid configuratio

Mechanical properties of glass fibre reinforced polypropylene disks produced by rotating, expansion and compression injection moulding

A special mould (RCEM, rotation, compression and expansion mould) intended for inducing complex stress fields during the filling stage of injection moulding was used to manipulate the microstructure of a short fibre reinforced polypropylene. Centred gated discs were injection moulded with different filling sequences (stationary, expansion, compression, expansion with continuous rotation and compression with continuous rotation). The mechanical behaviour of the mouldings was characterized in tensile and flexural loadings on specimens cut at different locations along the flow length. Complete discs were also tested in 4-point support flexural test at low velocity and at impact. The respective results are analysed and discussed in terms of the developed fibre orientation morphology