Popliteal-crural bypass through the posterior approach with lesser saphenous vein for limb salvage

AbstractPurpose: A review of popliteal-crural bypasses via the posterior approach was done to evaluate the results of this technique. Methods: During a period of 36 months, 21 patients with limb-threatening ischemia underwent 21 popliteal-crural bypasses via the posterior approach in the prone position with reversed lesser saphenous vein. All patients had limb-threatening ischemia, with rest pain in five patients, ulceration in nine patients, and gangrene in seven patients. Diabetes mellitus was present in 17 patients. Results: The inflow site was the supragenicular popliteal artery in 12 patients and the infragenicular popliteal artery in nine patients. The outflow sites were the tibioperoneal trunk in five patients, the posterior tibial artery in six patients, the peroneal artery in eight patients, and the anterior tibial artery in two patients. Of the seven patients with gangrene, three patients underwent transmetatarsal amputation and four underwent toe amputation. The limb salvage rate for the entire group was 100% at 24 months. No early graft failures were seen, and the 12-month and 24-month primary graft patency rates were 89% and 77%, respectively, with life-table analysis. The primary assisted patency rate was 95% at 12 and 24 months. Patency was determined with duplex scan graft surveillance. Conclusion: The posterior approach to popliteal-distal bypass is an acceptable alternative to traditional bypass procedure with excellent early patency and limb salvage results. The approach has the advantage of better utilization of lesser saphenous vein and easier operative exposure in patients with short segment infrapopliteal occlusive disease. (J Vasc Surg 2002;36:708-12.

Voice Cloning Using Artificial Intelligence and Machine Learning: A Review

This paper represents a thorough method for integrating emotions, texttospeech conversion, and state of the art voice cloning. The paper focuses on novel background noise adaptation, emotional voice synthesis, and multi-speaker voice cloning for better speech synthesis. The synthesis of emotive voices, multi-speaker voice cloning, and creative methods for modifying background noise to improve speech synthesis quality are among the topics covered in this study. Additionally, the study explores the domain of emotional artificial intelligence by adding a variety of emotions to artificial voices, improving user engagement through sympathetic reactions. The study also looks at how background noise can be altered to change it from a disturbing to a silent, non-disruptive state. The texttospeech systems usability in noisy conditions is greatly enhanced by this improvement. By integrating these components, the project makes a substantial contribution to text to speech, emotional AI, and voice cloning, creating new avenues for human-computer connection

Unsupervised Activity Segmentation by Joint Representation Learning and Online Clustering

We present a novel approach for unsupervised activity segmentation, which uses video frame clustering as a pretext task and simultaneously performs representation learning and online clustering. This is in contrast with prior works where representation learning and clustering are often performed sequentially. We leverage temporal information in videos by employing temporal optimal transport. In particular, we incorporate a temporal regularization term which preserves the temporal order of the activity into the standard optimal transport module for computing pseudo-label cluster assignments. The temporal optimal transport module enables our approach to learn effective representations for unsupervised activity segmentation. Furthermore, previous methods require storing learned features for the entire dataset before clustering them in an offline manner, whereas our approach processes one mini-batch at a time in an online manner. Extensive evaluations on three public datasets, i.e. 50-Salads, YouTube Instructions, and Breakfast, and our dataset, i.e., Desktop Assembly, show that our approach performs on par or better than previous methods for unsupervised activity segmentation, despite having significantly less memory constraints.Comment: Preprint. Under revie

Free radical 5-exo-dig cyclization as the key step in the synthesis of bis-butyrolactone natural products: experimental and theoretical studies

Radical cyclization reactions were performed by 5-exo-dig mode to yield cis-fused bicyclic systems, leading to the synthesis of bis-butyrolactone class of natural products. The study was aimed at understanding the impact of alkyl side chains of furanoside ring systems in L-ara configuration on the radical cyclization. It was amply demonstrated by experimental studies that the increase in the length of the alkyl side chain has an effect on the cyclization: while efficient cyclization reactions could be realized with methyl and ethyl side chains, the yields were significantly reduced in the case of n-pentyl side chain. Theoretical studies using DFT and (RO)MP2 methods were carried out to analyze the influence of the substitution pattern on the cyclization barriers

MgAICO3-HT catalyzed ring opening of oxiranes with TMSN3

1039-104

Multifaceted roles of transcription factors during plant embryogenesis

Transcription factors (TFs) are diverse groups of regulatory proteins. Through their specific binding domains, TFs bind to their target genes and regulate their expression, therefore TFs play important roles in various growth and developmental processes. Plant embryogenesis is a highly regulated and intricate process during which embryos arise from various sources and undergo development; it can be further divided into zygotic embryogenesis (ZE) and somatic embryogenesis (SE). TFs play a crucial role in the process of plant embryogenesis with a number of them acting as master regulators in both ZE and SE. In this review, we focus on the master TFs involved in embryogenesis such as BABY BOOM (BBM) from the APETALA2/Ethylene-Responsive Factor (AP2/ERF) family, WUSCHEL and WUSCHEL-related homeobox (WOX) from the homeobox family, LEAFY COTYLEDON 2 (LEC2) from the B3 family, AGAMOUS-Like 15 (AGL15) from the MADS family and LEAFY COTYLEDON 1 (LEC1) from the Nuclear Factor Y (NF-Y) family. We aim to present the recent progress pertaining to the diverse roles these master TFs play in both ZE and SE in Arabidopsis, as well as other plant species including crops. We also discuss future perspectives in this context

Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris

Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving overexpression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (ArgArg) at the end of B-chain of Glargine. KEX2 gene overexpression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw material

Strategies to modulate charge variants of a Biosmilar monoclonal antibody through cell culture conditions

Monoclonal antibodies (mAb) are the most successful and rapidly growing class of biopharmaceuticals used in treating several diseases. Biosimilar mAb, an approved version of an original biological medicinal product (reference product) with demonstrated similarity to the reference in terms of critical quality attributes, safety and efficacy, is an increasingly accepted solution to provide greater access at affordable cost to the patients across the world. But, given the complex nature of mAbs, developing a biosimilar using a new cell line and a process is challenging, especially with regards to matching the glycosylation and charge profiles to the appropriate level. It is reported that culture environment during the production of monoclonal antibody affects its various quality attributes including charge variant profiles1. The charge variants are usually formed due to chemical modification of amino acids by deamidation, oxidation, glycation and methylglyoxal adducts2, and may lead to increase in acidic charge variants. These unintended changes in the protein are mainly due to it being exposed during the long duration of the cell culture to an environment, like elevated temperature, nutrients from media and feed, metabolites from live and lysed cells, culture pH, which favours certain chemical modifications. Understanding and controlling cell culture process parameters are vital in developing a protein biologic to ensure process consistency and product quality. In the present study, we discuss a case study of development of a cell culture process to produce a proposed biosimilar mAb using a CHO cell line, and ways to modulate its charge variants in the cell culture. The initial screening experiments were performed in an ambr® 15 cell culture micro bioreactor system, from which an optimal 12-day process was chosen and subsequently tested in 3L and 10L bioreactors. Significant time-dependent increase in acidic charge variants was observed from day 10 to 12 at both bioreactor scales, while all other quality parameters remained largely unchanged during the last days of the culture. Further various strategies such as use of different basal media, feed, and additives (amino acids/metal ions and insulin), and changes in culture temperature and pH, were applied during the cell culture process to control the charge variants, in particular the acidic charge variants. The impact of various additives, cell culture pH, temperature on the charge profiles, as well as on productivity and glycosylation, during the development of this biosimilar mAb using a CHO cell line is discussed in detail. References: Liu, H., Nowak, C., Shao, M., Ponniah, G. and Neill, A. (2016), Impact of cell culture on recombinant monoclonal antibody product heterogeneity. Biotechnol Progress, 32: 1103–1112. Chumsae, C., Gifford, K., Lian, W., Liu, H., Radziejewski, C. H., & Zhou, Z. S. (2013). Arginine modifications by methylglyoxal: discovery in a recombinant monoclonal antibody and contribution to acidic species. Analytical chemistry, 85(23), 11401-11409

Protocol of a randomised controlled trial of real-time continuous glucose monitoring in neonatal intensive care 'REACT'.

INTRODUCTION: Hyperglycaemia is common in the very preterm infant and has been associated with adverse outcomes. Preventing hyperglycaemia without increasing the risk of hypoglycaemia has proved challenging. The development of real-time continuous glucose monitors (CGM) to inform treatment decisions provides an opportunity to reduce this risk. This study aims to assess the feasibility of CGM combined with a specifically designed paper guideline to target glucose control in the preterm infant. METHODS AND ANALYSES: The Real Time Continuous Glucose Monitoring in Neonatal Intensive Care (REACT) trial is an international multicentre randomised controlled trial. 200 preterm infants ≤1200 g and ≤24 hours of age will be randomly allocated to either real-time CGM or standard care (with blinded CGM data collection). The primary outcome is time in target 2.6-10 mmol/L during the study intervention assessed using CGM. Secondary outcomes include efficacy relating to glucose control, utility including staff acceptability, safety outcomes relating to incidence and prevalence of hypoglycaemia and health economic analyses. ETHICS AND DISSEMINATION: The REACT trial has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge Central); Medical Ethics Review Committee, VU University Medical Centre, Amsterdam, The Netherlands and the Research Ethics Committee, Sant Joan de Déu Research Foundation, Barcelona, Spain. Recruitment began in July 2016 and will continue until mid-2018. The trial has been adopted by the National Institute of Health Research Clinical Research Network portfolio (ID: 18826) and is registered with anInternational Standard Randomised Control Number (ISRCTN registry ID: 12793535). Dissemination plans include presentations at scientific conferences, scientific publications and efforts at stakeholder engagement. TRIAL REGISTRATION NUMBER: ISRCTN12793535; Pre-results