148 research outputs found

    Acanthamoeba containing endosymbiotic chlamydia isolated from hospital environments and its potential role in inflammatory exacerbation

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    Background: Environmental chlamydiae belonging to the Parachlamydiaceae are obligate intracellular bacteria that infect Acanthamoeba, a free-living amoeba, and are a risk for hospital-acquired pneumonia. However, whether amoebae harboring environmental chlamydiae actually survive in hospital environments is unknown. We therefore isolated living amoebae with symbiotic chlamydiae from hospital environments. Results: One hundred smear samples were collected from Hokkaido University Hospital, Sapporo, Japan; 50 in winter (February to March, 2012) and 50 in summer (August, 2012), and used for the study. Acanthamoebae were isolated from the smear samples, and endosymbiotic chlamydial traits were assessed by infectivity, cytokine induction, and draft genomic analysis. From these, 23 amoebae were enriched on agar plates spread with heatkilled Escherichia coli. Amoeba prevalence was greater in the summer-collected samples (15/30, 50%) than those of the winter season (8/30, 26.7%), possibly indicating a seasonal variation (p = 0.096). Morphological assessment of cysts revealed 21 amoebae (21/23, 91%) to be Acanthamoeba, and cultures in PYG medium were established for 11 of these amoebae. Three amoebae contained environmental chlamydiae; however, only one amoeba (Acanthamoeba T4) with an environmental chlamydia (Protochlamydia W-9) was shown the infectious ability to Acanthamoeba C3 (reference amoebae). While Protochlamydia W-9 could infect C3 amoeba, it failed to replicate in immortal human epithelial, although exposure of HEp-2 cells to living bacteria induced the proinflammatory cytokine, IL-8. Comparative genome analysis with KEGG revealed similar genomic features compared with other Protochlamydia genomes (UWE25 and R18), except for a lack of genes encoding the type IV secretion system. Interestingly, resistance genes associated with several antibiotics and toxic compounds were dentified. Conclusion: These findings are the first demonstration of the distribution in a hospital of a living Acanthamoeba carrying an endosymbiotic chlamydial pathogen

    Detection of significant antiviral drug effects on COVID-19 with reasonable sample sizes in randomized controlled trials : a modeling study

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    Background Development of an effective antiviral drug for Coronavirus Disease 2019 (COVID-19) is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence from clinical studies is limited. The lack of evidence from clinical trials may stem in part from the imperfect design of the trials. We investigated how clinical trials for antivirals need to be designed, especially focusing on the sample size in randomized controlled trials. Methods and findings A modeling study was conducted to help understand the reasons behind inconsistent clinical trial findings and to design better clinical trials. We first analyzed longitudinal viral load data for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) without antiviral treatment by use of a within-host virus dynamics model. The fitted viral load was categorized into 3 different groups by a clustering approach. Comparison of the estimated parameters showed that the 3 distinct groups were characterized by different virus decay rates (p-value < 0.001). The mean decay rates were 1.17 d−1 (95% CI: 1.06 to 1.27 d−1), 0.777 d−1 (0.716 to 0.838 d−1), and 0.450 d−1 (0.378 to 0.522 d−1) for the 3 groups, respectively. Such heterogeneity in virus dynamics could be a confounding variable if it is associated with treatment allocation in compassionate use programs (i.e., observational studies). Subsequently, we mimicked randomized controlled trials of antivirals by simulation. An antiviral effect causing a 95% to 99% reduction in viral replication was added to the model. To be realistic, we assumed that randomization and treatment are initiated with some time lag after symptom onset. Using the duration of virus shedding as an outcome, the sample size to detect a statistically significant mean difference between the treatment and placebo groups (1:1 allocation) was 13,603 and 11,670 (when the antiviral effect was 95% and 99%, respectively) per group if all patients are enrolled regardless of timing of randomization. The sample size was reduced to 584 and 458 (when the antiviral effect was 95% and 99%, respectively) if only patients who are treated within 1 day of symptom onset are enrolled. We confirmed the sample size was similarly reduced when using cumulative viral load in log scale as an outcome. We used a conventional virus dynamics model, which may not fully reflect the detailed mechanisms of viral dynamics of SARS-CoV-2. The model needs to be calibrated in terms of both parameter settings and model structure, which would yield more reliable sample size calculation. Conclusions In this study, we found that estimated association in observational studies can be biased due to large heterogeneity in viral dynamics among infected individuals, and statistically significant effect in randomized controlled trials may be difficult to be detected due to small sample size. The sample size can be dramatically reduced by recruiting patients immediately after developing symptoms. We believe this is the first study investigated the study design of clinical trials for antiviral treatment using the viral dynamics model

    Lattice Design Of Jhf Synchrotrons

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    Several kinds of lattice structures have been designed and examined for the JHF synchrotorons. The high(or imaginary) fl t lattice has been used as the 50 GeV main ring to avoid beam loss at the transition crossing. We have studied the feasibility to apply this scheme to the 3 GeV booster as a flexible momentum compaction lattice. These rings have wide tunablilities and flexibilities of the linear optics. The possibility of increasing the extraction energy of the booster to 6 GeV has been investigated. 1 INTRODUCTION The Japan Hadron Facility(JHF) consists of the 50 GeV main ring, the 3 GeV booster and the 200 MeV linac. Because the beam intensity of the main ring is extremely high (2\Theta10 14 ppp), a low beam loss is required. In order to avoid beam loss at the transition crossing, we have employed the imaginary fl t lattice which does not have a transition energy. The 3 GeV booster is a rapid cycle synchrotron of which repetition rate is 25 Hz. It will be constructed in the ex..

    NUMERICAL AND EXPERIMENTAL STUDY OF COOLING-STACKING INJECTION IN HIMAC SYNCHROTRON

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    The cooling-stacking injection at the HIMAC synchrotron was used to increase the intensity of Ar18+ ion beam. The beam stacking was realized in a horizontal freephase-space, which was created by the HIMAC electron cooler. The stack intensity of (1.5-2.5) / 109 ppp was accumulated at an injection intensity of (0.3-1.0)/109.The lifetime of stack ions is determined by vacuum pressure. The new injected ions were slowly lost at multiple scattering on residual gas atoms at diffusion heating in the vertical direction caused by the acceptance of 30 pi mmmrad and a reduction of cooling force at large betatron amplitudes. The results of numerical simulations and experimental study of cooling-stacking injection on the HIMAC synchrotron are presented

    A mathematical model for dynamics of soluble form of DNAM-1 as a biomarker for graft-versus-host disease.

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    DNAM-1 (CD226) is an activating immunoreceptor expressed on T cells and NK cells and involved in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously reported that a soluble form of DNAM-1 (sDNAM-1) is generated by shedding from activated T cells. Moreover, higher serum levels of sDNAM-1 in patients before allo-HSCT is a predictive biomarker for the development of aGVHD based on the retrospective univariate and multivariate analyses in allo-HSCT patients. However, it remains unclear how the serum levels of sDNAM-1 are regulated after allo-HSCT and whether they are associated with the development of aGVHD. Here, we constructed a mathematical model to assess the dynamics of sDNAM-1 after allo-HSCT by assuming that there are three types of sDNAM-1 (the first and the second were from alloreactive and non-alloreactive donor lymphocytes, respectively, and the third from recipient lymphocytes). Our mathematical model fitted well to the data set of sDNAM-1 in patients (n = 67) who had undergone allo-HSCT and suggest that the high proportion of the first type of sDNAM-1 to the total of the first and second types is associated with high risk of the development of severe aGVHD. Thus, sDNAM-1 after allo-HSCT can be a biomarker for the development of aGVHD

    超䜎速重むオン甚分割同軞型の研究

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     近幎䞍安定原子栞のビヌムを䜿った研究が急速に発展し぀぀ある䞍安定原子栞のビヌムは䞭性子過剰栞超重栞など極限領域の栞物理や宇宙に斌ける元玠合成過皋の研究など他の手段では実珟できない栞物理倩䜓栞物理を開拓できる他物性物理攟射化孊原子物理など様々な分野でも新しい研究領域を広げるこずが出来るこれに䌎いこれらの短寿呜栞を加速するための加速噚ぞの関心が急速に高たっおきたしかし高゚ネルギヌ粒子による栞砎砕反応で生成されむオン化された短寿呜栞は倚くの堎合荷電数察質量数比εが数十分の䞀であり䞭には1/100以䞋ずいう非垞に小さいものもあるこのような堎合むオン源から埗られるビヌム゚ネルギヌは栞子圓り1keV皋床ずなりこの時の速床は光速の0.1%皋床ずいう非垞に䜎い倀ずなるこのような超䜎速重むオンを加速する堎合には加速噚の初段に特別の前段加速噚が必芁になる高呚波四重極電堎を甚いおビヌムの加速ず集束を同時に行えるRFQ線圢加速噚(以䞋RFQず略す)はこのような目的に最適であるず考えられおいる わが囜においおは倧型ハドロン蚈画においお䞍安定栞ビヌムファシリティの建蚭が構想されおおりこれに䌎い入射゚ネルギヌが1keV/uεが1/60以䞊の超䜎速重むオンを加速できるRFQの開発研究が筆者らによっお行われおいる筆者の研究目的は超䜎速重むオンの加速を行えるRFQの実甚化を図るこずである 筆者らはε=1/30の超䜎速重むオンを実際に加速できる実機モデルの研究開発を行っおいるこの実機モデルは内盎埄90cm長さ70cmのモゞュヌル空胎を䞉台぀なぎ合わせた党長2.1mのマルチモゞュヌル型共振空胎であり運転呚波数は25.5MHzεが1/30以䞊のィオンを1keV/uから45.4keV/uたで加速出来るものである 本研究の成果は高呚波テスト及び加速テストの結果から倧幅な蚭蚈の倉曎をせずにこのSCRFQの実甚化が可胜であるずいう結論を埗た事である以䞋に本研究の成果に぀いお述べる  1.分割同軞型構造を採甚するこずにより共振呚波数のわりに空胎埄を   小さくする事が出来た  2.四電極にはノェむンを採甚しおいるノェむンずは軞方向に呚期的に   波圢を぀けた板状電極でありこれを甚いるずビヌムアパヌチャヌ内   の電堎分垃をKapchinskij-Teplyakovの電䜍関数の䜎次の項だけで正   確に衚すこずが出来るSCRFQにノェむンを採甚するのは筆者らが   初めおである  3.この加速噚は実機の実甚化を実珟するために䜜られたモデルである   ので電極及び加速空胎の蚭蚈手法加速噚の高呚波詊隓及び加速詊   隓の結果から実機の評䟡が行えるように蚭蚈補䜜を行なったたた   ステムフランゞを考案するこずによっお内導䜓ず倖導䜓で独立に加   工組立が行えか぀粟床よい電極の組み蟌みが行える構造(マルチモ   ゞュヌル構造)の開発に成功したこの構造の採甚により内導䜓の蚭   定粟床を倧幅に向䞊させるこずが出来た  4.察向電極には結合リングが取り付けおある結合リングの圹割は察向   電極を等電䜍に保ち電堎の二重極成分の混入を防ぐず共にノェむン   の䜍眮粟床を䞊げる事である   結合リングを取り付けお空胎ぞの入力電力ず共振呚波数の倉化量   ずの関係を調べたずころ入力電力85kW(デュヌティヌ10%)で共   振呚波数の䞊昇は130kHzであった䞀方結合リングを分割しお同   様の枬定を行ったずころ入力電力80kW(デュヌティヌ20%)で呚波   数の䞊昇は53kHzであった曎に結合リングの有無による加速性   胜の倉化を出射゚ミッタンスず透過効率の枬定結果から調べたが䞡   者の間に倉化は芋られなかったこのこずからSCRFQでは結合リン   グは必芁ない事が分かった  5.冷华系の蚭蚈は+䞀本の冷华管を甚いお行なった管の半埄や流量は   電極の熱による歪みで電堎分垃が1%以䞊ずれない事を条件ずしお決   定した高呚波結合噚はルヌプカップラヌを甚いる高電力に察応す   るためルヌプは銅パむプで䜜られおおり氎冷华を行う   結合リングが取り付けおある状態での冷华氎の枩床䞊昇は入力電   力85kW(デュヌティヌ10%)で平均0.5゜Cであった䞀方結合リ   ングを分割しお同様の枬定を行ったずころ入力電力80kW(デュヌ   ティヌ20%)で平均0.9゜Cであったこのこずから結合リングを倖せ   ばデュヌティヌ20%䜍たでであれば空胎をフルパワヌで運転しおも   珟圚の冷华系でも空胎の冷华胜力は十分であるこずが分かった  6.共振呚波数の調敎はステムずフランゞによっお囲たれた空間(窓)に生   じるむンダクタンス(ステムむンダクタンス)を調敎する事によっお   行う空胎の呚波数が25.45MHzずなる様にむンダクタンス(窓の面   積)を調敎し最終的にブロックチュヌナヌで呚波数を25.5MHzに   合わせたこの時の無負荷のQ倀は蚈算倀の玄80%であった  7.ノェむン間及びビヌム軞近傍の電堎分垃の枬定は誘電䜓を甚いた摂   動法によっお行なわれた枬定の結果ノェむン間の電堎の四回察称   性からのずれは目暙倀である±1%より良くノェむン党域にわたっお   ±0.67%以内であったたたビヌム軞近傍でのビヌム軞に沿った電堎   匷床分垃はKapchinskii-Teplyakovの電䜍関数に蚭蚈時のセルパラ   メヌタを代入した蚈算によっお定性的に説明できた  8.高電力詊隓ではたずモニタヌルヌプの范正を行い共振抵抗の枬定   Q倀の枬定を行いこれらの数倀を䜿っお求めたノェむン間電圧ず入力   電力の関係がほが䞀臎しおいるこずを確認したたた高電力運転時   の゚ヌゞング時間ず攟電の頻床の関係に぀いお調べた  9.ビヌム茞送系を入射偎ず出射偎に぀いおそれぞれ蚭蚈したたたビヌ   ムの茞送に必芁な入射偎のアむンツェルレンズむオンセパレヌタ   静電ステアラヌ出射偎のQダブレットの蚭蚈補䜜をしたたたビヌ   ムの性質及び加速性胜を評䟡するためのビヌムモニタヌずしおファラ   デヌカップ゚ミッタンスモニタヌビヌムスリットの蚭蚈補䜜をした  10.εが1/28のN+ 2を1keV/uから蚭蚈倀(45.4keV/u)たで加速する事に   成功した1keV/u以䞋の超䜎速重むオンの加速に成功した䟋は䞖   界的に芋おもほずんどない  11.加速テストでは入射及び出射゚ミッタンスビヌムの透過効率゚ネ   ルギヌスペクトルの枬定をN+ 2(ε=1/28)N+(ε=1/14)Ne+(ε=1/20)   に぀いおそれぞれ行なった  12.ノェむンの加工を二次元で行った二次元加工したノェむンの圱響は   透過効率に顕著に珟れ80%以䞊の透過効率を埗るにはノェむン間電   圧を蚭蚈倀より30%䞊げなければならなかった二次元加工したノェ   むンの圱響を考慮した蚈算コヌド(Modified PARMTEQ)で行った透   過効率の蚈算倀は蚈算コヌドPARMTEQによる蚈算倀よりも枬定倀   に近い事が分かった二次元で加工されたノェむンを䜿った加速噚の   加速性胜を実隓的に評䟡したのは筆者らが初めおである
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