Deep Space Transportation System Using the Sun-Earth L2 Point

Recently, various kinds of planetary explorations have become more feasible, taking the advantage of low thrust propulsion means such as ion engines that have come into practical use. The field of space activity has now been expanded even to the rim of the outer solar system. In this context, the Japan Aerospace Exploration Agency (JAXA) has started investigating a Deep Space Port built at the L2 Lagrange point in the Sun-Earth system. For the purpose of making the deep space port practically useful, there is a need to establish a method to making spaceship depart and return from/to the port. This paper first discusses the escape maneuvers originating from the L2 point under the restricted three-body problem. Impulsive maneuvers from the L2 point are extensively studied here, and using the results, optimal low-thrust escape strategies are synthesized. Furthermore, this paper proposes the optimal escape and acceleration maneuvers schemes using Electric Delta-V Earth Gravity Assist (EDVEGA) technique

Alcohol-induced pancreatitis

膵炎のうちもっとも頻度が高いアルコール性膵炎（AIP）の疫学，臨床像および発生機序に関する従来の知見を総括した。AIPの大多数は慢性膵炎である。通常は長期にわたる多量の飲酒を背景に発症するが，遺伝的素因および食事因子も重要な役割を演じる。発症初期には血中膵酵素の上昇をともなう腹痛が病像を支配するが，進展すると膵外分泌不全による消化吸収障害と膵内分泌不全による糖尿病が病像を支配するようになる。アルコール性慢性膵炎は非アルコール性慢性膵炎にくらべて確診時にすでに進展した症例が多く，合併症が多く，進行が早く，予後が悪い。死亡の主たる原因は癌の併発と糖尿病の合併症で，膵炎の急性増悪発作がこれにつぐ。併発する癌のなかでは膵癌よりもむしろ上部気道および上部消化管の癌が多い。発生機序としてはDuctal－Plug説とToxic－Metabolic説が有力であるが，最近は細 胞内膵酵素活性化説とFree　Radical説も注目をあびている。This paper is to review the literature on the epidemiology, clinical pictures and etiopathogenesis of alcohol-induced pancreatitis (AIP). The incidence of AIP has been increasing worldwide, paralleling the increase in alcohol consumption. AIP manifests itself following a longterm consumption of large amounts of alcohol. There is no known threshold value of alcohol consumption in terms of the risk of developing AIP, although the logarithm of the risk of developing AIP is lineally correlated with the amount of alcohol intake. Why some alcoholics develop pancreatitis whereas others with equal consumption of ethanol are spared remains to be explained. Therefore, two additional factors are considered to play important roles in developing AIP : genetic predisposition and diet. The majority of AIP IS chronic pancreatitis (AICP), although a minority can be acute pancreatitis (AIAP). AIAP shows somewhat higher morbidity and mortality than the common variety of acute pancreatitis. If recovered from an attack, AIAP shows morphological and functional restoration. AICP manifests itself with an acute attack of abdominal pain, insidious onset of abdominal pam, or a pain-free variety. An acute attack in AICP resemble that m AIAP ; often these two can be differentiated only by follow-up studies. AICP shows no morphological and functional restoration, and often shows progressive deterioration. Abdominal pain with elevated serum pancreatic enzymes is a predominant clinical picture m the early stage of AICP, whereas in the late stage symptoms and signs deriving from exocrine insufficiency (maldigestion) and endocrine insufficiency (pancreatic diabetes) begin to dominate the clinical pictures. AICP is in the more advanced stage and shows more complications than nonalcoholic chronic pancreatitis at the time of diagnosis. In addition, AICP shows more rapid progress and higher morbidity and mortality. The incidence of microangiopathy in pancreatic diabetes resemble that in primary diabetes, being higher in patients with a longer history of diabetes, those on insulin treatment and those under poorer control. Main causes of death are development of cancer in the upper respiratory and gastrointestinal tract and diabetic complications (hypoglycemic shock, renal failure, and intractable pneumonia), and acute attack of pancreatitis leads to death less frequently. Ductal-Plug theory and classical Toxic-Metabolic theory are most popular to explain the pathogenesis of AIP ; however, increasing evidence has been reported that oxygen free radicals and intracellular activation of zymogens by lysosomal enzymes may be involved in the pathogenesis

SirT1 Gain of Function Increases Energy Efficiency and Prevents Diabetes in Mice

SummaryIn yeast, worms, and flies, an extra copy of the gene encoding the Sirtuin Sir2 increases metabolic efficiency, as does administration of polyphenols like resveratrol, thought to act through Sirtuins. But evidence that Sirtuin gain of function results in increased metabolic efficiency in mammals is limited. We generated transgenic mice with moderate overexpression of SirT1, designed to mimic the Sirtuin gain of function that improves metabolism in C. elegans. These mice exhibit normal insulin sensitivity but decreased food intake and locomotor activity, resulting in decreased energy expenditure. However, in various models of insulin resistance and diabetes, SirT1 transgenics display improved glucose tolerance due to decreased hepatic glucose production and increased adiponectin levels, without changes in body weight or composition. We conclude that SirT1 gain of function primes the organism for metabolic adaptation to insulin resistance, increasing hepatic insulin sensitivity and decreasing whole-body energy requirements. These findings have important implications for Sirtuin-based therapies in humans

Foxo1 Links Hyperglycemia to LDL Oxidation and Endothelial Nitric Oxide Synthase Dysfunction in Vascular Endothelial Cells

OBJECTIVE: Atherosclerotic cardiovascular disease is the leading cause of death among people with diabetes. Generation of oxidized LDLs and reduced nitric oxide (NO) availability because of endothelial NO synthase (eNOS) dysfunction are critical events in atherosclerotic plaque formation. Biochemical mechanism leading from hyperglycemia to oxLDL formation and eNOS dysfunction is unknown. RESEARCH DESIGN AND METHODS: We show that glucose, acting through oxidative stress, activates the transcription factor Foxo1 in vascular endothelial cells. RESULTS: Foxo1 promotes inducible NOS (iNOS)-dependent NO-peroxynitrite generation, which leads in turn to LDL oxidation and eNOS dysfunction. We demonstrate that Foxo1 gain-of-function mimics the effects of hyperglycemia on this process, whereas conditional Foxo1 knockout in vascular endothelial cells prevents it. CONCLUSIONS: The findings reveal a hitherto unsuspected role of the endothelial iNOS-NO-peroxynitrite pathway in lipid peroxidation and eNOS dysfunction and suggest that Foxo1 activation in response to hyperglycemia brings about proatherogenic changes in vascular endothelial cell function

Study protocol for endoscopic ultrasonography-guided ethanol injection therapy for patients with pancreatic neuroendocrine neoplasm: a multicentre prospective study

Introduction The management of small pancreatic neuroendocrine neoplasms (PNENs) remains controversial. The standard treatment for PNENs is surgical resection; however, invasiveness of surgical procedure remains higher and the incidence of postoperative adverse events is still high. Recently, the efficacy and safety of endoscopic ultrasonography (EUS)-guided ethanol injection for small PNENs has been preliminarily demonstrated. Thus, a multicentre prospective study is being conducted to evaluate the efficacy and safety of EUS-guided ethanol injection therapy for small PNENs. Methods and analysis The major eligibility criteria are the presence of pathologically diagnosed grade (G) 1 tumour, a tumour size of <= 15 mm and non-functional PNEN or insulinoma. For treatment, we will use a 25-gauge needle and pure ethanol. Contrast-enhanced CT (CE-CT) will be performed on postoperative day 3-5, and if enhanced areas of the tumour are still apparent, an additional session is scheduled during the same hospitalisation period. We set the total amount of ethanol per session to 2 mL. To evaluate the efficacy and safety, CE-CT will be performed at 1 and 6 months after treatment. The primary endpoint is the percentage of subjects who achieved all of the following evaluated points. Efficacy will be evaluated based on the achievement of complete ablation (defined as no enhanced area within the tumour on CE-CT) at 1 and 6 months. Safety will be evaluated based on the avoidance of severe adverse events within 1 month after treatment, continuing severe pancreatic fistula at 1 month after treatment and the incidence and/or exacerbation of diabetes mellitus at 6 months after treatment. Ethics and dissemination This protocol has been approved by Okayama University Certified Review Board (approval number. CRB19-007). The results will be submitted to peer-reviewed journals and will be presented at international conferences