49 research outputs found
Iteration Methods for Solving Nonlinear Programming Problems
This paper proposes simple and practical iteration methods for finding an optimal solution of a nonlinear programming problem with inequality and equality constraints. The iteration methods seek a point which satisfies the Kuhn-Tucker conditions. It is shown that the sequence of points generated by the iteraion methods converges to the optimal solution. Numerical results show the efficency of the proposed methods
Prototyping Hexagonal Light Concentrators Using High-Reflectance Specular Films for the Large-Sized Telescopes of the Cherenkov Telescope Array
We have developed a prototype hexagonal light concentrator for the
Large-Sized Telescopes of the Cherenkov Telescope Array. To maximize the
photodetection efficiency of the focal-plane camera pixels for atmospheric
Cherenkov photons and to lower the energy threshold, a specular film with a
very high reflectance of 92-99% has been developed to cover the inner surfaces
of the light concentrators. The prototype has a relative anode sensitivity
(which can be roughly regarded as collection efficiency) of about 95 to 105% at
the most important angles of incidence. The design, simulation, production
procedure, and performance measurements of the light-concentrator prototype are
reported.Comment: 21 pages, 14 figures, accepted for publication in JINS
Human Sapovirus in Clams, Japan
Human sapovirus was detected in 4 of 57 clam packages by reverse transcription–PCR and sequence analysis. This represents the first finding of sapovirus contamination in food. Closely matching sequences have been detected in stool specimens from patients with gastroenteritis in Japan, which indicates a possible food-to-human transmission link
発症早期ALS患者に対する超高用量メチルコバラミンの有効性・安全性について : ランダム化比較試験
Importance:
Post hoc analysis in a phase 2/3 trial indicated ultra-high dose methylcobalamin slowed decline of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 16 as well as at week 182, without increase of adverse events, in patients with amyotrophic lateral sclerosis (ALS) who were enrolled within 1 year from onset.
Objective:
To validate the efficacy and safety of ultra-high dose methylcobalamin for patients with ALS enrolled within 1 year of onset.
Design:
A multicenter, placebo-controlled, double-blind, randomized phase 3 trial with 12-week observation and 16-week randomized period, conducted from October 2017 to September 2019.
Setting:
Twenty-five neurology centers in Japan.
Participants:
Patients with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in ALSFRS-R total score, a percent forced vital capacity over 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulant. The target number was 64 in both methylcobalamin and placebo groups. Of 203 patients enrolled in the observation, 130 patients (age, 61.0 ± 11.7 years; female, 56) met the criteria and were randomly assigned through an electronic web-response system to methylcobalamin or placebo (65 for each). Of these, 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage.
Interventions:
Intramuscular injection of methylcobalamin 50 mg or placebo twice weekly for 16 weeks.
Main outcomes and measures:
The primary endpoint was change in ALSFRS-R total score from baseline to week 16 in the full analysis set.
Results:
The least-squares mean difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 versus −4.63; 95% CI, 0.44–3.50; P = 0.012). The incidence of adverse events was similar between the two groups.
Conclusions and relevance:
Ultra-high dose methylcobalamin was efficacious in slowing functional decline and safe in the 16-week treatment period in ALS patients in the early stage and with moderate progression rate.
Trial registration:
UMIN-CTR Identifier: UMIN000029588 (umin.ac.jp/ctr); ClinicalTrials.gov Identifier: NCT03548311 (clinicaltrials.gov
Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation
Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis
Genetic variants in antioxidant pathway: Risk factors for hepatotoxicity in tuberculosis patients
Tuberculosis (TB) treatment can cause serious sequelae including adverse effects such as anti-TB drug-induced hepatotoxicity (ATDH). We performed a candidate gene-based association study between single nucleotide polymorphisms (SNPs) in 10 genes in the antioxidant pathway and ATDH susceptibility. The subjects comprised 100 Japanese patients with pulmonary TB who received a treatment regimen including isoniazid and rifampicin. Out of them, 18 patients had ATDH. Thirty-four tag SNPs in 10 genes were analyzed by PCR-restriction fragment length polymorphism or PCR-direct DNA sequencing. The frequencies of alleles and genotypes between patients with and without ATDH were compared in three different genetic models. Statistical analyses revealed that a C/C genotype at rs11080344 in NOS2A, a C/C genotype at rs2070401 in BACH1, and a G/A or A/A genotype at rs4720833 in MAFK independently conferred ATDH susceptibility. Remarkably, the association of the latter two tag SNPs with ATDH susceptibility was highly statistically significant (P = 0.0006) with an odds ratio of 9.730. This study is the first report to demonstrate that NOS2A, BACH1, and MAFK appear to be genetic determinants of ATDH in Japanese patients with TB. Furthermore, a combination of BACH1 and MAFK polymorphisms may be useful as new biomarkers to identify high-risk Japanese TB patients for ATDH
Joint Observation of the Galactic Center with MAGIC and CTA-LST-1
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations
高性能電気化学バイオセンサのための電極構造に関する研究
京都大学0048新制・課程博士博士(農学)甲第16930号農博第1946号新制||農||1001(附属図書館)学位論文||H24||N4691(農学部図書室)29605京都大学大学院農学研究科応用生命科学専攻(主査)教授 加納 健司, 教授 植田 充美, 教授 三芳 秀人学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDA
サイショウジジョウホウニモトズクヒセンケイケイカクモンダイノハンプクカイホウトコウゾウブツサイテキセッケイモンダイエノオウヨウ
京都大学0048新制・論文博士工学博士乙第3844号論工博第1177号新制||工||439(附属図書館)5880UT51-54-H144(主査)教授 三根 久, 教授 得丸 英勝, 教授 池田 峰夫学位規則第5条第2項該当Kyoto UniversityDA