Numerical and Experimental Investigation on the Surface Defect Generation during the Hot Extrusion of Al6063 Alloy.

The surface quality control of extruded products is a critical concern in the home appliance manufacturing industry owing to the increasing need for products with a high surface quality, in addition to the essential mechanical properties of the final product. The underlying issue with achieving high-quality extrusion products is that surface defects, especially those resulting in surface gloss differences, called white line defects, are only observed after surface treatment. In this study, we aim to investigate the cause of white line defect generation on the surface of an extruded product. Accordingly, an experimental extrusion program is established using an L-shaped die that has a noticeable change in its bearing length along the inner corner of its cross-sectional profile. Laboratory-scale experiments were performed for the L-shaped extrusion of homogenized Al 6063 alloy at various ram speeds, in order to induce surface defects, considering the production yield rate required for mass production. Subsequently, the microstructural changes near the surface failure region were investigated using an arbitrary Lagrangian-Eulerian (ALE) technique-based thermomechanical finite element (FE) analysis. To scale-up the defect observation method from laboratory-scale to production-scale manufacturing and confirm the reproducibility of the surface defect, scaled-up L-shaped extrusions were performed in an actual industrial production line. Finally, the potential cause of white line defect generation is discussed by comparing the numerical and metallurgical analyses, including the scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD) observations.

Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide, causing serious liver complications, including nonalcoholic steatohepatitis. Recent findings suggest that peripheral serotonin (5-hydroxytryptamine, 5HT) regulates energy homeostasis, including hepatic lipid metabolism. More specifically, liver-specific 5HT2A knockout mice exhibit alleviated hepatic lipid accumulation and hepatic steatosis. Here, structural modifications of pimavanserin (CNS drug), a 5HT2A antagonist approved for Parkinson's disease, led us to synthesize new peripherally acting 5HT2A antagonists. Among the synthesized compounds, compound 14a showed good in vitro activity, good liver microsomal stability, 5HT subtype selectivity, and no significant inhibition of CYP and hERG. The in vitro and in vivo blood-brain barrier permeability study proved that 14a acts peripherally. Compound 14a decreased the liver weight and hepatic lipid accumulation in high-fat-diet-induced obesity mice. Our study suggests new therapeutic possibilities for peripheral 5HT2A antagonists in NAFLD.

NMR uncovers direct interaction between human NEDD4-1 and p34SEI-1.

PTEN, an important tumor suppressor and a key regulator of the PI3K/AKT signaling pathway, is often deleted/mutated in different types of cancer. The E3 ubiquitin ligase NEDD4-1 catalyzes the polyubiquitination of PTEN, thereby acting as a negative regulator of PTEN. Stability of NEDD4-1, in turn, is tightly controlled by a 34 kDa oncoprotein, p34SEI-1 and it regulates PTEN degradation and activates PI3K/AKT pathway, resulting in cancer metastasis. p34SEI-1 affects not only the expression of NEDD4-1 during transcription and translation but also the subcellular localization of PTEN. This emphasizes the need to understand, at molecular level, the interaction between NEDD4-1 and p34SEI-1. A recent study showed that NEDD4-1 interacts with p34SEI-1 via its WWI domain. However, a detailed interaction for molecular level is yet unknown. We report that the WW1 domain of NEDD4-1 recognizes the SERTA domain containing the proline rich region (PRR motif) in p34SEI-1. TALOS analysis based on NMR data confirms three conserved ß-sheets in NEDD4-1 WW1 and the central ß-sheet of NEDD4-1 WW1 plays a role for protein stability by the backbone dynamics experiments. NMR titration data revealed the binding site for p34SEI-1 with NEDD4-1. Our data will provide insights into the molecular mechanism of NEDD4-1 and p34SEI-1 interaction, which will be directly used for drug design which inhibits the molecular interaction involved in different cancer signaling.

The use of 3 sugammadex out of 5 reversal of during recovery of rocuronium-induced neuromuscular blockade in a patient with post-tonsillectomy hemorrhage: a case report.

Post-tonsillectomy hemorrhage (PTH) is the most frequent complication of tonsillectomy, and occasionally results in a lethal outcome. A 21-year-old man (height 180 cm, weight 95 kg) was scheduled for a bilateral tonsillectomy and uvulopalatopharyngoplasty for treatment of obstructive sleep apnea. He required 5 rounds of general anesthesia due to recurrent PTH. The anesthesiologist used sugammadex a total of 3 times to achieve the successful reversal of the deep neuromuscular blockade (NMB) induced by rocuronium. After sugammadex 2 mg/kg was administered, the NMB was reversed in 2 minutes each time. Re-administration of rocuronium within a short time interval after sugammadex may result in unpredictable effects of neuromuscular blocking agents. Sugammadex made it possible to perform a rapid, complete reverse when the residual block was maintained by an incomplete reversal of anticholinesterase.

Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.

BACKGROUND: Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. METHODS: This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. RESULTS: The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). CONCLUSIONS: Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.

Antiemetic efficacy of capsicum plaster on acupuncture points in patients undergoing thyroid operation.

BACKGROUND: Postoperative nausea and vomiting (PONV) occurs in up to 63-84% of patients after thyroid surgery. This study aims to assess the effects of using a capsicum plaster to reduce PONV after thyroid surgery at either the Chinese acupuncture point (acupoint) Pericardium 6 (P6) or Korean hand acupuncture point K-D2. METHODS: One-hundred eighty-four patients who underwent thyroid surgery were randomized in four groups (n = 46 each): control group = inactive tape at P6 acupoints and on both shoulders as a nonacupoint; P6 group = capsicum plaster at P6 points and inactive tape on both shoulders; K-D2 group = capsicum plaster at K-D2 acupoints and inactive tape on both shoulders; Sham group = capsicum plaster on both shoulders and inactive tape at P6 acupoints. The capsicum plaster was applied before the induction of anesthesia and removed at 8 hr after surgery. RESULTS: The incidence and severity of nausea and vomiting and the need for rescue antiemetics were decreased in the patients in the P6 and K-D2 groups compared to the patients in the control and sham groups (P < 0.001). The patients in the P6 and K-D2 groups also reported that they were more satisfied (P < 0.05). CONCLUSIONS: We conclude that the capsicum plaster at the P6 and K-D2 acupoint was a promising antiemetic method for the patients undergoing thyroid surgery.

The genome sequence of the ethanologenic bacterium Zymomonas mobilis ZM4.

We report the complete genome sequence of Zymomonas mobilis ZM4 (ATCC31821), an ethanologenic microorganism of interest for the production of fuel ethanol. The genome consists of 2,056,416 base pairs forming a circular chromosome with 1,998 open reading frames (ORFs) and three ribosomal RNA transcription units. The genome lacks recognizable genes for 6-phosphofructokinase, an essential enzyme in the Embden-Meyerhof-Parnas pathway, and for two enzymes in the tricarboxylic acid cycle, the 2-oxoglutarate dehydrogenase complex and malate dehydrogenase, so glucose can be metabolized only by the Entner-Doudoroff pathway. Whole genome microarrays were used for genomic comparisons with the Z. mobilis type strain ZM1 (ATCC10988) revealing that 54 ORFs predicted to encode for transport and secretory proteins, transcriptional regulators and oxidoreductase in the ZM4 strain were absent from ZM1. Most of these ORFs were also found to be actively transcribed in association with ethanol production by ZM4.