Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase ρ

Factor-dependent transcription termination mechanisms are poorly understood. We determined a series of cryo–electron microscopy structures portraying the hexameric adenosine triphosphatase (ATPase) ρ on a pathway to terminating NusA/NusG-modified elongation complexes. An open ρ ring contacts NusA, NusG, and multiple regions of RNA polymerase, trapping and locally unwinding proximal upstream DNA. NusA wedges into the ρ ring, initially sequestering RNA. Upon deflection of distal upstream DNA over the RNA polymerase zinc-binding domain, NusA rotates underneath one capping ρ subunit, which subsequently captures RNA. After detachment of NusG and clamp opening, RNA polymerase loses its grip on the RNA:DNA hybrid and is inactivated. Our structural and functional analyses suggest that ρ, and other termination factors across life, may use analogous strategies to allosterically trap transcription complexes in a moribund state

PROBABILITY DISTRIBUTION OVER THE SET OF CLASSES IN ARABIC DIALECT CLASSIFICATION TASK

Subject of Research.We propose an approach for solving machine learning classification problem that uses the information about the probability distribution on the training data class label set. The algorithm is illustrated on a complex natural language processing task - classification of Arabic dialects. Method. Each object in the training set is associated with a probability distribution over the class label set instead of a particular class label. The proposed approach solves the classification problem taking into account the probability distribution over the class label set to improve the quality of the built classifier. Main Results. The suggested approach is illustrated on the automatic Arabic dialects classification example. Mined from the Twitter social network, the analyzed data contain word-marks and belong to the following six Arabic dialects: Saudi, Levantine, Algerian, Egyptian, Iraq, Jordan, and to the modern standard Arabic (MSA). The paper results demonstrate an increase of the quality of the built classifier achieved by taking into account probability distributions over the set of classes. Experiments carried out show that even relatively naive accounting of the probability distributions improves the precision of the classifier from 44% to 67%. Practical Relevance. Our approach and corresponding algorithm could be effectively used in situations when a manual annotation process performed by experts is connected with significant financial and time resources, but it is possible to create a system of heuristic rules. The implementation of the proposed algorithm enables to decrease significantly the data preparation expenses without substantial losses in the precision of the classification

CryoEM analysis of small plant biocatalysts at sub 2 resolution

Enzyme catalysis has emerged as a key technology for developing efficient, sustainable processes in the chemical, biotechnological and pharmaceutical industries. Plants provide large and diverse pools of biosynthetic enzymes that facilitate complex reactions, such as the formation of intricate terpene carbon skeletons, with exquisite specificity. High resolution structural analysis of these enzymes is crucial in order to understand their mechanisms and modulate their properties by targeted engineering. Although cryo electron microscopy cryoEM has revolutionized structural biology, its applicability to high resolution structural analysis of comparatively small enzymes has so far been largely unexplored. Here, it is shown that cryoEM can reveal the structures of plant borneol dehydrogenases of amp; 8764;120 kDa at or below 2 resolution, paving the way for the rapid development of new biocatalysts that can provide access to bioactive terpenes and terpenoid

Impact of COVID-19 on the oncological outcomes of colorectal cancer surgery in northern Italy in 2019 and 2020: multicentre comparative cohort study

BACKGROUND: This study compared patients undergoing colorectal cancer surgery in 20 hospitals of northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes. METHOD: This was a retrospective multicentre cohort analysis of patients undergoing colorectal cancer surgery in March to December 2019 versus March to December 2020. Independent predictors of disease stage (oncological stage, associated symptoms, clinical T4 stage, metastasis) and outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression. RESULTS: The sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean age 69.6 years). The proportion of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were respectively: 80.8 versus 84.5 per cent; 6.2 versus 8.7 per cent; 10.2 versus 10.3 per cent; and 3.0 versus 4.4 per cent. The proportions of surgical complications, palliative surgery and death in 2019 and 2020 were, respectively: 34.4 versus 31.9 per cent; 5.0 versus 7.5 per cent; and 1.7 versus 2.4 per cent. Cancers in 2020 (versus 2019) were more likely to be symptomatic (odds ratio 1.36 (95 per cent c.i. 1.09 to 1.69)), clinical T4 stage (odds ratio 1.38 (95 per cent c.i. 1.03 to 1.85)) and have multiple liver metastases (odds ratio 2.21 (95 per cent c.i. 1.24 to 3.94)), but were not more likely to be associated with surgical complications (odds ratio 0.79 (95 per cent c.i. 0.68 to 0.93)). CONCLUSION: Colorectal cancer patients who had surgery between March and December 2020 had an increased risk of advanced disease in terms of associated symptoms, cancer location, clinical T4 stage and number of liver metastases

Experimental Research on the Shear Connectors in Foam Concrete

In order to improve the longitudinal shear resistance between foam concrete and C-Channels, an investigation is carried out on the shear connectors in foam concrete with cold-formed steel double C-Channels embedment. Twenty-four tests have been carried out in two groups. Two types of connectors: flange connectors and web connectors are installed using self-drilling screws for a rapid construction. The experimental results show that they can effectively improve the longitudinal shear-resist capacity of the concrete. After the experiment, the specimens are dismantled for an interior observation. Based on the observation, the form of damage, the failure mechanism was discovered, and the equation of longitudinal shear capacity was developed. It is concluded that the failure involves independent slippage between two C-Channels and the shear connection fractures. Since the composite structure requires sufficient slip between the two materials, these types of shear connectors will have good enhancement for this type of composite structures subjected to dynamic loads

Evolution of laparoscopic left lateral sectionectomy without the Pringle maneuver: through resection of benign and malignant tumors to living liver donation

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors' experience using laparoscopic LLS for different indications including living liver donation. METHODS: Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients. RESULTS: All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8-46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115-300 min), and the median blood loss was of 50 ml (range, 0-500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5-27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2-10 days). CONCLUSIONS: Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation

Medical student views of and responses to expectations of professionalism

Funding this study is part of the corresponding author's (EAS) doctoral programme of research funded by the University of Aberdeen, and supervised by EH and JC. Acknowledgements we thank all the students who took part in this project, and Professor Rona Patey, the Director of the Institute of Education for Medical and Dental Sciences, University of Aberdeen, for her support of this project.Peer reviewedPostprin