Passive SOBP generation from a static proton pencil beam using 3D-printed range modulators for FLASH experiments

The University Proton Therapy facility in Dresden (UPTD), Germany, is equipped with an experimental room with a beamline providing a static pencil beam. High proton beam currents can be achieved at this beamline which makes it suitable for FLASH experiments. However, the established experimental setup uses only the entrance channel of the proton Bragg curve. In this work, a set of 3D-printed range modulators designed to generate spread out Bragg peaks (SOBPs) for radiobiological experiments at ultra-high dose rate at this beamline is described. A new method to optimize range modulators specifically for the case of a static pencil beam based on the central depth dose profile is introduced. Modulators for two different irradiation setups were produced and characterized experimentally by measurements of lateral and depth dose distributions using different detectors. In addition, Monte Carlo simulations were performed to assess profiles of the dose averaged linear energy transfer (LETD) in water. These newly produced range modulators will allow future proton FLASH experiments in the SOBP at UPTD with two different experimental setups

「ディアコニーと近代における内国伝道の歴史」第6章

本稿はドイツのキリスト教社会福祉「ディアコニー」の歴史について論述された「ディアコニーと近代における内国伝道の歴史」全10章のなかの第6章、ビスマルク時代から近代の部分である。町はずれの農園の納屋に追いやられるようにして暮らしていた数人のてんかん病の子どもたちの面倒を見ることからはじまったボーデルシュヴインク牧師の事業は、ベーテルの町を福祉の町に変え、現在約2500人の利用者と約2500人の看護士、またその家族や関連のスーパーマーケットや郵便局、大学をもつ町全体が福祉の町となった「ベーテル」について述べられている。それがキリスト教社会党を率いた親友シュテツカーと共にドイツの国を福祉国家へ築いていく過程が力を込めて記述されている。「ベーテル」については2005年本学で講演をされた北海道「ベテルの家」施設ほか、病院、教会の名前で日本でもよく知られている

Spectral and spatial shaping of laser-driven proton beams using a pulsed high-field magnet beamline

Intense laser-driven proton pulses, inherently broadband and highly divergent, pose a challenge to established beamline concepts on the path to application-adapted irradiation field formation, particularly for 3D. Here we experimentally show the successful implementation of a highly efficient (50% transmission) and tuneable dual pulsed solenoid setup to generate a homogeneous (8.5% uniformity laterally and in depth) volumetric dose distribution (cylindrical volume of 5 mm diameter and depth) at a single pulse dose of 0.7 Gy via multi-energy slice selection from the broad input spectrum. The experiments have been conducted at the Petawatt beam of the Dresden Laser Acceleration Source Draco and were aided by a predictive simulation model verified by proton transport studies. With the characterised beamline we investigated manipulation and matching of lateral and depth dose profiles to various desired applications and targets. Using a specifically adapted dose profile, we successfully performed first proof-of-concept laser-driven proton irradiation studies of volumetric in-vivo normal tissue (zebrafish embryos) and in-vitro tumour tissue (SAS spheroids) samples.Comment: Submitted to Scientific Report

Structural analysis of the Ss sialoglycoprotein specific for Henshaw blood group from human erythrocyte membranes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66122/1/j.1432-1033.1984.tb08155.x.pd

Alzheimer's Disease Amyloid-β Links Lens and Brain Pathology in Down Syndrome

Down syndrome (DS, trisomy 21) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21) encoding the Alzheimer's disease (AD) amyloid precursor protein (APP). Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-β peptides (Aβ), early-onset AD neuropathology, and age-dependent cognitive sequelae. The DS phenotype complex also includes distinctive early-onset cerulean cataracts of unknown etiology. Previously, we reported increased Aβ accumulation, co-localizing amyloid pathology, and disease-linked supranuclear cataracts in the ocular lenses of subjects with AD. Here, we investigate the hypothesis that related AD-linked Aβ pathology underlies the distinctive lens phenotype associated with DS. Ophthalmological examinations of DS subjects were correlated with phenotypic, histochemical, and biochemical analyses of lenses obtained from DS, AD, and normal control subjects. Evaluation of DS lenses revealed a characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear Aβ accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic Aβ aggregates (∼5 to 50 nm) identical to the lens pathology identified in AD. Peptide sequencing, immunoblot analysis, and ELISA confirmed the identity and increased accumulation of Aβ in DS lenses. Incubation of synthetic Aβ with human lens protein promoted protein aggregation, amyloid formation, and light scattering that recapitulated the molecular pathology and clinical features observed in DS lenses. These results establish the genetic etiology of the distinctive lens phenotype in DS and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder. Moreover, these findings confirm increased Aβ accumulation as a key pathogenic determinant linking lens and brain pathology in both DS and AD

Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption

<p>Abstract</p> <p>Background</p> <p>A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation.</p> <p>Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of <it>Trans</it>-fatty acids (TFA) has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG) during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG.</p> <p>Methods</p> <p>We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice.</p> <p>Results</p> <p>Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P < 0.05). Hearts from MSG-fed females weighed less than males (P < 0.05). 2-factor ANOVA indicated that the TFA diet induced over twice as many cardiac differentially expressed genes (DEGs) in males compared to females (P < 0.001); and 4 times as many male DEGs were downregulated including <it>Gata4</it>, <it>Mef2d </it>and <it>Srebf2</it>. Enrichment of functional Gene Ontology (GO) categories were related to transcription, phosphorylation and anatomic structure (P < 0.01). A number of genes were upregulated in males and downregulated in females, including pro-apoptotic histone deacetylase-2 (HDAC2). Sexual dimorphism was also observed in cardiac transcription from MSG-fed animals, with both sexes upregulating approximately 100 DEGs exhibiting sex-specific differences in GO categories. A comparison of cardiac gene expression between all diet combinations together identified a subset of 111 DEGs significant only in males, 64 DEGs significant in females only, and 74 transcripts identified as differentially expressed in response to dietary manipulation in both sexes.</p> <p>Conclusion</p> <p>Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to controls, which was reflected by significant differences in the physiological profile within the 4 diet groups. Identification of sexual dimorphism in cardiac transcription may provide the basis for sex-specific medicine in the future.</p

Coupled, Physics-Based Modeling Reveals Earthquake Displacements are Critical to the 2018 Palu, Sulawesi Tsunami

The September 2018, Mw 7.5 Sulawesi earthquake occurring on the Palu-Koro strike-slip fault system was followed by an unexpected localized tsunami. We show that direct earthquake-induced uplift and subsidence could have sourced the observed tsunami within Palu Bay. To this end, we use a physics-based, coupled earthquake–tsunami modeling framework tightly constrained by observations. The model combines rupture dynamics, seismic wave propagation, tsunami propagation and inundation. The earthquake scenario, featuring sustained supershear rupture propagation, matches key observed earthquake characteristics, including the moment magnitude, rupture duration, fault plane solution, teleseismic waveforms and inferred horizontal ground displacements. The remote stress regime reflecting regional transtension applied in the model produces a combination of up to 6 m left-lateral slip and up to 2 m normal slip on the straight fault segment dipping 65∘ East beneath Palu Bay. The time-dependent, 3D seafloor displacements are translated into bathymetry perturbations with a mean vertical offset of 1.5 m across the submarine fault segment. This sources a tsunami with wave amplitudes and periods that match those measured at the Pantoloan wave gauge and inundation that reproduces observations from field surveys. We conclude that a source related to earthquake displacements is probable and that landsliding may not have been the primary source of the tsunami. These results have important implications for submarine strike-slip fault systems worldwide. Physics-based modeling offers rapid response specifically in tectonic settings that are currently underrepresented in operational tsunami hazard assessment

Aqueous Dissolution of Alzheimer's Disease Ab Amyloid Deposits by Biometal Depletion

Zn(II) and Cu(II) precipitate Abeta in vitro into insoluble aggregates that are dissolved by metal chelators. We now report evidence that these biometals also mediate the deposition of Abeta amyloid in Alzheimer's disease, since the solubilization of Abeta from post-mortem brain tissue was significantly increased by the presence of chelators, EGTA, N,N,N',N'-tetrakis(2-pyridyl-methyl) ethylene diamine, and bathocuproine. Efficient extraction of Abeta also required Mg(II) and Ca(II). The chelators were more effective in extracting Abeta from Alzheimer's disease brain tissue than age-matched controls, suggesting that metal ions differentiate the chemical architecture of amyloid in Alzheimer's disease. Agents that specifically chelate copper and zinc ions but preserve Mg(II) and Ca(II) may be of therapeutic value in Alzheimer's disease