Lubiprostone: RU 0211, SPI 0211.

PubMed

2005-01-01

Lubiprostone [RU 0211, SPI 0211] is a bicyclic fatty acid that acts as a chloride channel opener, increasing intestinal water secretion. Lubiprostone, an orally-administered formulation, is one of a series of functional fatty acid compounds discovered by Dr Ryuji Ueno, and is currently undergoing development for the treatment of constipation, constipation-predominant irritable bowel syndrome (IBS-C) and postoperative ileus with Sucampo Pharmaceutical's. Lubiprostone activates a specific chloride channel (CLC2) on cells lining the gut, thereby naturally increasing intestinal fluid secretion. The increased fluid level softens the stool, promotes spontaneous bowel movements, and reduces abdominal discomfort/pain and bloating. The chloride channel is a protein that controls cell membrane transport of chloride ion. Lubiprostone acts on the ClC-2 chloride channel, which is located in the apical intestinal membrane. In November 2004, Takeda Pharmaceuticals entered into a collaboration and licensing agreement for Lubiprostone with Sucampo Pharmaceuticals for the treatment of chronic constipation and constipation-predominant Irritable Bowel Syndrome (c-IBS). Under the terms of the agreement, Takeda received the right to market the product in the US and Canada, while Sucampo reserved the co-promotion rights for these countries. Takeda's wholly-owned US subsidiary, Takeda Pharmaceuticals North America Inc., will sell lubiprostone once the product is approved by the US FDA. Takeda will also receive an option for marketing rights in other territories, including Japan and Europe. Takeda and Sucampo agreed on the exclusive manufacturing and supply of Lubiprostone by R-Tech Ueno, Ltd, a member of the Sucampo Group. Sucampo has the potential to receive up to dollar US 210 million in initial and milestone payments, some of which are contingent upon the successful achievement of several milestones. Takeda will fund a major part of development costs not only for chronic constipation

Reactive oxygen species upregulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells.

PubMed

Uchida, Takayuki; Sakashita, Yoshihiro; Kitahata, Kanako; Yamashita, Yui; Tomida, Chisato; Kimori, Yuki; Komatsu, Akio; Hirasaka, Katsuya; Ohno, Ayako; Nakao, Reiko; Higashitani, Atsushi; Higashibata, Akira; Ishioka, Noriaki; Shimazu, Toru; Kobayashi, Takeshi; Okumura, Yuushi; Choi, Inho; Oarada, Motoko; Mills, Edward M; Teshima-Kondo, Shigetada; Takeda, Shin'ichi; Tanaka, Eiji; Tanaka, Keiji; Sokabe, Masahiro; Nikawa, Takeshi

2018-06-01

Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume (Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798-4811, 2009). However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed that the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2 early-growth response protein (Egr)1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatments such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr1 and/or Egr2 to stimulate Cbl-b expression through the ERK1/2 pathway in L6 myoblasts, since treatment with Egr1/2 siRNA and an ERK1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at -110 to -60 bp of the Cbl-b promoter. Together, this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway.

Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients.

PubMed

Thom, Claire

2015-09-01

Claire Thom speaks to Gemma Westcott, Commissioning Editor: Claire Thom joined Astellas in 2013 as the Therapeutic Area Head for Oncology in Global Development. In that role, she also serves as the STAR leader for Oncology for Astellas. Prior to Astellas, she spent 12 years with Takeda. Her last position was Senior Vice President, Portfolio Management, Drug Development Management and Medical Informatics and Strategic Operations within the Medical Division (the Division within Millennium responsible for oncology clinical drug development within Takeda). During her 4 years at Millennium, at various times, she had responsibility within the Medical Division for leading portfolio management, business operations (medical finance, annual and mid-range financial planning, space planning and operations, headcount resourcing, development goals process), clinical development operations (clinical operations, programming, data management, statistics, medical writing, clinical outsourcing), drug development management (project management), medical informatics (technology support for the division) and the strategic project management office for the division. Prior to joining Millennium, Claire Thom spent 18 months working in Osaka, Japan, during which she was responsible for developing the oncology strategy for Takeda that culminated in the acquisition of Millennium. Before going to Japan, she held positions of varying responsibility within the Takeda US development organization including the management of regulatory affairs, safety, biometrics and data management, clinical research and quality assurance. Claire Thom has particular expertise in organizational design and efficiency; she has successfully worked through integrations across multiple functions and redesigned business processes. She has a PharmD from University of Illinois (IL, USA) and over 20 years of pharmaceutical experience including positions in medical affairs and new product planning (over 11 years at Searle

Estimation of seismic velocity changes at different depths associated with the 2014 Northern Nagano Prefecture earthquake, Japan ( M W 6.2) by joint interferometric analysis of NIED Hi-net and KiK-net records

NASA Astrophysics Data System (ADS)

Sawazaki, Kaoru; Saito, Tatsuhiko; Ueno, Tomotake; Shiomi, Katsuhiko

2016-12-01

To estimate the seismic velocity changes at different depths associated with a large earthquake, we apply passive image interferometry to two types of seismograms: KiK-net vertical pairs of earthquake records and Hi-net continuous borehole data. We compute the surface/borehole deconvolution waveform (DCW) of seismograms recorded by a KiK-net station and the autocorrelation function (ACF) of ambient noise recorded by a collocated Hi-net station, 26 km from the epicenter of the 2014 Northern Nagano Prefecture earthquake, Japan ( M W 6.2). Because the deeper KiK-net sensor and the Hi-net sensor are collocated at 150 m depth, and another KiK-net sensor is located at the surface directly above the borehole sensors, we can measure shallow (<150 m depth) and deep (>150 m depth) velocity changes separately. The sensitivity of the ACF to the velocity changes in the deeper zone is evaluated by a numerical wave propagation simulation. We detect relative velocity changes of -3.1 and -1.4% in the shallow and deep zones, respectively, within 1 week of the mainshock. The relative velocity changes recover to -1.9 and -1.1%, respectively, during the period between 1 week and 4 months after the mainshock. The observed relative velocity reductions can be attributed to dynamic strain changes due to the strong ground motion, rather than static strain changes due to coseismic deformation by the mainshock. The speed of velocity recovery may be faster in the shallow zone than in the deep zone because the recovery speed is controlled by initial damage in the medium. This recovery feature is analogous to the behavior of slow dynamics observed in rock experiments.

[Chairman's introductory remarks].

PubMed

Shimo, Masamune

2013-01-01

Remote medicine, as well as the technological development of IT, has been realized in various fields of medical care. Reports have been published of the actual utilization of a system of remote diagnosis by infectious disease surveillance in each region of Nagano Prefecture, a telepathology system in Nagano, operation case of a radiological image remote diagnosis. Situation in the lack of pathologists and radiologists, that changes in the way of working of the physician, or medical information digitized convey how the doctor involved in the diagnosis, any diagnosis based on the information that was received doctor such as whether to perform, various issues have been raised. Soot digitization of information.

Dengue vaccines: Are they safe for travelers?

PubMed

Halstead, Scott B; Aguiar, Maira

2016-01-01

The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries. An additional two dengue vaccines, developed by the National Institute of Allergy and Infectious Diseases (NIAID), USA and Takeda, are entering phase III testing. Dengvaxia is composed of four yellow fever 17D-DENV chimeras, the NIAID vaccine contains three mutagenized DENV and one DENV2/4 chimera while the Takeda vaccine contains an attenuated DENV 2 and three DENV 2-DENV chimeras. Which of these vaccines might be useful in protecting travelers against dengue infections and disease? Dengvaxia requires three doses administered over the course of one year but in addition has safety signals suggesting that susceptible individuals should not be vaccinated. The NIAID vaccine is promising as a travel vaccine as a single dose fully protected susceptible adults against live dengue 2 virus challenge. The protective efficacy and safety of the Takeda vaccine remain to be demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microbes Characteristics in Groundwater Flow System in Mountainous Area

NASA Astrophysics Data System (ADS)

Yamamoto, Chisato; Tsujimura, Maki; Kato, Kenji; Sakakibara, Koichi; Ogawa, Mahiro; Sugiyama, Ayumi; Nagaosa, Kazuyo

2017-04-01

We focus on a possibility of microbes as a tracer for groundwater flow investigation. Some previous papers showed that the total number of prokaryotes in groundwater has correlation with depth and geology (Parkes et al., 1994; Griebler et al., 2009; Kato et al., 2012). However, there are few studies investigating both microbe characteristics and groundwater flow system. Therefore, we investigated a relationship between the total number of prokaryotes and age of spring water and groundwater. Intensive field survey was conducted at four mountainous areas, namely Mt. Fuji (volcano), a headwater at Mt. Setohachi, a headwater at River Oi and a headwater at River Nagano underlain by volcanic lava at Mt. Fuji, granite at Mt. Setohachi and sedimentary rock at River Oi and River Nagano. We collected totally 40 spring water/ groundwater samples in these mountainous areas in October 2015, August, October and November 2016 and analyzed concentration of inorganic ions, the stable isotopes of oxygen - 18, deuterium, CFCs and SF6. Also, we counted prokaryotic cells under the epifluorescence microscopy after fixation and filteration. The total number of prokaryotes in the spring water/ groundwater ranged from 1.0×102 to 7.0×103cells mL-1 at the Mt. Fuji, 1.3×104 to 2.7×105cells mL-1 at Mt. Setohachi, 3.1×104cells mL-1 at River Oi and 1.8×105 to 3.2×106cells mL-1 at River Nagano. The SF6 age of the spring water/ groundwater ranged from 8 to 64 years at Mt. Fuji, 2 to 32.5 years at Mt. Setohachi, 2.5 years at River Oi and 15 to 16 years at River Nagano. The total number of prokaryotes showed a clear negative correlation with residence time of spring water/ groundwater in all regions. Especially the prokaryotes number increased in the order of 102 cells mL-1 with decreasing of residence time in approximately 10 years in the groundwater and spring water with the age less than 15 years.

Identifying the Right Disease Targets to Develop Better Drugs, Faster | NIH MedlinePlus the Magazine

MedlinePlus

... Association Foundation for the NIH Rheumatoid Arthritis and Lupus The Partners Government NIH Industry AbbVie Bristol-Myers ... Pfizer Sanofi Takeda Non-Profit Organizations Alliance for Lupus Research Foundation for HIH Lupus Research Institute Rheumatology ...

78 FR 17207 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

.... 20130471 G Sun Pharmaceutical Industries Limited; Takeda Pharmaceutical Company Limited; Sun Pharmaceutical.... Martin, Ph.D.; Gilead Sciences, Inc.; John C. Martin, Ph.D. 20130547 G Jindal Poly Films Limited; Exxon... Norbert W. Bischofberger, Ph.D.; Gilead Sciences, Inc.; Norbert W. Bischofberger, Ph.D. 20130611 G...

Drug evaluation: TAK-475--an oral inhibitor of squalene synthase for hyperlipidemia.

PubMed

Burnett, John R

2006-09-01

Takeda Pharmaceutical Co Ltd is developing TAK-475, a squalene synthetase inhibitor from a series of 4,1-benzoxazepine-3-acetic acid derivatives, for the potential oral treatment of hyperlipidemia. By March 2005, TAK-475 was undergoing phase III clinical trials in the US and Europe.

Uterine-Specific Knockout of Tsc-2: A Mouse Model for Lymphangioleiomyomatosis

DTIC Science & Technology

2013-10-01

Burlingame, Califor- nia ), anti-phospho-S6 (Ser 235/236), anti-S6 and 1:5000 anti- glyceraldehyde-3-phosphate dehydrogenase (GAPDH; Cell Sig- naling...Olson S, Nguyen TA. Hydronephrosis and urine retention in estrogen-implanted athymic nude mice. Vet Pathol. 2009;46(3): 505 –508. 40. Leavitt WW, Takeda

ERK5 signaling gets XIAPed: a role for ubiquitin in the disassembly of a MAPK cascade

PubMed Central

Klein, Aileen M; Cobb, Melanie H

2014-01-01

Mitogen-activated protein kinase (MAPK) cascades are tightly controlled through a series of well-characterized phospho-regulatory events. In this issue, Takeda et al (2014) identify the inhibitor of apoptosis protein, XIAP, as a key regulator of ERK5 activation via uncoupling of upstream kinase activity by non-degradative ubiquitination. PMID:25012518

The Science of Reading, 1994.

ERIC Educational Resources Information Center

Ikeda, Shinichi, Ed.; And Others

1994-01-01

This collection of the 1994 issues of the Japanese-language journal "The Science of Reading" presents 21 articles on a variety of questions dealing with reading. Most articles in the collection have summaries in English. Articles in the April issue are: "Efforts to Enliven the School Library" (M. Takeda); "A Mistake in Comprehending a Literary…

[Historical research of cinchona cultivation in Japan (Part 2). Useful tropical plants introduced from Java and India in the early Meiji era].

PubMed

Nagumo, Seiji; Sasaki, Yohei; Takido, Michio

2010-01-01

In the early Meiji era, Takeaki Enomoto made a proposal to the government that cinchona and coffee seedlings be introduced to Japan. In response, the Meiji government dispatched Masatsugu Takeda of the Ministry of Internal Affairs to Java and India from March to August 1878 for the purpose of investigating useful plants of tropical origin and introducing them to Japan. This paper clarifies the route to those destinations and the plants obtained locally. Using the seeds obtained from India during his travels, the cultivation of cinchona was attempted in 1882 for the first time in Japan. In Ogasawara, coffee cultivation was conducted, again for the first time in Japan, using coffee seeds brought back from Java. The cultivation of coffee was successful and served as the foundation of the Ogasawara coffee that exists to this day. Takeda also introduced a number of books and materials related to useful tropical plants available as a result of his travels, which contributed to the promotion of new industries and businesses in the Meiji era.

Measuring the contour of a wavefront using the Irradiance Transport Equation (ITE)

NASA Astrophysics Data System (ADS)

Castillo-Rodríguez, Luis; Granados-Agustín, Fermín; Fernández-Guasti, Manuel; Cornejo-Rodríguez, Alejandro

2006-01-01

The Irradiance Transport Equation (ITE), found by Teague, had been used in optics with different applications. One of the field where had been used is in optical testing, for example, with the method developed by Takeda. In this paper following the idea of using different optical and mathematical analysis method, theorical and experimental results are presented.

JPRS Report, Science & Technology, Japan, 27th Aircraft Symposium, Part 3

DTIC Science & Technology

1991-02-14

Kaoru Wakairo, et al.] Aircraft-Mounted Optical Data Bus (3): Bus Control Software, Performance Evaluation Test [Mitsumi Mayanägi, Minoru...Article by Hiroyasu Kawahara, Kaoru Wakairo, and Akira Watanabe, National Aerospace Laboratory; Tomoyuli Udagawa, Kengo Takeda, and Noboru Shobayashi...89 pp 518-521 [Article by Tadao Uchida, Mitsumi Mayanagi, Minoru Takizawa, Toshiharu Inagaki, Koki Hozumi, and Kazutoshi Ishikawa , National

Paleoseismic study of the Kamishiro Fault on the northern segment of the Itoigawa-Shizuoka Tectonic Line, Japan

NASA Astrophysics Data System (ADS)

Lin, Aiming; Sano, Mikako; Wang, Maomao; Yan, Bing; Bian, Di; Fueta, Ryoji; Hosoya, Takashi

2017-07-01

The Mw 6.2 (Mj 6.8) Nagano (Japan) earthquake of 22 November 2014 produced a 9.3-km long surface rupture zone with a thrust-dominated displacement of up to 1.5 m, which duplicated the pre-existing Kamishiro Fault along the Itoigawa-Shizuoka Tectonic Line (ISTL), the plate-boundary between the Eurasian and North American plates, northern Nagano Prefecture, central Japan. To characterize the activity of the seismogenic fault zone, we conducted a paleoseismic study of the Kamishiro Fault. Field investigations and trench excavations revealed that seven morphogenic paleohistorical earthquakes (E2-E8) prior to the 2014 Mw 6.2 Nagano earthquake (E1) have occurred on the Kamishiro Fault during the last ca. 6000 years. Three of these events (E2-E4) are well constrained and correspond to historical earthquakes occurring in the last ca. 1200 years. This suggests an average recurrence interval of ca. 300-400 years on the seismogenic fault of the 2014 Kamishiro earthquake in the past 1200 years. The most recent event prior to the 2014 earthquakes (E1) is E2 and the penultimate and antepenultimate faulting events are E3 and E4, respectively. The penultimate faulting event (E3) occurred during the period of AD 1800-1400 and is associated with the 1791 Mw 6.8 earthquake. The antepenultimate faulting event (E4) is inferred to have occurred during the period of ca. AD 1000-700, likely corresponding to the AD 841 Mw 6.5 earthquake. The oldest faulting event (E8) in the study area is thought to have occurred during the period of ca. 5600-6000 years. The throw rate during the early Holocene is estimated to be 1.2-3.3 mm/a (average, 2.2 mm/a) with an average amount of characteristic offset of 0.7-1.1 m produced by individual event. When compared with active intraplate faults on Honshu Island, Japan, these slip rates and recurrence interval estimated for morphogenic earthquakes on the Kamishiro Fault along the ISTL appear high and short, respectively. This indicates that present activity

Improvement of Binary Analysis Components in Automated Malware Analysis Framework

DTIC Science & Technology

2017-02-21

analyze malicious software (malware) with minimum human interaction. The system autonomously analyze malware samples by analyzing malware binary program...AFRL-AFOSR-JP-TR-2017-0018 Improvement of Binary Analysis Components in Automated Malware Analysis Framework Keiji Takeda KEIO UNIVERSITY Final...currently valid OMB control number . PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ORGANIZATION. 1. REPORT DATE (DD-MM-YYYY)      21-02-2017 2. REPORT

The motion of radio meteor reflection point of Geminids

NASA Astrophysics Data System (ADS)

Ohnishi, Kouji; Ishikawa, Toshiyuki; Hattori, Shinobu; Nishimura, Osamu; Miyazawa, Akiko; Yanagisawa, Masatoshi; Endo, Makoto; Kawamura, Masaki; Maruyama, Toshiyuki; Hosayama, Kai; Tokunaga, Mai; Maegawa, Kimio; Abe, Shinsuke

2001-11-01

Ham-band Radio Observation (HRO) is one of the observational techniques for the forward scatter observation of meteors. We observe the meteor echo with two-element loop antennas (F/B ratio is 10 dB) at the Nagano National College of Technology (Nagano, Japan) using the continuous transmission of beacon signals for meteor observations at 53.750 MHz, 50W from Fukui National College of Technology (Fukui, Japan). To prove that the radio echo is really the echo due to meteor, we have constructed the direction determination system using the paired antennas that can detect the direction roughly where the radio echo come from. The direction of one of this paired antennas was West toward Sabae and the other was East which has proved to be the most sensitive for this research. Using this system, we detected the change of the direction of reflection point of meteor radio signal of Geminids in 2000; from the westward to eastward before and after the culmination of the radiant which is consistent the formula of reflection point of meteors. At the same time, we detected the change of an intensity and a trend of the Doppler shift of meteor echoes. This result is consistent of the meteor wind data of MU Rader of Radio Science Center for Space & Atmosphere (RASC), Kyoto University.

Availability, usage, and factors affecting usage of electrophysical agents by physical therapists: a regional cross-sectional survey

PubMed Central

Abe, Yuichi; Goh, Ah-Cheng; Miyoshi, Kei

2016-01-01

[Purpose] The aim of this study was to investigate the availability, usage, and factors affecting usage of electrophysical agents by physical therapists in Nagano Prefecture, Japan. [Subjects and Methods] Questionnaires were sent to all 1,571 physical therapists working in 245 institutions within Nagano Prefecture. A total of 1,110 questionnaires were returned, out of which 1,099 (70%) questionnaires containing valid responses were analyzed. Frequencies and percentages were calculated for 22 modalities with regards to availability, usage, rate of usage, and confidence level in usage. Factors affecting usage and the relationship between rate of usage and confidence level (Spearman’s rho) were also determined. [Results] The top three responses for the various outcome measures were as follows: (1) hot packs (88%), low frequency stimulators (76%), and ultrasound (68%) for availability; (2) hot packs (72%), ultrasound (61%), and cold packs (59%) for usage; (3) hot packs (75%), cold spray (49%), and ultrasound (44%) for confidence in usage; and (4) equipment availability (80%), past experience (79%), and research evidence (78%) for factors affecting usage. There was a significant positive relationship between confidence and usage for all modalities, except for ultraviolet radiation, iontophoresis, and magnetic field. [Conclusion] Usage was strongly correlated with confidence, with the top three used modalities also being the ones with the highest confidence in usage. PMID:27942126

Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study.

PubMed

Sáez-Llorens, Xavier; Tricou, Vianney; Yu, Delia; Rivera, Luis; Tuboi, Suely; Garbes, Pedro; Borkowski, Astrid; Wallace, Derek

2017-06-01

months apart, with analyses that take into account baseline age and dengue serostatus. Takeda Vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of the angiotensin II receptor blocker azilsartan medoxomil in African-American patients with hypertension.

PubMed

Johnson, Wallace; White, William B; Sica, Domenic; Bakris, George L; Weber, Michael A; Handley, Alison; Perez, Alfonso; Cao, Charlie; Kupfer, Stuart; Saunders, Elijah B

2017-07-01

The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African-American patients with hypertension in a 6-week, double-blind, randomized, placebo-controlled trial, for which the primary end point was change from baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients, with a mean age of 52 years, 57% women, and baseline 24-hour BP of 146/91 mm Hg. Treatment differences in 24-hour systolic BP between AZL-M 40 mg and placebo (-5.0 mm Hg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80 mg and placebo (-7.8 mm Hg; 95% confidence interval, -10.7 to -4.9) were significant (P≤.001 vs placebo for both comparisons). Changes in the clinic BPs were similar to the ambulatory BP results. Incidence rates of adverse events were comparable among the treatment groups, including those of a serious nature. In African-American patients with hypertension, AZL-M significantly reduced ambulatory and clinic BPs in a dose-dependent manner and was well tolerated. © The Authors and Takeda Development Centers, Americas, Inc and Takeda Pharmaceuticals International. The Journal of Clinical Hypertension published by Wiley Periodicals, Inc.

Ixazomib for Relapsed or Refractory Multiple Myeloma: Review from an Evidence Review Group on a NICE Single Technology Appraisal.

PubMed

Armoiry, Xavier; Connock, Martin; Tsertsvadze, Alexander; Cummins, Ewen; Melendez-Torres, G J; Royle, Pam; Clarke, Aileen

2018-03-26

Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment. Takeda estimated the cost effectiveness of IXA-LEN-DEX using a de-novo partitioned-survival model with three health states (pre-progression, post-progression, and dead). In their first submission, this model was used to estimate the cost effectiveness of IXA-LEN-DEX vs. bortezomib plus dexamethasone (BORT-DEX) in second-line treatment, and of IXA-LEN-DEX vs. LEN-DEX in third-line treatment. To estimate the relative clinical performance of IXA-LEN-DEX vs. BORT-DEX, Takeda conducted network meta-analyses for important outcomes. The network meta-analysis for overall survival was found to be flawed in several respects, but mainly because a hazard ratio input for one of the studies in the network had been inverted, resulting in a large inflation of the claimed superiority of IXA-LEN-DEX over BORT-DEX and a considerable overestimation of its cost effectiveness. In subsequent submissions, Takeda withdrew second-line treatment as an option for IXA-LEN-DEX. The manufacturer's first submission comparing IXA-LEN-DEX with LEN-DEX for third-line therapy employed Tourmaline-MM1 data from third- and fourth-line patients as proxy for a third-line population. The appraisal committee did not consider this reasonable because randomization in Tourmaline-MM1 was stratified

Halley's comet exploration and the Japanese Usuda large antenna

NASA Technical Reports Server (NTRS)

Nomura, T.

1986-01-01

An overview of the Japanese PLANET-A project to investigate Halley's Comet is given. The objectives and scientific challenges involved in the project are given, and the nature of the contribution made by the large antenna array located at Usuda-Cho, Nagano Prefecture, Japan is discussed. The structural design of the MS-T5 and PLANET-A probes are given, as well as the tracking and control network for the probes. The construction, design, operating system and site selection for the Usuda antenna station are discussed.

Paleoseismic study of the Kamishiro Fault on the northern segment of the Itoigawa-Shizuoka Tectonic Line, Japan.

PubMed

Lin, Aiming; Sano, Mikako; Wang, Maomao; Yan, Bing; Bian, Di; Fueta, Ryoji; Hosoya, Takashi

2017-01-01

The M w 6.2 (Mj 6.8) Nagano (Japan) earthquake of 22 November 2014 produced a 9.3-km long surface rupture zone with a thrust-dominated displacement of up to 1.5 m, which duplicated the pre-existing Kamishiro Fault along the Itoigawa-Shizuoka Tectonic Line (ISTL), the plate-boundary between the Eurasian and North American plates, northern Nagano Prefecture, central Japan. To characterize the activity of the seismogenic fault zone, we conducted a paleoseismic study of the Kamishiro Fault. Field investigations and trench excavations revealed that seven morphogenic paleohistorical earthquakes (E2-E8) prior to the 2014 M w 6.2 Nagano earthquake (E1) have occurred on the Kamishiro Fault during the last ca. 6000 years. Three of these events (E2-E4) are well constrained and correspond to historical earthquakes occurring in the last ca. 1200 years. This suggests an average recurrence interval of ca. 300-400 years on the seismogenic fault of the 2014 Kamishiro earthquake in the past 1200 years. The most recent event prior to the 2014 earthquakes (E1) is E2 and the penultimate and antepenultimate faulting events are E3 and E4, respectively. The penultimate faulting event (E3) occurred during the period of AD 1800-1400 and is associated with the 1791 M w 6.8 earthquake. The antepenultimate faulting event (E4) is inferred to have occurred during the period of ca. AD 1000-700, likely corresponding to the AD 841 M w 6.5 earthquake. The oldest faulting event (E8) in the study area is thought to have occurred during the period of ca. 5600-6000 years. The throw rate during the early Holocene is estimated to be 1.2-3.3 mm/a (average, 2.2 mm/a) with an average amount of characteristic offset of 0.7-1.1 m produced by individual event. When compared with active intraplate faults on Honshu Island, Japan, these slip rates and recurrence interval estimated for morphogenic earthquakes on the Kamishiro Fault along the ISTL appear high and short, respectively. This indicates that

New Insights into the Hendra Virus Attachment and Entry Process from Structures of the Virus G Glycoprotein and Its Complex with Ephrin-B2

DTIC Science & Technology

2012-11-05

organization of measles virus fusion complexes. J Virol 83: 10480–10493. 24. Bishop KA, Hickey AC, Khetawat D, Patch JR, Bossart KN, et al. (2008...its receptor, sialyllactose. Structure 13: 803–815. 38. Colf LA, Juo ZS, Garcia KC (2007) Structure of the measles virus hemagglutinin. Nat Struct Mol...Biol 14: 1227–1228. 39. Hashiguchi T, Kajikawa M, Maita N, Takeda M, Kuroki K, et al. (2007) Crystal structure of measles virus hemagglutinin provides

The Use of Filariae as a Therapeutic Agent for Hypersensitivity Diseases

DTIC Science & Technology

2014-12-01

come into contact with the allergen. These cytokines activate innate lymphoid cells (ILCs) and help dendritic cells (DCs) polarize a Th2 environment...Experimental Allergy 40:299-306 58. Filbey KJ, Grainger JR, Smith KA, Boon L, van Rooijen N, et al. 2014. Innate and adaptive type 2 immune cell ...105. Kamijo S, Takeda H, Tokura T, Suzuki M, Inui K, et al. 2013. IL-33–mediated innate response and adaptive immune cells contribute to maximum

Investigation of Hematologic and Pathologic Response to Decompression.

DTIC Science & Technology

1978-05-10

in tadpole and very young kangaroos . Am. J. Physiol. 120:59—74 , 1937. 12. D’ C’~~~’ B.G. and Swanson , H. Bubble free decompression of blood samples...1955. 24. Takeda , Y. Studies of the metabol i~~ 5 and distribution of fibrino— gen in healthy men with autologous I-labe led fibrinogen. J. Clin...this connective tissue protein. However , the metabolism of bone collagen is affected by hormonal control (l0; 3l) and vitamin influences (3 ;ll). It

Development of Smart Precision Forest in Conifer Plantation in Japan Using Laser Scanning Data

NASA Astrophysics Data System (ADS)

Katoh, M.; Deng, S.; Takenaka, Y.; Cheung, K.; Oono, K.; Horisawa, M.; Hyyppä, J.; Yu, X.; Liang, X.; Wang, Y.

2017-10-01

Currently, the authors are planning to launch a consortium effort toward Japan's first smart precision forestry project using laser data and to develop this technology throughout the country. Smart precision forestry information gathered using the Nagano model (laser scanning from aircraft, drone, and backpack) is being developed to improve the sophistication of forest information, reduce labor-intensive work, maintain sustainable timber productivity, and facilitate supply chain management by laser sensing information in collaboration with industry, academia, and government. In this paper, we outline the research project and the technical development situation of unmanned aerial vehicle laser scanning.

Application of the Oriented-Eddy Collision Model to Complex Turbulent Flows

DTIC Science & Technology

2011-03-14

compare with data available from Matsumoto, Nagano, and Tsuji (1991) as well as L. Le Penven, J. N. Gence, and G. Comte -Bellot (1985). This provided a...0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5 time (s) Figure 20: Comparison to data from L. Le Penven, J. N. Gence, and G. Comte ...Bellot, case A. 0.005 0.05 0.1 0.2 0.25 0.3 0.15 time (s) Figure 21: Comparison to data from L. Le Penven, J. N. Gence, and G. Comte -Bellot, case B

Molecular Mechanism of Selectivity among G Protein-Coupled Receptor Kinase 2 Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thal, David M.; Yeow, Raymond Y.; Schoenau, Christian

2012-07-11

G protein-coupled receptors (GPCRs) are key regulators of cell physiology and control processes ranging from glucose homeostasis to contractility of the heart. A major mechanism for the desensitization of activated GPCRs is their phosphorylation by GPCR kinases (GRKs). Overexpression of GRK2 is strongly linked to heart failure, and GRK2 has long been considered a pharmaceutical target for the treatment of cardiovascular disease. Several lead compounds developed by Takeda Pharmaceuticals show high selectivity for GRK2 and therapeutic potential for the treatment of heart failure. To understand how these drugs achieve their selectivity, we determined crystal structures of the bovine GRK2-G{beta}{gamma} complexmore » in the presence of two of these inhibitors. Comparison with the apoGRK2-G{beta}{gamma} structure demonstrates that the compounds bind in the kinase active site in a manner similar to that of the AGC kinase inhibitor balanol. Both balanol and the Takeda compounds induce a slight closure of the kinase domain, the degree of which correlates with the potencies of the inhibitors. Based on our crystal structures and homology modeling, we identified five amino acids surrounding the inhibitor binding site that we hypothesized could contribute to inhibitor selectivity. However, our results indicate that these residues are not major determinants of selectivity among GRK subfamilies. Rather, selectivity is achieved by the stabilization of a unique inactive conformation of the GRK2 kinase domain.« less

First record of the hermit crab genus Cestopagurus Bouvier, 1897 (Crustacea: Decapoda: Anomura: Paguridae) from the South Pacific Ocean and description of a new species.

PubMed

Komai, Tomoyuki; Tsuchida, Shinji; Clark, Malcolm R

2014-09-14

A fifth species of the pagurid genus Cestopagurus Bouvier, 1897, is described and illustrated on the basis of a single male specimen collected at a depth of 499 m from Hinepuia submarine volcano in the Kermadec Arc, New Zealand. The new species, C. hinepuia, appears similar to C. puniceus Komai & Takeda, 2005 known from waters off Japan, but the different armature of chelipeds distinguishes the new species. It is the first representative of the genus recorded from the South Pacific Ocean. A key for identification of species of the genus is presented. 

Repeat microearthquakes observed in western Nagano, Japan and implications to rupture dynamics

NASA Astrophysics Data System (ADS)

Cheng, X.; Niu, F.; Silver, P.; Horiuchi, S.; Takai, K.

2005-12-01

Repeat earthquakes appear to be pervasive in many fault systems, and have been used to detect temporal variations, either coseismic or post seismic near fault zones as well as to understand dynamic rupture processes. For example, Rubin and Gillard (2000) found no evidence of "immediate repeaters" in the San Juan Bautista section of the San Andreas Fault. Consecutive repeat earthquakes occurred no closer than a distance equal to the radius of the first rupture, which is estimated by a stress drop of 10 MPa. Here we reported similar characteristics of repeat microearthquakes from a very different environment, a complicated intraplate fault system in Western Nagao, Central Japan. A magnitude 6.8 shallow earthquake (roughly right lateral strike slip) occurred in the study area in 1984. Very high level of seismicity continues since then. A very dense seismic network with 56 stations including two borehole seismometers has been set up to monitor the high level seismic activity in 1995. Continuous data have been recorded at a very high sampling rate 10 KHz. We have searched repeat events from a catalog of more than 20,000 microearthquakes with a magnitude between 0 and 4.5. We calculated the cross-correlation of all the possible pairs of events and found less than 1% of the events can be categorized as repeat events, which is extremely lower compared to those observed at San Andreas Fault. More than 80% of the repeaters are actually aftershocks with the second events occurred within one day after the first ones. To avoid the tradeoff between origin time and event depth, we use relative S-P travel times to determine the relative locations of these consecutive repeat events. Based on the signal-to-noise ratio, we were able to estimate S-P time to an accuracy of 0.01 - 0.1 ms (1/10 to 1 sample interval). The corresponding errors in relative location are estimated to be a few tenths to a few meters. We also found that the second events occurred at least one radius away from the first rupture, (i.e., no intermediate repeaters), similar to those observed by Rubin and Gillard (2000). Stress drop seems to be independent to earthquake size, and is estimated to be a few tens of mega-Pascal, which is slightly higher than those observed at the San Andreas Fault.

Population-based study of esophageal and small intestinal atresia/stenosis.

PubMed

Takahashi, Daijiro; Hiroma, Takehiko; Takamizawa, Shigeru; Nakamura, Tomohiko

2014-12-01

The aim of this study was to describe the prevalence of esophageal atresia/stenosis and small intestinal atresia/stenosis in Nagano, Japan, together with associated anomalies, prenatal diagnosis and survival. A population-based cohort study of the prevalence of esophageal atresia/stenosis and small intestinal atresia/stenosis was conducted in Nagano in January 1993-December 2011. The Mann-Whitney test, χ(2) test and Kruskal-Wallis test were used to compare variables. P < 0.05 was considered statistically significant. In total, 74 cases of esophageal atresia/stenosis and 87 cases of small intestinal atresia/stenosis (31 duodenal, 56 jejuno-ileal) were identified. Prevalences were 1.97 for esophageal atresia/stenosis and 2.23 for small intestinal atresia/stenosis (0.83 for duodenal atresia/stenosis and 1.49 for jejuno-ileal atresia/stenosis) per 10,000 births, respectively. The prevalence of esophageal atresia/stenosis increased significantly from 1993-2001 to 2002-2011 (relative risk [RR], 1.6), as did the prevalences of duodenal atresia/stenosis (RR, 2.2) and jejuno-ileal atresia/stenosis (RR, 3.1). Chromosomal anomalies, particularly trisomy 21, were seen significantly more often in association with duodenal atresia/stenosis (55%) than with esophageal atresia/stenosis (28%, P < 0.01) or jejuno-ileal atresia/stenosis (2%, P < 0.01). The proportion of patients associated with prenatally diagnosed chromosomal anomaly was higher compared to postnatal diagnosis (P < 0.01) in the esophageal atresia/stenosis group. The prevalence of esophageal and small intestinal atresia/stenosis increased significantly from 1993-2001 to 2002-2011. Prenatally diagnosed esophageal atresia/stenosis is associated with multiple anomalies, particularly chromosomal anomalies, compared to other small intestine atresia/stenosis. © 2014 Japan Pediatric Society.

Gramicidin S production by Bacillus brevis in simulated microgravity

NASA Technical Reports Server (NTRS)

Fang, A.; Pierson, D. L.; Mishra, S. K.; Koenig, D. W.; Demain, A. L.

1997-01-01

In a continuing study of microbial secondary metabolism in simulated microgravity, we have examined gramicidin S (GS) production by Bacillus brevis strain Nagano in NASA High Aspect Rotating Vessels (HARVs), which are designed to simulate some aspects of microgravity. Growth and GS production were found to occur under simulated microgravity. When performance under simulated microgravity was compared with that under normal gravity conditions in the bioreactors, GS production was found to be unaffected by simulated microgravity. The repressive effect of glycerol in flask fermentations was not observed in the HARV. Thus the negative effect of glycerol on specific GS formation is dependent on shear and/or vessel geometry, not gravity.

Technology evaluation: C242-DM1, ImmunoGen Inc.

PubMed

Smith, S

2001-04-01

C242-DM1 is a tumor-activated immunotoxin under development by GlaxoSmithKline plc (formerly SmithKline Beecham plc), under licence from ImmunoGen Inc, as a potential treatment for colon tumor. It consists of a colon cancer-specific humanized antibody, C242, conjugated to the maytansine derivative DM1. In preclinical studies, C242-DM1 caused complete tumor regression in animal models of both human pancreatic and non-small cell lung cancer (NSCLC) at non-toxic doses. C242-DM1 has also been evaluated in an immunoconjugate combination with J-591 (Cornell University). The J591-DM1 immunoconjugate demonstrated effective, antigen-specific delivery of a highly cytotoxic drug to PSMA-positive Pca cells in vitro and in vivo with low systemic toxicity. Results from studies in monkeys showed that C242-DM1 had no significant toxicity or side effects, when administered at doses higher than those that were previously shown to completely eradicate human colon tumors in mice [271420]. ImmunoGen acquired the right to evaluate, and an option to license, technology related to maytansines from Takeda. In February 1999, ImmunoGen and SmithKline Beecham signed a US $45 million development and commercialization agreement for C242-DM1 [313493]. In August 1997, Immunogen received an SBIR grant to advance development of huC242-DM1 [258356]. EP-00425235, held by ImmunoGen, covers conjugated forms of ansamitocin (maytansine) derivatives. Takeda holds several patents for the production of ansamitocin and its analogs, the first one being JP-53124692.

Three Dimensional Speckle Imaging Employing a Frequency-Locked Tunable Diode Laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cannon, Bret D.; Bernacki, Bruce E.; Schiffern, John T.

2015-09-01

We describe a high accuracy frequency stepping method for a tunable diode laser to improve a three dimensional (3D) imaging approach based upon interferometric speckle imaging. The approach, modeled after Takeda, exploits tuning an illumination laser in frequency as speckle interferograms of the object (specklegrams) are acquired at each frequency in a Michelson interferometer. The resulting 3D hypercube of specklegrams encode spatial information in the x-y plane of each image with laser tuning arrayed along its z-axis. We present laboratory data of before and after results showing enhanced 3D imaging resulting from precise laser frequency control.

[Career planning for explanation of clinical test results and program of inspections: developing medical technologists for team medical care].

PubMed

Uchida, Misuko

2013-04-01

Current medical care is subdivided according to medical advances, and sophistication and new techniques are necessary. In this setting, doctors and nurses have been explaining to and consulting patients about their medical examinations; however, in recent years, medical technologists have performed these duties at the start of the team's medical care. Therefore, we think it is possible for patients to receive clear and convincing explanations. Most patients cannot understand their examination data, which are written using numbers and charts, etc. Recently, the Nagano Medical Technologist Society has been developing technologists who could explain examination results to patients. This development training included hospitality and communication. The certificate of completion will be issued in March when the program starts.

Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells.

PubMed

Lajczak, Natalia K; Saint-Criq, Vinciane; O'Dwyer, Aoife M; Perino, Alessia; Adorini, Luciano; Schoonjans, Kristina; Keely, Stephen J

2017-09-01

Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT-777 (50 μM), but not by the farnesoid X receptor agonist, GW4064 (10 μM). INT-777 also stimulated colonic HβD1 and HβD2 release from wild-type, but not Takeda GPCR 5 -/- , mice. DCA stimulated phosphorylation of the p65 subunit of NF-κB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF-κB inhibitor, BMS-345541 (25 μM), inhibited DCA-induced HβD2, but not HβD1, release. We conclude that bile acids can differentially regulate colonic epithelial HβD expression and secretion and discuss the implications of our findings for intestinal health and disease.-Lajczak, N. K., Saint-Criq, V., O'Dwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. © FASEB.

[Application of Mass Spectrometry to the Diagnosis of Cancer--Chairman's Introductory Remarks].

PubMed

Yatomi, Yutaka

2015-09-01

In this symposium, the latest application of mass spectrometry to laboratory medicine, i.e., to the early diagnosis of cancer, was introduced. Dr. Masaru YOSHIDA, who has been using metabolome analysis to discover biomarker candidates for gastroenterological diseases, presented an automated early diagnosis system for early stages of colon cancer based on metabolome analysis and using a minute amount of blood. On the other hand, Dr. Sen TAKEDA, who has developed a new approach by employing both mass spectrometry and machine-learning for cancer diagnosis, presented a device for the clinical diagnosis of cancer using probe electrospray ionization (PESI) and machine-learning called the dual penalized logistic regression machine (dPLRM).

A new species of Fizesereneia Takeda & Tamura, 1980 (Crustacea: Brachyura: Cryptochiridae) from the Red Sea and Oman.

PubMed

Van Der Meij, Sancia E T; Berumen, Michael L; Paulay, Gustav

2015-03-16

A new species of cryptochirid crab, Fizesereneia panda van der Meij, is described and illustrated based on specimens collected from the scleractinian corals Lobophyllia cf. hemprichii and L. cf. corymbosa from the Farasan Banks, Farasan Islands, and the reefs off Thuwal in the Saudi Arabian Red Sea, and from Symphyllia recta from reefs in the Gulf of Oman. This is the second cryptochirid species with the Red Sea as type locality. It can be separated from its congeners by the subrectangular carapace, raised midline and the complete division of the carapace depressions, and reddish black colour pattern of these concavities in live specimens. This new species is the seventh assigned to Fizesereneia. A DNA barcode for the new species has been deposited in GenBank.

[Food borne outbreak caused by the well water contaminated norovirus].

PubMed

Tokutake, Yumi; Kobayashi, Masato; Akiyama, Miho; Aiki, Chikako; Nishio, Osamu

2006-05-01

In May 2004, 65 people from 18 groups of visitors to guesthouse (a traditional Japanese guesthouse) in the Nagano Prefecture, Japan developed acute gastroenteritis. Although these cases originally attributed to food poisoning, based on epidemiological and dietary surveys, there was nothing that is associated as a cause food. The same wall water was used throughout the guesthouse except in the kitchen, so testing was conducted on this water. Lordsdale variant strain of Norovirus was detected from both of the well water and the feces of patients and staff. The well supplying to the guesthouse was only 10 meters deep and fecal coliform group was also detected in the well water from the guesthouse. This suggested that the water source was contaminated by human feces.

Improved modeling of turbulent forced convection heat transfer in straight ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rokni, M.; Sunden, B.

1999-08-01

This investigation concerns numerical calculation of turbulent forced convective heat transfer and fluid flow in their fully developed state at low Reynolds number. The authors have developed a low Reynolds number version of the nonlinear {kappa}-{epsilon} model combined with the heat flux models of simple eddy diffusivity (SED), low Reynolds number version of generalized gradient diffusion hypothesis (GGDH), and wealth {proportional_to} earning {times} time (WET) in general three-dimensional geometries. The numerical approach is based on the finite volume technique with a nonstaggered grid arrangement and the SIMPLEC algorithm. Results have been obtained with the nonlinear {kappa}-{epsilon} model, combined with themore » Lam-Bremhorst and the Abe-Kondoh-Nagano damping functions for low Reynolds numbers.« less

Computer modeling of in terferograms of flowing plasma and determination of the phase shift

NASA Astrophysics Data System (ADS)

Blažek, J.; Kříž, P.; Stach, V.

2000-03-01

Interferograms of the flowing gas contain information about the phase shift between the object and the reference beams. The determination of the phase shift is the first step in getting information about the inner distribution of the density in cylindrically symmetric discharges. Slightly modified Takeda method based on the Fourier transformation is applied to determine the phase information from the interferogram. The least squares spline approximation is used for approximation and smoothing intensity profiles. At the same time, cubic splines with their end-knots conditions naturally realize “hanning windows” eliminating unwanted edge effects. For the purpose of numerical testing of the method, we developed a code that for a density given in advance reconstructs the corresponding interferogram.

The Relationship between Attitudes toward Suicide and Family History of Suicide in Nagano Prefecture, Japan.

PubMed

Tsukahara, Teruomi; Arai, Hiroaki; Kamijo, Tomoko; Kobayashi, Yoshikiyo; Washizuka, Shinsuke; Arito, Heihachiro; Nomiyama, Tetsuo

2016-06-22

Certain attitudes toward suicide may be a risk factor for suicide among the bereaved. To explore this possibility, we examined the relationship between attitudes toward suicide and family history of suicide. We focused on two specific attitudes indicating resignation in a survey: #1 "When a person chooses to die by suicide, the suicide is inevitable" (i.e., inevitability belief); and #2 "A suicide cannot be stopped by any person, because suicide is unpreventable" (i.e., unpreventable belief). The data of 5117 fully completed questionnaires were analyzed. Logistic regression analysis revealed that the two attitudes of resignation were significantly associated with a family history of suicide. The adjusted odds ratio for #1 was 1.39 (95% CI, 1.07-1.79) for individuals having experienced suicide by a family member or relative, while that for #2 was 1.57 (95% CI, 1.27-1.95) for experiencing a suicide by a family member or relative and 1.25 (95% CI, 1.05-1.49) for experiencing a suicide by a friend, business associate, partner or other. These two attitudes of resignation toward suicide were significantly associated with a family history of suicide. These attitudes might increase suicide risk among the bereaved.

TRANSFORMATION FACTORS OF ENVIRONMENTAL CONSCIOUSNESS AND ACTION IN IIDA CITY RESIDENTS - ATTEITION TO ENVIRONMENTAL MEASURES AND SOCIAL CAPITAL

NASA Astrophysics Data System (ADS)

Shirai, Nobuo; Higuchi, Kazukiyo; Tokai, Akihiro

Iida City in Nagano Prefecture is a town with an advanced environmental strategy including citizenry participation in the town's environment plan, a network of EMS (Environmental Management system) businesses, and a citizens' solar power system. In this study, a questionnaire of Iida residents was carried out to determine their environmental consciousness, and the effect on their actions. It also examined the influence of current environmental measures on the residents, and the relation between the level of social capital and residents' environmental considerations. The results indicate that the environmental consideration level of the senior citizen group is higher than that of the entire Japan in Iida City, and environmental measures has improved the residents' environmental consciousness. And it is thought the environmental consideration level of the senior citizen group is related to the level of social capital.

Spectroscopic characterization of manganese minerals.

PubMed

Lakshmi Reddy, S; Padma Suvarna, K; Udayabhaska Reddy, G; Endo, Tamio; Frost, R L

2014-01-03

Manganese minerals ardenite, alleghanyite and leucopoenicite originated from Madhya Pradesh, India, Nagano prefecture Japan, Sussex Country and Parker Shaft Franklin, Sussex Country, New Jersey respectively are used in the present work. In these minerals manganese is the major constituent and iron if present is in traces only. An EPR study of on all of the above samples confirms the presence of Mn(II) with g around 2.0. Optical absorption spectrum of the mineral alleghanyite indicates that Mn(II) is present in two different octahedral sites and in leucophoenicite Mn(II) is also in octahedral geometry. Ardenite mineral gives only a few Mn(II) bands. NIR results of the minerals ardenite, leucophoenicite and alleghanyite are due to hydroxyl and silicate anions which confirming the formulae of the minerals. Copyright © 2013 Elsevier B.V. All rights reserved.

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.

PubMed

Akiguchi, Ichiro; Pallàs, Mercè; Budka, Herbert; Akiyama, Haruhiko; Ueno, Masaki; Han, Jingxian; Yagi, Hideo; Nishikawa, Tomohumi; Chiba, Yoichi; Sugiyama, Hiroshi; Takahashi, Ryoya; Unno, Keiko; Higuchi, Keiichi; Hosokawa, Masanori

2017-08-01

Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. β/A4(Aβ) protein-like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age-associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood-brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age-related increase in phosphorylated tau in SAMP8 mice brains, but early age-related Aβ deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence-accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders. © 2017 Japanese Society of Neuropathology.

Structure of the inhibitory region of troponin by site directed spin labeling electron paramagnetic resonance

PubMed Central

Brown, Louise J.; Sale, Ken L.; Hills, Ron; Rouviere, Clement; Song, Likai; Zhang, Xiaojun; Fajer, Piotr G.

2002-01-01

Site-directed spin labeling EPR (SDSL-EPR) was used to determine the structure of the inhibitory region of TnI in the intact cardiac troponin ternary complex. Maeda and collaborators have modeled the inhibitory region of TnI (skeletal 96–112: the structural motif that communicates the Ca2+ signal to actin) as a kinked α-helix [Vassylyev, D., Takeda, S., Wakatsuki, S., Maeda, K. & Maeda, Y. (1998) Proc. Natl. Acad. Sci. USA 95, 4847–4852), whereas Trewhella and collaborators have proposed the same region to be a flexible β-hairpin [Tung, C. S., Wall, M. E., Gallagher, S. C. & Trewhella, J. (2000) Protein Sci. 9, 1312–1326]. To distinguish between the two models, residues 129–145 of cardiac TnI were mutated sequentially to cysteines and labeled with the extrinsic spin probe, MTSSL. Sequence-dependent solvent accessibility was measured as a change in power saturation of the spin probe in the presence of the relaxation agent. In the ternary complex, the 129–137 region followed a pattern characteristic of a regular 3.6 residues/turn α-helix. The following region, residues 138–145, showed no regular pattern in solvent accessibility. Measurements of 4 intradomain distances within the inhibitory sequence, using dipolar EPR, were consistent with an α-helical structure. The difference in side-chain mobility between the ternary (C⋅I⋅T) and binary (C⋅I) complexes revealed a region of interaction of TnT located at the N-terminal end of the inhibitory sequence, residues 130–135. The above findings for the troponin complex in solution do not support either of the computational models of the binary complex; however, they are in very good agreement with a preliminary report of the x-ray structure of the cardiac ternary complex [Takeda, S. Yamashita, A., Maeda, K. & Maeda, Y. (2002) Biophys. J. 82, 832]. PMID:12239350

Industry update: what is new in the field of therapeutic delivery?

PubMed

Harris, Elaine

2018-02-01

The present industry update covers the period 1-30 November 2017. Sources of information include company press releases, regulatory and patent agencies' notices, scientific literature and various news websites. A number of companies reported positive clinical trial results for therapeutic candidates enabled by different delivery strategies including Vascular Therapies, Adapt and Altemia. November also saw the announcement of some significant collaborations and acquisitions; Cerenis Therapeutics acquired Lypro Biosciences, which gives them access to a proprietary drug delivery nanotechnology platform, NanoDisk ® , and Takeda announced a collaboration with Portal Instruments to develop a needle-free delivery device for its biological therapeutics. From a patenting perspective, Allergan's strategy of transferring the rights of some of their patents to Saint Regis Mohawk Tribe has drawn scrutiny (and criticism) from US Senators.

Receptors as a master key for synchronization of rhythms

NASA Astrophysics Data System (ADS)

Nagano, Seido

2004-03-01

A simple, but general scheme to achieve synchronization of rhythms was derived. The scheme has been inductively generalized from the modelling study of cellular slime mold. It was clarified that biological receptors work as apparatuses that can convert external stimulus to the form of nonlinear interaction within individual oscillators. Namely, the mathematical model receptor works as a nonlinear coupling apparatus between nonlinear oscillators. Thus, synchronization is achieved as a result of competition between two kinds of non-linearities, and to achieve synchronization, even a small external stimulation via model receptors can change the characteristics of individual oscillators significantly. The derived scheme is very simple mathematically, but it is a very powerful scheme as numerically demonstrated. The biological receptor scheme should significantly help understanding of synchronization phenomena in biology since groups of limit cycle oscillators and receptors are ubiquitous in biological systems. Reference: S. Nagano, Phys Rev. E67, 056215(2003)

Optical Observation of LEO Debris Caused by Feng Yun 1C

NASA Astrophysics Data System (ADS)

Kurosaki, Hirohisa; Yanagisawa, Toshifumi; Nakajima, Atsushi

Many pieces of space debris are in low earth orbit (LEO), and may be a serious problem in the near future. They are very hazardous to spacecraft such as the ISS, in which humans stay for long periods. In January 2007, China performed an experimental destruction of the meteorological satellite FengYun-1C in low earth orbit using a ballistic missile. Optical instruments for space debris observation were installed on Mt. Nyukasa in Nagano Prefecture by JAXA, and the resulting low earth orbit debris was observed with the small telescope there. We have developed an image-processing technique, the line-detection method, to extract such effects as the streaks created by meteors, LEO satellites, and LEO debris. We succeeded in detecting the trajectories of specified FengYun-1C debris whose TLE were known. In this paper, the detection and observation of low earth orbit debris are discussed.

Vedolizumab: first global approval.

PubMed

Poole, Raewyn M

2014-07-01

Vedolizumab [Entyvio(®) (US, Europe)], a humanized monoclonal antibody α4β7 integrin receptor antagonist, has been developed by Millennium Pharmaceuticals (d/b/a Takeda Pharmaceuticals International) for the treatment of ulcerative colitis and Crohn's disease. Vedolizumab has received its first global approval for the treatment of ulcerative colitis and Crohn's disease in the US, for use in adult patients with moderate-to-severe disease who have had an inadequate response, loss of response or intolerance to one or more standard therapies (corticosteroids, immunomodulators or tumour necrosis factor-α inhibitor) or demonstrated dependence on corticosteroids. Vedolizumab has since been approved for ulcerative colitis and Crohn's disease in the EU, Norway, Iceland and Liechtenstein. This article summarizes the milestones in the development of vedolizumab leading to its first approval for the treatment of ulcerative colitis and Crohn's disease.

[Utilization of Big Data in Medicine and Future Outlook].

PubMed

Kinosada, Yasutomi; Uematsu, Machiko; Fujiwara, Takuya

2016-03-01

"Big data" is a new buzzword. The point is not to be dazzled by the volume of data, but rather to analyze it, and convert it into insights, innovations, and business value. There are also real differences between conventional analytics and big data. In this article, we show some results of big data analysis using open DPC (Diagnosis Procedure Combination) data in areas of the central part of JAPAN: Toyama, Ishikawa, Fukui, Nagano, Gifu, Aichi, Shizuoka, and Mie Prefectures. These 8 prefectures contain 51 medical administration areas called the second medical area. By applying big data analysis techniques such as k-means, hierarchical clustering, and self-organizing maps to DPC data, we can visualize the disease structure and detect similarities or variations among the 51 second medical areas. The combination of a big data analysis technique and open DPC data is a very powerful method to depict real figures on patient distribution in Japan.

Numerical prediction of transitional features of turbulent forced gas flows in circular tubes with strong heating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ezato, K.; Shehata, A.M.; Kunugi, T.

1999-08-01

In order to treat strongly heated, forced gas flows at low Reynolds numbers in vertical circular tubes, the {kappa}-{epsilon} turbulence model of Abe, Kondoh, and Nagano (1994), developed for forced turbulent flow between parallel plates with the constant property idealization, has been successfully applied. For thermal energy transport, the turbulent Prandtl number model of Kays and Crawford (1993) was adopted. The capability to handle these flows was assessed via calculations at the conditions of experiments by Shehata (1984), ranging from essentially turbulent to laminarizing due to the heating. Predictions forecast the development of turbulent transport quantities, Reynolds stress, and turbulentmore » heat flux, as well as turbulent viscosity and turbulent kinetic energy. Overall agreement between the calculations and the measured velocity and temperature distributions is good, establishing confidence in the values of the forecast turbulence quantities--and the model which produced them. Most importantly, the model yields predictions which compare well with the measured wall heat transfer parameters and the pressure drop.« less

[Quality of life in patients with atopic dermatitis: using the Japanese version of the SF-36 health status questionnaire].

PubMed

Fukuroku, Keiko; Nagano, Takuzou; Ogino, Satoshi

2002-12-01

Atopic dermatitis is a common skin disorder with an age onset mainly from infancy to adolescence. Patients with this disorder usually have a long history of repeated relief and relapse. The aim of the present studies is to quantify the relationship between the QOL score of patients and symptomatic characteristics (including severity measured by SF-36). From November 2000 to February 2001, the study recruited 281 patients with atopic dermatitis who had been treated at the Nagano dermatology and allergology clinic. The results of this study demonstrated that the symptoms severity and pruritus grade had strong influences on QOL score, and the location of pruritic lesion on the neck had the strongest influence on their self-perceived health status. The patients group with moderate atopic dermatitis who showed pruritus lesion in face, neck, and or knee, and female had consistently lower scores than male on all of the subscales. In conclusion, it is critically important to control of pruritus, and to develop an appropriate management.

N : P stoichiometry in a forested runoff during storm events: comparisons with regions and vegetation types.

PubMed

Guo, Lanlan; Chen, Yi; Zhang, Zhao; Fukushima, Takehiko

2012-01-01

Nitrogen and phosphorus are considered the most important limiting elements in terrestrial and aquatic ecosystems. however, very few studies have focused on which is from forested streams, a bridge between these two systems. To fill this gap, we examined the concentrations of dissolved N and P in storm waters from forested watersheds of five regions in Japan, to characterize nutrient limitation and its potential controlling factors. First, dissolved N and P concentrations and the N : P ratio on forested streams were higher during storm events relative to baseflow conditions. Second, significantly higher dissolved inorganic N concentrations were found in storm waters from evergreen coniferous forest streams than those from deciduous broadleaf forest streams in Aichi, Kochi, Mie, Nagano, and with the exception of Tokyo. Finally, almost all the N : P ratios in the storm water were generally higher than 34, implying that the storm water should be P-limited, especially for Tokyo.

N : P Stoichiometry in a Forested Runoff during Storm Events: Comparisons with Regions and Vegetation Types

PubMed Central

Guo, Lanlan; Chen, Yi; Zhang, Zhao; Fukushima, Takehiko

2012-01-01

Nitrogen and phosphorus are considered the most important limiting elements in terrestrial and aquatic ecosystems. however, very few studies have focused on which is from forested streams, a bridge between these two systems. To fill this gap, we examined the concentrations of dissolved N and P in storm waters from forested watersheds of five regions in Japan, to characterize nutrient limitation and its potential controlling factors. First, dissolved N and P concentrations and the N : P ratio on forested streams were higher during storm events relative to baseflow conditions. Second, significantly higher dissolved inorganic N concentrations were found in storm waters from evergreen coniferous forest streams than those from deciduous broadleaf forest streams in Aichi, Kochi, Mie, Nagano, and with the exception of Tokyo. Finally, almost all the N : P ratios in the storm water were generally higher than 34, implying that the storm water should be P-limited, especially for Tokyo. PMID:22547978

Habitual hot-spring bathing by a group of Japanese macaques (Macaca fuscata) in their natural habitat.

PubMed

Zhang, Peng; Watanabe, Kunio; Eishi, Tokida

2007-12-01

Japanese macaques (Macaca fuscata) in a free-ranging group in Jigokudani valley, Nagano prefecture, are known to bathe in a hot spring. We used scan sampling in a study aimed at elucidating the causal factors and possible social transmission of this behavior. From 1980-2003, 31% of a total 114 females in the group habitually bathed in the hot spring. The habit was more widespread in dominant matrilines than in subordinate matrilines. Infants whose mothers bathed were more likely to bathe than infants of mothers who did not bathe. The number of monkeys bathing was clearly influenced by ambient air temperature. More monkeys bathed in the hot spring in winter than in summer. The results support the thermoregulation hypothesis of hot-spring bathing. Bathing behavior varies among age and sex categories of monkeys, with adult females and juveniles bathing more often than adult males and subadults. We compared hot-spring bathing with other thermoregulatory behaviors in various primate populations. (c) 2007 Wiley-Liss, Inc.

Donated chemical probes for open science

PubMed Central

Ackloo, Suzanne; Arrowsmith, Cheryl H; Bauser, Marcus; Baryza, Jeremy L; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J; Bunnage, Mark E; Carter, Adrian J; Damerell, David; Dötsch, Volker; Drewry, David H; Edwards, Aled M; Edwards, James; Elkins, Jon M; Fischer, Christian; Frye, Stephen V; Gollner, Andreas; Grimshaw, Charles E; IJzerman, Adriaan; Hanke, Thomas; Hartung, Ingo V; Hitchcock, Steve; Howe, Trevor; Hughes, Terry V; Laufer, Stefan; Li, Volkhart MJ; Liras, Spiros; Marsden, Brian D; Matsui, Hisanori; Mathias, John; O'Hagan, Ronan C; Owen, Dafydd R; Pande, Vineet; Rauh, Daniel; Rosenberg, Saul H; Roth, Bryan L; Schneider, Natalie S; Scholten, Cora; Singh Saikatendu, Kumar; Simeonov, Anton; Takizawa, Masayuki; Tse, Chris; Thompson, Paul R; Treiber, Daniel K; Viana, Amélia YI; Wells, Carrow I; Willson, Timothy M; Zuercher, William J; Knapp, Stefan

2018-01-01

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project. PMID:29676732

Hope or hype in the treatment of schizophrenia - what's the role of the physician?

PubMed

Bressan, Rodrigo A; Grohs, Geder E M; Matos, Gabriela; Shergill, Sukhi

2018-01-01

According to the experience of people with schizophrenia, their psychiatrists' attitude towards the outcome of their illness is lacking in hope, which directly affects mutual faith in treatment. Here we discuss the scientific basis of hope and show its instrumental role in optimising the best treatment strategies for schizophrenia. Declaration of interest R.A.B has received honoraria for educational input and non-financial support from Ache; honoraria for educational input from Lundbeck; grants, honoraria for educational input and non-financial support from Janssen; all outside the submitted work. G.E.M.G. has received honoraria for educational input and non-financial support from Janssen outside the submitted work. G.M. reports support from Janssen-Cilag, outside the submitted work, and is an employee at Janssen-Cilag. S.S. has received grants and honoraria for educational input from EnVivo Pharmaceuticals, Takeda, AbbVie and Janssen Pharmaceuticals, outside the submitted work.

An industry update: the latest news in therapeutic delivery.

PubMed

Harris, Elaine

2017-11-01

The present industry update covers the period 1-31 July 2017. Information was sourced primarily from company press releases, regulatory and patent agencies, scientific literature and various news websites. There was positive approval news this month for GlaxoSmithKline for its new self-injecting treatment for systemic lupus erythematosus but less positive news for Ocular Therapeutix, a new drug application for its treatment for postoperative ocular pain, DEXTENZA™ was rejected for a second time. Endo Pharmaceuticals agreed to withdraw its opioid formulation Opana ® Er due to abuse concerns. Collaborations for novel therapeutic delivery research were announced this month by Takeda and BioSurfaces, Catelent and Rutgers University, Lilly and Purdue University and Titan Pharmaceuticals with Walter Reed and the Southwest Research Institute. A number of companies announced significant financing deals to allow for the clinical development of products with enhanced delivery options including Sebacia and Diasome.

Reciprocal interactions between bile acids and gut microbiota in human liver diseases.

PubMed

Ikegami, Tadashi; Honda, Akira

2018-01-01

The gut microbiota (GM) play a central role in their host's metabolism of bile acids (BAs) by regulating deconjugation, dehydroxylation, dehydrogenation, and epimerization reactions to generate unconjugated free BAs and secondary BAs. These BAs generated by the GM are potent signaling molecules that interact with BA receptors, such as the farnesoid X receptor and Takeda G-protein-coupled receptor 5. Each BA has a differential affinity to these receptors; therefore, alterations in BA composition by GM could modify the intensity of receptor signaling. Bile acids also act as antimicrobial agents by damaging bacterial membranes and as detergents by altering intracellular macromolecular structures. Therefore, BAs and the GM reciprocally control each other's compositions. In this review, we discuss the latest findings on the mutual effects of BAs and GM on each other; we also describe their roles in the pathophysiology of liver disease progression and potential therapeutic applications of targeting this cross-talk. © 2017 The Japan Society of Hepatology.

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis.

PubMed

Ha, Christina; Kornbluth, Asher

2014-12-01

The management of Crohn's disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn's disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn's disease and ulcerative colitis.

Vedolizumab as a Treatment for Crohn’s Disease and Ulcerative Colitis

PubMed Central

Ha, Christina

2014-01-01

The management of Crohn’s disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn’s disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn’s disease and ulcerative colitis. PMID:27524947

Ground Motion Studies for Large Future Accelerator

NASA Astrophysics Data System (ADS)

Takeda, Shigeru; Oide, Katsunobu

1997-05-01

The future large accelerator, such as TeV linear collider, should have extremely small emittance to perform the required luminosity. Precise alignment of machine components is essential to prevent emittance dilution. The ground motion spoils alignment of accelerator elements and results in emittance growth. The ground motion in the frequency range of seismic vibration is mostly coherent in the related accelerator. But the incoherent diffusive or Brownian like motion becomes dominant at frequency region less than seismic vibration [1, 2, 3]. Slow ground motion with respect to the machine performance is discussed including the method of tunnel construction. Our experimental results and recent excavated results clarify that application of TBMs is better excavating method than NATM (Drill + Blast) for accelerator tunnel to prevent emittance dilution. ([1] V. Shiltsev, Proc. of IWAA95 Tsukuba, 1995. [2] Shigeru Takeda et al., Proc. of EPAC96, 1996. [3] A. Sery, Proc. of LINAC96, 1996.)

World Antibody-Drug Conjugate Summit, October 15-16, 2013, San Francisco, CA.

PubMed

Klinguer-Hamour, Christine; Strop, Pavel; Shah, Dhaval K; Ducry, Laurent; Xu, April; Beck, Alain

2014-01-01

The World Antibody-Drug Conjugate (WADC) Summits organized by Hanson Wade are currently the largest meetings fully dedicated to ADCs. The first global ADC Summit was organized in Boston in October 2010. Since 2011, two WADC are held every year in Frankfurt and San Francisco, respectively. The 2013 WADC San Francisco event was structured around plenary sessions with keynote speakers from AbbVie, Agensys, ImmunoGen, Immunomedics, Genentech, Pfizer and Seattle Genetics. Parallel tracks were also organized addressing ADC discovery, development and optimization of chemistry, manufacturing and control (CMC) issues. Discovery and process scientists, regulatory experts (US Food and Drug Administration), academics and clinicians were present, including representatives from biotechnology firms (Concortis, CytomX Therapeutics, Glykos, Evonik, Igenica, Innate Pharma, Mersana Therapeutics, Polytherics, Quanta Biodesign, Redwood Bioscience, Sutro Biopharma, SynAffix), pharmaceutical companies (Amgen, Genmab, Johnson and Johnson, MedImmune, Novartis, Progenics, Takeda) and contract research or manufacturing organizations (Baxter, Bayer, BSP Pharmaceuticals, Fujifilm/Diosynth, Lonza, Pierre Fabre Contract Manufacturing, Piramal, SAFC, SafeBridge).

The Japanese Marten Favors Actinidia arguta, a Forest Edge Liane as a Directed Seed Disperser.

PubMed

Yasumoto, Yui; Takatsuki, Seiki

2015-06-01

This study demonstrates the potential of the Japanese marten (Martes melampus) to serve as a directed seed disperser of Actinidia arguta, a representative forest edge liane. Fecal compositions of the Japanese marten in a western part of Tokyo, Japan were analyzed by the point-frame method. It fed on fruits in autumn (73.1%) and winter (63.0%), and the seeds of A. arguta were most frequently eaten (47.4%). Although the vegetation in the study area was dominated by forest (95.5%), seeds found in the marten feces were dominated by those of forest edge plants (92.1%), suggesting a strong selective bias, both habitat and food, toward these species. The density of marten feces was also higher at forest edges than forest interiors. A. arguta plants were more abundant at forest edges than within the forest at Afan Wood, Nagano Prefecture. These results suggest that the Japanese marten selectively uses forest edges as a location for feeding and defecation and thus functions as a directed seed disperser of A. arguta.

The Earth rotation and revolution effect on the daily and annual variation of sporadic meteor echo

NASA Astrophysics Data System (ADS)

Ohnishi, Kouji; Hattori, Shinobu; Nishimura, Osamu; Ishikawa, Toshiyuki; Aoki, Yoshie; Iijima, Yukiko; Kobayashi, Aya; Maegawa, Kimio; Abe, Shinsuke

2001-11-01

The Earth rotation and revolution will affect the daily and annual variation of sporadic meteor echo. We try to investigate such effect using Ham-band Radio Observation (HRO). Our system is constructed with paired two-element loop antennas (F/B ratio is 10 dB) at Nagano, Japan using the beacon signals at 53.750 MHz, 50W from Sabae, Fukui, Japan. The direction of one of this paired antenna was West toward Sagae and the other was East, so that this system could be roughly detected the direction of the reflected radio echoes. Using this system, (1) The total echo rose from midnight with the peak coming at about 6:00 and decreasing to the noon. This is well known daily variation due to the Earth rotation. (2) The peak echoes time by Eastward antenna and by Westward antennas was different; Westward was at 3:00 and Eastward was at 10:00. This daily variation is interpreted as the effect of the Earth rotation and revolution and the specular reflection property of forward meteor scattering observation.

Consequences of organizational commitment in abolished company sports team - a case study in Japan.

PubMed

Honda, Yuki; Hochi, Yasuyuki; Mizuno, Motoki

2012-01-01

The purpose of this study was to show that how the abolishment of company sports team influenced the organizational commitment in employees. In this study, Three-Component Model of Organizational Commitment (Meyer and Allen, 1997) was tested with 16 employees (10 males, 6 females) of T Company in NAGANO prefecture. The average age of the participants was 44, 50 years (SD=±0.85). And from 16 employees, 3 male employees were measured on organizational commitment with interview test. According to the analysis, the relation between organizational commitment in employees and the abolishment of company sports team was not positive significant correlation. Furthermore, results of interview test did not show the relation between organizational commitment in employees and the abolishment of company sports team. However, results of interview test showed the relation with organizational commitment of players in T Company sports team. Consequently, the goal to possess a sports team in T Company was not to boost organizational commitment in employees. In addition, it is necessary to reconsider the correlation among employees engaged in T Company in the future.

Curidium Medica, plc.

PubMed

Caffo, Nathan A

2008-05-01

Curidium Medica, plc is a personalized medicine company intent on developing targeted medicines and their associated companion diagnostics to treat patients more effectively and safely. Through the use of its proprietary gene-expression analysis tool, Homomatrix ® , Curidium aims to reveal different patient subgroups characterized by distinct underlying disease mechanisms. This is anticipated to lead to the identification of diagnostics to subclassify patients within heterogeneous disease populations and improved therapies for different patient subgroups, ultimately resulting in the development of personalized medicines using companion diagnostics and targeted treatments. The company's initial focus on diseases of the CNS has resulted in the identification of a blood diagnostic tool, PsychINDx™, which classifies patients with schizophrenia/bipolar disorder into four subgroups. PsychINDx may have the potential to improve the treatment of patients with schizophrenia/bipolar disorder. Curidium aims to continue to use this approach to improve patient treatments in a variety of therapeutic areas and heterogeneous diseases. The first such additional application using Homomatrix has been initiated within a strategic research alliance with Takeda (Osaka, Japan) in the area of major depressive disorder.

Donated chemical probes for open science.

PubMed

Müller, Susanne; Ackloo, Suzanne; Arrowsmith, Cheryl H; Bauser, Marcus; Baryza, Jeremy L; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J; Bunnage, Mark E; Carter, Adrian J; Damerell, David; Dötsch, Volker; Drewry, David H; Edwards, Aled M; Edwards, James; Elkins, Jon M; Fischer, Christian; Frye, Stephen V; Gollner, Andreas; Grimshaw, Charles E; IJzerman, Adriaan; Hanke, Thomas; Hartung, Ingo V; Hitchcock, Steve; Howe, Trevor; Hughes, Terry V; Laufer, Stefan; Li, Volkhart Mj; Liras, Spiros; Marsden, Brian D; Matsui, Hisanori; Mathias, John; O'Hagan, Ronan C; Owen, Dafydd R; Pande, Vineet; Rauh, Daniel; Rosenberg, Saul H; Roth, Bryan L; Schneider, Natalie S; Scholten, Cora; Singh Saikatendu, Kumar; Simeonov, Anton; Takizawa, Masayuki; Tse, Chris; Thompson, Paul R; Treiber, Daniel K; Viana, Amélia Yi; Wells, Carrow I; Willson, Timothy M; Zuercher, William J; Knapp, Stefan; Mueller-Fahrnow, Anke

2018-04-20

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project. © 2018, Müller et al.

Sm-Nd, Rb-Sr, and Mn-Cr Ages of Yamato 74013

NASA Technical Reports Server (NTRS)

Nyquist, L. E.; Shih, C.- Y.; Reese, Y.D.

2009-01-01

Yamato 74013 is one of 29 paired diogenites having granoblastic textures. The Ar-39 - Ar-40 age of Y-74097 is approximately 1100 Ma. Rb-Sr and Sm-Nd analyses of Y-74013, -74037, -74097, and -74136 suggested that multiple young metamorphic events disturbed their isotopic systems. Masuda et al. reported that REE abundances were heterogeneous even within the same sample (Y-74010) for sample sizes less than approximately 2 g. Both they and Nyquist et al. reported data for some samples showing significant LREE enrichment. In addition to its granoblastic texture, Y-74013 is characterized by large, isolated clots of chromite up to 5 mm in diameter. Takeda et al. suggested that these diogenites originally represented a single or very small number of coarse orthopyroxene crystals that were recrystallized by shock processes. They further suggested that initial crystallization may have occurred very early within the deep crust of the HED parent body. Here we report the chronology of Y-74013 as recorded in chronometers based on long-lived Rb-87 and Sm-147, intermediate- lived Sm-146, and short-lived Mn-53.

Pharmacology of Ramelteon, a Selective MT1/MT2 Receptor Agonist: A Novel Therapeutic Drug for Sleep Disorders

PubMed Central

Miyamoto, Masaomi

2009-01-01

An estimated one-third of the general population is affected by insomnia, and this number is increasing due to more stressful working conditions and the progressive aging of society. However, current treatment of insomnia with hypnotics, gamma-aminobutyric acid A (GABAA) receptor modulators, induces various side effects, including cognitive impairment, motor disturbance, dependence, tolerance, hangover, and rebound insomnia. Ramelteon (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin MT1/MT2 receptor agonist. Unlike the sedative hypnotics that target GABAA receptor complexes, ramelteon is a chronohypnotic that acts on the melatonin MT1 and MT2 receptors, which are primarily located in the suprachiasmatic nucleus, the body's “master clock.” As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades. Ramelteon has demonstrated sleep-promoting effects in clinical trials, and coupled with its favorable safety profile and lack of abuse potential or dependence, this chronohypnotic provides an important treatment option for insomnia. PMID:19228178

Topology changes in a water-oil swirling flow

NASA Astrophysics Data System (ADS)

Carrión, Luis; Herrada, Miguel A.; Shtern, Vladimir N.

2017-03-01

This paper reveals the flow topology hidden in the experimental study by Fujimoto and Takeda ["Topology changes of the interface between two immiscible liquid layers by a rotating lid," Phys. Rev. E 80, 015304(R) (2009)]. Water and silicone oil fill a sealed vertical cylindrical container. The rotating top disk induces the meridional circulation and swirl of both fluids. As the rotation strength Reo increases, the interface takes shapes named, by the authors, hump, cusp, Mt. Fuji, and bell. Our numerical study reproduces the interface geometry and discloses complicated flow patterns. For example at Reo = 752, where the interface has the "Mt. Fuji" shape, the water motion has three bulk cells and the oil motion has two bulk cells. This topology helps explain the interface geometry. In addition, our study finds that the steady axisymmetric flow suffers from the shear-layer instability for Reo > 324, i.e., before the interface becomes remarkably deformed. The disturbance energy is concentrated in the water depth. This explains why the instability does not significantly affect the interface shape in the experiment.

Transfer of D-phenylalanine from gramicidin S synthetase 1 to gramicidin S synthetase 2 in gramicidin S synthesis.

PubMed

Hori, K; Kanda, M; Miura, S; Yamada, Y; Saito, Y

1983-01-01

The transfer of phenylalanine from gramicidin S synthetase 1 (GS 1) to gramicidin S synthetase 2 (GS 2) was studied by the use of combinations of wild-type GS 1 with various GS 2s from a wild strain and gramicidin S non-producing mutant strains of Bacillus brevis Nagano. The combinations of mutant GS 2s lacking 4'-phosphopantetheine (from BI-4, C-3, E-1, and E-2) did not transfer D-phenylalanine from GS 1, although they could activate all the constituent amino acids. Other mutant GS 2s containing 4'-phosphopantetheine, except GS 2 from BII-3 (proline-activation lacking) accepted D-phenylalanine from intact GS 1. To ascertain more directly whether 4'-phosphopantetheine is involved in the transfer of D-phenylalanine from GS 1 to GS 2, pepsin digests of GS 2 that accepted [14C]phenylalanine were analyzed by Sephadex G-50 column chromatography and thin-layer chromatography (TLC). Radioactivity of [14C]phenylalanine was always associated with a peptide containing 4'-phosphopantetheine. Furthermore, the position of radioactivity was distinct from the position of 4'-phosphopantetheine on TLC after alkaline treatment or performic acid oxidation of the digests.

Flow-field differences and electromagnetic-field properties of air and N2 inductively coupled plasmas

NASA Astrophysics Data System (ADS)

Yu, Minghao; Yamada, Kazuhiko; Takahashi, Yusuke; Liu, Kai; Zhao, Tong

2016-12-01

A numerical model for simulating air and nitrogen inductively coupled plasmas (ICPs) was developed considering thermochemical nonequilibrium and the third-order electron transport properties. A modified far-field electromagnetic model was introduced and tightly coupled with the flow field equations to describe the Joule heating and inductive discharge phenomena. In total, 11 species and 49 chemical reactions of air, which include 5 species and 8 chemical reactions of nitrogen, were employed to model the chemical reaction process. The internal energy transfers among translational, vibrational, rotational, and electronic energy modes of chemical species were taken into account to study thermal nonequilibrium effects. The low-Reynolds number Abe-Kondoh-Nagano k-ɛ turbulence model was employed to consider the turbulent heat transfer. In this study, the fundamental characteristics of an ICP flow, such as the weak ionization, high temperature but low velocity in the torch, and wide area of the plasma plume, were reproduced by the developed numerical model. The flow field differences between the air and nitrogen ICP flows inside the 10-kW ICP wind tunnel were made clear. The interactions between the electromagnetic and flow fields were also revealed for an inductive discharge.

Safety Evaluation of the Lighting at the Entrance of a Very Long Road Tunnel: A Case Study in Ilam.

PubMed

Mehri, Ahmad; Hajizadeh, Roohalah; Farhang Dehghan, Somayeh; Nassiri, Parvin; Jafari, Sayed Mohammad; Taheri, Fereshteh; Zakerian, Seyed Abolfazl

2017-06-01

At the entrance of a tunnel, reflection of sunlight from the surrounding environment and a lack of adequate lighting usually cause some vision problems. The purpose of this study was to perform a safety evaluation of lighting on a very long road in Ilam, Iran. The average luminance was measured using a luminance meter (model S3; Hagner, Solna, Sweden). A camera (model 108, 35-mm single-lens reflex; Yashica, Nagano, Japan) was used to take photographs of the safe stopping distance from the tunnel entrance. Equivalent luminance was determined according to the Holliday polar diagram. Considering the average luminance at the tunnel entrance (116.7 cd/m 2 ) and using Adrian's equation, the safe level of lighting at the entrance of the tunnel was determined to be 0.7. A comparison between the results of the safe levels of lighting at the entrance of the tunnel and the De Boer scale showed that the phenomenon of black holes is created at the tunnel entrance. This may lead to a misadaptation of the drivers' eyes to the change in luminance level at the entrance of the tunnel, thereby increasing the risk of road accidents in this zone.

FIT: statistical modeling tool for transcriptome dynamics under fluctuating field conditions

PubMed Central

Iwayama, Koji; Aisaka, Yuri; Kutsuna, Natsumaro

2017-01-01

Abstract Motivation: Considerable attention has been given to the quantification of environmental effects on organisms. In natural conditions, environmental factors are continuously changing in a complex manner. To reveal the effects of such environmental variations on organisms, transcriptome data in field environments have been collected and analyzed. Nagano et al. proposed a model that describes the relationship between transcriptomic variation and environmental conditions and demonstrated the capability to predict transcriptome variation in rice plants. However, the computational cost of parameter optimization has prevented its wide application. Results: We propose a new statistical model and efficient parameter optimization based on the previous study. We developed and released FIT, an R package that offers functions for parameter optimization and transcriptome prediction. The proposed method achieves comparable or better prediction performance within a shorter computational time than the previous method. The package will facilitate the study of the environmental effects on transcriptomic variation in field conditions. Availability and Implementation: Freely available from CRAN (https://cran.r-project.org/web/packages/FIT/). Contact: anagano@agr.ryukoku.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online PMID:28158396

Study for Nuclear Structures of 22-35Na Isotopes via Measurements of Reaction Cross Sections

NASA Astrophysics Data System (ADS)

Suzuki, Shinji

2014-09-01

T. Ohtsubo, M. Nagashima, T. Ogura, Y. Shimbara (Grad. Sch. of Sc., Niigata Univ.), M.Takechi, H. Geissel, M. Winkler (GSI), D. Nishimura, T. Sumikama (Dept. of Phys., Tokyo Univ. of Sc.), M. Fukuda, M. Mihara, H. Uenishi (Dept. of Phys., Osaka Univ.), T. Kuboki, T. Suzuki, T. Yamaguchi, H. Furuki, C. S. Lee, K. Sato (Dept. of Phys., Saitama Univ.), A. Ozawa, H. Ohnishi, T. Moriguchi, S. Fukuda, Y. Ishibashi, D. Nagae, R. Nishikiori, T. Niwa (Inst. of Phys., Univ. of Tsukuba), N. Aoi (RCNP), Rui-Jiu Chen, N. Inabe, D. Kameda, T. Kubo, M. Lantz, T. Ohnishi, K. Okumura, H. Sakurai, H. Suzuki, H. Takeda, S. Takeuchi, K. Tanaka, Y. Yanagisawa (RIKEN), De-Qing Fang, Yu-Gang Ma (SINAP), T. Izumikawa (RI Ctr., Niigata Univ.), and S. Momota (Fac. of Engn., Kochi Univ. of Tech.) Reaction cross sections (σR) for 22-35Na isotopes have been measured at around 240 MeV/nucleon. The σR for 22-35Na were measured for the first time. Enhancement in cross sections is clearly observed from the systematics for stable nuclei, for isotopes with large mass numbers. These enhancement can be mainly ascribed to the nuclear deformation. We will discuss the nuclear structure (neutron skin, nuclear shell structure) for neutron-excess Na isotopes. T. Ohtsubo, M. Nagashima, T. Ogura, Y. Shimbara (Grad. Sch. of Sc., Niigata Univ.), M.Takechi, H. Geissel, M. Winkler (GSI), D. Nishimura, T. Sumikama (Dept. of Phys., Tokyo Univ. of Sc.), M. Fukuda, M. Mihara, H. Uenishi (Dept. of Phys., Osaka Univ.), T. Kuboki, T. Suzuki, T. Yamaguchi, H. Furuki, C. S. Lee, K. Sato (Dept. of Phys., Saitama Univ.), A. Ozawa, H. Ohnishi, T. Moriguchi, S. Fukuda, Y. Ishibashi, D. Nagae, R. Nishikiori, T. Niwa (Inst. of Phys., Univ. of Tsukuba), N. Aoi (RCNP), Rui-Jiu Chen, N. Inabe, D. Kameda, T. Kubo, M. Lantz, T. Ohnishi, K. Okumura, H. Sakurai, H. Suzuki, H. Takeda, S. Takeuchi, K. Tanaka, Y. Yanagisawa (RIKEN), De-Qing Fang, Yu-Gang Ma (SINAP), T. Izumikawa (RI Ctr., Niigata Univ.), and S. Momota (Fac. of Engn

Subsurface Resistivity Structures in and Around Strike-Slip Faults - Electromagnetic Surveys and Drillings Across Active Faults in Central Japan -

NASA Astrophysics Data System (ADS)

Omura, K.; Ikeda, R.; Iio, Y.; Matsuda, T.

2005-12-01

Electrical resistivity is important property to investigate the structure of active faults. Pore fluid affect seriously the electrical properties of rocks, subsurface electrical resistivity can be an indicator of the existence of fluid and distribution of pores. Fracture zone of fault is expected to have low resistivity due to high porosity and small gain size. Especially, strike-slip type fault has nearly vertical fracture zone and the fracture zone would be detected by an electrical survey across the fault. We performed electromagnetic survey across the strike-slip active faults in central Japan. At the same faults, we also drilled borehole into the fault and did downhole logging in the borehole. We applied MT or CSAMT methods onto 5 faults: Nojima fault which appeared on the surface by the 1995 Great Kobe earthquake (M=7.2), western Nagano Ohtaki area(1984 Nagano-ken seibu earthquake (M=6.8), the fault did not appeared on the surface), Neodani fault which appeared by the 1891 Nobi earthquake (M=8.0), Atera fault which seemed to be dislocated by the 1586 Tensyo earthquake (M=7.9), Gofukuji fault that is considered to have activated about 1200 years ago. The sampling frequencies of electrical and magnetic field were 2 - 1024Hz (10 frequencies) for CSAMT survey and 0.00055 - 384Hz (40 frequencies) for MT survey. The electromagnetic data were processed by standard method and inverted to 2-D resistivity structure along transects of the faults. Results of the survey were compared with downhole electrical logging data and observational descriptions of drilled cores. Fault plane of each fault were recognized as low resistivity region or boundary between relatively low and high resistivity region, except for Gofukuji fault. As for Gofukuji fault, fault was located in relatively high resistivity region. During very long elapsed time from the last earthquake, the properties of fracture zone of Gofukuji fault might changed from low resistivity properties as observed for

Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.

PubMed

Mitri, Ghaith; Wittbrodt, Eric T; Turpin, Robin S; Tidwell, Beni A; Schulman, Kathy L

2016-04-01

following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. No outside funding supported this study. Turpin is an employee of Takeda

Cannabidiol-2',6'-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro.

PubMed

Takeda, Shuso; Hirayama, Akari; Urata, Shino; Mano, Nobutaka; Fukagawa, Keiko; Imamura, Midori; Irii, Ayumi; Kitajima, Satomi; Masuyama, Tomoko; Nomiyama, Mai; Tatei, Sachiko; Tomita, Saari; Kudo, Taichi; Noguchi, Momoko; Yamaguchi, Yasuhiro; Okamoto, Yoshiko; Amamoto, Toshiaki; Fukunishi, Yoshifumi; Watanabe, Kazuhito; Omiecinski, Curtis John; Aramaki, Hironori

2011-01-01

15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein (ox-LDL), a major causal factor for atherosclerosis. Both enzymatic (15-LOX) and non-enzymatic (Cu(2+)) mechanisms have been proposed for the production of ox-LDL. We have recently reported that cannabidiol-2',6'-dimethyl ether (CBDD) is a selective and potent inhibitor of 15-LOX-catalyzed linoleic acid oxygenation (Takeda et al., Drug Metab. Dispos., 37, 1733-1737 (2009)). In the LDL, linoleic acid is present as cholesteryl linoleate, the major fatty acid esterified to cholesterol, and is susceptible to oxidative modification by 15-LOX or Cu(2+). In this investigation, we examined the efficacy of CBDD on i) 15-LOX-catalyzed oxygenation of cholesteryl linoleate, and ii) ox-LDL formation catalyzed by 15-LOX versus Cu(2+)-mediated non-enzymatic generation of this important mediator. The results obtained demonstrate that CBDD is a potent and selective inhibitor of ox-LDL formation generated by the 15-LOX pathway. These studies establish CBDD as both an important experimental tool for characterizing 15-LOX-mediated ox-LDL formation, and as a potentially useful therapeutic agent for treatment of atherosclerosis.

What Drives Farmers to Make Top-Down or Bottom-Up Adaptation to Climate Change and Fluctuations? A Comparative Study on 3 Cases of Apple Farming in Japan and South Africa

PubMed Central

Fujisawa, Mariko; Kobayashi, Kazuhiko; Johnston, Peter; New, Mark

2015-01-01

Agriculture is one of the most vulnerable sectors to climate change. Farmers have been exposed to multiple stressors including climate change, and they have managed to adapt to those risks. The adaptation actions undertaken by farmers and their decision making are, however, only poorly understood. By studying adaptation practices undertaken by apple farmers in three regions: Nagano and Kazuno in Japan and Elgin in South Africa, we categorize the adaptation actions into two types: farmer initiated bottom-up adaptation and institution led top-down adaptation. We found that the driver which differentiates the type of adaptation likely adopted was strongly related to the farmers’ characteristics, particularly their dependence on the institutions, e.g. the farmers’ cooperative, in selling their products. The farmers who rely on the farmers’ cooperative for their sales are likely to adopt the institution-led adaptation, whereas the farmers who have established their own sales channels tend to start innovative actions by bottom-up. We further argue that even though the two types have contrasting features, the combinations of the both types of adaptations could lead to more successful adaptation particularly in agriculture. This study also emphasizes that more farm-level studies for various crops and regions are warranted to provide substantial feedbacks to adaptation policy. PMID:25822534

[Family influences on future smoking habits among junior high school students in Japan].

PubMed

Wakabayashi, Chihiro

2007-11-01

To examine the effects of health-related behavior and family smoking habits on the future smoking habits of junior high school students in two Japanese cities with different life expectancies. A cross-sectional study was conducted in January 2005 of all second-grade students in a junior high school in city A located in Aomori prefecture (399 students) and city B located in Nagano prefecture (447 students). Life expectancies in city B were 4.2 years longer in men and 2.9 years longer in women than in city A. Data on feelings about future smoking habits, dislike of tobacco smoke, family smoking habits and health-related behavior were collected. The proportion of boys who went on to become smokers was higher in city A (18.7%) than in city B (10.3%). The proportions of smoking mothers and other smoking family members were also higher in city A, while the proportion of students who disliked tobacco smoke was lower. For girls in both cities, there was a significant positive association between future smoking and maternal smoking. The findings suggest that maternal smoking habits are especially strongly correlated with future smoking in girls. The family smoking environment and health-related behavior should therefore be considered in measures to prevent smoking by students.

Carbonate ion-enriched hot spring water promotes skin wound healing in nude rats.

PubMed

Liang, Jingyan; Kang, Dedong; Wang, Yingge; Yu, Ying; Fan, Jianglin; Takashi, En

2015-01-01

Hot spring or hot spa bathing (Onsen) is a traditional therapy for the treatment of certain ailments. There is a common belief that hot spring bathing has therapeutic effects for wound healing, yet the underlying molecular mechanisms remain unclear. To examine this hypothesis, we investigated the effects of Nagano hot spring water (rich in carbonate ion, 42°C) on the healing process of the skin using a nude rat skin wound model. We found that hot spring bathing led to an enhanced healing speed compared to both the unbathed and hot-water (42°C) control groups. Histologically, the hot spring water group showed increased vessel density and reduced inflammatory cells in the granulation tissue of the wound area. Real-time RT-PCR analysis along with zymography revealed that the wound area of the hot spring water group exhibited a higher expression of matrix metalloproteinases-2 and -9 compared to the two other control groups. Furthermore, we found that the enhanced wound healing process induced by the carbonate ion-enriched hot spring water was mediated by thermal insulation and moisture maintenance. Our results provide the evidence that carbonate ion-enriched hot spring water is beneficial for the treatment of skin wounds.

Bite force measurements with hard and soft bite surfaces.

PubMed

Serra, C M; Manns, A E

2013-08-01

Bite force has been measured by different methods and over a wide variety of designs. In several instruments, the fact that bite surface has been manufactured with stiff materials might interfere in obtaining reliable data, by a more prompt activation of inhibitory reflex mechanisms. The purpose of this study was to compare the maximum voluntary bite force measured by a digital occlusal force gauge (GM10 Nagano Keiki, Japan) between different opponent teeth, employing semi-hard or soft bite surfaces. A sample of 34 young adults with complete natural dentition was studied. The original semi-hard bite surface was exchanged by a soft one, made of leather and rubber. Maximum voluntary bite force recordings were made for each tooth group and for both bite surfaces. Statistical analyses (Student's t-test) revealed significant differences, with higher scores while using the soft surface across sexes and tooth groups (P < 0·05). Differential activation of periodontal mechanoreceptors of a specific tooth group is mainly conditioned by the hardness of the bite surface; a soft surface induces greater activation of elevator musculature, while a hard one induces inhibition more promptly. Thus, soft bite surfaces are recommended for higher reliability in maximum voluntary bite force recordings. © 2013 John Wiley & Sons Ltd.

On the seasonal transition from winter to spring in Europe and the "seasonal feeling" relating to "Fasnacht" in comparison with those in East Asia (Toward an interdisciplinary activity on climate and cultural understanding education)

NASA Astrophysics Data System (ADS)

Kato, Kuranoshin; Kato, Haruko; Hamaki, Tatsuya

2016-04-01

As mentioned in the introduction of the EGU2016 abstract (Kato et al., submitted to CL5.06/AS4.9), there are many stages with rapid seasonal transitions in East Asia, resulting in the variety of "seasonal feeling". The seasonal cycle has been an important background for generation of the arts. On the other hand, around Germany located near the western edge of the Eurasian Continent, there are so many music or literature works in which the "May" is treated as the special season (comparison of the climate and songs on "spring" (or "May") between Japan and Germany was tried in a book by Kato, H. and K. Kato, although written in Japanese). The Japanese researchers on German Literature suggested that there are basically two seasons "winter" and "summer" around Germany, with the transitional stages of spring and autumn. The concepts of the battle between winter and summer, and driving winter away, and so on, around Germany seem to show rather different seasonal feelings from that around the Japan Islands (Oshio 1982; Miyashita 1982; Takeda 1980). A traditional event there called "Fasnacht" for driving winter away is held in March or slightly earlier stage (Takeda 1980; Ueda and Ebato 1988). Kato et al. (EGU2016, submitted to CL5.06/AS4.9) will report the synoptic climatological features on the seasonal transition from winter to spring in Europe based on the daily data, by comparing with that in East Asia. In this presentation, we will discuss on the climatological background for the "seasonal feeling" leading to such as the battle between winter and summer, driving winter away, including "Fasnacht", also by referring to some songs (children's songs, etc.). At the same time, the analysis results on the seasonal transition from winter to spring in Europe in comparison with those in East Asia by Kato et al. (EGU2016) will be also referred to. On the other hand, although it is around the end of March when the "wintertime pressure pattern" on the daily surface weather maps in

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in Nagano, Japan: clinical, radiological, and cytokine studies of 13 patients.

PubMed

Oide, T; Ohara, S; Oguchi, K; Maruyama, M; Yazawa, M; Inoue, K; Sekijima, Y; Tokuda, T; Ikeda, S

2004-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) has so far been reported almost exclusively from the USA and Europe. We carried out this study to define the clinical characteristics of this syndrome in Japanese patients. Prospectively, we identified 13 Japanese patients with RS3PE (5 men and 8 women, age 72.7 +/- 11.8 years (mean +/- SD)) without underlying neoplasm. Their clinical features were summarized, pertinent laboratory data including serum/synovial interleukin-6 (IL-6) concentrations were obtained, and extensive radiologic studies using magnetic resonance imaging and 67gallium-citrate (67Ga) whole body scintigram were performed. All patients suffered from proximal arthralgia/myalgia in addition to typical distal symptoms of RS3PE, and all experienced systemic symptoms such as fever, malaise, and weight loss. In laboratory examinations, anemia and elevated inflammatory markers were often remarkable. Magnetic resonance imaging showed severe tenosynovitis of the hands. 67Ga-scintigram revealed radioisotope accumulation in both proximal and distal joints of the extremities. IL-6 activity was markedly elevated both in the serum (mean 82.4 +/- 62.1 (SD) pg/ml, normal range 0.157-2.94) and in the synovial fluid (mean 3350 +/- 633 (SD) pg/ml). Compared with cases reported previously from the USA/Europe, Japanese patients with RS3PE are characterized by more prominent systemic symptoms/signs associated with marked inflammatory responses including elevated IL-6 activity. All patients had proximal as well as distal synovitis which could be demonstrated by 67Ga-scintigram. These clinical features were very similar to those of polymyalgia rheumatica, suggesting that RS3PE and polymyalgia rheumatica are closely related disorders which may have a common pathogenesis.

Antidepressants in paediatric depression: do not look back in anger but around in awareness.

PubMed

Brent, David A; Gibbons, Robert D; Wilkinson, Paul; Dubicka, Bernadka

2018-02-01

In this paper, we summarise and critique a network meta-analysis (NMA) of antidepressant efficacy and tolerability for paediatric depression and an accompanying editorial. Although we agree that many of the extant studies are flawed, this meta-analysis showed clear efficacy of fluoxetine in the NMA, and for sertraline and escitalopram in pairwise analyses. Consequently, these papers underestimate the benefits of antidepressants for paediatric depression, and provide support for current practice guideline, which recommends the use of an antidepressant if the patient does not respond to psychotherapy. In these circumstances, fluoxetine should be the first choice, with escitalopram and sertraline as alternatives. Declaration of interest D.A.B. receives royalties from Guilford Press, has or will receive royalties from the electronic self-rated version of the C-SSRS from eResearch Technology, Inc., is on the editorial board of UpToDate, and is a reviewer for Healthwise. R.D.G. serves as an expert witness for the US Department of Justice, Pfizer, Wyeth and GSK; and is the founder of Adaptive Testing Technologies. P.W. receives personal fees from Lundbeck and Takeda. B.D. reports a licensing agreement with Lundbeck for a psychosocial treatment manual for depression. No other disclosures were reported.

Anti-tumor efficacy of a novel CLK inhibitor via targeting RNA splicing and MYC-dependent vulnerability.

PubMed

Iwai, Kenichi; Yaguchi, Masahiro; Nishimura, Kazuho; Yamamoto, Yukiko; Tamura, Toshiya; Nakata, Daisuke; Dairiki, Ryo; Kawakita, Yoichi; Mizojiri, Ryo; Ito, Yoshiteru; Asano, Moriteru; Maezaki, Hironobu; Nakayama, Yusuke; Kaishima, Misato; Hayashi, Kozo; Teratani, Mika; Miyakawa, Shuichi; Iwatani, Misa; Miyamoto, Maki; Klein, Michael G; Lane, Wes; Snell, Gyorgy; Tjhen, Richard; He, Xingyue; Pulukuri, Sai; Nomura, Toshiyuki

2018-06-01

The modulation of pre-mRNA splicing is proposed as an attractive anti-neoplastic strategy, especially for the cancers that exhibit aberrant pre-mRNA splicing. Here, we discovered that T-025 functions as an orally available and potent inhibitor of Cdc2-like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T-025 reduced CLK-dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive-associated biomarker of T-025. Mechanistically, the level of CLK2 expression correlated with the magnitude of global skipped exons in response to T-025 treatment. MYC activation, which altered pre-mRNA splicing without the transcriptional regulation of CLKs, rendered cancer cells vulnerable to CLK inhibitors with synergistic cell death. Finally, we demonstrated in vivo anti-tumor efficacy of T-025 in an allograft model of spontaneous, MYC-driven breast cancer, at well-tolerated dosage. Collectively, our results suggest that the novel CLK inhibitor could have therapeutic benefits, especially for MYC-driven cancer patients. © 2018 Takeda Pharmaceutical Company Published under the terms of the CC BY 4.0 license.

Maxillo-Mandibular Cemento-ossifying Fibroma: A Rare Case Report.

PubMed

Peravali, Ranjit Kumar; Bhat, H Hari Kishore; Reddy, Sreenatha

2015-03-01

Cemento-ossifying fibroma (COF) is a benign fibro osseous lesion of the jaws which has been described as a demarcated or rarely encapsulated neoplasm consisting of fibrous tissue and varying amounts of mineralized material resembling bone and/or cementum (Dinkar et al. in IJDA 2(4):45-47, 2010). Majority of lesions occur in the mandible and only few cases of COFs of the maxillary sinus and bilateral COFs of the mandible have been reported in literature (Dinkar et al. in IJDA 2(4):45-47, 2010; Tamiolakis et al. in Acta Stomatol Croat 39(3):319-321, 2005; Hamner et al. in Oral Surg Oral Med Oral Pathol 26(4):579-587, 1968; Gunaseelan et al. in Oral Med Oral Pathol Oral Radiol Endod 104:e21-e25, 2007). These lesions have a very low recurrence rate (Ertug et al. in Quintessence Int 35(10):808-810, 2004) and are generally treated by enucleation. In this paper we present a rare case of COF occurring in both the maxilla and mandible of the same patient. Only one such case (Takeda and Fujioka in Int J Oral Maxillofac Surg 16(3):368-371, 1987) has been reported in literature so far.

Frontal-parietal synchrony in elderly EEG for visual search.

PubMed

Phillips, Steven; Takeda, Yuji

2010-01-01

Aging involves selective changes in attentional control. However, its precise effect on visual attention is difficult to discern from behavioural studies alone. In this paper, we employ a recently developed phase-locking measure of synchrony as an indicator of top-down/bottom-up control of attention to assess attentional control in the elderly. Fourteen participants (63-74 years) searched for a target item (coloured, oriented rectangular bar) among a display set of distractors. For the feature search condition, where none of the distractors shared a feature with the target, search time did not increase with display set size (two, or four items). For the conjunctive search condition, where each distractor shared either a colour or orientation feature with the target, search time increased with display size. Phase-locking analysis revealed a significant increase in high gamma-band (36-56 Hz) synchrony indicating greater bottom-up control for feature than conjunctive search. In view of our earlier study on younger (21-32 years) adults (Phillips and Takeda, 2009), these results suggest that older participants are more likely to use bottom-up control of attention, possibly triggered by their greater susceptibility to attentional capture, than younger participants. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Cannabidiol-2′,6′-dimethyl Ether as an Effective Protector of 15-Lipoxygenase-Mediated Low-Density Lipoprotein Oxidation in Vitro

PubMed Central

Takeda, Shuso; Hirayama, Akari; Urata, Shino; Mano, Nobutaka; Fukagawa, Keiko; Imamura, Midori; Irii, Ayumi; Kitajima, Satomi; Masuyama, Tomoko; Nomiyama, Mai; Tatei, Sachiko; Tomita, Saari; Kudo, Taichi; Noguchi, Momoko; Yamaguchi, Yasuhiro; Okamoto, Yoshiko; Amamoto, Toshiaki; Fukunishi, Yoshifumi; Watanabe, Kazuhito; Omiecinski, Curtis John; Aramaki, Hironori

2014-01-01

15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein (ox-LDL), a major causal factor for atherosclerosis. Both enzymatic (15-LOX) and non-enzymatic (Cu2+) mechanisms have been proposed for the production of ox-LDL. We have recently reported that cannabidiol-2′,6′-dimethyl ether (CBDD) is a selective and potent inhibitor of 15-LOX-catalyzed linoleic acid oxygenation (Takeda et al., Drug Metab. Dispos., 37, 1733–1737 (2009)). In the LDL, linoleic acid is present as cholesteryl linoleate, the major fatty acid esterified to cholesterol, and is susceptible to oxidative modification by 15-LOX or Cu2+. In this investigation, we examined the efficacy of CBDD on i) 15-LOX-catalyzed oxygenation of cholesteryl linoleate, and ii) ox-LDL formation catalyzed by 15-LOX versus Cu2+-mediated non-enzymatic generation of this important mediator. The results obtained demonstrate that CBDD is a potent and selective inhibitor of ox-LDL formation generated by the 15-LOX pathway. These studies establish CBDD as both an important experimental tool for characterizing 15-LOX-mediated ox-LDL formation, and as a potentially useful therapeutic agent for treatment of atherosclerosis. PMID:21804214

Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line.

PubMed Central

Takahashi, Shigeru; Matsuura, Naomi; Kurokawa, Takako; Takahashi, Yuji; Miura, Takashi

2002-01-01

We reported previously that the 5'-flanking region (nucleotides -1976 to -1655) of the human haem oxygenase-1 ( hHO-1 ) gene enhances hHO-1 promoter activity in human hepatoma HepG2 cells, but not in HeLa cells [Takahashi, Takahashi, Ito, Nagano, Shibahara and Miura (1999) Biochim. Biophys. Acta 1447, 231-235]. To define more precisely the regulatory elements involved, in the present study we have functionally dissected this region and localized the enhancer to a 50 bp fragment (-1793 to -1744). Site-direct mutagenesis analysis revealed that two regions were responsible for this enhancer activity, i.e. a hepatocyte nuclear factor-4 (HNF-4) homologous region and a GC box motif homologous region. Mutation in either region alone moderately decreased enhancer activity. However, mutations in both regions reduced promoter activity to the basal level. Electrophoretic mobility-shift assays demonstrated that the P5-2 fragment (-1793 to -1744) interacted with at least two nuclear factors, i.e. HNF-4 and Sp1/Sp3. Co-transfection experiments using Drosophila SL2 cells revealed that HNF-4 and Sp1/Sp3 synergistically stimulated the enhancer activity of the P5-2 fragment. These results indicate that co-operation of HNF-4 with Sp1 or Sp3 leads to the activation of hHO-1 gene expression in hepatoma cells. PMID:12133007

Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line.

PubMed

Takahashi, Shigeru; Matsuura, Naomi; Kurokawa, Takako; Takahashi, Yuji; Miura, Takashi

2002-11-01

We reported previously that the 5'-flanking region (nucleotides -1976 to -1655) of the human haem oxygenase-1 ( hHO-1 ) gene enhances hHO-1 promoter activity in human hepatoma HepG2 cells, but not in HeLa cells [Takahashi, Takahashi, Ito, Nagano, Shibahara and Miura (1999) Biochim. Biophys. Acta 1447, 231-235]. To define more precisely the regulatory elements involved, in the present study we have functionally dissected this region and localized the enhancer to a 50 bp fragment (-1793 to -1744). Site-direct mutagenesis analysis revealed that two regions were responsible for this enhancer activity, i.e. a hepatocyte nuclear factor-4 (HNF-4) homologous region and a GC box motif homologous region. Mutation in either region alone moderately decreased enhancer activity. However, mutations in both regions reduced promoter activity to the basal level. Electrophoretic mobility-shift assays demonstrated that the P5-2 fragment (-1793 to -1744) interacted with at least two nuclear factors, i.e. HNF-4 and Sp1/Sp3. Co-transfection experiments using Drosophila SL2 cells revealed that HNF-4 and Sp1/Sp3 synergistically stimulated the enhancer activity of the P5-2 fragment. These results indicate that co-operation of HNF-4 with Sp1 or Sp3 leads to the activation of hHO-1 gene expression in hepatoma cells.

Characteristics of metabolic and lifestyle risk factors in young Japanese patients with coronary heart disease: a comparison with older patients.

PubMed

Azegami, Masako; Hongo, Minoru; Yanagisawa, Setsuko; Yamazaki, Akie; Sakaguchi, Kesami; Yazaki, Yoshikazu; Imamura, Hiroshi

2006-05-01

Coronary heart disease (CHD) is recognized as a lifestyle-related disease and is the second leading cause of death in Japan. However, the cardiac risk factor profile of young patients with CHD has not been clarified in suburban areas of Japan. Our study aimed to determine metabolic and lifestyle risk factors in young patients and compare them with older patients living in suburban areas of Nagano Prefecture. A multicenter study was conducted in 86 young (aged less than 40 years) and 91 older (aged 50 years and over) patients diagnosed with CHD from 1992 to 2002. There was a strong association between obesity and the occurrence of CHD events in young patients (odds ratio = 3.61, P = 0.006). Lifestyle in the young patients was characterized by a lack of physical activity and regular physical activity was found to decrease the risk of the CHD events in these patients (odds ratio = 0.31, P = 0.030). In older patients, hypertension was identified as an independent risk factor for CHD events. The results of the present study have demonstrated that obesity and a lack of regular physical exercise are independent risk factors for CHD events in younger patients. Thus, the data may be useful for the effective screening of high-risk individuals and the development of educational programs for the prevention of CHD, especially in younger Japanese.

Safety and efficacy of noncardiac surgical procedures in the management of patients with trisomy 13: A single institution-based detailed clinical observation.

PubMed

Shibuya, Soichi; Miyake, Yuichiro; Takamizawa, Shigeru; Nishi, Eriko; Yoshizawa, Katsumi; Hatata, Tomoko; Yoshizawa, Kazuki; Fujita, Kenya; Noguchi, Masahiko; Ohata, Jun; Hiroma, Takehiko; Nakamura, Tomohiko; Kosho, Tomoki

2018-05-01

Intensive treatment including surgery for patients with trisomy 13 (T13) remains controversial. This study aimed to evaluate the safety and efficacy of noncardiac surgical intervention for T13 patients. Medical records of patients with karyotypically confirmed T13 treated in the neonatal intensive care unit in Nagano Children's Hospital from January 2000 to October 2016 were retrospectively reviewed, and data from patients who underwent noncardiac surgery were analyzed. Of the 20 patients with T13, 15 (75%) underwent a total of 31 surgical procedures comprising 15 types, including tracheostomy in 10 patients and gastrostomy in 4. Operative time, anesthesia time, and amount of bleeding are described for the first time in a group of children with T13. All the procedures were completed safely with no anesthetic complications or surgery-related death. The overall rate of postoperative complications was 19.3%. Patients receiving tracheostomy had stable or improved respiratory condition. Six of them were discharged home and were alive at the time of this study. These results suggest at least short-term safety and efficacy of major noncardiac surgical procedures, and long-term efficacy of tracheostomy on survival or respiratory stabilization for home medical care of children with T13. Noncardiac surgical intervention is a reasonable choice for patients with T13. © 2018 Wiley Periodicals, Inc.

Green tea consumption and breast cancer risk in Japanese women: a case-control study.

PubMed

Iwasaki, Motoki; Mizusawa, Junki; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Tsugane, Shoichiro

2014-01-01

Although many in vitro and animal studies have suggested a protective effect of green tea against breast cancer, only a few epidemiological studies have examined this association, and findings have been inconsistent. We examined the association between green tea consumption and breast cancer risk in consideration of the hormone receptor status of tumors and investigated whether the association was modified by dietary and genetic factors based on a hospital-based case-control study in Nagano, Japan. A total of 369 pairs completed a validated food frequency questionnaire and provided blood samples. Four single nucleotide polymorphisms (SNPs) were genotyped: CYP19A1 (rs10046), COMT (rs4680), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131). We found no inverse association between green tea consumption and breast cancer risk. Compared with women who drank less than 120 ml of green tea per day, the adjusted odds ratio for women who drank more than 600 ml was 1.27 (95% confidence interval = 0.75-2.14; P for trend = 0.20). We also found no inverse association for either tumor subtype. No substantial effect modification was observed for menopausal status, 4 SNPs, or dietary intake of folate or isoflavone. This study provides additional evidence that green tea consumption is not associated with a decreased risk.

Leisure-time physical activity and breast cancer risk by hormone receptor status: effective life periods and exercise intensity.

PubMed

Suzuki, Reiko; Iwasaki, Motoki; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Shimazu, Taichi; Tsugane, Shoichiro

2010-11-01

Physical activity may decrease breast cancer risk. However, it is unclear what intensity of exercise and during which life periods this effect on decreasing risk is efficiently expressed, and whether the associations differ by the estrogen-/progesterone- receptor (ER/PR) status of tumors. We investigated associations between age- and intensity-specific leisure-time physical activity and ER/PR-defined breast cancer risk. We conducted a hospital-based case-control study in Nagano, Japan. Subjects were 405 cases newly diagnosed (>99% known ER/PR) from 2001 to 2005, who were age-/area-matched with 405 controls. Activity was assessed with a self-reported questionnaire which considered intensity level (moderate and/or strenuous) at different ages (at 12 and 20 years, and in the previous 5 years). Odds ratios (ORs) and 95% confidence intervals were calculated using logistic regression. Strenuous but not moderate physical activity at age 12 was inversely associated with pre- and postmenopausal breast cancer risk across ER/PR subtypes [overall OR(≥ 5 days/week vs. none) = 0.24 (0.14-0.43)]. Moderate physical activity in the previous 5 years was significantly associated with a decrease in risk for postmenopausal ER + PR + tumors only [OR(≥ 1 day/week vs. none) = 0.35 (0.18-0.67)]. Strenuous activity in teens and moderate activity after menopause may contribute to a reduction in breast cancer risk.

Ignavibacterium album gen. nov., sp. nov., a moderately thermophilic anaerobic bacterium isolated from microbial mats at a terrestrial hot spring and proposal of Ignavibacteria classis nov., for a novel lineage at the periphery of green sulfur bacteria.

PubMed

Iino, Takao; Mori, Koji; Uchino, Yoshihito; Nakagawa, Tatsunori; Harayama, Shigeaki; Suzuki, Ken-Ichiro

2010-06-01

A moderately thermophilic chemoheterotrophic bacterium, strain Mat9-16(T), was isolated from microbial mats developed in hot spring water streams from Yumata, Nagano, Japan. Cells of strain Mat9-16(T) were strictly anaerobic, Gram-stain-negative, non-sporulating, non-motile and short to long rods (2.0-15.5 mum in length). Strain Mat9-16(T) grew fermentatively with optimum growth at 45 degrees C, pH 7.0-7.5 and 1 % NaCl (w/v). Phylogenetic analysis based on the 16S rRNA gene revealed that strain Mat9-16(T) was affiliated with an uncultivated lineage, and the nearest cultivated neighbours were green sulfur bacteria belonging to the class Chlorobea with 77-83 % sequence similarity. However, strain Mat9-16(T) could not grow phototrophically and did not possess light-harvesting structures, morphologically and genetically, such as the chlorosomes of green sulfur bacteria. On the basis of phenotypic features and phylogenetic position, a novel genus and species are proposed for strain Mat9-16(T), to be named Ignavibacterium album gen. nov., sp. nov. (=NBRC 101810(T) =DSM 19864(T)). We also propose to place the cultivated bacterial lineage accommodating the sole representative Mat9-16(T) in a novel class, Ignavibacteria classis nov. In addition, we present a formal description of the phylum-level taxon 'Chlorobi' as Chlorobi phyl. nov.

Nectinepsin: a new extracellular matrix protein of the pexin family. Characterization of a novel cDNA encoding a protein with an RGD cell binding motif.

PubMed

Blancher, C; Omri, B; Bidou, L; Pessac, B; Crisanti, P

1996-10-18

We report the isolation and characterization of a novel cDNA from quail neuroretina encoding a putative protein named nectinepsin. The nectinepsin cDNA identifies a major 2.2-kilobase mRNA that is detected from ED 5 in neuroretina and is increasingly abundant during embryonic development. A nectinepsin mRNA is also found in quail liver, brain, and intestine and in mouse retina. The deduced nectinepsin amino acid sequence contains the RGD cell binding motif of integrin ligands. Furthermore, nectinepsin shares substantial homologies with vitronectin and structural protein similarities with most of the matricial metalloproteases. However, the presence of a specific sequence and the lack of heparin and collagen binding domains of the vitronectin indicate that nectinepsin is a new extracellular matrix protein. Furthermore, genomic Southern blot studies suggest that nectinepsin and vitronectin are encoded by different genes. Western blot analysis with an anti-human vitronectin antiserum revealed, in addition to the 65- and 70-kDa vitronectin bands, an immunoreactive protein of about 54 kDa in all tissues containing nectinepsin mRNA. It seems likely that the form of vitronectin found in chick egg yolk plasma by Nagano et al. ((1992) J. Biol. Chem. 267, 24863-24870) is the protein that corresponds to the nectinepsin cDNA. This new protein could be an important molecule involved in the early steps of the development.

Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2-17 years in Asia and Latin America: 18-month interim data from a phase 2, randomised, placebo-controlled study.

PubMed

Sáez-Llorens, Xavier; Tricou, Vianney; Yu, Delia; Rivera, Luis; Jimeno, José; Villarreal, Ana Cecilia; Dato, Epiphany; Mazara, Sonia; Vargas, Maria; Brose, Manja; Rauscher, Martina; Tuboi, Suely; Borkowski, Astrid; Wallace, Derek

2018-02-01

Development of vaccines that are effective against all four dengue virus serotypes (DENV-1-4) in all age groups is important. Here, we present 18-month interim data from an ongoing study undertaken to assess the immunogenicity and safety of Takeda's tetravalent dengue vaccine (TDV) candidate over 48 months in children living in dengue-endemic countries. We undertook a phase 2, multicentre, randomised, double-blind, placebo-controlled study at three sites in the Dominican Republic, Panama, and the Philippines. We randomly assigned children aged 2-17 years to receive either two TDV doses 3 months apart (group 1), one TDV dose (group 2), one TDV dose and a booster dose 1 year later (group 3), or placebo (group 4). We did the randomisation (1:2:5:1) using an interactive web response system stratified by age. The primary endpoint of this 18-month interim analysis was DENV serotype-specific antibody geometric mean titres (GMTs) in the per-protocol immunogenicity subset on days 1, 28, 91, 180, 365, 393, and 540. Secondary safety endpoints were the proportions of participants with serious adverse events and with virologically confirmed dengue in the safety set, and solicited and unsolicited adverse events in the immunogenicity subset. This trial is registered with ClinicalTrials.gov, number NCT02302066. Between Dec 5, 2014, and Feb 13, 2015, 1800 children were randomly assigned to group 1 (n=201), group 2 (n=398), group 3 (n=1002), and group 4 (n=199). 1794 participants received at least one dose of TDV or placebo (safety set), of whom 562 participated in the immunogenicity subset and 509 were included in the per-protocol set. Antibody titres remained elevated 18 months after vaccination in all TDV groups. At day 540, in groups 1, 2, 3, and 4, respectively, DENV-1 GMTs were 476 (95% CI 286-791), 461 (329-647), 1056 (804-1388), and 92 (49-173); DENV-2 GMTs were 1212 (842-1744), 1242 (947-1628), 1457 (1182-1796), and 177 (93-337); DENV-3 GMTs were 286 (171-478), 298 (205

Effect of Trelagliptin on Quality of Life in Patients with Type 2 Diabetes Mellitus: Study Protocol.

PubMed

Ishii, Hitoshi; Suzaki, Yuki; Miyata, Yuko

2017-12-01

Long-term glycemic control in type 2 diabetes is critical to prevent or delay the onset of macrovascular and microvascular complications. Medication adherence is an integral component of type 2 diabetes management. Minimizing the dosing frequency of antidiabetic drugs may reduce treatment burden for patients and improve medication adherence. This study has been proposed to assess the reduction in treatment burden during 12 weeks' administration of trelagliptin, a weekly dosing dipeptidyl peptidase-4 (DPP-4) inhibitor, compared with a daily dosing DPP-4 inhibitor in patients with type 2 diabetes. This is a multicenter, randomized, open-label, parallel-group, comparative study to be conducted at approximately 15 sites across Japan. A total of 240 patients are to be randomized 1:1 to receive trelagliptin or a daily DPP-4 inhibitor for 12 weeks. Efficacy and safety will be compared between the two groups. The primary endpoint is the change in total score for all items of the diabetes-therapy-related QOL questionnaire from treatment start to treatment end. The study will be conducted with the highest respect for the individual participants in accordance with the protocol, the Declaration of Helsinki, the Ethical Guidelines for Clinical Research, the ICH Consolidated Guideline for Good Clinical Practice, and applicable local laws and regulations. Takeda Pharmaceutical Company Limited. Japic CTI-173482.

Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System

PubMed Central

Mertens, Kim L.; Kalsbeek, Andries; Soeters, Maarten R.; Eggink, Hannah M.

2017-01-01

Bile acids are best known as detergents involved in the digestion of lipids. In addition, new data in the last decade have shown that bile acids also function as gut hormones capable of influencing metabolic processes via receptors such as FXR (farnesoid X receptor) and TGR5 (Takeda G protein-coupled receptor 5). These effects of bile acids are not restricted to the gastrointestinal tract, but can affect different tissues throughout the organism. It is still unclear whether these effects also involve signaling of bile acids to the central nervous system (CNS). Bile acid signaling to the CNS encompasses both direct and indirect pathways. Bile acids can act directly in the brain via central FXR and TGR5 signaling. In addition, there are two indirect pathways that involve intermediate agents released upon interaction with bile acids receptors in the gut. Activation of intestinal FXR and TGR5 receptors can result in the release of fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1), both capable of signaling to the CNS. We conclude that when plasma bile acids levels are high all three pathways may contribute in signal transmission to the CNS. However, under normal physiological circumstances, the indirect pathway involving GLP-1 may evoke the most substantial effect in the brain. PMID:29163019

Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse.

PubMed

Murtaza, Babar; Berrichi, Meryem; Bennamar, Chahid; Tordjmann, Thierry; Djeziri, Fatima Z; Hichami, Aziz; Leemput, Julia; Belarbi, Meriem; Ozdener, Hakan; Khan, Naim A

2017-10-01

Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca 2+ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca 2+ pool and also recruited, in part, Ca 2+ from extracellular environment via the opening of store-operated Ca 2+ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca 2+ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Asthma-chronic obstructive pulmonary disease overlap syndrome in Poland. Findings of an epidemiological study.

PubMed

Brzostek, Dorota; Kokot, Marek

2014-12-01

Recent years have seen an increased interest in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). In 2012, Takeda Polska conducted a non-interventional epidemiological study aimed at identifying the typical phenotype of ACOS patients receiving pulmonary care. The study enrolled a total of 12,103 of smoking patients above 45 years of age (mean age: 61.5 years; mean duration of smoking: 28.4 pack-years). A total of 68.6% of patients represented the frequent-exacerbation phenotype (mean number of exacerbations during 12 months: 2.11), and 56.4% of patients from the group comprising 12,103 participants were hospitalized at least once during their lifetime due to a respiratory system disease (mean number: 3.82 ±3.76). The most commonly found asthma symptoms included paroxysmal dyspnoea with wheezing, and good response to inhaled steroids. The most frequently identified COPD-associated symptoms were: long-lasting reduction in forced expiratory volume in 1 s (FEV1) (< 80% after administering a bronchodilator) and chronic productive cough. Eighty-five percent of patients were diagnosed with concomitant diseases, predominantly arterial hypertension (62.9%) and metabolic diseases (metabolic syndrome, obesity, type 2 diabetes - 46.4% in total). A clinically severe course of ACOS and the presence of concomitant diseases should be regarded as factors justifying an individual selection of inhalation therapy which specifically takes into account anti-inflammatory treatment and patient safety.

Advances in Japanese pear breeding in Japan

PubMed Central

Saito, Toshihiro

2016-01-01

The Japanese pear (Pyrus pyrifolia Nakai) is one of the most widely grown fruit trees in Japan, and it has been used throughout Japan’s history. The commercial production of pears increased rapidly with the successive discoveries of the chance seedling cultivars ‘Chojuro’ and ‘Nijisseiki’ around 1890, and the development of new cultivars has continued since 1915. The late-maturing, leading cultivars ‘Niitaka’ and ‘Shinko’ were released during the initial breeding stage. Furthermore, systematic breeding by the Horticultural Research Station (currently, NARO Institute of Fruit Tree Science, National Agriculture and Food Research Organization (NIFTS)) began in 1935, which mainly aimed to improve fruit quality by focusing on flesh texture and black spot disease resistance. To date, 22 cultivars have been released, including ‘Kosui’, ‘Hosui’, and ‘Akizuki’, which are current leading cultivars from the breeding program. Four induced mutant cultivars induced by gamma irradiation, which exhibit some resistance to black spot disease, were released from the Institute of Radiation Breeding. Among these cultivars, ‘Gold Nijisseiki’ has become a leading cultivar. Moreover, ‘Nansui’ from the Nagano prefectural institute breeding program was released, and it has also become a leading cultivar. Current breeding objectives at NIFTS mainly combine superior fruit quality with traits related to labor and cost reduction, multiple disease resistance, or self-compatibility. Regarding future breeding, marker-assisted selection for each trait, QTL analyses, genome-wide association studies, and genomic selection analyses are currently in progress. PMID:27069390

[Factors facilitating the return of the elderly to their homes after discharge from a geriatric intermediate care facility].

PubMed

Ishizaki, T

1992-02-01

Geriatric intermediate care facilities (GICFs) were started with subsidies from the Ministry of Health and Welfare in 1987 to encourage return of the elderly from hospitals to their homes rather than other destinations such as nursing homes or hospitals. Contrary to the initial expectation, only half of users (the elderly) have returned home. In order to examine the factors influencing destination after discharge from GICFs, characteristics of the users of a GICF and their primary caregivers were analyzed in a rural community in Nagano. The users were grouped according to their discharge destinations (i.e. 1: home, 2: hospital, 3: nursing home and other GICFs) and compared with respect to the users' and caregivers' socio-demographic characteristics, the length of stay, the users' activities of daily living (ADL) and mental status, the type of place before admission and after discharge, and the caring capacity of the family (i.e. manpower, housing conditions, household economic level and social support). A multiple logistic regression analysis revealed that the following factors were correlated to their return home: good ADL, a short admission period, good level of health of caregivers, adequate space in the residence, negative perception of the caregivers regarding the costs of GICF, and economic level of the household. Evaluation of these factors at an early stage of admission to GICFs may enable prediction of whether or not a user can be successfully discharged to return home.

Molecular Dynamics Simulations Reveal Proton Transfer Pathways in Cytochrome C-Dependent Nitric Oxide Reductase

PubMed Central

Pisliakov, Andrei V.; Hino, Tomoya; Shiro, Yoshitsugu; Sugita, Yuji

2012-01-01

Nitric oxide reductases (NORs) are membrane proteins that catalyze the reduction of nitric oxide (NO) to nitrous oxide (N2O), which is a critical step of the nitrate respiration process in denitrifying bacteria. Using the recently determined first crystal structure of the cytochrome c-dependent NOR (cNOR) [Hino T, Matsumoto Y, Nagano S, Sugimoto H, Fukumori Y, et al. (2010) Structural basis of biological N2O generation by bacterial nitric oxide reductase. Science 330: 1666–70.], we performed extensive all-atom molecular dynamics (MD) simulations of cNOR within an explicit membrane/solvent environment to fully characterize water distribution and dynamics as well as hydrogen-bonded networks inside the protein, yielding the atomic details of functionally important proton channels. Simulations reveal two possible proton transfer pathways leading from the periplasm to the active site, while no pathways from the cytoplasmic side were found, consistently with the experimental observations that cNOR is not a proton pump. One of the pathways, which was newly identified in the MD simulation, is blocked in the crystal structure and requires small structural rearrangements to allow for water channel formation. That pathway is equivalent to the functional periplasmic cavity postulated in cbb 3 oxidase, which illustrates that the two enzymes share some elements of the proton transfer mechanisms and confirms a close evolutionary relation between NORs and C-type oxidases. Several mechanisms of the critical proton transfer steps near the catalytic center are proposed. PMID:22956904

Association between lower air pressure and the onset of ischemic colitis: a case-control study.

PubMed

Kimura, Takefumi; Shinji, Akihiro; Tanaka, Naoki; Koinuma, Masayoshi; Yamaura, Maki; Nagaya, Tadanobu; Joshita, Satoru; Komatsu, Michiharu; Umemura, Takeji; Horiuchi, Akira; Wada, Shuichi; Tanaka, Eiji

2017-09-01

Ischemic colitis (IC) often affects the elderly. Proarteriosclerotic factors, such as hypertension and smoking, and cardiovascular disease are considered major contributors to IC. Although a possible link between certain cerebrocardiovascular disorders and meteorological phenomena has been reported, the relationship between IC onset and weather changes remains uninvestigated. This study examined whether specific meteorological factors were associated with the occurrence of IC. We retrospectively enrolled 303 patients who had been diagnosed with IC between January 2003 and June 2010 at Suwa Red Cross Hospital in Nagano Prefecture, Japan. The meteorological data of the days on which IC patients visited the hospital (IC+ days) were compared with those of the days on which IC patients did not (IC- days). Univariate analysis indicated that IC+ days had significantly lower air pressure (P<0.001), depressed air pressure from the previous day (P<0.001), and fewer daylight hours (P<0.001), as well as higher air temperature (P=0.017), air humidity (P=0.004), wind velocity (P<0.001), and rainfall (P=0.012) compared with IC- days. Multivariate logistic regression analysis of the meteorological data showed that air pressure (odds ratio: 0.935, P<0.001) and change in air pressure from the previous day (odds ratio: 0.934, P<0.001) were related to onset of IC. Lower air pressure and decrease in air pressure from the previous day are possible novel factors associated with the development of IC.

Potential use of bitter melon (Momordica charantia) derived compounds as antidiabetics: In silico and in vivo studies.

PubMed

Elekofehinti, Olusola Olalekan; Ariyo, Esther Opeyemi; Akinjiyan, Moses Orimoloye; Olayeriju, Olanrewaju Sam; Lawal, Akeem Olalekan; Adanlawo, Isaac Gbadura; Rocha, Joao Batista Teixeira

2018-05-12

Momordica charantia (bitter lemon) belongs to the cucurbitaceae family which has been extensively used in traditional medicines for the cure of various ailments such as cancer and diabetes. The underlying mechanism of M. charantia to maintain glycemic control was investigated. GLP-1 and DPP-4 gene modulation by M. charantia (5-20% inclusion in rats diet) was investigated in vivo by RT-PCR and possible compounds responsible for diabetic action predicted through in silico approach. Phytochemicalss previously characterized from M. charantia were docked into glucacon like peptide-1 receptor (GLP-1r), dipeptidyl peptidase (DPP4) and Takeda-G-protein-receptor-5 (TGR5) predicted using Autodock Vina. The results of the in silico suggests momordicosides D (ligand for TGR5), cucurbitacin (ligand for GLP-1r) and charantin (ligand for DPP-4) as the major antidiabetic compounds in bitter lemon leaf. M. charantia increased the expression of GLP-1 by about 295.7% with concomitant decreased in expression of DPP-4 by 87.2% with 20% inclusion in rat's diet. This study suggests that the mechanism underlying the action of these compounds is through activation of TGR5 and GLP-1 receptor with concurrent inhibition of DPP4. This study confirmed the use of this plant in diabetes management and the possible bioactive compounds responsible for its antidiabetic property are charantin, cucurbitacin and momordicoside D and all belong to the class of saponins. Copyright © 2018 Elsevier B.V. All rights reserved.

[Dengue, zika, chikungunya and the development of vaccines].

PubMed

Kantor, Isabel N

2018-01-01

Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

[Dengue, Zika and Chikungunya].

PubMed

Kantor, Isabel N

2016-01-01

Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

Confirmation of gastric tube bedside placement with the sky blue method.

PubMed

Imamura, Takashi; Maeda, Hajime; Kinoshita, Hidetoshi; Shibukawa, Yasuko; Suda, Kiyomi; Fukuda, Yutaka; Goto, Aya; Nagasawa, Katsutoshi

2014-02-01

The purpose was to review our experiences and determine if applying the sky blue method is reliable in confirming gastric tube (GT) placement in neonates. The study population consisted of 44 infants (55 placements) who were admitted to the Takeda General Hospital between April 2012 and March 2013 and who required GT exchange. The sky blue method using indigo carmine (IC) was indicated for planned tube exchange only. Diluted IC was injected into the gastric space via the old GT just before the tube exchange. The tube was exchanged using a standard method. Then, we checked whether the diluted IC could be collected through the new GT or not. The reasons for GT placement were a gestational age of < 35 weeks in 31 (56.4%), poor sucking or swallowing disorders in 17 (30.4%), and respiratory disorders in 7 (12.7%) of the 55 placements. GT placement using the sky blue method was considered successful in 52 placements (94.4%), with the remaining 3 placements (5.6%) considered to be failures due to the inability to obtain IC from the gastric space. No adverse events were observed during the tube exchange period. Based on the results, the sky blue method can be considered to be reliable method for the confirmation of GT placement. These results also suggest that the number of radiologic evaluations performed to confirm correct replacement of the GT in infants can be reduced in the future.

Penicillin-binding protein 4 of Escherichia coli: molecular cloning of the dacB gene, controlled overexpression, and alterations in murein composition.

PubMed

Korat, B; Mottl, H; Keck, W

1991-03-01

The penicillin-binding protein 4 (PBP4), from Escherichia coli, a DD-carboxypeptidase/DD-endopeptidase, was purified in an enzymatically active form to homogeneity by affinity chromatography on 6-aminopenicillanic acid/Sepharose and heparin/Sepharose. Polyclonal antibodies raised against the pure protein were used to identify and isolate PBP4 overproducing clones from an E. coli expression library, which was established on the basis of a temperature-inducible runaway replication plasmid. Three positive clones were isolated, one of which carried the intact structural gene dacB that codes for PBP4, on a 1.9kb SmaI-EcoRI fragment, whereas the other two carried truncated forms of this gene. The direction of transcription was determined. The PBP4 overproducing strain, when grown in rich medium, tolerated 160-fold overexpression. After disrupting cells by sonication, the majority (80%) of the overproduced PBP4 was detected in the 100,000 X g supernatant. Southern blotting analysis using the cloned dacB gene as a probe revealed that, in contrast to that described by Takeda et al. (1981), the plasmid pLC18-38 of the Clarke-Carbon collection does not code for PBP4. The overall composition of murein, synthesized in vitro or in vivo by the PBP4 overproducing strain, as determined by high-performance liquid chromatography analysis, suggests that PBP4 is not involved in transpeptidation but exclusively catalyses a DD-carboxypeptidase and DD-endopeptidase reaction.

In vitro comparison of two widely used surgical sealants for treating alveolar air leak.

PubMed

Zhang, Ruoyu; Bures, Maximilian; Höffler, Klaus; Jonigk, Danny; Haverich, Axel; Krueger, Marcus

2014-12-01

Controversies surrounding the efficacy of sealants against alveolar air leak (AAL) are abundant in the literature. We sought to test the widely used sealants, TachoSil (Takeda Pharmaceutical Company Limited, Osaka, Japan) and BioGlue (CryoLife Europa Ltd., Surrey, United Kingdom) in an in vitro model. Materials and After creation of a focal superficial defect (40 × 25 mm) in swine lungs (n=40), AAL was assessed with increasing inspired tidal volume (TVi). Upon sealant application in a randomized order, AAL was assessed in the same way until sealant burst. At TVi =400, 500, 600, and 700 mL, BioGlue achieved sealing in 19, 19, 16, and 14 tests, while TachoSil sealed in 19, 14, 4, and no test, respectively. The maximally tolerated pressure of BioGlue was higher than TachoSil (40.3 ± 3.0 vs. 36.0 ± 4.9 cm H2O, p=0.003). Cohesive and adhesive failures were found in 10 and 1 tests of BioGlue, respectively, while all burst failures of TachoSil were adhesive. Concerning elasticity, TachoSil allowed more expansion of the covered defect than BioGlue (6.3 ± 3.9 vs. 1.4 ± 1.0 mm, p<0.001). The tested sealants demonstrated high sealing efficacy. While BioGlue was superior in resisting higher ventilation pressure, TachoSil possessed better elasticity. Georg Thieme Verlag KG Stuttgart · New York.

Self-duality and phase structure of the 4D random-plaquette Z2 gauge model

NASA Astrophysics Data System (ADS)

Arakawa, Gaku; Ichinose, Ikuo; Matsui, Tetsuo; Takeda, Koujin

2005-03-01

In the present paper, we shall study the 4-dimensional Z lattice gauge model with a random gauge coupling; the random-plaquette gauge model (RPGM). The random gauge coupling at each plaquette takes the value J with the probability 1-p and - J with p. This model exhibits a confinement-Higgs phase transition. We numerically obtain a phase boundary curve in the (p-T)-plane where T is the "temperature" measured in unit of J/k. This model plays an important role in estimating the accuracy threshold of a quantum memory of a toric code. In this paper, we are mainly interested in its "self-duality" aspect, and the relationship with the random-bond Ising model (RBIM) in 2-dimensions. The "self-duality" argument can be applied both for RPGM and RBIM, giving the same duality equations, hence predicting the same phase boundary. The phase boundary curve obtained by our numerical simulation almost coincides with this predicted phase boundary at the high-temperature region. The phase transition is of first order for relatively small values of p<0.08, but becomes of second order for larger p. The value of p at the intersection of the phase boundary curve and the Nishimori line is regarded as the accuracy threshold of errors in a toric quantum memory. It is estimated as p=0.110±0.002, which is very close to the value conjectured by Takeda and Nishimori through the "self-duality" argument.

Characterization of the protective capacity and immunogenicity of the 69-kD outer membrane protein of Bordetella pertussis

PubMed Central

1990-01-01

Immunization with the 69-kD outer membrane protein (OMP) of Bordetella pertussis protected neonatal mice against lethal respiratory challenge with B. pertussis 18323. Active immunization elicited a serum IgG anti- 69-kD OMP response at the time of challenge, with IgG anti-69-kD OMP antibodies detected in bronchoalveolar lavage fluid after challenge. Intravenous administration of BPE8, a monoclonal IgG1 anti-69-kD OMP, also protected young mice against B. pertussis challenge. Intravenously injected BPE8 was detected in the lungs of mice at the time of aerosol challenge, suggesting that the presence of specific antibody in the lungs may mediate protection. Thus the 69-kD OMP of B. pertussis is a protective antigen in mice that elicits specific serum antibody that can transude to the lung. The 69-kD OMP was detected in a preparation of a Takeda acellular vaccine by immunoblot analysis and a serum antibody response to the 69-kD OMP was observed in 18-mo-old children boosted with this preparation of Japanese acellular vaccine. Our results demonstrate that the B. pertussis 69-kD OMP is a protective antigen in animals, is immunogenic in humans, and is present in a preparation of acellular pertussis vaccine that is widely used in Japan. These findings indicate that the 69-kD OMP should be seriously considered as a candidate for inclusion in new formulations of antigenically defined acellular pertussis vaccines. PMID:2295882

Flavonoid-rich extract of Chromolaena odorata modulate circulating GLP-1 in Wistar rats: computational evaluation of TGR5 involvement.

PubMed

Omotuyi, Olaposi Idowu; Nash, Oyekanmi; Inyang, Olumide Kayode; Ogidigo, Joyce; Enejoh, Ojochenemi; Okpalefe, Okiemute; Hamada, Tsuyoshi

2018-02-01

Chromolaena odorata is a major bio-resource in folkloric treatment of diabetes. In the present study, its anti-diabetic component and underlying mechanism were investigated. A library containing 140 phytocompounds previously characterized from C. odorata was generated and docked (Autodock Vina) into homology models of dipeptidyl peptidase (DPP)-4, Takeda-G-protein-receptor-5 (TGR5), glucagon-like peptide 1 (GLP1) receptor, renal sodium dependent glucose transporter (SGLUT)-1/2 and nucleotide-binding oligomerization domain (NOD) proteins 1&2. GLP-1 gene (RT-PCR) modulation and its release (EIA) by C. odorata were confirmed in vivo. From the docking result above, TGR5 was identified as a major target for two key C. odorata flavonoids (5,7-dihydroxy-6-4-dimethoxyflavanone and homoesperetin-7-rutinoside); sodium taurocholate and C. odorata powder included into the diet of the animals both raised the intestinal GLP-1 expression versus control ( p  < 0.05); When treated with flavonoid-rich extract of C. odorata (CoF) or malvidin, circulating GLP-1 increased by 130.7% in malvidin-treated subjects (0 vs. 45 min). CoF treatment also resulted in 128.5 and 275% increase for 10 and 30 mg/kg b.w., respectively. The results of this study support that C. odorata flavonoids may modulate the expression of GLP-1 and its release via TGR5. This finding may underscore its anti-diabetic potency.

Repositioning Of Tak-475 In Mevalonate Kinase Disease: Translating Theory Into Practice.

PubMed

Marcuzzi, Annalisa; Loganes, Claudia; Celeghini, Claudio; Kleiner, Giulio

2017-09-11

Mevalonate Kinase Deficiency (MKD, OMIM #610377) is a rare autosomal recessive metabolic and inflammatory disease. In MKD, defective function of the enzyme mevalonate kinase (MK), due to a mutation in the MVK gene, leads to the shortage of mevalonate-derived intermediates, which results in unbalanced prenylation of proteins and altered metabolism of sterols. These defects lead to a complex multisystem inflammatory and metabolic syndrome. Although biologic therapies aimed at blocking the inflammatory cytokine interleukin-1 (IL-1) can significantly reduce inflammation, they cannot completely control the clinical symptoms that affects the nervous system. For this reason, MKD can still be considered an orphan drug disease. Cellular models for MKD can be obtained by biochemical inhibition of mevalonate-derived isoprenoids. Of note, these cells present an exaggerated response to inflammatory stimuli that can be reduced by treatment with zaragozic acid, an inhibitor of squalene synthase (SQS) able to increase the availability of isoprenoids intermediates upstream the enzymatic block. A similar action might be obtained by lapaquistat acetate (TAK-475, Takeda), a drug that underwent extensive clinical trials as a cholesterol lowering agent 10 years ago, with a good safety profile. Here we describe the preclinical evidence supporting the possible repositioning of TAK-475 from its originally intended use to the treatment of MKD and discuss its potential to modulate the mevalonate pathway in inflammatory diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? There Is Only One True Winner.

PubMed

Halstead, Scott B

2018-06-01

The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1. It is also possible that chimeric structure does not present the correct virion conformation permitting the development of protective neutralizing antibodies. A premonitory signal shared by the Sanofi Pasteur and the Takeda vaccines was the failure of fully immunized subhuman primates to prevent low-level viremia and/or anamnestic antibody responses to live DENV challenge. The vaccine developed by the National Institute of Allergy and Infectious Diseases (National Institutes of Health [NIH]) has met virtually all of the goals needed to demonstrate preclinical efficacy and safety for humans. Each monovalent vaccine was comprehensively studied for reactogenicity and immunogenicity in human volunteers. Protective immunity in subjects receiving tetravalent candidate vaccines was evidenced by the fact that when vaccinated subjects were given further doses of vaccine or different strains of DENV the result was "solid immunity," a nonviremic and nonanamnestic immune response. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Pre-bombardment crystallization ages of basaltic clasts from Antarctic howardites EET87503 and EET87513

NASA Technical Reports Server (NTRS)

Nyquist, L. E.; Shih, C.-Y.; Wiesmann, H.; Bansal, B. M.

1994-01-01

Igneous clasts of basaltic eucrites are found in both howardites and polymict eucrites. We have studied the Rb-Sr and Sm-Nd isotopic systematics of a number of such clasts, of metamorphic grades 1-6, using the classification of Takeda and Graham. Here, we report Rb-Sr, (147)Sm-(143)Nd, and (145)Sm-(142)Nd studies of clast, 53 from Antarctic howardite EET87503. Although there is no evidence of disturbance of trace element systematics by Antarctic weathering, the Rb-Sr and conventional Sm-Nd isotopic systematics are severely disturbed, which we ascribe to thermal metamorphism. The Ar-Ar age spectrum shows ages ranging from approximately 3.85-3.55 Ga in an unusual 'down stairstep'. The (146)Sm-(142)Nd systematics, however, show the presence of live (146)Sm(t(sub 1/2) = 103 Ma), with (146)Sm/(144)Sm = 0.0061 +/- 0.0007 at the time of crystallization. This result is very similar to that previously obtained for basaltic clast, 18 from howardite EET87513 (paired with EET87503), which has concordant Rb-Sr and Sm-Nd ages of approximately 4.5 Ga. Thus, the two clasts are nearly the same age, and we conclude further than the EET87503,53 clast crystallized within 33 +/- 19 Ma of the LEW86010 angrite by comparing initial (146)Sm/(144)Sm to that of the angrite. We suggest that disturbances in the isotopic systematics of EET87503,53 are consanguineous with pyroxene homogenization.

A new technique for cranioplasty with L-shaped titanium plates and combination ceramic implants composed of hydroxyapatite and tricalcium phosphate (Ceratite).

PubMed

Miyake, H; Ohta, T; Tanaka, H

2000-02-01

The use of hydroxyapatite-based ceramics for cranioplasties has recently increased in Japan, because of the good cosmetic outcomes, biocompatibility, strength, osteoconductive properties, and lack of risk of disease transmission associated with these materials. However, miniplate fixation has not been possible for ceramic implants. We describe a new technique for miniplate fixation of ceramic implants. Combination ceramic implants composed of hydroxyapatite and tricalcium phosphate (Ceratite; NGK Spark Plug Co., Aichi, Japan) were used for cranioplasties. A slot and a pair of holes were cut in each Ceratite implant, for use as a fixation unit. We have also developed a new L-shaped titanium plate (HOMS Engineering Inc., Nagano, Japan) that fits into the fixation unit. We first insert an L-shaped titanium plate through the slot from the back surface of the Ceratite implant. We then bend the plate outward at the front surface of the Ceratite implant and fix it to the cranium of the patient with titanium screws. The Ceratite implant is usually firmly fixed to the cranium of the patient with three L-shaped titanium plates. Using L-shaped titanium plates and Ceratite implants, we successfully performed cranioplasties for seven patients with cranial defects resulting from external decompression craniotomies. The Ceratite implant exactly fit the bone window for each patient. Surgical maneuvers were simple and easy for all patients, permitting shorter operating times. All Ceratite implants were firmly fixed, and no postoperative infections have occurred. Our new technique for cranioplasty is simple and allows rigid fixation of Ceratite implants.

Characterisation of diffuse pollutions from forested watersheds in Japan during storm events - its association with rainfall and watershed features.

PubMed

Zhang, Zhao; Fukushima, Takehiko; Onda, Yuichi; Mizugaki, Shigeru; Gomi, Takashi; Kosugi, Ken'ichirou; Hiramatsu, Shinya; Kitahara, Hikaru; Kuraji, Koichiro; Terajima, Tomomi; Matsushige, Kazuo; Tao, Fulu

2008-02-01

Forest areas have been identified as important sources of nonpoint pollution in Japan. The managers must estimate stormwater quality and quantities from forested watersheds to develop effective management strategies. Therefore, stormwater runoff loads and concentrations of 10 constituents (total suspended solids, dissolved organic carbon, PO(4)-P, dissolved total phosphorus, total phosphorus, NH(4)-N, NO(2)-N, NO(3)-N, dissolved total nitrogen, and total nitrogen) for 72 events across five regions (Aichi, Kochi, Mie, Nagano, and Tokyo) were characterised. Most loads were significantly and positively correlated with stormwater variables (total event rainfall, event duration, and rainfall intensity), but most discharge-weighted event concentrations (DWECs) showed negative correlations with rainfall intensity. Mean water quality concentration during baseflow was correlated significantly with storm concentrations (r=0.41-0.77). Although all pollutant load equations showed high coefficients of determination (R(2)=0.55-0.80), no models predicted well pollutant concentrations, except those for the three N constituents (R(2)=0.59-0.67). Linear regressions to estimate stormwater concentrations and loads were greatly improved by regional grouping. The lower prediction capability of the concentration models for Mie, compared with the other four regions, indicated that other watershed or storm characteristics should be included in the prediction models. Significant differences among regions were found more frequently in concentrations than in loads for all constituents. Since baseflow conditions implied available pollutant sources for stormwater, the similar spatial characteristics of pollutant concentrations between baseflow and stormflow conditions were an important control for stormwater quality.

Use of the Physiotherapy Evidence Database (PEDro) in Japan

PubMed Central

TAKASAKI, Hiroshi; ELKINS, Mark R.; MOSELEY, Anne M.

2016-01-01

Background: The Physiotherapy Evidence Database (PEDro) may help users to overcome some obstacles to evidence-based physiotherapy. Understanding the extent to which Japanese physiotherapists access research evidence via the PEDro website may suggest strategies to enhance evidence-based physiotherapy in Japan. Objectives: To quantify usage of PEDro in Japan, to compare this to usage in other countries, and to examine variations in PEDro usage within Japan. Design: An observational study of PEDro usage with geographic analysis. Methods: Data about visits to the home-page and searches of the database were recorded for 4 years. These data were analysed by each region of the World Confederation for Physical Therapy, each country in the Asia Western Pacific region, and each prefecture in Japan. Results: From 2010 to 2013, users of PEDro made 2.27 million visits to the home-page and ran 6.28 million searches. Usage (ie, number of searches normalised by population) was highest in Europe, followed by North America Carribean, South America, Asia Western Pacific, and Africa. Within the Asia Western Pacific region, population-normalised usage was highest in Australia, then New Zealand and Singapore. Japan ranked 10 among the 26 countries in the region. Within Japan, the highest population-normalised usage was in the Nagano, Kumamoto and Aomori prefectures, which was ten-fold higher usage than in some other prefectures. Conclusions: Although Japan has higher PEDro usage than many other countries in the Asia Western Pacific region, some prefectures had very low usage, suggesting that evidence-based practice may not be being adopted uniformly across Japan. PMID:28289582

Identification of Species in Tripterygium (Celastraceae) Based on DNA Barcoding.

PubMed

Zhang, Xiaomei; Li, Na; Yao, Yuanyuan; Liang, Xuming; Qu, Xianyou; Liu, Xiang; Zhu, Yingjie; Yang, Dajian; Sun, Wei

2016-11-01

Species of genus Tripterygium (Celastraceae) have attracted much attention owing to their excellent effect on treating autoimmune and inflammatory diseases. However, due to high market demand causing overexploitation, natural populations of genus Tripterygium have rapidly declined. Tripterygium medicinal materials are mainly collected from the wild, making the quality of medicinal materials unstable. Additionally, identification of herbal materials from Tripterygium species and their adulterants is difficult based on morphological characters. Therefore, an accurate, convenient, and stability method is urgently needed. In this wok, we developed a DNA barcoding technique to distinguish T. wilfordii HOOK. f., T. hypoglaucum (LÉVL.) HUTCH, and T. regelii SPRAGUE et TAKEDA and their adulterants based on four uniform and standard DNA regions (internal transcribed spacer 2 (ITS2), matK, rbcL, and psbA-trnH). DNA was extracted from 26 locations of fresh leaves. Phylogenetic tree was constructed with Neighbor-Joining (NJ) method, while barcoding gap was analyzed to assess identification efficiency. Compared with the other DNA barcodes applied individually or in combination, ITS2+psbA-trnH was demonstrated as the optimal barcode. T. hypoglaucum and T. wilfordii can be considered as conspecific, while T. regelii was recognized as a separate species. Furthermore, identification of commercial Tripterygium samples was conducted using BLAST against GenBank and Species Identification System for Traditional Chinese Medicine. Our results indicated that DNA barcoding is a convenient, effective, and stability method to identify and distinguish Tripterygium and its adulterants, and could be applied as the quality control for Tripterygium medicinal preparations and monitoring of the medicinal herb trade in markets.

Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn's Disease Patients Stratified by Age.

PubMed

Yajnik, Vijay; Khan, Nabeel; Dubinsky, Marla; Axler, Jeffrey; James, Alexandra; Abhyankar, Brihad; Lasch, Karen

2017-02-01

The efficacy and safety of vedolizumab, a gut-selective α 4 β 7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18-80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials. Safety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years. At baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn's disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person-years) and adverse events leading to hospitalization (14.8 per 100 person-years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death. The safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted. Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).

[Influenza telephone consultation target the general public--2003-2004, 2004-2005].

PubMed

Yamadera, Shizuko; Kobune, Fumio; Komatsu, Toshihiko; Suzuki, Kazuyoshi; Nakayama, Mikio; Hagiwara, Toshikatsu; Matsumoto, Miyako; Yamamoto, Kiichi; Renard, Junko; Oya, Akira

2007-07-01

The NPO Biomedical Science Association provided telephone consultation, including contacts by fax and email, targeting the general public within the framework of influenza control measures worked out by the Japanese Ministry of Health, Labor and Welfare (MHLW). We received 2,813 inquiries during the 2003-2004 flu season and 2,444 inquiries during the 2004-2005 season. By month, the highest number was in October-November, accounting for 42.6%. The preceding season showed a similar trend. By gender, 72.5% of those seeking advice were women. By area of residence, the highest number was living in metropolitan Tokyo, and the remainder lived in the prefectures of Kanagawa, Chiba, Saitama, Nagano, Shizuoka, and Ibaraki in this order. We received no inquiries from the prefectures of Shimane or Saga. By occupation, housewives accounted for 1,114 inquiries (45.6%), followed by private companies with 447 inquiries (18.3%) and health-care providers with 227 inquiries (9.3%), similar to the 2003-2004 flu season. By subject, 1,545 inquiries concerned vaccines (62.2%) mainly, the pros and cons of vaccination, adverse reactions, and the number of inoculations required. Inquiries about pregnancy, infants and young children, and breast-feeding accounted for 19.2%. Inquiries on vaccine shortages during the 2004-2005 flu season (7), SARS (22), and bird flu (22) decreased compared to the previous season, while the number of consultations on antiviral agents increased (209). In discussing how information on influenza should be communicated to the public, we propose that "Influenza Q & A" provided by the Infectious Diseases Surveillance Center of the NIID, MHLW, should include information on influenza specifically addressing pregnant woman and breast-feeding or child-rearing mothers.

Discrimination of wine from grape cultivated in Japan, imported wine, and others by multi-elemental analysis.

PubMed

Shimizu, Hideaki; Akamatsu, Fumikazu; Kamada, Aya; Koyama, Kazuya; Okuda, Masaki; Fukuda, Hisashi; Iwashita, Kazuhiro; Goto-Yamamoto, Nami

2018-04-01

Differences in mineral concentrations were examined among three types of wine in the Japanese market place: Japan wine, imported wine, and domestically produced wine mainly from foreign ingredients (DWF), where Japan wine has been recently defined by the National Tax Agency as domestically produced wine from grapes cultivated in Japan. The main objective of this study was to examine the possibility of controlling the authenticity of Japan wine. The concentrations of 18 minerals (Li, B, Na, Mg, Si, P, S, K, Ca, Mn, Co, Ni, Ga, Rb, Sr, Mo, Ba, and Pb) in 214 wine samples were determined by inductively coupled-plasma mass spectrometry (ICP-MS) and ICP-atomic emission spectrometry (ICP-AES). In general, Japan wine had a higher concentration of potassium and lower concentrations of eight elements (Li, B, Na, Si, S, Co, Sr, and Pb) as compared with the other two groups of wine. Linear discriminant analysis (LDA) models based on concentrations of the 18 minerals facilitated the identification of three wine groups: Japan wine, imported wine, and DWF with a 91.1% classification score and 87.9% prediction score. In addition, an LDA model for discrimination of wine from four domestic geographic origins (Yamanashi, Nagano, Hokkaido, and Yamagata Prefectures) using 18 elements gave a classification score of 93.1% and a prediction score of 76.4%. In summary, we have shown that an LDA model based on mineral concentrations is useful for distinguishing Japan wine from other wine groups, and can contribute to classification of the four main domestic wine-producing regions of Japan. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Evolution of convection vortices associated with sudden impulses observed by SuperDARN

NASA Astrophysics Data System (ADS)

Hori, T.; Shinbori, A.; Nishitani, N.; Fujita, S.

2014-12-01

Spatial evolution of transient ionospheric convection induced by sudden impulses (SIs) recorded by ground magnetometers is studied statistically by using SuperDARN (SD) data. An advantage of using SD data instead of ground magnetic fields is that ionospheric flows measured by the radars are not virtually biased by the spatially-varying ionospheric conductance or the magnetospheric currents. First we surveyed the Sym-H index for Jan., 2007 to Dec., 2012 to identify SI events with a peak amplitude |dSym-H| greater than 10 nT. Next we searched all SD data over the northern hemisphere during the SI events for ionospheric backscatters which give us the light-of-sight velocity of horizontal ionospheric flows. For each SI event, the collected ionospheric flow data were sorted into the four periods: the pre-SI period, the pre-Main Impulse (MI), middle-MI, and post-MI periods. In the present study, we examine the differences in flow velocity between the pre-SI period and the three MI periods to clarify how ionospheric flows change in association with SIs. As a result, the ionospheric flow shifts eastward on the dusk side and westward on the dawn side at the higher latitudes during positive SIs (SI+), while it shows a roughly westward/eastward shift on the dusk/dawn side, respectively, during negative SIs (SI-). These polarities of flow shifts are basically consistent with the higher latitude portions of the DP current for the MI phase as shown by Araki [1994] and Araki and Nagano [1988]. In terms of temporal evolution, the SI-induced transient flows remain slightly longer for SI- than for SI+. These findings suggest that the compression and expansion of the magnetosphere affect in different manners the magnetosphere-ionosphere coupled convection system.

Assessment of the Target Engagement and D-Serine Biomarker Profiles of the D-Amino Acid Oxidase Inhibitors Sodium Benzoate and PGM030756.

PubMed

Howley, Eimear; Bestwick, Michael; Fradley, Rosa; Harrison, Helen; Leveridge, Mathew; Okada, Kengo; Fieldhouse, Charlotte; Farnaby, Will; Canning, Hannah; Sykes, Andy P; Merchant, Kevin; Hazel, Katherine; Kerr, Catrina; Kinsella, Natasha; Walsh, Louise; Livermore, David G; Hoffman, Isaac; Ellery, Jonathan; Mitchell, Phillip; Patel, Toshal; Carlton, Mark; Barnes, Matt; Miller, David J

2017-11-01

Irregular N-methyl-D-aspartate receptor (NMDAR) function is one of the main hypotheses employed to facilitate understanding of the underlying disease state of schizophrenia. Although direct agonism of the NMDAR has not yielded promising therapeutics, advances have been made by modulating the NMDAR co-agonist site which is activated by glycine and D-serine. One approach to activate the co-agonist site is to increase synaptic D-serine levels through inhibition of D-amino acid oxidase (DAO), the major catabolic clearance pathway for this and other D-amino acids. A number of DAO inhibitors have been developed but most have not entered clinical trials. One exception to this is sodium benzoate which has demonstrated efficacy in small trials of schizophrenia and Alzheimer's disease. Herein we provide data on the effect of sodium benzoate and an optimised Takeda compound, PGM030756 on ex vivo DAO enzyme occupancy and cerebellar D-serine levels in mice. Both compounds achieve high levels of enzyme occupancy; although lower doses of PGM030756 (1, 3 and 10 mg/kg) were required to achieve this compared to sodium benzoate (300, 1000 mg/kg). Cerebellar D-serine levels were increased by both agents with a delay of approximately 6 h after dosing before the peak effect was achieved. Our data and methods may be useful in understanding the effects of sodium benzoate that have been seen in clinical trials of schizophrenia and Alzheimer's disease and to support the potential clinical assessment of other DAO inhibitors, such as PGM030756, which demonstrate good enzyme occupancy and D-serine increases following administration of low oral doses.

Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled DIabetic REtinopathy Candesartan Trials.

PubMed

Porta, M; Hainer, J W; Jansson, S-O; Malm, A; Bilous, R; Chaturvedi, N; Fuller, J H; Klein, R; Orchard, T; Parving, H-H; Sjølie, A-K

2011-06-01

The teratogenic consequences of angiotensin-converting enzyme inhibitors angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy are well described. However, the consequences of exposure during the first trimester are unclear, especially in diabetes. We report the experience from DIRECT (DIabetic REtinopathy and Candesartan Trials), three placebo-controlled studies designed to examine the effects of an ARB, candesartan, on diabetic retinopathy. Over 4 years or longer, 178 normotensive women with type 1 diabetes (86 randomised to candesartan, 32 mg once daily, and 92 assigned to placebo) became pregnant (total of 208 pregnancies). More than half of patients were exposed to candesartan or placebo prior to or in early pregnancy, but all discontinued it at an estimated 8 weeks from the last menstrual period. Full-term pregnancies (51 vs 50), premature deliveries (21 vs 27), spontaneous miscarriages (12 vs 15), elective terminations (15 vs 14) and other outcomes (1 vs 2) were similar in the candesartan and placebo groups. There were two stillbirths and two 'sick babies' in the candesartan group, and one stillbirth, eight 'sick babies' and one cardiac malformation in the placebo group. The risk for fetal consequences of ARBs in type 1 diabetes may not be high if exposure is clearly limited to the first trimester. Long-term studies in fertile women can be conducted with ARBs during pregnancy, provided investigators diligently stop their administration upon planning or detection of pregnancy. ClinicalTrials.gov DIRECT-Prevent 1 NCT00252733; DIRECT-Protect 1 NCT00252720; DIRECT-Protect 2 NCT00252694. The study was funded jointly by AstraZeneca and Takeda.

Further Evidence for Geochemical Diversity, and Possible Bimodality, Among Cumulate Eucrites

NASA Astrophysics Data System (ADS)

Warren, P. H.; Kallemeyn, G. W.

1992-07-01

We have used INAA, RNAA, and fused-bead analysis to determine the bulk compositions of numerous Antarctic eucrites (and also the LEW88516 SNC meteorite). Only a few of the most unusual eucrites can be discussed in the limited space here. Takeda et al. (1988) noted that Y791195 is a slowly cooled eucrite, with an equant, medium-grained texture, and pyroxene exsolution lamellae up to 10 micrometers across. In Y791195,81-3, we find lamellae up to 14 micrometers across. In this respect, Y791195 resembles RKPA80224, in which exsolution lamellae up to 12 micrometers across. We have previously discussed the evidence that RKPA80224 is a mildly accumulative rock that formed from an unusually low-mg parent melt. Our second analysis of RKPA80224 only partly confirms the unusually low incompatible trace element (ITE) content, but the Ce anomaly is consistently small (Ce/La = 0.90-1.02 x CI), and based on a weighted mean composition the implied parent melt is still unlike any noncumulate eucrite (see Fig. 1, which shows results from mass balance calculations modeling the sample as a mixture of cumulus px and plag, plus trapped melt). A parent melt similar to an extreme low-mg, variant of the "Nuevo Laredo Trend" would plausibly account for RKPA80224. The spectrum of possible parents for Y791195 is similar, even though its "true" Sm content is slightly obscured by weathering (Ce/La = 1.4 x CI). The [Sm] used in the figure is scaled to the highest CI-normalized REE concentration. Data of Mittlefehldt and Lindstrom (1991) indicate that except for exterior samples "showing extreme rustiness," Sm even in weathered eucrites is generally not altered beyond a few tens of pct. relative (sample size seems to account for more of the variation in [Sm] among interior, non-rusty samples). Even assuming a Sm content twice that assumed in the figure, the parent melt still must be well to the low-MgO/FeO, low-Sm side of all known eucrites. The LEW87002 eucrite is brecciated, but probably

Ketamine: stimulating antidepressant treatment?

PubMed

Malhi, Gin S; Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A; Gitlin, Michael; Kennedy, Sidney H; Ketter, Terence A; Lam, Raymond W; McShane, Rupert; Mitchell, Alex J; Ostacher, Michael J; Rizvi, Sakina J; Thase, Michael E; Tohen, Mauricio

2016-05-01

SmithKline, and Sunovion Pharmaceuticals; royalties from American Psychiatric Publishing, Inc. Also, AstraZeneca Pharmaceuticals LP provided publication support to Parexel for preparation of a manuscript. Spouse employee and stockholder of Janssen Pharmaceuticals. R.W.L. Honoraria for speaking/advising/consulting, and/or received research funds: AstraZeneca, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson and Johnson, Lundbeck, Lundbeck Institute, Pfizer, Servier, St. Jude Medical, Takeda University, Health Network Foundation, and Vancouver Coastal Health Research Institute. R.M. Investigator Janssen trials of esketamine; 'paid-for' ketamine clinic operated by Oxford Health NHS Foundation Trust - fees used to support the Trust. M.J.O. Consultant: Sunovion and Acadia Pharmaceuticals. Full-time employee of U.S. Department of Veterans Affairs. M.E.T. Advisory/Consultant: Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb Company, Cerecor inc., Eli Lilly & Co., Forest Laboratories, Gerson Lehrman Group, Fabre-Kramer Pharmaceuticals, Inc., GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante Inc., Merck and Co. Inc. (formerly Schering Plough and Organon), Moksha8, Naurex Inc., Neuronetics Inc., Novartis, Ortho-McNeil Pharmaceuticals (Johnson & Johnson; Janssen), Otsuka, Pamlab, L.L.C. (Nestle), Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Shire US Inc., Sunovion Pharmaceuticals Inc., Trius Therapeutical Inc. and Takeda. Grant support: Agency for Healthcare Research and Quality, Alkermes, AssureRx, Avanir, Forest Pharmaceuticals, Janssen, National Institute of Mental Health, and Otsuka Pharmaceuticals. Speakers Bureau: None since June, 2010. Equity Holdings: MedAvante, Inc. Royalties: American Psychiatric Foundation, Guilford Publications, Herald House, W.W. Norton & Company

Cholesterol 7α-hydroxylase protects the liver from inflammation and fibrosis by maintaining cholesterol homeostasis[S

PubMed Central

Liu, Hailiang; Pathak, Preeti; Boehme, Shannon; Chiang, John Y. L.

2016-01-01

Cholesterol 7α-hydroxylase (CYP7A1) plays a critical role in control of bile acid and cholesterol homeostasis. Bile acids activate farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) to regulate lipid, glucose, and energy metabolism. However, the role of bile acids in hepatic inflammation and fibrosis remains unclear. In this study, we showed that adenovirus-mediated overexpression of Cyp7a1 ameliorated lipopolysaccharide (LPS)-induced inflammatory cell infiltration and pro-inflammatory cytokine production in WT and TGR5-deficient (Tgr5−/−) mice, but not in FXR-deficient (Fxr−/−) mice, suggesting that bile acid signaling through FXR protects against hepatic inflammation. Nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-luciferase reporter assay showed that FXR agonists significantly inhibited TNF-α-induced NF-κB activity. Furthermore, chromatin immunoprecipitation and mammalian two-hybrid assays showed that ligand-activated FXR interacted with NF-κB and blocked recruitment of steroid receptor coactivator-1 to cytokine promoter and resulted in inhibition of NF-κB activity. Methionine/choline-deficient (MCD) diet increased hepatic inflammation, free cholesterol, oxidative stress, apoptosis, and fibrosis in CYP7A1-deficient (Cyp7a1−/−) mice compared with WT mice. Remarkably, adenovirus-mediated overexpression of Cyp7a1 effectively reduced hepatic free cholesterol and oxidative stress and reversed hepatic inflammation and fibrosis in MCD diet-fed Cyp7a1−/− mice. Current studies suggest that increased Cyp7a1 expression and bile acid synthesis ameliorate hepatic inflammation through activation of FXR, whereas reduced bile acid synthesis aggravates MCD diet-induced hepatic inflammation and fibrosis. Maintaining bile acid and cholesterol homeostasis is important for protecting against liver injury and nonalcoholic fatty liver disease. PMID:27534992

Sizing up the stars

NASA Astrophysics Data System (ADS)

Boyajian, Tabetha S.

For the main part of this dissertation, I have executed a survey of nearby, main sequence A, F, and G-type stars with the CHARA Array, successfully measuring the angular diameters of forty-four stars to better than 4% accuracy. The results of these observations also yield empirical determinations of stellar linear radii and effective temperatures for the stars observed. In addition, these CHARA-determined temperatures, radii, and luminosities are fit to Yonsei-Yale isochrones to constrain the masses and ages of the stars. These quantities are compared to the results found in Allende Prieto & Lambert (1999), Holmberg et al. (2007), and Takeda (2007), who indirectly determine these same properties by fitting models to observed photometry. I find that for most cases, the models underestimate the radius of the star by ~ 12%, while in turn they overestimate the effective temperature by ~ 1.5-4%, when compared to my directly measured values, with no apparent correlation to the star's metallicity or color index. These overestimated temperatures and underestimated radii in these works appear to cause an additional offset in the star's surface gravity measurements, which consequently yield higher masses and younger ages, in particular for stars with masses greater than ~ 1.3 [Special characters omitted.] . Alternatively, these quantities I measure are also compared to direct measurements from a large sample of eclipsing binary stars in Andersen (1991), and excellent agreement is seen within both data sets. Finally, a multi-parameter solution is found to fit color-temperature-metallicity values of the stars in this sample to provide a new calibration of the effective temperature scale for these types of stars. Published work in the field of stellar interferometry and optical spectroscopy of early-type stars are presented in Appendix D and E, respectively. INDEX WORDS: Interferometry, Infrared, Stellar Astronomy, Fundamental Properties, Effective Temperatures, Stellar Radii

Testing iSpec for the determination of atmospheric parameters and abundances of δ Cephei and RR Lyrae

NASA Astrophysics Data System (ADS)

Blanco-Cuaresma, S.; Anderson, R. I.; Eyer, L.; Mowlavi, N.

2017-03-01

Classical Cepheids and RR Lyrae stars are radially pulsating stars where the spectral type varies according to pulsation phase. Several studies used synthesis and the equivalent width method to determine the variations of effective temperature, surface gravity and metallicity for classical Cepheids and RR Lyrae stars (Luck and Andrievsky 2004; Kovtyukh et al. 2005; Andrievsky et al 2005; Luck et al 2008; Takeda et al. 2013; Fossati et al. 2014). We evaluated the applicability of iSpec (Blanco-Cuaresma et al. 2014 - http://www.blancocuaresma.com/s/), which has been extensively used with non-pulsating FGK stars, and derived atmospheric parameters as a function of phase for δ Cephei and RR Lyrae (the two prototypes stars for each class). The results showed that when we apply a non-adapted traditional spectroscopic method to pulsating stars, derived gravities do not seem to follow a physically logical evolution. Nevertheless, metallicity is globally stable and effective temperature variations globally agree with expectations from the radius variations indicated by the radial velocity variability. Max/min values and average results agree with the literature. In terms of broadening parameters, macroturbulent and projected rotation velocities are very difficult to disentangle even if their profiles are not exactly the same. Individual chemical abundances as function of phase are stable as it was expected (the chemical composition of the star should not vary). We plan to use this information to identify absorption lines that are reliable and stable (less affected by blending) during the whole pulsating cycle. This new line selection may help to improve the determination of atmospheric parameters and it could allow us to be more confident in the study of other less known Cepheids and RR Lyrae stars.

Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease.

PubMed

Rosario, M; Dirks, N L; Gastonguay, M R; Fasanmade, A A; Wyant, T; Parikh, A; Sandborn, W J; Feagan, B G; Reinisch, W; Fox, I

2015-07-01

Vedolizumab, an anti-α(4)β(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing. To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling. Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data. Vedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L). Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3). © 2015 Takeda Pharmaceuticals International Co published by John Wiley & Sons

Radioactive contamination processes during 14-21 March after the Fukushima accident: What does atmospheric electric field measurements tell us?

NASA Astrophysics Data System (ADS)

Takeda, M.; Yamauchi, M.; Makino, M.; Owada, T.; Miyagi, I.

2012-04-01

Ionizing radiation from the radioactive material is known to increase atmospheric electric conductivity, and hence to decrease vertical downward atmospheric DC electric field at ground level, or potential gradient (PG). In the past, the drop of PG has been observed after rain-induced radioactive fallout (wet contamination) after nuclear tests or after the Chernobyl disaster. After the nuclear accident Fukushima Dai-ichi nuclear power plant (FNPP) that started 11 March 2011, the PG also at Kakioka, 150 km southwest from the FNPP, also dropped a by one order of magnitude. Unlike the past examples, the PG drop was two-stepped on 14 March and 20 March. Both correspond to two largest southward release of radioactive material according to the data from the radiation dose rate measurement network. We compare the Kakioka's PG data with the radiation dose rate data at different places to examine the fallout processes of both on 14 March and on 20 March. The former turned out to be dry contamination by surface wind, leaving a substantial amount of fallout floating near the ground. The latter turned out to be wet contamination by rain after transport by relatively low-altitude wind, and the majority of the fallout settled to the ground at this time. It is recommended that all nuclear power plant to have a network of PG observation surrounding the plant. Takeda, et al. (2011): Initial effect of the Fukushima accident on atmospheric electricity, Geophys. Res. Lett., 38, L15811, doi:10.1029/2011GL048511. Yamauchi, et al. (2012): Settlement process of radioactive dust to the ground inferred from the atmospheric electric field measurement, Ann. Geophys., 30, 49-56, doi:10.5194/angeo-30-49-2012.

Alogliptin after acute coronary syndrome in patients with type 2 diabetes.

PubMed

White, William B; Cannon, Christopher P; Heller, Simon R; Nissen, Steven E; Bergenstal, Richard M; Bakris, George L; Perez, Alfonso T; Fleck, Penny R; Mehta, Cyrus R; Kupfer, Stuart; Wilson, Craig; Cushman, William C; Zannad, Faiez

2013-10-03

To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708.).

Orthopyroxene as a recorder of primitive achondrite petrogenesis: Major-, minor-, and trace-element systematics of orthopyroxene in Lodran. [Abstract only

NASA Technical Reports Server (NTRS)

Papike, J. J.; Spilde, M. N.; Fowler, G. W.; Shearer, C. K.

1994-01-01

Considerable attention has been paid recently to the primitive achondrites because they may form a link between chondrites and more differentiated achondrite meteorites. A recent paper by Miyamoto and Takeda addresses the thermal history of lodranites Yamato 74357 and MAC 88177 as inferred from chemical zoning of pyroxene and olivine determined by electron microprobe analyses. Their results suggested that interstitial melt was present and then extracted. We have taken the analysis of Lodran-type meteorites one step further by incorporating the techniques of Electromagnetic Pulse/Wavelength Dispersive Spectroscopy (EMP/WDS) compositional imaging and scanning ion mass spectroscopy (SIMS) analysis. Orthopyroxene in Lodran is strongly zoned in CaO, Al2O3, TiO2, and Cr2O3 within the last 10-30 microns from the grain boundaries. The rims are reversely zoned in Mg-Fe, exhibiting Mg enrichment, and compositions change from a fairly uniform Wo3En94 within the grains to Wo1En96 at the rims. CaO drops from 1.6 to 0.6 wt% and Al2O3, TiO2, and Cr2O3 exhibit similar depletions. MnO is fairly uniform throughout the grains at around 0.5 wt%. Olivine is also reversely zoned with respect to not only grain boundaries but also to fractures within the grains, giving many olivine grains a complex, patchy zoning pattern. Some of the core-rim trace-element systematics for orthopyroxene are illustrated. Because of the rather narrow zoned rims in Lodran orthopyroxene and the low trace-element abundances, it is difficult to clearly resolve the trace-element systematics. Nevertheless it is evident that the cores are enriched in the incompatible trace elements Ce, Nd, Dy, Er, Yb, Y, and Zr relative to the rims.

Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: synthesis and biological activity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate.

PubMed

Yamada, Masami; Ichikawa, Takashi; Ii, Masayuki; Sunamoto, Mie; Itoh, Katsumi; Tamura, Norikazu; Kitazaki, Tomoyuki

2005-11-17

To develop a new therapeutic agent for sepsis, screening of the Takeda chemical library was carried out using mouse macrophages stimulated with lipopolysaccharide (LPS) to identify a new class of small-molecule inhibitors of inflammatory mediator production. The lead compound 5a was discovered, from which a series of novel cyclohexene derivatives I bearing a sulfamoyl and ester group were designed, synthesized and tested for their inhibitory activity against nitric oxide (NO) production. Derivatives I were synthesized by the coupling of sulfonyl chlorides and anilines with concomitant double bond migration in the presence of triethylamine, and phenyl ring substitution and modification of the ester and cyclohexene moieties were carried out. Among the compounds synthesized, ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate [(R)-(+)-5n, TAK-242] was found to exhibit the most potent suppressive activity for the production of not only NO but also inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) induced by LPS-stimulated mouse macrophages with IC50 values of 1.8, 1.9 and 1.3 nM, respectively. It shows marked beneficial effects in vivo also. Intravenous administration of (R)-(+)-5n at doses of 0.1 mg/kg or more suppressed the production of NO and various cytokines [TNF-alpha, IL-6 and IL-1beta] in the mouse endotoxin shock model. Furthermore, it protected mice from death dose-dependently and all mice survived at a dose of 3 mg/kg. The minimum effective dose to protect mice from lethality in this model was 0.3 mg/kg, which was consistent with those for inhibitory effects on the production of NO and cytokines. Compound (R)-(+)-5n is currently undergoing clinical trials for the treatment of sepsis.

Strategy of thunderstorm measurement with super dense ground-based observation network

NASA Astrophysics Data System (ADS)

Takahashi, Y.; Sato, M.

2014-12-01

It's not easy to understand the inside structure and developing process of thunderstorm only with existing meteorological instruments since its horizontal extent of the storm cell is sometimes smaller than an order of 10 km while one of the densest ground network in Japan, AMEDAS, consists of sites located every 17 km in average and the resolution of meteorological radar is 1-2 km in general. Even the X-band radar realizes the resolution of 250 m or larger. Here we suggest a new super dense observation network with simple and low cost sensors that can be used for measurement both of raindrop and vertical electric field change caused by cloud-to-ground lightning discharge. This sensor consists of two aluminum plates with a diameter of 10-20 cm. We carried out an observation campaign in summer of 2013 in the foothills of Mt. Yastugatake, Yamanashi and Nagano prefectures in Japan, installing 6 plate-type sensors at a distance of about 4 km. Horizontal location, height and charge amount of each lightning discharge are estimated successfully based on the information of electric field changes at several observing sites. Moreover, it was found that the thunderstorm has a very narrow structure well smaller than 300 m that cannot be measured by any other ways, counting the positive and negative pulses caused by attachment of raindrop to the sensor plate, respectively. We plan to construct a new super dense observation network in the north Kanto region, Japan, where the lightning activity is most prominent in summer Japan, distributing more than several tens of sensors at every 4 km or shorter, such as an order of 100 m at minimum. This kind of new type network will reveal the unknown fine structures of thunderstorms and open the door for constructing real time alert system of torrential rainfall and lightning stroke especially in the city area.

Overstory and Understory CO2 and Energy Fluxes of a Black Spruce Forest in Interior Alaska

NASA Astrophysics Data System (ADS)

Ikawa, H.; Nakai, T.; Busey, R.; Kim, Y.; Kobayashi, H.; Nagai, S.; Ueyama, M.; Saito, K.; Suzuki, R.; Hinzman, L. D.

2014-12-01

Bird Image as a support for the NSF grand number 1107524. HI acknowledges J. H. Matthes for helping the footprint algorism, R. Hirata, D. McGuire, and E. Euskirchen for fruitful discussion, and Y. Harazono and H. Nagano for providing parts of meteorological data. We thank N. Bauer for editing.

Forms of trace arsenic, cesium, cadmium, and lead transported into river water for the irrigation of Japanese paddy rice fields

NASA Astrophysics Data System (ADS)

Nakaya, Shinji; Chi, Hai; Muroda, Kengo; Masuda, Harue

2018-06-01

In this study, we focus on the behavior of geogenic, toxic trace elements, particularly As, Cs, Cd, and Pb, during their transportation in two rivers for irrigation commonly used in monsoon Asia; one river originates from an active volcano, Mt. Asama, and the other originates from a currently inactive volcano, Yatsugatake Mountains in Nagano, Japan. These rivers were investigated to understand the role of river water as a pollutant of rice and other aquatic plants (via irrigation) and aquatic animals. The results indicated that the behavior of toxic trace elements in river water are likely controlled by their interactions with particulate Fe, Al, and Ti compounds. The majority of Pb and Cd is transported as particulate matter with Fe, Al, and Ti, while the majority of As is transported in the dissolved form, predominantly as arsenate, with low abundance of particulate matter. Cs is transported either as the dissolved form or as particulate matter in both rivers. The investigated elements are transported in the rivers as particulate and dissolved forms, and the ratio of these forms is controlled by the pH and presence of particulate Fe, Al, and Ti phases in the river water. With respect to Cs in both rivers, the parameter governing the concentration and transportation of Cs, in the bimodal form (i.e., particulate and dissolved forms), through the river possibly shifts from sorption to pH by particulate Fe-Al-Ti, according to the abrupt increase in the concentration of Cs in the river. The chemical attraction of particulate Fe-Al-Ti for Cs is weaker than that for Pb and Cd, indicating that the lower electronegativity of Cs weakens the chemical attraction on a colloid for the competitive sorption with the other trace elements. The different relationships between As and Fe in the river and in the irrigation water and soil water, as well as those in paddy rice, suggested that As in paddy rice is not directly derived from As in the irrigation water from the river under

Modeling crustal deformation and rupture processes related to upwelling of deep CO2-rich fluids during the 1965-1967 Matsushiro Earthquake Swarm in Japan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cappa, F.; Rutqvist, J.; Yamamoto, K.

2009-05-15

In Matsushiro, central Japan, a series of more than 700,000 earthquakes occurred over a 2-year period (1965-1967) associated with a strike-slip faulting sequence. This swarm of earthquakes resulted in ground surface deformations, cracking of the topsoil, and enhanced spring-outflows with changes in chemical compositions as well as carbon dioxide (CO{sub 2}) degassing. Previous investigations of the Matsushiro earthquake swarm have suggested that migration of underground water and/or magma may have had a strong influence on the swarm activity. In this study, employing coupled multiphase flow and geomechanical modelling, we show that observed crustal deformations and seismicity can have been drivenmore » by upwelling of deep CO{sub 2}-rich fluids around the intersection of two fault zones - the regional East Nagano earthquake fault and the conjugate Matsushiro fault. We show that the observed spatial evolution of seismicity along the two faults and magnitudes surface uplift, are convincingly explained by a few MPa of pressurization from the upwelling fluid within the critically stressed crust - a crust under a strike-slip stress regime near the frictional strength limit. Our analysis indicates that the most important cause for triggering of seismicity during the Matsushiro swarm was the fluid pressurization with the associated reduction in effective stress and strength in fault segments that were initially near critically stressed for shear failure. Moreover, our analysis indicates that a two order of magnitude permeability enhancement in ruptured fault segments may be necessary to match the observed time evolution of surface uplift. We conclude that our hydromechanical modelling study of the Matsushiro earthquake swarm shows a clear connection between earthquake rupture, deformation, stress, and permeability changes, as well as large-scale fluid flow related to degassing of CO{sub 2} in the shallow seismogenic crust. Thus, our study provides further evidence of

Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout.

PubMed

White, William B; Saag, Kenneth G; Becker, Michael A; Borer, Jeffrey S; Gorelick, Philip B; Whelton, Andrew; Hunt, Barbara; Castillo, Majin; Gunawardhana, Lhanoo

2018-03-29

cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).

Gastroenterologists' Perceptions Regarding Ulcerative Colitis and Its Management: Results from a Large-Scale Survey.

PubMed

Lasch, Karen; Liu, Stephen; Ursos, Lyann; Mody, Reema; King-Concialdi, Kristen; DiBonaventura, Marco; Leberman, Julie; Dubinsky, Marla

2016-10-01

of the study as well as article processing charges and the open access fee for this publication were funded by Takeda Pharmaceuticals International, Inc. (TPI).

Effects of azilsartan compared to other angiotensin receptor blockers on left ventricular hypertrophy and the sympathetic nervous system in hemodialysis patients.

PubMed

Kusuyama, Takanori; Ogata, Hirohito; Takeshita, Hiroaki; Kohno, Hiroaki; Shimodozono, Shinichi; Iida, Hidetaka; Tsukazaki, Takashi

2014-10-01

Hypertension is a major risk factor for cardiovascular and cerebrovascular events, and most patients with hypertension are administered antihypertensive drugs. However, not all patients achieve normal blood pressure levels. The new angiotensin receptor blocker azilsartan (Takeda Pharmaceutical Company Limited, Osaka, Japan) has been reported to have a strong hypotensive effect. Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers. This study included 17 hypertensive patients on HD, who had been administered angiotensin receptor blockers, except for azilsartan, for more than 6 months before enrolling, and after enrollment, they were switched to azilsartan. Blood tests, Holter electrocardiogram, ambulatory blood pressure monitoring, and echocardiography were performed at baseline and at the 6-month follow-up. The blood pressure from baseline to 6 months had significantly decreased (24-h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg, P = 0.008), awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg, P = 0.01, sleep-time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg, P = 0.005). There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan (from 550.1 ± 282.9 pg/mL, to 351.7 ± 152.3 pg/mL, P = 0.002; from 117.0 ± 26.4 g/m(2) to 111.3 ± 23.9 g/m(2), P = 0.01, respectively). Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers. Thus, the switch to azilsartan might improve prognosis of hemodialysis patients. We suggest that the strong anti-hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class-effect and a stronger suppression of sympathetic nervous system. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

Foreshock search over a long duration using a method of setting appropriate criteria

NASA Astrophysics Data System (ADS)

Toyomoto, Y.; Kawakata, H.; Hirano, S.; Doi, I.

2016-12-01

Recently, small foreshocks have been detected using cross-correlation techniques (e.g., Bouchon et al., 2011) in which the foreshocks are identified when the cross-correlation coefficient (CC) exceeded a certain threshold. For some shallow intraplate earthquakes, foreshocks whose hypocenters were estimated to be adjacent to the main shock hypocenter were detected from several tens of minutes before the main shock occurrence (Doi and Kawakata, 2012; 2013). At least two problems remain in the cross-correlation techniques employed. First, previous studies on foreshocks used data whose durations are at most a month (Kato et al., 2013); this is insufficient to check if such events occurred only before the main shock occurrence or not. Second, CC is used for detection criteria without considering validity of the threshold. In this study, we search for foreshocks of an M 5.4 earthquake in central Nagano prefecture in Japan on June 30, 2011 with a vertical-component waveform at N.MWDH (Hi-net) station due to one of the cataloged foreshocks (M 1) as a template to calculate CC. We calculate CC between the template and continuous waveforms of the same component at the same station for two years before the main shock occurrence, and we try to overcome the problems mentioned above. We find that histogram of CC is well modeled with the normal distribution, which is similar to previous studies on tremors (e.g., Ohta and Ide, 2008). According to the model, the expected number of misdetection is less than 1 when CC > 0.63. Therefore, we regard that the waveform is due to a foreshock when CC > 0.63. As a result, foreshocks are detected only within thirteen hours immediately before the main shock occurrence for the two years. By setting an appropriate threshold, we conclude that foreshocks just before the main shock occurrence are not stationary events. Acknowledgments: We use continuous waveform records of NIED high sensitivity seismograph network in Japan (Hi-net) and the JMA

Reynolds-averaged Navier-Stokes investigation of high-lift low-pressure turbine blade aerodynamics at low Reynolds number

NASA Astrophysics Data System (ADS)

Arko, Bryan M.

Design trends for the low-pressure turbine (LPT) section of modern gas turbine engines include increasing the loading per airfoil, which promises a decreased airfoil count resulting in reduced manufacturing and operating costs. Accurate Reynolds-Averaged Navier-Stokes predictions of separated boundary layers and transition to turbulence are needed, as the lack of an economical and reliable computational model has contributed to this high-lift concept not reaching its full potential. Presented here for what is believed to be the first time applied to low-Re computations of high-lift linear cascade simulations is the Abe-Kondoh-Nagano (AKN) linear low-Re two-equation turbulence model which utilizes the Kolmogorov velocity scale for improved predictions of separated boundary layers. A second turbulence model investigated is the Kato-Launder modified version of the AKN, denoted MPAKN, which damps turbulent production in highly strained regions of flow. Fully Laminar solutions have also been calculated in an effort to elucidate the transitional quality of the turbulence model solutions. Time accurate simulations of three modern high-lift blades at a Reynolds number of 25,000 are compared to experimental data and higher-order computations in order to judge the accuracy of the results, where it is shown that the RANS simulations with highly refined grids can produce both quantitatively and qualitatively similar separation behavior as found in experiments. In particular, the MPAKN model is shown to predict the correct boundary layer behavior for all three blades, and evidence of transition is found through inspection of the components of the Reynolds Stress Tensor, spectral analysis, and the turbulence production parameter. Unfortunately, definitively stating that transition is occurring becomes an uncertain task, as similar evidence of the transition process is found in the Laminar predictions. This reveals that boundary layer reattachment may be a result of laminar

Thunderstorm monitoring with VLF network and super dense meteorological observation system

NASA Astrophysics Data System (ADS)

Takahashi, Yukihiro; Sato, Mitsuteru

2015-04-01

It's not easy to understand the inside structure and developing process of thunderstorm only with existing meteorological instruments since its horizontal extent of the storm cell is sometimes smaller than an order of 10 km while one of the densest ground network in Japan, AMEDAS, consists of sites located every 17 km in average and the resolution of meteorological radar is 1-2 km in general. Even the X-band radar realizes the resolution of 250 m or larger. Here we suggest a thunderstorm monitoring system consisting of the network of VLF radio wave receivers and the super dense meteorological observation system with simple and low cost plate-type sensors that can be used for measurement both of raindrop and vertical electric field change caused by cloud-to-ground lightning discharge, adding to basic equipments for meteorological measurements. The plate-type sensor consists of two aluminum plates with a diameter of 10-20 cm. We carried out an observation campaign in summer of 2013 in the foothills of Mt. Yastugatake, Yamanashi and Nagano prefectures in Japan, installing 6 plate-type sensors at a distance of about 4 km. Horizontal location, height and charge amount of each lightning discharge are estimated successfully based on the information of electric field changes at several observing sites. Moreover, it was found that the thunderstorm has a very narrow structure smaller than 300 m that cannot be measured by any other ways, counting the positive and negative pulses caused by attachment of raindrop to the sensor plate, respectively. We plan to construct a new super dense observation network in the north Kanto region, Japan, where the lightning activity is most prominent in summer Japan and surrounded by our VLF systems developed for detecting sferics from lightning discharge, distributing more than several tens of sensors at every 4 km or shorter, such as an order of 100 m at minimum. This kind of new type network will reveal the unknown fine structures of

High-Speed Observations of Dynamic Fracture Propagation in Solids and Their Implications in Earthquake Rupture Dynamics

NASA Astrophysics Data System (ADS)

Uenishi, Koji

2016-04-01

This contribution outlines our experimental observations of seismicity-related fast fracture (rupture) propagation in solids utilising high-speed analog and digital photography (maximum frame rate 1,000,000 frames per second) over the last two decades. Dynamic fracture may be triggered or initiated in the monolithic or layered seismic models by detonation of micro explosives, a projectile launched by a gun, laser pulses and electric discharge impulses, etc. First, we have investigated strike-slip rupture along planes of weakness in transparent photoelastic (birefringent) materials at a laboratory scale and shown (at that time) extraordinarily fast rupture propagation in a bi-material system and its possible effect on the generation of large strong motion in the limited narrow areas in the Kobe region on the occasion of the 1995 Hyogo-ken Nanbu, Japan, earthquake (Uenishi Ph.D. thesis 1997, Uenishi et al. BSSA 1999). In this series of experiments, we have also modelled shallow dip-slip earthquakes and indicated a possible origin of the asymmetric ground motion in the hanging and foot-walls. In the photoelastic photographs, we have found the unique dynamic wave interaction and generation of specific shear and interface waves numerically predicted by Uenishi and Madariaga (Eos 2005), and considered as a case study the seismic motion associated with the 2014 Nagano-ken Hokubu (Kamishiro Fault), Japan, dip-slip earthquake (Uenishi EFA 2015). Second, we have experimentally shown that even in a monolithic material, rupture speed may exceed the local shear wave speed if we employ hyperelasically behaving materials like natural rubber (balloons) (Uenishi Eos 2006, Uenishi ICF 2009, Uenishi Trans. JSME A 2012) but fracture in typical monolithic thin fluid films (e.g. soap bubbles, which may be treated as a solid material) propagates at an ordinary subsonic (sub-Rayleigh) speed (Uenishi et al. SSJ 2006). More recent investigation handling three-dimensional rupture propagation

AMCP Partnership Forum: Driving Value and Outcomes in Oncology.

PubMed

2017-05-01

arrangements. Addressing these challenges could lead to improving cancer treatment. The AMCP Partnership Forum titled "Driving Value and Outcomes in Oncology" and the development of this report were supported by AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Foundation Medicine, IntrinsiQ Specialty Solutions, Janssen Oncology and Johnson and Johnson Health Systems, Eli Lilly and Company, National Pharmaceutical Council, Novartis Pharmaceuticals Corporation, Pharmaceutical Research and Manufacturers of America, Sanofi, Takeda Oncology, and Xcenda.

Bile Acids Increase Independently From Hypocaloric Restriction After Bariatric Surgery.

PubMed

Jahansouz, Cyrus; Xu, Hongliang; Hertzel, Ann V; Serrot, Federico J; Kvalheim, Nicholas; Cole, Abigail; Abraham, Anasooya; Luthra, Girish; Ewing, Kristin; Leslie, Daniel B; Bernlohr, David A; Ikramuddin, Sayeed

2016-12-01

To measure changes in the composition of serum bile acids (BA) and the expression of Takeda G-protein-coupled receptor 5 (TGR5) acutely after bariatric surgery or caloric restriction. Metabolic improvement after bariatric surgery occurs before substantial weight loss. BA are important metabolic regulators acting through the farnesoid X receptor and TGR5 receptor. The acute effects of surgery on BA and the TGR5 receptor in subcutaneous white adipose tissue (WAT) are unknown. A total of 27 obese patients with type 2 diabetes mellitus were randomized to Roux-en-Y gastric bypass (RYGB) or to hypocaloric diet (HC diet) restriction (NCT 1882036). A cohort of obese patients with and without type 2 diabetes mellitus undergoing vertical sleeve gastrectomy was also recruited (n = 12) as a comparison. After vertical sleeve gastrectomy, the level of BA increased [total: 1.17 ± 1.56 μmol/L to 4.42 ± 3.92 μmol/L (P = 0.005); conjugated BA levels increased from 0.99 ± 1.42 μmol/L to 3.59 ± 3.70 μmol/L (P = 0.01) and unconjugated BA levels increased from 0.18 ± 0.24 μmol/L to 0.83 ± 0.70 μmol/L (P = 0.009)]. With RYGB, there was a trend toward increased BA [total: 1.37 ± 0.97 μmol/L to 3.26 ± 3.01 μmol/L (P = 0.07); conjugated: 1.06 ± 0.81 μmol/L to 2.99 ± 3.02 μmol/L (P = 0.06)]. After HC diet, the level of unconjugated BA decreased [0.92 ± 0.55 μmol/L to 0.32 ± 0.43 μmol/L (P = 0.05)]. The level of WAT TGR5 gene expression decreased after surgery, but not in HC diet. Protein levels did not change. The levels of serum BA increase after bariatric surgery independently from caloric restriction, whereas the level of WAT TGR5 protein is unaffected.

Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity.

PubMed

Segawa, H; Fukasawa, Y; Miyamoto, K; Takeda, E; Endou, H; Kanai, Y

1999-07-09

We have isolated a cDNA from rat small intestine that encodes a novel Na+-independent neutral amino acid transporter with distinctive characteristics in substrate selectivity and transport property. The encoded protein, designated L-type amino acid transporter-2 (LAT-2), shows amino acid sequence similarity to the system L Na+-independent neutral amino acid transporter LAT-1 (Kanai, Y., Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., and Endou, H. (1998) J. Biol. Chem. 273, 23629-23632) (50% identity) and the system y+L transporters y+LAT-1 (47%) and KIAA0245/y+LAT-2 (45%) (Torrents, D., Estevez, R., Pineda, M., Fernandez, E., Lloberas, J., Shi, Y.-B., Zorzano, A., and Palacin, M. (1998) J. Biol. Chem. 273, 32437-32445). LAT-2 is a nonglycosylated membrane protein. It requires 4F2 heavy chain, a type II membrane glycoprotein, for its functional expression in Xenopus oocytes. LAT-2-mediated transport is not dependent on Na+ or Cl- and is inhibited by a system L-specific inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), indicating that LAT-2 is a second isoform of the system L transporter. Compared with LAT-1, which prefers large neutral amino acids with branched or aromatic side chains, LAT-2 exhibits remarkably broad substrate selectivity. It transports all of the L-isomers of neutral alpha-amino acids. LAT-2 exhibits higher affinity (Km = 30-50 microM) to Tyr, Phe, Trp, Thr, Asn, Ile, Cys, Ser, Leu, Val, and Gln and relatively lower affinity (Km = 180-300 microM) to His, Ala, Met, and Gly. In addition, LAT-2 mediates facilitated diffusion of substrate amino acids, as distinct from LAT-1, which mediates amino acid exchange. LAT-2-mediated transport is increased by lowering the pH level, with peak activity at pH 6.25, because of the decrease in the Km value without changing the Vmax value. Because of these functional properties and a high level of expression of LAT-2 in the small intestine, kidney, placenta, and brain, it is suggested that the

Contradicting Estimates of Location, Geometry, and Rupture History of Highly Active Faults in Central Japan

NASA Astrophysics Data System (ADS)

Okumura, K.

2011-12-01

Accurate location and geometry of seismic sources are critical to estimate strong ground motion. Complete and precise rupture history is also critical to estimate the probability of the future events. In order to better forecast future earthquakes and to reduce seismic hazards, we should consider over all options and choose the most likely parameter. Multiple options for logic trees are acceptable only after thorough examination of contradicting estimates and should not be a result from easy compromise or epoche. In the process of preparation and revisions of Japanese probabilistic and deterministic earthquake hazard maps by Headquarters for Earthquake Research Promotion since 1996, many decisions were made to select plausible parameters, but many contradicting estimates have been left without thorough examinations. There are several highly-active faults in central Japan such as Itoigawa-Shizuoka Tectonic Line active fault system (ISTL), West Nagano Basin fault system (WNBF), Inadani fault system (INFS), and Atera fault system (ATFS). The highest slip rate and the shortest recurrence interval are respectively ~1 cm/yr and 500 to 800 years, and estimated maximum magnitude is 7.5 to 8.5. Those faults are very hazardous because almost entire population and industries are located above the fault within tectonic depressions. As to the fault location, most uncertainties arises from interpretation of geomorphic features. Geomorphological interpretation without geological and structural insight often leads to wrong mapping. Though non-existent longer fault may be a safer estimate, incorrectness harm reliability of the forecast. Also this does not greatly affect strong motion estimates, but misleading to surface displacement issues. Fault geometry, on the other hand, is very important to estimate intensity distribution. For the middle portion of the ISTL, fast-moving left-lateral strike-slip up to 1 cm/yr is obvious. Recent seismicity possibly induced by 2011 Tohoku

Antimicrobial resistance patterns of colonizing Streptococcus pneumoniae among young child-mother pairs in the rural highlands of the Peruvian Andes

PubMed Central

Howard, Leigh; Edwards, Kathryn; Griffin, Marie; Gil, Ana; Minaya, Gina; Mercado, Erik; Ochoa, Theresa; Lanata, Claudio; Grijalva, Carlos G

2017-01-01

tetracyclines was common despite very little reported use of these antibiotics in people. Additional studies should evaluate whether this high prevalence of resistance is a result of local prescribing practices or unintentional environmental exposures. ADDIN EN.REFLIST Disclosures K. Edwards, Novartis: Grant Investigator, Research grant. M. Griffin, MedImmune: Grant Investigator, Grant recipient. C. Lanata, Takeda: Scientific Advisor, Consulting fee. C. G. Grijalva, Pfizer: Consultant, Consulting fee.

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.

PubMed

Bonds, D E; Craven, T E; Buse, J; Crouse, J R; Cuddihy, R; Elam, M; Ginsberg, H N; Kirchner, K; Marcovina, S; Mychaleckyj, J C; O'Connor, P J; Sperl-Hillen, J-A

2012-06-01

National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.

Allspice and Clove As Source of Triterpene Acids Activating the G Protein-Coupled Bile Acid Receptor TGR5

PubMed Central

Ladurner, Angela; Zehl, Martin; Grienke, Ulrike; Hofstadler, Christoph; Faur, Nadina; Pereira, Fátima C.; Berry, David; Dirsch, Verena M.; Rollinger, Judith M.

2017-01-01

Worldwide, metabolic diseases such as obesity and type 2 diabetes have reached epidemic proportions. A major regulator of metabolic processes that gained interest in recent years is the bile acid receptor TGR5 (Takeda G protein-coupled receptor 5). This G protein-coupled membrane receptor can be found predominantly in the intestine, where it is mainly responsible for the secretion of the incretins glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). The aim of this study was (i) to identify plant extracts with TGR5-activating potential, (ii) to narrow down their activity to the responsible constituents, and (iii) to assess whether the intestinal microbiota produces transformed metabolites with a different activity profile. Chenodeoxycholic acid (CDCA) served as positive control for both, the applied cell-based luciferase reporter gene assay for TGR5 activity and the biotransformation assay using mouse fecal slurry. The suitability of the workflow was demonstrated by the biotransformation of CDCA to lithocholic acid resulting in a distinct increase in TGR5 activity. Based on a traditional Tibetan formula, 19 plant extracts were selected and investigated for TGR5 activation. Extracts from the commonly used spices Syzygium aromaticum (SaroE, clove), Pimenta dioica (PdioE, allspice), and Kaempferia galanga (KgalE, aromatic ginger) significantly increased TGR5 activity. After biotransformation, only KgalE showed significant differences in its metabolite profile, which, however, did not alter its TGR5 activity compared to non-transformed KgalE. UHPLC-HRMS (high-resolution mass spectrometry) analysis revealed triterpene acids (TTAs) as the main constituents of the extracts SaroE and PdioE. Identification and quantification of TTAs in these two extracts as well as comparison of their TGR5 activity with reconstituted TTA mixtures allowed the attribution of the TGR5 activity to TTAs. EC50s were determined for the main TTAs, i.e., oleanolic acid (2.2 ± 1.6 μM), ursolic

Lack of replication of four candidate SNPs implicated in human male fertility traits: a large-scale population-based study.

PubMed

Sato, Youichi; Tajima, Atsushi; Tsunematsu, Kouki; Nozawa, Shiari; Yoshiike, Miki; Koh, Eitetsue; Kanaya, Jiro; Namiki, Mikio; Matsumiya, Kiyomi; Tsujimura, Akira; Komatsu, Kiyoshi; Itoh, Naoki; Eguchi, Jiro; Imoto, Issei; Yamauchi, Aiko; Iwamoto, Teruaki

2015-06-01

Scientific Research (C) (23510242) (to A.Ta.) from the Japan Society for the Promotion of Science, the European Union (BMH4-CT96-0314) (to T.I.), and the Takeda Science Foundation (to A.Ta.). None of the authors has any competing interests to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

AMCP Partnership Forum: Managing Care in the Wave of Precision Medicine.

PubMed

2018-05-23

definitions, thresholds, and standards to guide evidence generation in precision medicine. Second, current information silos are preventing the sharing of valuable data. Collaboration among stakeholders is needed to support better information sharing, awareness, and education of precision medicine for patients. The recommendations brought forward by this diverse group of experts provide a set of solutions to spur widespread use and application of precision medicine. Taken together, successful adoption and use of precision medicine will require input and collaboration from all sectors of health care, especially patients. DISCLOSURES This AMCP Partnership Forum and the development of the proceedings document were supported by Amgen, Foundation Medicine, Genentech, Gilead, MedImpact, National Pharmaceutical Council, Precision for Value, Sanofi, Takeda, and Xcenda.

Kinetic restriction of simple gases in porous carbons: transition-state theory study.

PubMed

Nguyen, Thanh X; Bhatia, Suresh K

2008-01-01

The separation of simple gases such as N2, Ar, CO2, and CH4 is an industrially important problem, particularly for the mitigation of greenhouse emissions. Furthermore, these gases are widely accepted as standard probing gases for the characterization of the microstructure of porous solids. However, a consistent set of microstructural parameters of a microporous solid determined from the use of adsorption measurements of these different gases is not always achieved because of differences in their pore accessibility. This is a long-standing and poorly understood problem. Here, we present the calculated results of the crossing time of N2, Ar, CO2, and CH4 between two neighboring cages through a constricted window in a realistic structural model of saccharose char, generated from hybrid reverse Monte Carlo (HRMC) simulation (Nguyen, T. X.; Bhatia, S. K.; Jain, S. K.; Gubbins, K. E. Mol. Simul. 2006, 32, 567-577) using transition state theory (TST), as described in our recent work (Nguyen, T. X.; Bhatia, S. K. J. Phys. Chem. 2007, 111, 2212-2222). The striking feature in these results is that whereas very fast diffusion of carbon dioxide within the temperature range of 273-343 K, with crossing time on the molecular dynamics scale (10-4-10-6 s), leads to instantaneous equilibrium and no hysteresis on the experimental time scale, slower diffusion of Ar and N2 at the low temperature of analysis indicates an accessibility problem. These results rationalize the experimental results of hysteresis for N2 at 77 K and Ar at 87 K but not for CO2 at 273 K in Takeda 3 A carbon molecular sieves. Furthermore, it is shown that CH4 diffusion through narrow pore mouths can be hindered even at ambient temperature. Finally, we show that the use of pore size and wall thickness distributions extracted from the adsorption of Ar at 87 K using the finite wall thickness (FWT) model (Nguyen, T. X.; Bhatia, S. K. Langmuir 2004, 20, 3532-3535 and Nguyen, T. X.; Bhatia, S. K. J. Phys. Chem. B 2004

Activities of JAXA's Innovative Technology Center on Space Debris Observation

NASA Astrophysics Data System (ADS)

Yanagisawa, T.; Kurosaki, H.; Nakajima, A.

The innovative technology research center of JAXA is developing observational technologies for GEO objects in order to cope with the space debris problem. The center had constructed the optical observational facility for space debris at Mt. Nyukasa, Nagano in 2006. As observational equipments such as CCD cameras and telescopes were set up, the normal observation started. In this paper, the detail of the facilities and its activities are introduced. The observational facility contains two telescopes and two CCD cameras. The apertures of the telescopes are 35cm and 25 cm, respectively. One CCD camera in which 2K2K chip is installed can observe a sky region of 1.3 times 1.3-degree using the 35cm telescope. The other CCD camera that contains two 4K2K chips has an ability to observe 2.6 times 2.6-degree's region with the 25cm telescope. One of our main objectives is to detect faint GEO objects that are not catalogued. Generally, the detection limit of GEO object is determined by the aperture of the telescope. However, by improving image processing techniques, the limit may become low. We are developing some image processing methods that use many CCD frames to detect faint objects. We are trying to use FPGA (Field Programmable Gate Array) system to reduce analyzing time. By applying these methods to the data taken by a large telescope, the detection limit will be significantly lowered. The orbital determination of detected GEO debris is one of the important things to do. Especially, the narrow field view of an optical telescope hinders us from re-detection of the GEO debris for the orbital determination. Long observation time is required for one GEO object for the orbital determination that is inefficient. An effective observation strategy should be considered. We are testing one observation method invented by Umehara that observes one inertia position in the space. By observing one inertia position for two nights, a GEO object that passed through the position in the

PREFACE: The 16th International Symposium on Boron, Borides and Related Materials (ISBB 2008)

NASA Astrophysics Data System (ADS)

Tanaka, Takaho

2009-07-01

supported by Tokyo University of Science, Suwa and foundations including, the Kajima Foundation, Foundation for Promotion of Material Science and Technology of Japan and Nippon Sheet Glass Foundation for Materials Science and Engineering, as well as companies including JFE Steel Corporation, Shincron Co, Ltd, Toyo Kohan Co, Ltd, Fukuda Metal Foil and Powder Co, Ltd, Japan New Metals Co, Ltd, H C Starck Ltd and Fritsch Japan Co, Ltd. Editors Chair Takaho Tanaka (National Institute for Materials Science, Japan) Vice chairs Koun Shirai (Osaka University, Japan) Kaoru Kimura (The University of Tokyo, Japan) Ken-ichi Takagi (Tokyo City University, Japan) Touetsu Shishido (Tohoku University, Japan) Shigeru Okada (Kokushikan University) Hideaki Itoh (Nagoya University,Japan) Katsumitsu Nakamura (Nihon University, Japan) Organizing committee of ISBB 2008 K Takagi Chairman (Tokyo City University) T Tanaka Program Committee Chairman (National Institute for Materials Science) K Kimura Secretary (The University of Tokyo) J Akimitsu (Aoyama University)K Shirai (Osaka University) H Itoh (Nagoya University)T Shishido (Tohoku University) K Nakamura (Nihon University)K Soga (Tokyo University of Science) K Nishiyama (Tokyo University of Science, Suwa)M Takeda (Nagaoka University of Technology) S Okada (Kokushikan University)Y Yamazaki (Toyo Kohan Co, Ltd) International Scientific Committee 0f ISBB (2008-2011) K Takagi Chairman (Japan) B Albert (Germany) J-F Halet (France) M Takeda (Japan) M Antadze (Georgia) H Hillebrecht (Germany) T Tanaka (Japan) J Bauer (France) W Jung (Germany) R Telle (Germany) I Boustani (Germany) K Kimura (Japan) M Trenary (USA) D Emin (USA) T Mori (Japan) O Tsagareishvili (Georgia) M Engler (Germany) P D Ownby (USA) H Werheit (Germany) N Frage (Israel) P Rogl (Austria) G Will (Germany) Yu Grin (Germany) S Shalamberidze (Georgia) O Yucel (Turkey) V N Gurin (Russia) N Shitsevalova (Ukraine) G Zhang (China)

PREFACE: Nanosafe 2012: International Conferences on Safe Production and Use of Nanomaterials

NASA Astrophysics Data System (ADS)

Tardif, François

2013-04-01

, FR) Co-chair: Georgios KATALAGARIANAKIS (EC, BE) Mélanie AUFFAN (CEREGE, FR) Jorge BOCZKOWSKI (INSERM, FR) Jean-Yves BOTTERO (CEREGE, FR) Jacques BOUILLARD (INERIS, FR) Derk BROUWER (TNO, NL) Marie CARRIERE (CEA, FR) Claude EMOND (U. MONTREAL, CA) Cassandra ENGEMAN (UCSB, USA) Eric GAFFET (CNRS, FR) François GENSDARMES (IRSN, FR) Alexei GRINBAUM (CEA, FR) Antje GROBE (U.STUTTGART, DE) Peter HOET (KUL, BE) Eric QUEMENEUR (CEA, FR) Olivier LE BIHAN (INERIS, FR) Robert MUIR (NANEUM, UK) Tinh NGUYEN (NIST, USA) Bernd NOWACK (EMPA, CH) Günter OBERDÖRSTER (U. ROCHESTER, USA) David PUI (U. MINNESOTA, USA) Michael RIEDIKER (IST, CH) Yves SAMSON (CEA, FR) Ken TAKEDA (U. TOKYO, JP) Olivier WITSCHGER (INRS, FR) The PDF contains a list of sponsor logos, the conference programme and planning documents.

Molecular basis of non-syndromic hypospadias: systematic mutation screening and genome-wide copy-number analysis of 62 patients.

PubMed

Kon, M; Suzuki, E; Dung, V C; Hasegawa, Y; Mitsui, T; Muroya, K; Ueoka, K; Igarashi, N; Nagasaki, K; Oto, Y; Hamajima, T; Yoshino, K; Igarashi, M; Kato-Fukui, Y; Nakabayashi, K; Hayashi, K; Hata, K; Matsubara, Y; Moriya, K; Ogata, T; Nonomura, K; Fukami, M

2015-03-01

mild and severe hypospadias and that HSD3B2 mutations cause non-syndromic hypospadias as a sole clinical manifestation. Most importantly, this is the first report documenting possible oligogenicity of non-syndromic hypospadias. This study was funded by the Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology; by the Grant-in-Aid from the Japan Society for the Promotion of Science; by the Grants from the Ministry of Health, Labour and Welfare, from the National Center for Child Health and Development and from the Takeda Foundation. The authors have no competing interests to disclose. Not applicable. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Diabetes area participation analysis: a review of companies and targets described in the 2008 - 2010 patent literature.

PubMed

Carpino, Philip A; Goodwin, Bryan

2010-12-01

emerging targets and v) the pharmacological rationale underlying several targets with the largest patent counts. Type 2 diabetes is a complex disease with many potential points of intervention for pharmacotherapy. A majority of anti-diabetic patent applications claim chemical matter for just eight targets which include five enzymes, a GPCR, a family of nuclear hormone receptors and a class of sodium-dependent glucose co-transporters (11β-HSD1, DGAT1, DPP IV, glucokinase, GPR119, PPAR-α, -δ, -γ, SGLT1 and SGLT2, and stearoyl-CoA desaturase 1 (SCD1)). The major pharmaceutical companies are all pursuing some combination of these top eight targets. Several companies stand out for the breadth of new targets under investigation (e.g., F. Hoffmann-La Roche, Merck & Co., Pfizer, Takeda Pharmaceuticals, Sanofi-Aventis).

Peginesatide in patients with anemia undergoing hemodialysis.

PubMed

Fishbane, Steven; Schiller, Brigitte; Locatelli, Francesco; Covic, Adrian C; Provenzano, Robert; Wiecek, Andrzej; Levin, Nathan W; Kaplan, Mark; Macdougall, Iain C; Francisco, Carol; Mayo, Martha R; Polu, Krishna R; Duliege, Anne-Marie; Besarab, Anatole

2013-01-24

adverse events were similar in the treatment groups in the EMERALD studies. The cardiovascular safety of peginesatide was similar to that of the comparator ESA in the pooled cohort. Peginesatide, administered monthly, was as effective as epoetin, administered one to three times per week, in maintaining hemoglobin levels in patients undergoing hemodialysis. (Funded by Affymax and Takeda Pharmaceutical; ClinicalTrials.gov numbers, NCT00597753 [EMERALD 1], NCT00597584 [EMERALD 2], NCT00598273 [PEARL 1], and NCT00598442 [PEARL 2].).

Re-examination of the original questionnaire documents for the 1944 Tonankai, 1945 Mikawa, and 1946 Nanaki earthquakes

NASA Astrophysics Data System (ADS)

Harada, Tomoya; Satake, Kenji; Furumura, Takashi

2016-04-01

With the object of estimating seismic intensity, the Earthquakes Research Institute (ERI) of the University of Tokyo performed questionnaire surveys for the significant (destructive or large/great) earthquakes from 1943 to 1988 (Kayano, 1990, BERI). In these surveys, Kawasumi (1943)'s 12-class seismic intensity scale similar to the Modified Mercalli scale (MM-scale) was used. Survey results for earthquakes after 1950 were well investigated and published (e.g. Kayano and Komaki, 1977, BERI; Kayano and Sato, 1975, BERI), but the survey results for earthquakes in the 1940s have not been published and original documents of the surveys was missing. Recently, the original sheets of the surveys for the five earthquakes in the 1940s with more than 1,000 casualties were discovered in the ERI warehouse, although they are incomplete (Tsumura et al, 2010). They are from the 1943 Tottori (M 7.2), 1944 Tonankai (M 7.9), 1945 Mikawa (M 6.8), 1946 Nankai (M 8.0), and 1948 Fukui (M 7.1) earthquakes. In this study, we examined original questionnaire and summary sheets for the 1944 Tonankai, 1945 Mikawa, and 1946 Nanaki earthquakes, and estimated the distributions of seismic intensity, various kinds of damage, and human behaviors in detail. Numbers of the survey points for the 1944, 1945, and 1946 event are 287, 145, and 1,014, respectively. The numbers for the 1944 and 1945 earthquakes are much fewer than that of the 1946 event, because they occurred during the last years of World War II. The 1944 seismic intensities in the prefectures near the source region (Aichi, Mie, Shizuoka, and Gifu Pref.) tend to be high. However, the 1944 intensities are also high and damage is serious at the Suwa Lake shore in Nagano Pref. which is about 240 km far from the source region because seismic waves are amplified dramatically in the thick sediment in the Suwa Basin. Seismic intensities of the 1945 Mikawa earthquake near the source region in Aichi Pref. were very high (X-XI). However, the

Towards a Unified Source-Propagation Model of Cosmic Rays

NASA Astrophysics Data System (ADS)

Taylor, M.; Molla, M.

2010-07-01

It is well known that the cosmic ray energy spectrum is multifractal with the analysis of cosmic ray fluxes as a function of energy revealing a first “knee” slightly below 1016 eV, a second knee slightly below 1018 eV and an “ankle” close to 1019 eV. The behaviour of the highest energy cosmic rays around and above the ankle is still a mystery and precludes the development of a unified source-propagation model of cosmic rays from their source origin to Earth. A variety of acceleration and propagation mechanisms have been proposed to explain different parts of the spectrum the most famous of course being Fermi acceleration in magnetised turbulent plasmas (Fermi 1949). Many others have been proposd for energies at and below the first knee (Peters & Cimento (1961); Lagage & Cesarsky (1983); Drury et al. (1984); Wdowczyk & Wolfendale (1984); Ptuskin et al. (1993); Dova et al. (0000); Horandel et al. (2002); Axford (1991)) as well as at higher energies between the first knee and the ankle (Nagano & Watson (2000); Bhattacharjee & Sigl (2000); Malkov & Drury (2001)). The recent fit of most of the cosmic ray spectrum up to the ankle using non-extensive statistical mechanics (NESM) (Tsallis et al. (2003)) provides what may be the strongest evidence for a source-propagation system deviating significantly from Boltmann statistics. As Tsallis has shown (Tsallis et al. (2003)), the knees appear as crossovers between two fractal-like thermal regimes. In this work, we have developed a generalisation of the second order NESM model (Tsallis et al. (2003)) to higher orders and we have fit the complete spectrum including the ankle with third order NESM. We find that, towards the GDZ limit, a new mechanism comes into play. Surprisingly it also presents as a modulation akin to that in our own local neighbourhood of cosmic rays emitted by the sun. We propose that this is due to modulation at the source and is possibly due to processes in the shell of the originating supernova. We

AMCP Partnership Forum: Improving Quality, Value, and Outcomes with Patient-Reported Outcomes.

PubMed

2018-03-01

manufacturers should engage key stakeholders early and throughout the drug development process to ensure the most valid and representative PROs and patient populations will be included. To streamline the PRO collection process, participants suggested engaging pharmacists and other providers who may have more frequent interaction with patients. Participants also recommended that PRO collection and analysis should use common technology platforms, streamline components of clinician care to reduce workflow, and be integrated with claims data to provider payers a better understanding of patient health in real time. Finally, additional work should be done to develop patient-reported outcome measures that contain relevant measures for all healthcare stakeholders. While significant challenges remain in PRO development and adoption, participants agreed that greater use can only be achieved through collaboration and patient-centered care. The AMCP Partnership Forum titled "Improving Quality, Value, and Outcomes with Patient-Reported Outcomes" and the development of this proceedings report were supported by Amgen, Boehringer Ingelheim Pharmaceuticals, Genentech, GlaxoSmithKline, Novartis Pharmaceuticals, Novo Nordisk, Precision for Value, Premier, Sanofi, Takeda Pharmaceuticals USA, and Xcenda.

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.

PubMed

Prince, H Miles; Kim, Youn H; Horwitz, Steven M; Dummer, Reinhard; Scarisbrick, Julia; Quaglino, Pietro; Zinzani, Pier Luigi; Wolter, Pascal; Sanches, Jose A; Ortiz-Romero, Pablo L; Akilov, Oleg E; Geskin, Larisa; Trotman, Judith; Taylor, Kerry; Dalle, Stephane; Weichenthal, Michael; Walewski, Jan; Fisher, David; Dréno, Brigitte; Stadler, Rudolf; Feldman, Tatyana; Kuzel, Timothy M; Wang, Yinghui; Palanca-Wessels, Maria Corinna; Zagadailov, Erin; Trepicchio, William L; Zhang, Wenwen; Lin, Hui-Min; Liu, Yi; Huebner, Dirk; Little, Meredith; Whittaker, Sean; Duvic, Madeleine

2017-08-05

patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

PubMed

Essat, Munira; Tappenden, Paul; Ren, Shijie; Bessey, Alice; Archer, Rachel; Wong, Ruth; Lobo, Alan; Hoque, Sami

2016-03-01

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from GEMINI 1, a Phase 3, multicentre, randomised, double-blinded, placebo-controlled study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate-to-severe active UC with an inadequate response to, loss of response to or intolerance of conventional therapy or anti-tumour necrosis factor (TNF)-α. The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post hoc subgroup analyses in patients with or without prior anti-TNF-α therapy, vedolizumab performed better then placebo (p value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab, and the frequency and types of adverse events were similar in the vedolizumab and placebo groups, but the evidence was limited to short-term follow-up. There were a number of limitations and uncertainties in the clinical evidence base, which warrants caution in its interpretation--in particular, the post hoc subgroup analyses and high dropout rates in the maintenance phase of GEMINI 1. The company also presented a network meta-analysis of vedolizumab versus other biologic therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects, since fixed

[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

PubMed

Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

2003-01-01

recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after

AMCP Partnership Forum: Advancing Value-Based Contracting.

PubMed

2017-11-01

of a VBC for facilitating discussion with key policy makers and regulators; (b) determine strategies for advancing the development and utilization of performance benchmarks; (c) identify best practices in evaluating, implementing, and monitoring VBCs; and (d) develop action plans to mitigate legal and regulatory barriers to VBCs. More than 30 national and regional health care leaders representing health plans, integrated delivery systems, pharmacy benefit managers, employers, data and analytics companies, and biopharmaceutical companies participated. Speakers, panelists, and stakeholders attended the forum and explored the current environment for VBCs, identified challenges to the expansion of VBCs, offered potential solutions to those challenges, and developed an action plan for addressing selected challenges. The forum recommendations will be used by AMCP to establish a coalition of organizations to seek broader acceptance of VBCs in the marketplace and by policymakers. The recommendations will also help AMCP provide tools and resources to stakeholders in managing VBCs. This Partnership Forum was supported by Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, the National Pharmaceutical Council, Novo Nordisk, Premier, the Pharmaceutical Research and Manufacturers of America, RxAnte, Takeda, and Xcenda.

Vedolizumab for Treating Moderately to Severely Active Crohn's Disease After Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

PubMed

Rafia, Rachid; Scope, Alison; Harnan, Sue; Stevens, John W; Stevenson, Matt; Lobo, Alan

2016-12-01

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe, active Crohn's disease. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned as the Evidence Review Group (ERG) and produced a critical review of the evidence of the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The GEMINI II and III trials formed the main supporting evidence for the intervention. Both studies were phase III, randomised, double-blind, placebo-controlled, multicentre trials designed to evaluate the efficacy and safety of vedolizumab. They included patients who were naïve to tumour necrosis factor alpha antagonist (anti-TNF-α) therapy and patients who had an inadequate response to, loss of response to or intolerance of immunomodulators or anti-TNF-α agents. GEMINI II was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment (dosing at weeks 0 and 2, with assessment at week 6) and maintenance treatment (during weeks 6-52). In contrast, GEMINI III was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only, with doses at weeks 0, 2 and 6, and assessment at weeks 6 and 10. In the absence of any direct head-to-head, randomised, controlled trials comparing vedolizumab with other relevant biologic therapies (adalimumab and infliximab) for the treatment of moderate-to-severe Crohn's disease, the company conducted a network meta-analysis, which compared vedolizumab, adalimumab, infliximab and placebo for the outcomes of clinical response, enhanced clinical response, clinical remission and discontinuation due to adverse events. The company model estimated the incremental

Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis.

PubMed

Fisher, Mark; Nathan, Steven D; Hill, Christian; Marshall, Jade; Dejonckheere, Fred; Thuresson, Per-Olof; Maher, Toby M

2017-03-01

for Roche-Genentech and Boehringer Ingelheim and has received research funding from both companies. Hill was previously employed by InterMune UK until October 2014. Hill and Marshall are employees of MAP BioPharma, which has received funding from F. Hoffmann-La Roche for consulting services. Dejonckheere and Thuresson are employees of F. Hoffmann-La Roche. Maher has received grants, consulting fees, and speaker fees from GlaxoSmithKline and UCB, and grants from Novartis. He has also received consulting fees and speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Lanthio, InterMune International AG, F. Hoffmann-La Roche, Sanofi-Aventis, and Takeda. Maher is supported by a National Institute for Health Research Clinician Scientist Fellowship (NIHR Ref: CS: -2013-13-017). Study concept and design were contributed by Fisher, Hill, Marshall, and Dejonckheere. Fisher, Nathan, and Thuresson collected the data, along with Hill and Marshall. Data interpretation was performed by Fisher, Maher, Nathan, and Dejonckheere. The manuscript was written primarily by Fisher, along with Maher and Dejonckheere, and revised by Fisher and Maher, along with the other authors.

Influence of graphite and serpentine minerals along landslide failure surfaces

NASA Astrophysics Data System (ADS)

Alberti, Stefano; Battista Crosta, Giovanni; Wang, Gonghui; Dattola, Giuseppe; Bertolo, Davide

2017-04-01

simulate the formation of the shear zone and the post-failure mobility of high-speed landslides, monitoring pore-pressure generation, and mobilized shear resistance together with shear displacement. Reference List: Ambrosi, C., & Crosta, G. B. (2006). Large sackung along major tectonic features in the Central Italian Alps. Engineering Geology, 83(1), 183-200. Craw, D. (2002). Geochemistry of late metamorphic hydrothermal alteration and graphitisation of host rock, Macraes gold mine, Otago Schist, New Zealand. Chemical Geology, 191(4), 257-275. Nakamura, Y., Oohashi, K., Toyoshima, T., Satish-Kumar, M., & Akai, J. (2015). Strain-induced amorphization of graphite in fault zones of the Hidaka metamorphic belt, Hokkaido, Japan. Journal of Structural Geology, 72, 142-161. Sassa K, Fukuoka H, Wang FW (1997) Mechanism and risk assessment of landslide- triggered-debris flows: lesson from the 1996.12.6 Otari debris flow disaster, Nagano, Japan. In: Cruden DM, Fell R (eds) Landslide risk assessment, proceedings of the international workshop on landslide risk assessment. Honolulu, 19-21 February, pp 347-356 Zulauf, G., Kleinschmidt, G., & Oncken, O. (1990). Brittle deformation and graphitic cataclasites in the pilot research well KTB-VB (Oberpfalz, FRG). Geological Society, London, Special Publications, 54(1), 97-103. Yamasaki, S., Chigira, M., & Petley, D. N. (2016). The role of graphite layers in gravitational deformation of pelitic schist. Engineering Geology, 208, 29-38.

[Frontier of mycobacterium research--host vs. mycobacterium].

PubMed

Okada, Masaji; Shirakawa, Taro

2005-09-01

of M. tuberculosis and the development of novel therapy. Dr. Chiyoji Abe (Nippon Becton Dickinson Co.) reviewed the molecular basis of the resistance to anti-tuberculosis drugs. Most cases of resistance are related to simple nucleotide substitutions rather than to acquisition of new elements. Dr. Kiyoshi Takeda (Kyushu University) showed interesting finding. He analyzed whether Toll-like receptor (TLR)-mediated activation of innate immunity in host defense against mycobacterial infection. MyD88/TRIF double defi-indicating that innate immunity is involved in anti-mycobacterial infection. (1) SNP (single nucleotide polymorphism) analysis in association with Mycobacterium tuberculosis: Taro SHIRAKAWA (Department of Health Promotion & Human Behavior, Kyoto University Medical School, and RIKEN SRC Center) Candidate gene approach was made on 18 SNPs in 11 genes in association with M. tuberculosis. Patients with multi-drug resistance against M. tuberculosis are also subjected. SNPs in NRAMP1 gene were associated with the disease, and drug resistance, its mechanisms remain unknown. (2) Search for genes susceptible to pulmonary Mycobacterium avium complex infection: Naoto KEICHO (Department of Respiratory Diseases, Research Institute, International Medical Center of Japan) Interaction among pathogens and host factors is important for development of infectious diseases. We are trying to identify host genetic factors involved in susceptibility to nonimmunocompromized pulmonary Mycobacterium avium complex (MAC) infection by candidate gene approach and genome-wide approach. Elucidation of functional significance of susceptibility gene polymorphisms will lead to a new strategy for control and prevention of the disease. (3) T cell immunity against Tuberculosis in host and the establishment of novel vaccine: Masaji OKADA (Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center) T cell (CTL, Th1) immunity including granulysin play an important role in

Estimating the Economic Impact of Adding Panobinostat to a U.S. Formulary for Relapsed and/or Refractory Multiple Myeloma: A Budget Impact and Cost-Benefit Model.

PubMed

Bloudek, Lisa; Roy, Anuja; Kish, Jonathan K; Siegel, David S; Jagannath, Sundar; Globe, Denise; Orloski, Laurie; Kuriakose, Emil T

2016-08-01

. Panobinostat-bortezomib-dexamethasone had a low cost per treated patient per month without progression, owing to the minimal increase in expenditure over existing bortezomib-based regimens and long median PFS, compared with median duration of treatment. Adding panobinostat to a plan formulary as a treatment option is expected to be cost neutral (and potentially cost saving in the context of new and more expensive treatment regimens). With a low cost per month without progression, panobinostat-bortezomib-dexamethasone represents good value for the money. Funding for this study was sponsored by Novartis, East Hanover, New Jersey. Bloudek and Kish are employees of Xcenda, a consulting company contracted by Novartis to conduct this analysis. Roy, Globe, and Kuriakose are employees of Novartis. Siegel is on the advisory boards and speaker's bureau of Celgene, Onyx/Amgen, Millennium/Takeda, and Novartis and is on the advisory boards of Merck. Jagannath is a consultant to Sanofi, Bristol-Meyers Squibb, and Celgene. Orloski is a contractor to Xcenda and provided medical writing support, which was funded by Novartis. Study design and concept were contributed by Bloudek, Roy, and Kish, assisted by Globe. Bloukek took the lead in data collection, along with Kish, and data interpretation was performed by Siegal, Jagannath, Globe, and Kuriakose. The manuscript was written primarily by Orloski, along with Roy and Kish, and revised by Roy, along with Siegal, Jagannath, Globe, Orloski, and Kuriakose.

Orthopyroxenes as Recorders of Diogenite Petrogenesis: Nature and Causes of Intragrain Chemical Variability

NASA Astrophysics Data System (ADS)

Papike, J. J.; Spilde, M. N.

1993-07-01

.g., (100) augite lamellae in an OPX host], and (3) relatively random variability (e.g., exsolution of spinel). Figure 1 (an OPX from Garland) provides evidence for smooth core-to-rim diffusion profiles. Iron and Mn increase while Mg and Cr decrease from core to rim. Also, Al remains relatively constant, Si decreases, and Ti shows an increase, near the grain edge, on the core-to-rim traverse. These chemical systematics were likely caused by a reaction between the cumulate OPX grain and trapped melt. The trapped melt was apparently enriched in Fe and Mn and depleted in Cr relative to OPX. In conclusion, postcrystallization resetting of cumulate grain chemical systematics must be carefully assessed before the data can be "inverted" to estimates of parental melt compositions. Acknowledgment: This research was supported by NASA grant NAGW-3347 and the Institute of Meteoritics. References: [1] Shearer C. K. et al. (1993) LPS XXIV, 1289-1290. [2] Lambert D. D. and Simmons E. C. (1987) Am. J. Sci., 287, 1-32. [3] Takeda H. et. al. (1979) Proc. 3rd Symp. Antarc. Met., 82-108. [4] Papike J. J. et. al. (1993) LPS XXIV, 1109-1110. Fig. 1 appears here in the hard copy.

Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews.

PubMed

Levis, Brooke; Benedetti, Andrea; Riehm, Kira E; Saadat, Nazanin; Levis, Alexander W; Azar, Marleine; Rice, Danielle B; Chiovitti, Matthew J; Sanchez, Tatiana A; Cuijpers, Pim; Gilbody, Simon; Ioannidis, John P A; Kloda, Lorie A; McMillan, Dean; Patten, Scott B; Shrier, Ian; Steele, Russell J; Ziegelstein, Roy C; Akena, Dickens H; Arroll, Bruce; Ayalon, Liat; Baradaran, Hamid R; Baron, Murray; Beraldi, Anna; Bombardier, Charles H; Butterworth, Peter; Carter, Gregory; Chagas, Marcos H; Chan, Juliana C N; Cholera, Rushina; Chowdhary, Neerja; Clover, Kerrie; Conwell, Yeates; de Man-van Ginkel, Janneke M; Delgadillo, Jaime; Fann, Jesse R; Fischer, Felix H; Fischler, Benjamin; Fung, Daniel; Gelaye, Bizu; Goodyear-Smith, Felicity; Greeno, Catherine G; Hall, Brian J; Hambridge, John; Harrison, Patricia A; Hegerl, Ulrich; Hides, Leanne; Hobfoll, Stevan E; Hudson, Marie; Hyphantis, Thomas; Inagaki, Masatoshi; Ismail, Khalida; Jetté, Nathalie; Khamseh, Mohammad E; Kiely, Kim M; Lamers, Femke; Liu, Shen-Ing; Lotrakul, Manote; Loureiro, Sonia R; Löwe, Bernd; Marsh, Laura; McGuire, Anthony; Mohd Sidik, Sherina; Munhoz, Tiago N; Muramatsu, Kumiko; Osório, Flávia L; Patel, Vikram; Pence, Brian W; Persoons, Philippe; Picardi, Angelo; Rooney, Alasdair G; Santos, Iná S; Shaaban, Juwita; Sidebottom, Abbey; Simning, Adam; Stafford, Lesley; Sung, Sharon; Tan, Pei Lin Lynnette; Turner, Alyna; van der Feltz-Cornelis, Christina M; van Weert, Henk C; Vöhringer, Paul A; White, Jennifer; Whooley, Mary A; Winkley, Kirsty; Yamada, Mitsuhiko; Zhang, Yuying; Thombs, Brett D

2018-06-01

original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Solar Noble Gases in Polymict Ureilites and an Update on Ureilite Noble Gas Data

NASA Astrophysics Data System (ADS)

Ott, U.; Lohr, H. P.; Begemann, F.

1993-07-01

/^21Ne)(sub)c ratio of the cosmogenic component, indicative of irradiation under very low shielding conditions, but otherwise abundances and abundance ratios for the momomict ureilites LEW 85328 and Acfer 277 appear quite "ordinary" when compared to other monomict ureilites [6,10]. References: [1] Wasson J. T. et al. (1976) GCA, 40, 1449-1458. [2] Berkley J. L. et al. (1980) GCA, 44, 1579-1597. [3] Takeda H. (1989) EPSL, 93, 181- 194. [4] Warren P. H. and Kallemeyn G. W. (1989) Meteoritics, 24, 233-246. [5] Clayton R. N. and Mayeda T. K. (1988) GCA, 52, 1313-1318. [6] Gobel R. et al. (1978) JGR, 83, 855-867. [7] Ott U. et al. (1984) Meteoritics, 19, 287-288. [8] Black D. C. (1972) GCA, 36, 347-375. [9] Ott U. et al. (1990) Meteoritics, 25, 396. [10] Schultz L. and Kruse H. (1989) Meteoritics, 24, 155-172. [11] Jaques A. L. and Fitzgerald M. J. (1982) GCA, 46, 893-900. [12] Grady M. M. and Pillinger C. T. (1988) Nature, 331, 321-323. Table 1, which appears here in the hard copy, shows noble gases in monomict ureilites Acfer 277 and LEW 85328 and polymict ureilite EET 87720. Fig. 1 appears here in the hard copy.

The association between sperm sex chromosome disomy and semen concentration, motility and morphology.

PubMed

McAuliffe, M E; Williams, P L; Korrick, S A; Dadd, R; Perry, M J

2012-10-01

(1818) was not associated with abnormal semen parameters. A potential limitation of this study, as well as those currently in the published literature, is that it is cross-sectional. Cross-sectional analyses by nature do not lend themselves to inference about directionality for any observed associations; therefore, we cannot determine which variable is the cause and which one is the effect. Additionally, the use of WHO cutoff criteria for dichotomizing semen parameters may not fully define fertility status; however, in this study, fertility status was not an outcome we were attempting to assess. This is the largest study to date seeking to understand the association between sperm sex chromosome disomy and semen parameters, and the first to use multivariate modeling to understand this relationship. The findings are similar to those in the published literature and highlight the need for mechanistic studies to better characterize the interrelationships between sex chromosome disomy and standard indices of sperm health. This work was supported by grants from NIOSH (T42 OH008416) and NIEHS (R01 ES009718, P30 ES000002 and R01 ES017457). The authors declare no competing interests. At the time this work was conducted and the initial manuscript written, MEM was affiliated with the Environmental Health Department at the Harvard School of Public Health. Currently, MEM is employed by Millennium: The Takeda Oncology Company. N/A.

The association between sperm sex chromosome disomy and semen concentration, motility and morphology

PubMed Central

McAuliffe, M.E.; Williams, P.L.; Korrick, S.A.; Dadd, R.; Perry, M.J.

2012-01-01

total sex chromosome disomy were not associated with an increase in the odds of a man having abnormal semen parameters. In addition, autosomal chromosome disomy (1818) was not associated with abnormal semen parameters. LIMITATIONS, REASONS FOR CAUTION A potential limitation of this study, as well as those currently in the published literature, is that it is cross-sectional. Cross-sectional analyses by nature do not lend themselves to inference about directionality for any observed associations; therefore, we cannot determine which variable is the cause and which one is the effect. Additionally, the use of WHO cutoff criteria for dichotomizing semen parameters may not fully define fertility status; however, in this study, fertility status was not an outcome we were attempting to assess. WIDER IMPLICATIONS OF THE FINDINGS This is the largest study to date seeking to understand the association between sperm sex chromosome disomy and semen parameters, and the first to use multivariate modeling to understand this relationship. The findings are similar to those in the published literature and highlight the need for mechanistic studies to better characterize the interrelationships between sex chromosome disomy and standard indices of sperm health. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from NIOSH (T42 OH008416) and NIEHS (R01 ES009718, P30 ES000002 and R01 ES017457). The authors declare no competing interests. At the time this work was conducted and the initial manuscript written, MEM was affiliated with the Environmental Health Department at the Harvard School of Public Health. Currently, MEM is employed by Millennium: The Takeda Oncology Company. TRIAL REGISTRATION NUMBER N/A. PMID:22892419

Budget Impact of Adding Ivabradine to Standard of Care in Patients with Chronic Systolic Heart Failure in the United States.

PubMed

Borer, Jeffrey S; Kansal, Anuraag R; Dorman, Emily D; Krotneva, Stanimira; Zheng, Ying; Patel, Harshali K; Tavazzi, Luigi; Komajda, Michel; Ford, Ian; Böhm, Michael; Kielhorn, Adrian

2016-09-01

treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers. This study was funded by Amgen. Patel is employed by Amgen; Kielhorn was employed by Amgen at the time of the study but is no longer affiliated with Amgen. Borer, Böhm, Ford, and Komajda have received scientific support, consultative fees, and/or speakers honoraria from Servier and Amgen in connection with SHIFT, the trial underlying this analysis. Borer also has received consultative fees from Celladon, Pfizer, ARMGO, Cardiorentis, Novartis, and Takeda USA. Kansal, Dorman, Krotneva, and Zheng are employees of Evidera, which was hired to assist with this study. Tavazzi has received research grants and consultation fees from Servier in connection with this study and has had advisory board memberships with Boston Scientific, Servier, Cardiorentis, Medtronic, St. Jude Medical, and CVie Therapeutics. Study concept and design were contributed by Dorman and Keilhorn, along with the other authors. Tavazzi, Komajda, Ford, BÖhm, and Borer oversaw collection of the data. Tavazzi, Komajda, Ford, BÖhm, and Borer (along with Karl Swedberg) formed the Executive Committee of SHIFT, the trial underlying this analysis. The manuscript was written by Kansal, along with the other authors, and revised by Borer and Patel, with assistance from the other authors.

PREFACE: International Conference on Strongly Correlated Electron Systems 2014 (SCES2014)

NASA Astrophysics Data System (ADS)

2015-03-01

The 2014 International Conference on Strongly Correlated Electron Systems (SCES) was held in Grenoble from the 7th to 11th of July on the campus of the University of Grenoble. It was a great privilege to have the conference in Grenoble after the series of meetings in Sendai (1992), San Diego (1993), Amsterdam (1994), Goa (1995), Zürich (1996), Paris (1998), Nagano (1999), Ann Arbor (2001), Krakow (2002), Karlsruhe (2004), Vienna (2005), Houston (2007), Buzios (2008), Santa Fe (2010), Cambridge (2011) and Tokyo (2013). Every three years, SCES joins the triennial conference on magnetism ICM. In 2015, ICM will take place in Barcelona. The meeting gathered an audience of 875 participants who actively interacted inside and outside of conference rooms. A large number of posters (530) was balanced with four parallel oral sessions which included 86 invited speakers and 141 short oral contributions. A useful arrangement was the possibility to put poster presentations on the website so participants could see them all through the conference week. Each morning two plenary sessions were held, ending on Friday with experimental and theoretical summaries delivered by Philipp Gegenwart (Augsburg) and Andrew Millis (Columbia). The plenary sessions were given by Gabriel Kotliar (Rutgers), Masashi Kawasaki (Tokyo), Jennifer Hoffman (Harvard), Mathias Vojta (Dresden), Ashvin Vishwanath (Berkeley), Andrea Cavalleri (Hamburg), Marc-Henri Julien (Grenoble), Neil Mathur (Cambridge), Giniyat Khaliullin (Stuttgart), and Toshiro Sakakibara (Tokyo). The parallel oral sessions were prepared by 40 symposium organizers selected by the chairman (Antoine Georges) and co-chairman (Kamran Behnia) of the Program Committee with the supplementary rule that speakers had not delivered an invited talk at the previous SCES conference held in 2013 in Tokyo. Special attention was given to help young researchers via grants to 40 overseas students. Perhaps due to the additional possibility of cheap

Vlasov simulations of electron hole dynamics in inhomogeneous magnetic field

NASA Astrophysics Data System (ADS)

Kuzichev, Ilya; Vasko, Ivan; Agapitov, Oleksiy; Mozer, Forrest; Artemyev, Anton

2017-04-01

particular, our simulations suggest that slow EHs (which generation is usually attributed to the Buneman instability) can arise due to slowing down of fast EH generated by electron-beam instability. The estimate of the potential drop along EHs allow to estimate the parallel potential drop provided by EHs in a particular plasma system. 1. Matsumoto, H., H. Kojima, T. Miyatake, Y. Omura, M. Okada, I. Nagano, and M. Tsutsui, Electrotastic Solitary Waves (ESW) in the magnetotail: BEN wave forms observed by GEOTAIL, Geophys. Res. Lett., 21, 2915-2918, doi:10.1029/94GL01284, 1994. 2. Norgren, C., M. Andŕe, A. Vaivads, and Y. V. Khotyaintsev, Slow electron phase space holes: Magnetotail observations, Geophys. Res. Lett., 42, 1654-1661, doi:10.1002/2015GL063218, 2015. 3. Malaspina, D. M., J. R. Wygant, R. E. Ergun, G. D. Reeves, R. M. Skoug, and B. A. Larsen, Electric field structures and waves at plasma boundaries in the inner magnetosphere, Journal of Geophysical Research (Space Physics), 120, 4246-4263, doi:10.1002/2015JA021137, 2015. 4. Franz, J. R., P. M. Kintner, J. S. Pickett, and L.-J. Chen, Properties of small-amplitude electron phase-space holes observed by Polar, Journal of Geophysical Research (Space Physics), 110, A09212, doi:10.1029/2005JA011095, 2005. 5. Cattell, C., C. Neiman, J. Dombeck, J. Crumley, J. Wygant, C. A. Kletzing, W. K. Peterson, F. S. Mozer, and M. André (2003), Large amplitude solitary waves in and near the Earth's magnetosphere, magnetopause and bow shock: Polar and Cluster observations, Nonlinear Processes Geophys., 10, 13-26. 6. Mandrake, L., P. L. Pritchett, and F. V. Coroniti, Electron beam generated solitary structures in a nonuniform plasma system, Geophys. Res. Lett., 27, 2869-2872, doi:10.1029/2000GL003785, 2000. The work of I.K. was supported by Russian Foundation for Basic Research 16-32-00721 mol_a. The work of I.V., O.A. and F.M. was supported by JHU/APL contract 922613 (RBSPEFW).

AMCP Partnership Forum: FDAMA Section 114-Improving the Exchange of Health Care Economic Data.

PubMed

2016-07-01

& Co., National Pharmaceutical Council, Pharmaceutical Research and Manufacturers of America, Precision for Value, Pfizer, Takeda Pharmaceuticals, U.S.A., and Xcenda. All sponsors participated in the forum and participated in revising and approving the manuscript.

Seismic structure of the upper crust in the Albertine Rift from travel-time and ambient-noise tomography - a comparison

NASA Astrophysics Data System (ADS)

Jakovlev, Andrey; Kaviani, Ayoub; Ruempker, Georg

2017-04-01

5 km Low velocities surround the mountain range from western and southern sides and coincide with the location of the rift valley. The Rwenzori Mountains itself and the eastern rift shoulder are represented by increased velocities. At greater depths of 10 - 15 km some differences in the models care observed. Thus, beneath the Rwenzories the travel time tomography shows low S-velocities, whereas the ambient noise tomography exhibits high S-velocities. This can be possibly explained by the fact that the ambient noise tomography is characterized by higher vertical resolution. Also, the number of the rays used for tomographic inversion in the ambient noise tomography is significantly smaller. This study was partly supported by the grant of Russian Foundation of Science #14-17-00430. References: Barmin, M.P., Ritzwoller, M.H. & Levshin, A.L., 2001. A fast and reliable method for surface wave tomography, Pure appl. Geophys., 158, 1351-1375. Bensen G.D., Ritzwoller M.H., Barmin M.P., Levshin A.L., Lin F., Moschetti M.P., Shapiro N.M., Yang Y., 2001, A fast and reliable method for surface wave tomography. Geophys. J. Int. 169, 1239-1260, doi: 10.1111/j.1365-246X.2007.03374.x. Boué P., Poli P., Campillo M., Roux P., 2014, Reverberations, coda waves and ambient-noise: correlations at the global scale and retrieval of the deep phases. Earth planet. Sci. Lett., 391, 137-145. Briand X., Campillo M., Brenguier F., Boué P., Poli P., Roux P., Takeda T. AGU Fall Meeting. San Francisco, CA; 2013. Processing of terabytes of data for seismic noise analysis with the Python codes of the Whisper Suite. 9-13 December, in Proceedings of the , Abstract n°IN51B-1544. Koulakov, I. (2009), LOTOS code for local earthquake tomographic inversion. Benchmarks for testing tomographic algorithms, Bull. Seismol. Soc. Am., 99, 194-214, doi:10.1785/0120080013.

Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance.

PubMed

Saxena, R; Georgopoulos, N A; Braaten, T J; Bjonnes, A C; Koika, V; Panidis, D; Welt, C K

2015-06-01

associated with insulin (-0.16 ± 0.05, P = 0.0029) and glucose levels (-0.20 ± 0.05, P = 0.0002) 120 min after an oral glucose test. The study was large and contained replication cohorts, but was limited by a small number of controls in the Greek cohort and a small number of cases in the second Boston cohort. The second Boston group was identified using electronic medical record review, but was validated for the cardinal features of PCOS. This study demonstrates a cross-ethnic PCOS risk locus in FSHR in women of European ancestry with PCOS. The variant may influence FSH receptor responsiveness as suggested by the associated change in FSH levels. The relationship between a variant near RAB5B and SUOX and glucose stimulated insulin and glucose levels suggests an influence of one of these genes on glucose tolerance, but the absence of a relationship with PCOS points to potential differences in the international PCOS patient populations. The project was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, award 1-10-CT-57 from the American Diabetes Association and the Partners Healthcare Center for Personalized Genetics Project Grant. C.K.W. is a consultant for Takeda Pharmaceuticals. NCT00166569. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial.

PubMed

Ueki, Kohjiro; Sasako, Takayoshi; Okazaki, Yukiko; Kato, Masayuki; Okahata, Sumie; Katsuyama, Hisayuki; Haraguchi, Mikiko; Morita, Ai; Ohashi, Ken; Hara, Kazuo; Morise, Atsushi; Izumi, Kazuo; Ishizuka, Naoki; Ohashi, Yasuo; Noda, Mitsuhiko; Kadowaki, Takashi

2017-12-01

SmithKline, Kissei Pharmaceutical, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Novo Nordisk, Ono Pharmaceutical, Pfizer, Sanwa Kagaku Kenkyusho, Shionogi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, and Takeda. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical effectiveness and cost-effectiveness of interventions for the treatment of anogenital warts: systematic review and economic evaluation.

PubMed

Thurgar, Elizabeth; Barton, Samantha; Karner, Charlotta; Edwards, Steven J

2016-03-01

treatment. Podophyllotoxin 0.5% solution (Condyline(®), Takeda Pharmaceutical Company Ltd; Warticon(®) solution, Stiefel Laboratories Ltd) was found to be the most effective topical treatment evaluated. Networks for other outcomes included fewer treatments, which restrict conclusions on the comparative effectiveness of interventions. In total, 84 treatment strategies were assessed using the economic model. Podophyllotoxin 0.5% solution first line followed by carbon dioxide (CO2) laser therapy second line if AGWs did not clear was most likely to be considered a cost-effective use of resources at a willingness to pay of £20,000-30,000 per additional quality-adjusted life-year gained. The result was robust to most sensitivity analyses conducted. Limited reporting in identified studies of baseline characteristics for the enrolled population generates uncertainty around the comparability of the study populations and therefore the generalisability of the results to clinical practice. Subgroup analyses were planned based on type, number and size of AGWs, all of which are factors thought to influence treatment effect. Lack of data on clinical effectiveness based on these characteristics precluded analysis of the differential effects of treatments in the subgroups of interest. Despite identification of 60 studies, most comparisons in the MTC are informed by only one RCT. Additionally, lack of head-to-head RCTs comparing key treatments, together with minimal reporting of results in some studies, precluded comprehensive analysis of all treatments for AGWs. The results generated by the MTC are in agreement with consensus opinion that ablative techniques are clinically more effective at completely clearing AGWs after treatment. However, the evidence base informing the MTC is limited. A head-to-head RCT that evaluates the comparative effectiveness of interventions used in clinical practice would help to discern the potential advantages and disadvantages of the individual treatments

Identification and replication of prediction models for ovulation, pregnancy and live birth in infertile women with polycystic ovary syndrome.

PubMed

Kuang, Hongying; Jin, Susan; Hansen, Karl R; Diamond, Michael P; Coutifaris, Christos; Casson, Peter; Christman, Gregory; Alvero, Ruben; Huang, Hao; Bates, G Wright; Usadi, Rebecca; Lucidi, Scott; Baker, Valerie; Santoro, Nanette; Eisenberg, Esther; Legro, Richard S; Zhang, Heping

2015-09-01

large sample sizes. Younger age, lower baseline free androgen index and insulin, shorter duration of attempting conception, and higher baseline sex hormone-binding globulin significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs of 0.66-0.76) and calibration plots and chi-square tests indicated stable predictive power of the identified variables (P-values ≥0.07 for all goodness-of-fit and validation tests). This is a secondary analysis. Although our primary objective was to confirm previously reported results and identify new predictors of ovulation and pregnancy outcomes among PPCOS-II participants, our approach is exploratory and warrants further replication. We have largely confirmed the predictors that were identified in the PPCOS-I trial. However, we have also revealed new predictors, particularly the role of smoking. While a history of ever smoking was not a significant predictor for live birth, a closer look at current, quit, and never smoking revealed that current smoking was a significant risk factor. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C. reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc. and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax, Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals

AMCP Partnership Forum: Enabling the Exchange of Clinical and Economic Information Pre-FDA Approval.

PubMed

2017-01-01

, since PIE is a novel category of information. New legislation could provide a safe harbor and clarity that PIE does not violate preapproval promotion and the Federal Food, Drug, and Cosmetic Act and its regulations. The AMCP Partnership Forum on Enabling the Exchange of Clinical and Economic Data Pre-FDA Approval and the development of this proceedings document were supported by AbbVie, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Celgene, Intarcia Therapeutics, Eli Lilly and Company, GlaxoSmithKline, Merck, National Pharmaceutical Council, Novo Nordisk, Pfizer, Pharmaceutical Research and Manufacturers of America, Precision for Value, Sanofi, Takeda Pharmaceuticals, U.S.A., and Xcenda. All sponsors participated in the forum and in revising and approving the manuscript.

Patterns of Statin Use in a Real-World Population of Patients at High Cardiovascular Risk.

PubMed

Lin, Iris; Sung, Jennifer; Sanchez, Robert J; Mallya, Usha G; Friedman, Mark; Panaccio, Mary; Koren, Andrew; Neumann, Peter; Menzin, Joseph

2016-06-01

interest in Regeneron Pharmaceuticals. Neumann has served on advisory boards for Merck & Co, Takeda Pharmaceutical Company, Genentech, Novartis, Bayer AG, UCB, Sanofi US, Robert Wood Johnson Foundation, and Cubist and serves as consultant for Boston Health Economics, Forrest, P urdue, and Smith and Nephew. This research has been presented in part at the International Society for Pharmacoeconomics and Outcomes Research, 20th Annual International Meeting, May 16-20, 2015, Philadelphia, Pennsylvania. All authors contributed to the study design, protocol development, and results interpretation. Lin and Menzin were responsible for conducting the study analyses. All authors were involved in manuscript development and approved the submitted version.

Racial and Ethnic Disparities in Meeting MTM Eligibility Criteria Based on Star Ratings Compared with the Medicare Modernization Act.

PubMed

Spivey, Christina A; Wang, Junling; Qiao, Yanru; Shih, Ya-Chen Tina; Wan, Jim Y; Kuhle, Julie; Dagogo-Jack, Samuel; Cushman, William C; Chisholm-Burns, Marie

2018-02-01

sensitivity analyses. Disparities were not completely explained by differences in patient characteristics based on the Blinder-Oaxaca approach. The multinomial logistic regression of each main analysis found significant adjusted relative risk ratios (RRR) between whites and blacks for 2009 (RRR = 0.459, 95% CI = 0.438-0.481); 2013 (RRR = 0.449, 95% CI = 0.434-0.465); and 2015 (RRR = 0.436, 95% CI = 0.425-0.446) and between whites and Hispanics for 2009 (RRR = 0.559, 95% CI = 0.528-0.593); 2013 (RRR = 0.544, 95% CI = 0.521-0.569); and 2015 (RRR = 0.503, 95% CI = 0.488-0.518). These findings indicate a significant reduction in racial and ethnic disparities when using star ratings eligibility criteria; for example, black-white disparities in the likelihood of meeting MTM eligibility criteria were reduced by 55.1% based on star ratings compared with MMA in 2013. Similar patterns were found in most sensitivity and disease-specific analyses. This study found that minorities were more likely than whites to be MTM-eligible under the star ratings criteria. In addition, MTM eligibility criteria based on star ratings would reduce racial and ethnic disparities associated with MMA in the general Medicare population and those with specific chronic conditions. Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R01AG049696. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Cushman reports an Eli Lilly grant and uncompensated consulting for Takeda Pharmaceuticals outside this work. The other authors have no potential conflicts of interest to report. Study concept and design were contributed by Wang and Shih, along with Wan, Kuhle, Spivey, and Cushman. Wang, Qiao, and Wan took the lead in data collection, with assistance from the other authors. Data interpretation was performed by Wang, Kuhle

Impact of a Patient Support Program on Patient Adherence to Adalimumab and Direct Medical Costs in Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis, and Ankylosing Spondylitis.

PubMed

Rubin, David T; Mittal, Manish; Davis, Matthew; Johnson, Scott; Chao, Jingdong; Skup, Martha

2017-08-01

12 months following the index date using t-tests. A total of 2,386 patients were included in the study and were allocated to the PSP (n = 1,199) and non-PSP (n = 1,187) cohorts. Baseline characteristics were similar between cohorts. During the follow-up period, adalimumab adherence was 14% greater in the PSP cohort than for the non-PSP cohort (67.0% vs. 58.8%; P < 0.001). The discontinuation rate for adalimumab was 14% lower in the PSP cohort compared with the non-PSP cohort (39.7% vs. 46.2%; P = 0.001). Univariate analyses showed that PSP patients had 23% lower 12-month medical costs (excluding costs for biologic treatment) than did non-PSP patients ($18,322 vs. $23,679; P = 0.003). Disease-related medical costs were 22% lower for PSP than for non-PSP patients ($8,001 vs. $10,202; P = 0.045). Total costs were 10% lower for PSP than for non-PSP patients ($35,741 vs. $39,713; P = 0.030). Patient enrollment in the PSP was associated with greater adherence, improved persistence, and reduced medical (all-cause and disease-related) and total health care costs for patients receiving adalimumab therapy. Design, study conduct, and financial support for this study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. All authors contributed to the development of the publication and maintained control over the final content. Rubin has received consulting fees or research support from AbbVie, Amgen, Emmi, Genentech, Ironwood, Janssen, Pfizer, Prometheus, Shire, and Takeda. Skup and Mittal are employees and stockholders of AbbVie. Chao was an employee of AbbVie at the time of the study and may hold AbbVie stock. Johnson and Davis are employees of Medicus Economics, which received payment from AbbVie to participate in this research. Study concept and design were contributed by Rubin, Mittal, Chao, and Skup, along with Davis and Johnson. Davis and Johnson took the lead in data collection, with assistance from the other

EDITORIAL: Welcome to the 2012 volume Welcome to the 2012 volume

NASA Astrophysics Data System (ADS)

Garcia, Ephrahim

2012-01-01

, Los Angeles, USA Professor Y Matsuzaki, Nagoya University, Japan Professor W M Ostachowicz, Polish Academy of Sciences, Gdansk, Poland Dr K Peters, North Carolina State University, Raleigh, USA Professor M Shahinpoor, University of New Mexico, Albuquerque, USA Dr H Sodano, Arizona State University, Tempe, USA Professor G Song, University of Houston, TX, USA Professor W J Staszewski, AGH University of Science and Technology, Kraków, Poland Professor N Takeda, University of Tokyo, Japan Professor Q Wang, University of Manitoba, Canada Professor N M Wereley, University of Maryland, College Park, USA Professor W J Wu, National Taiwan University, Taiwan I look forward to the continued success and prosperity of SMS in 2012!

Silicate Inclusions in IAB Irons: Correlations Between Metal Composition and Inclusion Properties, and Inferences for Their Origin

NASA Astrophysics Data System (ADS)

Benedix, G. K.; McCoy, T. J.; Keil, K.

1995-09-01

changes observed here indicate that the silicates were interacting with a single evolving metallic magma. We suggest that the requirement for a common system is more compatible with core formation [5,6] than with impact-melt pools [2,4]. References: [1] McCoy T. J. et al. (1993) Meteoritics, 28, 552-560. [2] Choi B.-G. et al. (1995) GCA, 59, 593-612. [3] Benedix G. K. et al. (1995) LPS XXVI, 99-100. [4] Wasson J. T. et al. (1980) Z. Naturforsch., 35a, 781-795. [5] Kracher A. (1982) GRL, 9, 412-415. [6] Kracher A. (1985) Proc. LPSC 15th, in JGR, 90, C689-C698. [7] Bunch T. E. et al. (1970) Contrib. Mineral. Petrol., 25, 297-340. [8] McCoy et al. (1995) Meteoritics, in preparation. [9] Scott E. R. D. and Bild R. W. (1974) GCA, 38, 1379-1391. [10] Takeda H. et al. (1993) Meteoritics, 28, 447.

High energy neutrinos from astrophysical accelerators of cosmic ray nuclei

NASA Astrophysics Data System (ADS)

Anchordoqui, Luis A.; Hooper, Dan; Sarkar, Subir; Taylor, Andrew M.

2008-02-01

.1181983223S.P.LaiJ.M.GirartR.CrutcherAstrophys. J.5982003392W.BednarekMon. Not. R. Astron. Soc.3452003847W.BednarekR.J.ProtheroeAstropart. Phys.162002397P.BlasiA.V.OlintoPhys. Rev. D591999023001F.W.SteckerAstropart. Phys.262007398F.W. Stecker, arXiv:astro-ph/0610208.A γ-ray signal from the nearby starburst galaxy NGC253 was reported by the CANGAROO-II Collaboration but their subsequent re-analysis of the data is consistent with the expectation from backgrounds:C.ItohCANGAROO-II CollaborationAstron. Astrophys.3962002L1(Erratum-ibid. 462 (2007) 67)T.A. Thompson, E. Quataert, E. Waxman, A. Loeb, arXiv:astro-ph/0608699.D.J.BirdFly’s Eye CollaborationPhys. Rev. Lett.7119933401D.R.BergmanHiRes CollaborationNucl. Phys. Proc. Suppl.136200440T.Abu-ZayyadHiRes-MIA CollaborationAstrophys. J.5572001686M.NaganoJ. Phys. G181992423V.BerezinskyA.Z.GazizovS.I.GrigorievaPhys. Rev. D742006043005R.U.AbbasiHiRes CollaborationPhys. Rev. Lett.922004151101V.BerezinskyA.Z.GazizovS.I.GrigorievaPhys. Lett. B6122005147V.S.BerezinskyS.I.GrigorievaB.I.HnatykAstropart. Phys.212004617See Fig. 21 in:L.AnchordoquiM.T.DovaA.MariazziT.McCauleyT.PaulS.ReucroftJ.SwainAnn. Phys.3142004145D.AllardE.ParizotE.KhanS.GorielyA.V.OlintoAstron. Astrophys.4432005L29D.AllardE.ParizotA.V.OlintoAstropart. Phys.27200761T.Abu-ZayyadHigh Resolution Fly’s Eye CollaborationAstropart. Phys.232005157P. Sommers, et al., Pierre Auger Collaboration, arXiv:astro-ph/0507150.R.U.AbbasiHiRes CollaborationAstrophys. J.6222005910B.N. Afanasiev, et al., Yakutsk Collaboration, in: M. Nagano (Ed.), Proceedings of the Tokyo Workshop on Techniques for the Study of the Extremely High Energy Cosmic Rays, 1993.J. Knapp, private communication.J.RanftPhys. Rev. D51199564R.S.FletcherT.K.GaisserP.LipariT.StanevPhys. Rev. D5019945710J.EngelT.K.GaisserT.StanevP.LipariPhys. Rev. D4619925013N.N.KalmykovS.S.OstapchenkoA.I.PavlovNucl. Phys. Proc. Suppl.52B19977It is important to stress that the Auger data are still at a preliminary stage and the

PREFACE: Nanosafe2010: International Conference on Safe Production and Use of Nanomaterials

NASA Astrophysics Data System (ADS)

Sentein, Carole; Schuster, Frédéric; Tardif, François

2011-07-01

. Rochester, USA)David PUI (U. Minnesota, USA)Eric QUEMENEUR (CEA, FR)Robert SCHALLER (EPFL, CH)Carole SENTEIN (CEA, FR)Ken TAKEDA (U. Tokyo, JP)Louis TREPIED (MINEFE, FR)Jacques VENDEL (IRSN, FR)Olivier WITSCHGER (INRS, FR) List of Participants AGUY SCordouan, FR ALLEMAN LEcole des Mines de Douai, FR ALPER MUniv. California Berkeley, US ALVES O LUNICAMP, BR AMDAOUD MUniv. Joseph Fourier, FR AMODEO TINERIS, FR AMYOTTE PDalhousie Univ., CA ARAKELIAN M CFundacion Argentina de Nanotecnologia, AR ARZAMASTSEVA ETomsk Polytechnic Univ., RU ASCHBERGER KEuropean Commission-JRC, IT ASHTON AJPCS, GB ASIMAKOPOULOU ACERTH/CPER, GR AUBLANT J-MLNE, FR AUDE-GARCIA CCEA, FR AUFFAN MCEREGE, FR AUGER ACEA, FR BAEK MSeoul Woman's Univ., KR BAEZA AUniv. Paris 7 Diderot, FR BAGUET DCEA, FR BARONE FIstituto Superiore di Sanità, IT BAU SINRS, FR BELLEVILLE PCEA, FR BENAZET SSNPE-Matériaux Energétiques, FR BERGER L-MFraunhofer Institute, DE BERGES MDGUV-IFA, DE BERNARD CNIST, US BERNARD DARKEMA, FR BERNE PCEA, FR BERRET J-FUniv. Paris 7 Diderot, FR BIGORGNE ECNRS, FR BILLAT BPMS, FR BLOCH DCEA, FR BOGDANOVIC-GUILLON AFreelance journalist, FR BOIVIN DRESPIREX France, FR BOLAND SUniv. Paris 7 Diderot, FR BOMBARDIER PFAURE QEI, FR BORASCHI DInstitute of Biomedical Technologies, IT BOTTERO J-YCEREGE, FR BRADLEY JLux Research, US BREGOLI LVeneto Nanotech, IT BRIGNON J-MINERIS, FR BROCHOT CIRSN, FR BROUWER DTNO Quality of Life, NL BUDIMAN TTSE-Systems, DE CABOCHE JEcole des Mines de Douai, FR CALLET GCEA, FR CALOGINE DINERIS, FR CAPONIGRO ALoreal, FR CARRIERE MCEA, FR CASSETTE SThales Research & Technology, FR CHARPENTIER DINERIS, FR CHEN C-CTaiwan Univ., TW CHEN LHealth Canada, CA CHEVALLET MCEA, FR CHOI S-JSeoul Woman's Univ., KR CHOU C-CChung Cheng University, TW CHUNG H-ESeoul Woman's Univ., KR CIMPAN MUniv. Bergen, NO CIOBANU NTU Munich, DE CLARK KInstitute for Work and Health, CH CONJEAUD HUniv. Paris 7 Diderot, FR COSTA PEREIRA CNational Health Institute, PT CROOKS MTSI, GB CUPERTINO DC

PREFACE Preface

NASA Astrophysics Data System (ADS)

Takahashi, Migaku; Saito, Hitoshi; Yoshimura, Satoru; Takanashi, Koki; Sahashi, Masashi; Tsunoda, Masakiyo

2011-01-01

IgarashiHitachi, CRL, JapanK TajimaAkita Univ., Japan H ItoKansai Univ., JapanM TakedaJAEA, Japan H IwasakiToshiba, JapanY TakemuraYokohama Nat'l Univ., Japan H KatoYamagata Univ., JapanM TanakaUniv. of Tokyo, Japan M KonotoAIST, JapanA TsukamotoNihon Univ., Japan H KubotaAIST, JapanS YabukamiTohoku Gakuin Univ., Japan Treasury Committee of ISAMMA 2010 M SahashiTohoku Univ., Japan, ChairS SaitoTohoku Univ., Japan K IshiyamaTohoku Univ., JapanT TanakaEhime Univ., Japan K NakagawaNihon Univ., JapanN TezukaTohoku Univ., Japan T OgawaTohoku Univ., Japan Executive Committee of ISAMMA 2010 M TakahashiTohoku Univ., Japan, ChairS SaitoTohoku Univ., Japan K TakanashiTohoku Univ., Japan, Vice-chairY SakurabaTohoku Univ., Japan K MiyakeTohoku Univ., JapanT ShimaTohoku Gakuin Univ., Japan T OgawaTohoku Univ., JapanN TezukaTohoku Univ., Japan S OkamotoTohoku Univ., JapanM TsunodaTohoku Univ., Japan M OoganeTohoku Univ., Japan We are grateful to all the participants for their valuable contributions and active discussions. We gratefully acknowledge the financial support from 17 Japanese companies (ASAKA RIKEN CO., LTD, Fujikin Incorporated, Furukawa Electric Co., Ltd, Hitachi Metals, Ltd, IZUMI-TEC CO., LTD, Miwa Electric Industrial CO., LTD, MIWA MFG CO., LTD, NEOARK Corporation, Optima Corporation, PRESTO CO., LTD, SHOWA DENKO K.K., TAIYO YUDEN CO., LTD, TDK Corporation, TEIJIN LIMITED, Ube Material Industries, Ltd, ULVAC, Inc, and V TEX Corporation) and 7 foundations (SENDAI TOURISM & CONVENTION BUREAU, The Iwatani Naoji Foundation, Tohoku University Electro-Related Departments Global COE Program 'Center of Education and Research for Information Electronics Systems', The Murata Science Foundation, Research Foundation for Materials Science, Nippon Sheet Glass Foundation for Materials Science and Engineering, and Aoba Foundation for The Promotion of Engineering).

PREFACE: Exploring surfaces and buried interfaces of functional materials by advanced x-ray and neutron techniques Exploring surfaces and buried interfaces of functional materials by advanced x-ray and neutron techniques

NASA Astrophysics Data System (ADS)

Sakurai, Kenji

2010-12-01

measurement. Advances in such technologies are bringing with them new opportunities in surface and buried interface science. In the not too distant future, we will publish a special issue or a book detailing such progress. Exploring surfaces and buried interfaces of functional materials by advanced x-ray and neutron techniques contents Lateral uniformity in chemical composition along a buried reaction front in polymers using off-specular reflectivity Kristopher A Lavery, Vivek M Prabhu, Sushil Satija and Wen-li Wu Orientation dependence of Pd growth on Au electrode surfaces M Takahasi, K Tamura, J Mizuki, T Kondo and K Uosaki A grazing incidence small-angle x-ray scattering analysis on capped Ge nanodots in layer structures Hiroshi Okuda, Masayuki Kato, Keiji Kuno, Shojiro Ochiai, Noritaka Usami, Kazuo Nakajima and Osami Sakata High resolution grazing-incidence in-plane x-ray diffraction for measuring the strain of a Si thin layer Kazuhiko Omote X-ray analysis of mesoporous silica thin films templated by Brij58 surfactant S Fall, M Kulij and A Gibaud Review of the applications of x-ray refraction and the x-ray waveguide phenomenon to estimation of film structures Kouichi Hayashi Epitaxial growth of largely mismatched crystals on H-terminated Si(111) surfaces Hidehito Asaoka Novel TiO2/ZnO multilayer mirrors at 'water-window' wavelengths fabricated by atomic layer epitaxy H Kumagai, Y Tanaka, M Murata, Y Masuda and T Shinagawa Depth-selective structural analysis of thin films using total-external-reflection x-ray diffraction Tomoaki Kawamura and Hiroo Omi Structures of Yb nanoparticle thin films grown by deposition in He and N2 gas atmospheres: AFM and x-ray reflectivity studies Martin Jerab and Kenji Sakurai Ga and As composition profiles in InP/GaInAs/InP heterostructures—x-ray CTR scattering and cross-sectional STM measurements Yoshikazu Takeda, Masao Tabuchi and Arao Nakamura Polarized neutron reflectivity study of a thermally treated MnIr/CoFe exchange bias system Naoki

EDITORIAL: Welcome to the 2013 volume Welcome to the 2013 volume

NASA Astrophysics Data System (ADS)

Garcia, Ephrahim

2013-01-01

and Technology, Kraków, Poland Professor N Takeda, University of Tokyo, Japan Professor D-H Wang, Chongqing University, China Professor Q Wang, University of Manitoba, Canada Professor N M Wereley, University of Maryland, College Park, USA Professor W J Wu, National Taiwan University, Taiwan We will continue to engage our community of researchers and encourage the development of new smart materials and structural systems and devices that rely on new and exciting, controllable electro-active elements.

Welcome to the 2014 volume of Smart Materials and Structures

NASA Astrophysics Data System (ADS)

Garcia, Ephrahim

2014-01-01

last year after many years in service as Associate Editors. Associate Editors in 2013: Professor G Akhras, Royal Military College of Canada, Ontario, Canada Professor C Boller, University of Saarland, Saarbrücken, Germany Fraunhofer-Institut für Zerstörungsfreie Prüfverfahren, Dresden, Germany Professor J Cagnol, École Centrale Paris, France Professor G Carman, University of California-Los Angeles, USA Professor S-B Choi, Inha University, Incheon, Korea Professor S H Choi, NASA Langley Research Center, Hampton, VA, USA Professor A Del Grosso, Università degli Studi di Genova, Italy Professor A Erturk, Georgia Institute of Technology, GA, USA Professor U Gabbert, Universität Magdeburg, Germany Professor A Güemes, Universidad Politecnica de Madrid, Spain Professor S Gopalakrishnan, Indian Institute of Science, Bangalore, India Professor J Kim, Inha University, Incheon, Korea Professor K J Kim, University of Nevada, Reno, USA Professor S J Kim, Seoul National University, Korea Professor D Lagoudas, Texas A&M University, College Station, USA Professor R Lammering, Helmut-Schmidt-Universität/Universität der Bundeswehr Hamburg, Hamburg, Germany Professor C K Lee, National Taiwan University, Taiwan Professor W Li, University of Wollongong, Australia Professor W H Liao, Chinese University of Hong Kong, China Professor Y Liu, Harbin Institute of Technology, China Professor C S Lynch, University of California-Los Angeles, USA Professor S Masri, University of Southern California, Los Angeles, USA Professor W M Ostachowicz, Polish Academy of Sciences, Gdansk, Poland Professor K Peters, North Carolina State University, Raleigh, USA Professor M Shahinpoor, University of Maine, Orono, USA Professor H Sodano, University of Florida, Gainsville, USA Professor G Song, University of Houston, TX, USA Professor W J Staszewski, AGH University of Science and Technology, Kraków, Poland Professor N Takeda, University of Tokyo, Japan Professor D-H Wang, Chongqing University, China

Special issue: diagnostics of atmospheric pressure microplasmas

NASA Astrophysics Data System (ADS)

Bruggeman, Peter; Czarnetzki, Uwe; Tachibana, Kunihide

2013-11-01

464004 [14] Sousa J S and Puech V 2013 J. Phys. D: Appl. Phys. 46 464005 [15] Takeda K et al 2013 J. Phys. D: Appl. Phys. 46 464006 [16] Vallade J and Massines F 2013 J. Phys. D: Appl. Phys. 46 464007 [17] Wang C and Wu W 2013 J. Phys. D: Appl. Phys. 46 464008 [18] Schröter S et al 2013 J. Phys. D: Appl. Phys. 46 464009 [19] Rusterholtz D L et al 2013 J. Phys. D: Appl. Phys. 46 464010 [20] Huang B-D et al 2013 J. Phys. D: Appl. Phys. 46 464011 [21] Pothiraja R et al 2013 J. Phys. D: Appl. Phys. 46 464012 [22] Marinov I et al 2013 J. Phys. D: Appl. Phys. 46 464013 [23] Akishev Y et al 2013 J. Phys. D: Appl. Phys. 46 464014 [24] Brandenburg R et al 2013 J. Phys. D: Appl. Phys. 46 464015 [25] Houlahan T J Jret al 2013 J. Phys. D: Appl. Phys. 46 464016 [26] Benedikt J et al 2013 J. Phys. D: Appl. Phys. 46 464017 [27] McKay K et al 2013 J. Phys. D: Appl. Phys. 46 464018 [28] Selected papers from the 2nd International Workshop on Microplasmas 2005 J. Phys. D: Appl. Phys. 38 1633-759 [29] Special issue: 3rd International Workshop on Microplasmas 2007 Control. Plasma Phys. 47 3-128 [30] Cluster issue on Microplasmas: 4th International Workshop on Microplasmas 2008 J. Phys. D: Appl. Phys. 41 1904001 [31] Microplasmas: scientific challenges and technological opportunities 2010 Eur. Phys. J. D 60 437-608 [32] Becker K H, Schoenbach K H and Eden J G 2006 J. Phys. D: Appl. Phys. 39 R55 [33] Iza F, Kim G J, Lee S M, Lee J K, Walsh J L, Zhang Y T and Kong M G 2008 Plasma Process. Polym. 5 322-44 [34] Tachibana K 2006 Trans. Electr. Electron. Eng. 1 145-55 [35] Samukawa S et al 2012 J. Phys. D: Appl. Phys. 45 253001

Realizing Controllable Quantum States

NASA Astrophysics Data System (ADS)

Takayanagi, Hideaki; Nitta, Junsaku

-T[stmbol] superconducting thin films with special arrangements of antidots / R. Wöerdenweber, P. Dymashevski and V. R. Misko. Quantum tunneling of relativistic fluxons / K. Konno et al. -- 6. Quantum information processing in solid states. Qubit decoherence by low-frequency noise / K. Rabenstein, V. A. Sverdlov and D. V. Averin. A critique of two-level approximation / K. Savran and T. Hakioǧlu. Josephson arrays as quantum channels / A. Romito, C. Bruder and R. Fazio. Fighting decoherence in a Josephson qubit circuit / E. Collin et al. Fast switching current detection at low critical currents / J. Walter, S. Corlevi and D. Haviland. Asymmetric flux bias for coupled qubits to observe entangled states / Y. Shimazu. Interaction of Josephson qubits with strong QED cavity modes: dynamical entanglement transfer and navigation / G. Falci et al. Controlling decoherence of transported quantum spin information in semiconductor spintronics / B. Nikolic and S. Souma. Decoherence due to telegraph and 1/f noise in Josephson qubits / E. Paladino et al. Detection of entanglement in NMR quantum information processing / R. Rahimi, K. Takeda and M. Kitagawa. Multiphoton absorption and SQUID switching current behaviors in superconducting flux-qubit experiments / H. Takayanagi et al. -- 7. Quantum information theory. Quantum query complexities / K. Iwama. A construction for non-stabilizer Clifford codes / M. Hagiwara and H. Imai. Quantum pushdown automata that can deterministically solve a certain problem / Y. Murakami et al. Trading classical for quantum computation using indirection / R. van Meter. Intractability of the initial arrangement of input data on qubits / Y. Kawano et al. Reversibility of modular squaring / N. Kunihiro, Y. Takahashi and Y. Kawano. Study of proximity effect at D-wave superconductors in quasiclassical methods / Y. Tanuma, Y. Tanaka and S. Kashiwaya -- 8. Spintronics in band electrons. Triplet superconductors: exploitable basis for scalable quantum computing / K. S. Wood et al. Spin

EDITORIAL: Focus on Dilute Magnetic Semiconductors FOCUS ON DILUTE MAGNETIC SEMICONDUCTORS

NASA Astrophysics Data System (ADS)

Chambers, Scott A.; Gallagher, Bryan

2008-05-01

Chisholm, J D Budai and D P Norton Role of charge carriers for ferromagnetism in cobalt-doped rutile TiO2 T Fukumura, H Toyosaki, K Ueno, M Nakano and M Kawasaki Ab-initio study of exchange constants and electronic structure in diluted magnetic group-IV semiconductors Silvia Picozzi and Marjana Ležaić Phase coherent transport in (Ga,Mn)As D Neumaier, K Wagner, U Wurstbauer, M Reinwald, W Wegscheider and D Weiss Hydrogen interstitials-mediated ferromagnetism in MnxGe1-x magnetic semiconductors Xin-Xin Yao, Shi-Shen Yan, Shu-Jun Hu, Xue-Ling Lin, Chong Han, Yan-Xue Chen, Guo-Lei Liu and Liang-Mo Mei Electronic structures of magnetic semiconductors FeCr2Se4 and Fe0.5Cu0.5Cr2Se4 B I Min, Seung Su Baik, H C Choi, S K Kwon and J-S Kang Investigation of pure and Co2+-doped ZnO quantum dot electronic structures using the density functional theory: choosing the right functional Ekaterina Badaeva, Yong Feng, Daniel R Gamelin and Xiaosong Li Magnetic properties of sol-gel-derived doped ZnO as a potential ferromagnetic semiconductor: a synchrotron-based study N R S Farley, K W Edmonds, A A Freeman, G van der Laan, C R Staddon, D H Gregory and B L Gallagher Local electronic structure of Cr in the II-VI diluted ferromagnetic semiconductor Zn1-xCrxTe M Kobayashi, Y Ishida, J I Hwang, G S Song, A Fujimori, C S Yang, L Lee, H-J Lin, D J Huang, C T Chen, Y Takeda, K Terai, S-I Fujimori, T Okane, Y Saitoh, H Yamagami, K Kobayashi, A Tanaka, H Saito and K Ando Lack of ferromagnetism in n-type cobalt-doped ZnO epitaxial thin films T C Kaspar, T Droubay, S M Heald, P Nachimuthu, C M Wang, V Shutthanandan, C A Johnson, D R Gamelin and S A Chambers XMCD studies on Co and Li doped ZnO magnetic semiconductors Thomas Tietze, Milan Gacic, Gisela Schütz, Gerhard Jakob, Sebastian Brück and Eberhard Goering Ferromagnetic semiconductors and the role of disorder B W Wessels An extensive comparison of anisotropies in MBE grown (Ga,Mn)As material C Gould, S Mark, K Pappert, R G Dengel, J Wenisch, R P

Mapping fire effects on ash and soil properties. Current knowledge and future perspectives.

NASA Astrophysics Data System (ADS)

Pereira, Paulo; Cerda, Artemi; Strielko, Irina

2014-05-01

scales and the future perspectives. References Finley, C.D., Glenn, N.F. (2010) Fire and vegetation type effects on soil hydrophobicity and infiltration in the sagebrussh-steppe: II. Hyperspectral analysis. Journal of Arid Environments, 74: 660-666. Fox, D.A., Maselli, F., Carrega, P. (2008) Using SPOT images and field sampling to map burn severity and vegetation factors affecting post-fire erosion risk. Catena, 75: 326-335. Gimeno-Garcia. E., Andreu., V., Rubio, J.L. (2004) Spatial patterns of soil temperatures during experiemntal fires. Geoderma, 118: 17-34. Hirobe, M., Tokushi, N., Wachrinrat, C., Takeda, H. (2003) Fire history influences on the spatial heterogeneity of soil nitrogen transformations in three adjacent stands in a dry tropical forest in Thailand. Plant and Soil, 249: 309-318. Kokaly, R.F., Rockwell, B.W., Haire, S.L., King, T.V.V. (2007) Characterization of post fire surface cover, soils, and burn severity at the Cerro Grande fire, New Mexico, using hyperspectral and multispectral remote sensing. Remote Sensing of the Environment, 106: 305-325. Lewis, S.A., Hudak, A.T., Ottmar, R.D., Robichaud, P.R., Lentile, L.B., Hood, S.M., Cronan, J.B., Morgan, P. (2012) Using hyperspectral imagery to estimate forest floor consumption from wildfire in boreal forests of Alaska. International Journal of Wildland Fire, 20: 255-271. Lewis, S.A., Robichaud, P.R., Frazier, B.E., Wu, J.Q., Laes, D.Y.M. (2008) Using hyperspectral imagery to predict post-wildfire soil repellency. Geomorphology, 98, 192-205. Miller, J.D., Yool, S. (2002) Mapping forest post-fire canopy consumption in several overstory types using multi-temporal Landsat TM and ETM data. Remote Sensing of the Environment, 82: 481-496. Outeiro, L., Aspero, F., Ubeda, X. (2008) Geostatistical methods to study spatial variability of soil cation after a prescribed fire and rainfall. Catena, 74: 310-320. Parsons, A., Robichaud, P.R., Lewis, S.A., Napper, C., Clark, J.T. (2010) Field guide for mapping post-fire soil

The First 24 Years of Reverse Monte Carlo Modelling, Budapest, Hungary, 20-22 September 2012

NASA Astrophysics Data System (ADS)

Keen, David A.; Pusztai, László

2013-11-01

structure of the plastic crystalline and liquid phases of CBr2Cl2: neutron diffraction and reverse Monte Carlo modellingSzilvia Pothoczki1, László Temleitner, Luis Carlos Pardo, Gabriel Julio Cuello, Muriel Rovira-Esteva and Josep Lluis Tamarit Insights into the determination of molecular structure from diffraction data using a Bayesian algorithmA Henao, M Rovira-Esteva, A Vispa, J Ll Tamarit, E Guardia and L C Pardo Nanostructure determination from the pair distribution function: a parametric study of the INVERT approachMatthew J Cliffe and Andrew L Goodwin Empirical potential structure refinement of semi-crystalline polymer systems: polytetrafluoroethylene and polychlorotrifluoroethyleneA K Soper, K Page and A Llobet spinvert: a program for refinement of paramagnetic diffuse scattering dataJoseph A M Paddison, J Ross Stewart and Andrew L Goodwin Inter-molecular correlations in liquid Se2Br2Hironori Shimakura, Yukinobu Kawakita, Koji Ohara, László Pusztai, Yuiko Wakisaka and Shin'ichi Takeda RMCgui: a new interface for the workflow associated with running Reverse Monte Carlo simulationsMartin T Dove and Gary Rigg

Particle processing technology

NASA Astrophysics Data System (ADS)

Sakka, Yoshio

2014-02-01

. Mater. 12 013001 [3] Sakka Y and Uchikoshi T 2010 KONA Powder Particle J. 28 74 (kona.or.jp/search/28_074.pdf) [4] Naguib M, Mashtalir O, Carle J, Presser V, Lu J, Hultman L, Gogotsi Y and Barsoum M W 2012 ACS Nano 6 1322 [5] Sakka Y and Suzuki T S 2005 J. Ceram. Soc. Japan 113 26 [6] Grasso S, Sakka Y and Maizza G 2009 Sci. Technol. Adv. Mater. 10 053001 [7] Nakao H, Tokonami S, Hamada T, Shiigi H, Nagaoka T, Iwate F and Takeda Y 2012 Nanoscale 4 6814 [8] Miyazawa K and Hotta K 2010 J. Cryst. Growth 312 2764 [9] Suehiro T, Xie R and Hirosaki N 2013 Indust. Eng. Chem. Res. 52 7453 [10] Zhu Q, Li J-G, Li X, Sun X and Sakka Y 2011 Sci. Technol. Adv. Mater. 12 055001 [11] Li J, Li J-G, Zhang Z, Wu X, Liu S, Li X, Sun X and Sakka Y 2012 Sci. Technol. Adv. Mater. 13 035007 [12] Kawamura F, Yusa H and Taniguchi T 2012 Appl. Phys. Lett. 100 251910 [13] Watanabe K and Taniguchi T 2011 Int. J. Appl. Ceram. Technol. 8 977 [14] Deng Z-Y, Ferreira J M F and Sakka Y 2008 J. Am. Ceram. Soc. 91 3825 [15] Uda M, Okuyama H, Suzuki T S and Sakka Y 2012 Sci. Technol. Adv. Mater. 13 025009 [16] Takeya H, Kato R, Wakahara T, Miyazawa K, Yamaguchi T, Ozaki T, Okazaki H and Takano Y 2013 Mater. Res. Bull. 48 343 [17] Wakahara T, D'Angelo P, Miyazawa K, Nemoto Y, Ito O, Tanigaki N, Bradley D D C and Anthopoulos T D 2012 J. Am. Chem. Soc. 134 7204 [18] Wiecinska P, Sakka Y, Suzuki T S, Uchikoshi T, Mizerski T and Szafran M 2013 J. Ceram. Soc. Japan 121 89 [19] Kawakita M, Uchikoshi T, Kawakita J and Sakka Y 2009 J. Am. Ceram. Soc. 92 984 [20] Hu C, Sakka Y, Grasso S, Nishimura T, Guo S and Tanaka H 2011 Scr. Mater. 64 765 [21] Hu C, Sakka Y, Nishimura T, Guo S, Grasso S and Tanaka H 2011 Sci. Technol. Adv. Mater. 12 044603 [22] Kakisawa H and Sumitomo T 2011 Sci. Technol. Adv. Mater. 12 064710 [23] Grasso S, Hu C F, Maizza G, Kim B N and Sakka Y 2011 J. Am. Ceram. Soc. 94 1405 [24] Grasso S, Kim B N, Hu C F, Maizza G and Sakka Y 2010 J. Am. Ceram. Soc. 93 2460 [25] Zhang H B, Kim B N, Morita K

PREFACE: Physics approaches to protein interactions and gene regulation Physics approaches to protein interactions and gene regulation

NASA Astrophysics Data System (ADS)

Nussinov, Ruth; Panchenko, Anna R.; Przytycka, Teresa

2011-06-01

the same time reversibility and diversity in their interactions. Interestingly, as is shown in the paper by Mészáros et al, even though some disordered regions and proteins have a tendency to fold upon binding, the structures of their complexes still reveal their inherent flexibility. Indeed, disordered proteins and their complexes have certain properties which distinguish them from proteins with well-defined structures. This is evident from the papers by Lobanov and Galzitskaya, and Mészáros et al, which show that such characteristic features of disordered proteins allow their successful computational prediction from the sequence alone. Computational prediction of protein disorder has been used in another study by Takeda et al where the authors investigate the role of disorder in the function of a specific actin capping protein. The paper presents normal mode analysis with the elastic network model to examine the mechanisms of intrinsic flexibility and its biological role in actin function. Analysis of the underlying mechanisms and key factors in protein recognition might be essential for the prediction of protein-protein interactions. The papers by Tuncbag et al and Hashimoto et al demonstrate how incorporating the physico-chemical properties of binding interfaces and their atomic details obtained from protein crystal structures might be used to increase the accuracy of predicted protein-protein interactions and provide data on relative orientations of interacting proteins and on the locations of binding sites. Moreover, analysis of protein-protein interactions might require further fine-tuning for different types of assemblies, like that shown in the example of homooligomers by Hashimoto et al. Studies of protein-protein interactions at the molecular level have contributed considerably to understanding the principles of large-scale organization of the cellular interactome. Using graph theory as a unifying language, many characteristic properties of bimolecular