Analysis of spinner straightening utilizing the finite element method

This paper presents analysis methods utilizing the Finite Element Method for spinner straightening, and shows a guideline for optimum conditions. Two types of analysis methods were composed. Model [F-Expl], “full actual model with explicit scheme”, considers the rotational movement of dies as the actual process using the explicit scheme. Model [BndCr], “a model carrying out fundamental analysis on one cross section based on simple bending in the Finite Element Method (FEM)”, uses the FEM only for calculation of simple bending without rotation for obtaining the deformed bar shape. A series of experiments were conducted in an actual production line as well as the analyses by Model [F-Expl] and [BndCr]. The examination mainly focused upon the effect of straightening intensity by changing the die positions. The experimental and analytical results show some mechanism of straightening and a basic guideline for the optimum working condition

Factors associated with unwillingness to seek professional help for depression: a web-based survey

Abstract Objective Depression is a prevalent disorder that has a substantial impact on not only individuals but also society as a whole. Despite many effective depression interventions, delay in initial treatment contact is problematic. The Internet is a possible tool for low-cost dissemination of appropriate information and awareness raising about depressive disorders among the general public. This study aimed to identify factors associated with unwillingness to seek professional help for depression in Internet users. Results This web-based cross-sectional study surveyed 595 participants who scored over the cutoff point for depression on a self-rated mental-health questionnaire for depression, had never been assessed or treated by a mental health professional, and were experiencing depressive symptoms for at least 6 months. Among the 595 participants, 329 (55.3%) reported they were unwilling to seek professional help for depression. Regression analysis indicated that unwillingness to seek professional help for depression was associated with male sex and financial issues as a depression trigger, and that willingness to seek professional help was associated with problems with interpersonal relationships. The Internet warrants further complementary investigation to elucidate factors associated with unwillingness to seek professional help for depression

Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.

モルフィナンアルカロイド生産のための微生物プラットホームの確立. 京都大学プレスリリース. 2016-02-05.Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l(-1) from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (R)-reticuline in E. coli. Furthermore, by adding two genes to the thebaine production system, we demonstrate the biosynthesis of hydrocodone, a clinically important opioid. Improvements in opiate production in this E. coli system represent a major step towards the development of alternative opiate production systems

Analysis of spinner straightening utilizing the finite element method

This paper presents analysis methods utilizing the Finite Element Method for spinner straightening, and shows a guideline for optimum conditions. Two types of analysis methods were composed. Model [F-Expl], “full actual model with explicit scheme”, considers the rotational movement of dies as the actual process using the explicit scheme. Model [BndCr], “a model carrying out fundamental analysis on one cross section based on simple bending in the Finite Element Method (FEM)”, uses the FEM only for calculation of simple bending without rotation for obtaining the deformed bar shape. A series of experiments were conducted in an actual production line as well as the analyses by Model [F-Expl] and [BndCr]. The examination mainly focused upon the effect of straightening intensity by changing the die positions. The experimental and analytical results show some mechanism of straightening and a basic guideline for the optimum working condition

(R,S)-Tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli

Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) found in diverse pharmaceutical compounds, is used as a starting material for the production of BIA. THP also has various neurobiological properties but is difficult to synthesize. Therefore, a simple method for THP production is desired. Recent studies have shown that microbes, especially bacteria, can serve as platforms for synthesizing these complex compounds; however, because bacteria lack organelles, the designed synthetic pathway cannot be compartmentalized. Thus, the metabolic flow is frequently inhibited or disrupted by undesirable reactions. Indeed, in the first attempt to synthesize THP using a single strain of engineered Escherichia coli, the yield was quite low (<5 μM), mainly because of the oxidation of THP by tyrosinase, an essential enzyme in our production system. To circumvent these problems, we constructed a stepwise (R, S)-THP production system, in which the dopamine-producing step and the subsequent THP-producing step were separated. The yield of (R, S)-THP reached 1.0 mM (287 mg/L), the highest yielding BIA production method using a microbe reported to date. Furthermore, we demonstrated that (R, S)-THP produced by stepwise fermentation is useful for the production of reticuline, an important BIAs intermediate. Based on these observations, applying the stepwise fermentation method is discussed

Microbial production of novel sulphated alkaloids for drug discovery

Natural products from plants are useful as lead compounds in drug discovery. Plant benzylisoquinoline alkaloids (BIAs) exhibit various pharmaceutical activities. Although unidentified BIAs are expected to be of medicinal value, sufficient quantities of such BIAs, for biological assays, are sometimes difficult to obtain due to their low content in natural sources. Here, we showed that high productivity of BIAs in engineered Escherichia coli could be exploited for drug discovery. First, we improved upon the previous microbial production system producing (S)-reticuline, an important BIA intermediate, to obtain yields of around 160 mg/L, which was 4-fold higher than those of the previously reported highest production system. Subsequently, we synthesised non-natural BIAs (O-sulphated (S)-reticulines) by introducing human sulphotransferases into the improved (S)-reticuline production system. Analysis of human primary cells treated with these BIAs demonstrated that they affected a biomarker expression in a manner different from that by the parent compound (S)-reticuline, suggesting that simple side-chain modification altered the characteristic traits of BIA. These results indicated that highly productive microbial systems might facilitate the production of scarce or novel BIAs and enable subsequent evaluation of their biological activities. The system developed here could be applied to other rare natural products and might contribute to the drug-discovery process as a next-generation strategy

Surgical treatment of rectal cancer with a Retzius shunt: a case report

Abstract Background A case of a short circuit (Retzius shunt) from the inferior mesenteric vein (IMV) to the inferior vena cava (IVC) without accompanying portal hypertension due to liver cirrhosis is rare. Case presentation An 83-year-old woman who was followed after surgery for thyroid and breast cancer was incidentally found to have rectal cancer on computed tomography (CT). Preoperative three-dimensional CT showed a venous malformation forming a short circuit (Retzius shunt) from the IMV to the IVC. Laparoscopic anterior rectal resection was performed. Operative findings included the Retzius vein crossing the abdominal aorta and the inferior mesenteric artery (IMA) to the IVC and a number of engorged vessels in the mesentery. The Retzius vein and IMA were clipped without major bleeding, and tumor-specific mesorectal excision was then performed. The patient’s postoperative clinical course was good, and she was discharged without complications. Conclusions Preoperative imaging enabled identification of an unexpected rare disease, thus reinforcing the importance of preoperative imaging