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Heterozygous carriers of galactocerebrosidase mutations that cause Krabbe disease have impaired microglial function and defective repair of myelin damage

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Neural Regeneration Research 2018年第3期13卷 393-401页

作者： Nicole j.Scott-Hewitt christopher j.Folts Mark D.Noble Department of Biomedical Genetics University of Rochester School of Medicine and Dentistry

This review addresses two puzzling findings related to mutations in galactocerebrosidase （GALC） that cause Krabbe disease （KD）, a severe lysosomal storage disorder characterized by extensive myelin damage in children with mutations in both GALC alleles. First, heterozygous carriers of KD-causing mutations, which include the biological parents of children with KD, exhibit increased risk for developing other diseases. Second, variants in the GALC locus increase the risk of developing multiple sclerosis （MS）, another disease characterized by extensive myelin damage. What explains these correlations？ In studies on cuprizone-induced myelin damage in heterozygous （GALC＋/–） mice carrying one copy of a mutation that causes KD-like disease, the extent of damage was similar in GALC＋/– and wild-type （WT） mice. In contrast, GALC＋/- mice had striking defects in repair of cuprizone-induced damage. We further found unexpected microglial defects in myelin debris clearance and in the ability to up-regulate the Trem2 microglial protein critical for debris uptake. These defects were rescued by exposure to a lysosomal re-acidifying drug discovered in our studies on KD, and which provides multiple clinically relevant benefits in the twitcher （GALC＋/–） mouse model of KD. Thus, heterozygous GALC mutations cause effects on biological function that may help to understand the increased disease risk in heterozygous carriers of such mutations and to understand why GALC variations increase the risk of MS. Our findings indicate that while some genetic risk factors may contribute to complex diseases by increasing the risk of tissue damage, others may do so by compromising tissue repair.

关键词： vulnerability locus multiple sclerosis Krabbe disease galactocerebrosidase microglia myelin repair lysosomal storage disorders heterozygous carriers Trem2 demyelination

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Using Bayesian multitemporal classification to monitor tropical forest cover changes in Kalimantan,Indonesia

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International journal of Digital Earth 2022年第1期15卷 2061-2077页

作者： Inggit Lolita Sari christopher j.Weston Glenn j.Newnham Liubov Volkova Faculty of Science School of Ecosystem and Forest SciencesThe University of MelbourneCreswickAustralia Research Center for Remote Sensing National Research and Innovation Agency (BRIN)JakartaIndonesia CSIRO Land and Water Clayton SouthAustralia

Significant areas of native forest in Kalimantan,on the island of Borneo,have been cleared for the expansion of plantations of oil palm and *** this study multisource remote sensing was used to develop a time series of land cover maps that distinguish native forest from *** a study area in east Kalimantan,Landsat images were combined with either ALOS PALSAR or Sentinel-1 images to map four land cover classes(native forest,oil palm plantation,rubber plantation,non-forest).Bayesian multitemporal classification was applied to increase map accuracy and maps were validated using a confusion matrix;final map overall accuracy was>90%.Over 18 years from 2000 to 2018 nearly half the native forests in the study area were converted to either non-forest or plantations of either rubber or oil palm,with the highest losses between 2015 and *** upwards from 2008 large areas of degraded or cleared forests,mapped as non-forest,were converted to oil palm *** of native forests to plantation mainly occurred in lowland and wetland forest,while significant forest regrowth was detected in degraded *** maps will help Indonesia with strategies and policies for balancing economic growth and conservation.

关键词： Multitemporal classification Bayesian networks Landsat ALOS PALSAR sentinel-1 Indonesia

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Adaptively driven X-ray diffraction guided by machine learning for autonomous phase identification

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npj Computational Materials 2023年第1期9卷 2036-2043页

作者： Nathan j.Szymanski christopher j.Bartel Yan Zeng Mouhamad Diallo Haegyeom Kim Gerbrand Ceder Department of Materials Science&Engineering UC BerkeleyBerkeleyCA 94720USA Materials Sciences Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Machine learning(ML)has become a valuable tool to assist and improve materials characterization,enabling automated interpretation of experimental results with techniques such as X-ray diffraction(XRD)and electron *** ML models are fast once trained,there is a key opportunity to bring interpretation in-line with experiments and make on-the-fly decisions to achieve optimal measurement effectiveness,which creates broad opportunities for rapid learning and information extraction from ***,we demonstrate such a capability with the development of autonomous and adaptive *** coupling an ML algorithm with a physical diffractometer,this method integrates diffraction and analysis such that early experimental information is leveraged to steer measurements toward features that improve the confidence of a model trained to identify crystalline *** validate the effectiveness of an adaptive approach by showing that ML-driven XRD can accurately detect trace amounts of materials in multi-phase mixtures with short measurement *** improved speed of phase detection also enables in situ identification of short-lived intermediate phases formed during solid-state reactions using a standard in-house *** findings showcase the advantages of in-line ML for materials characterization and point to the possibility of more general approaches for adaptive experimentation.

关键词： phase diffraction autonomous

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Timescales of geological processes: Preface

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Geoscience Frontiers 2019年第1期10卷 1-3页

作者： Andrew Putnis christopher j.Spencer Tom Raimondo The Institute for Geoscience Research School of Earth and Planetary Science Curtin University School of Natural and Built Environments University of South Australia

*** One of the major challenges in Geoscience is to understand how the formation and evolution of the Earth System are governed by timescales-that is,how the various geological processes that continue to contribute to its present-day structure and composition operated in the deep *** traditional view of such processes refers to events that occur at immense spatial scales and over hundreds of millions of years,constrained in most cases by the ages of rocks determined using isotopic dating methods or the fossil ***,the modern view of geological processes has increasingly acknowledged that their durations can be significantly shorter than previously thought possible,or indeed detectable without recent analytical *** are a prime example of rapid,high energy and episodic events that have a profound effect on subsequent processes such as metamorphism,fluid transport,and ore formation e the evidence of which is written in microstructures,compositional zoning,and P-T *** studies have also revealed that the reaction rates between fluids and rocks can be extremely rapid relative to geological *** has led to the notion that geological processes are not necessarily continuous over millions of years but may,in fact,be sporadic,with long periods where essentially no reactions take place punctuated by periods of intense activity.

关键词： In Preface Timescales of geological processes

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InterStoreDB:A Generic Integration Resource for Genetic and Genomic Data

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journal of Integrative Plant Biology 2012年第5期54卷 345-355页

作者： christopher G. Love Ambrose E. Andongabo jun Wang Pierre W. C. Carion christopher j.Rawlings Graham j. King Ludwig Institute for Cancer Research Centre for Medical Research Royal Melbourne Hospital Royal Parade Parkville Victoria 3050 Australia Department of Biomathematics and Bioinformatics Rothamsted Research Harpenden Herts AL5 2JQ UK Queen Mary University of London Charterhouse Square London EC1M 6BQ UK Southern Cross Plant Science Southern Cross University P.O. Box 157 Lismore NSW 2480 Australia

Associating phenotypic traits and quantitative trait loci （QTL） to causative regions of the underlying genome is a key goal in agricultural research. InterStoreDB is a suite of integrated databases designed to assist in this process. The individual databases are species independent and generic in design, providing access to curated datasets relating to plant populations, phenotypic traits, genetic maps, marker loci and QTL, with links to functional gene annotation and genomic sequence data. Each component database provides access to associated metadata, including data provenance and parameters used in analyses, thus providing users with information to evaluate the relative worth of any associations identified. The databases include CropStoreDB, for management of population, genetic map, QTL and trait measurement data, SeqStoreDB for sequence-related data and AlignStoreDB, which stores sequence alignment information, and allows navigation between genetic and genomic datasets. Genetic maps are visualized and compared using the CMAP tool, and functional annotation from sequenced genomes is provided via an EnsEMBL-based genome browser. This framework facilitates navigation of the multiple biological domains involved in genetics and genomics research in a transparent manner within a single portal. We demonstrate the value of InterStoreDB as a tool for Brassica research. InterStoreDB is available from： http：//***

关键词： QTL bioinformatics databases.

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On Systems of Boundary Value Problems for Differential Inclusions

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Acta Mathematica Sinica,English Series 2007年第3期23卷 549-556页

作者： Lynn ERBE christopher C.TISDELL Patricia j.Y.WONG Department of Mathematics The University of Nebraska-LincolnLincolnNE 68588-0130USA School of Mathematics and Statistics The University of New South WalesSydney 2052Australia School of Electrical and Electronic Engineering Nanyang Technological University50 Nanyan9 AvenueSingapore 639798Singapore

Herein we consider the existence of solutions to second-order, two-point boundary value problems （BVPs） for systems of ordinary differential inclusions. Some new Bernstein-Nagumo conditions are presented that ensure a priori bounds on the derivative of solutions to the differential inclusion. These a priori bound results are then applied, in conjunction with appropriate topological methods, to prove some new existence theorems for solutions to systems of BVPs for differential inclusions. The new conditions allow of the treatment of systems of BVPs without growth restrictions.

关键词： boundary value problem, systems of differential inclusions, existence of solutions a priori bounds Bernstein-Nagumo condition

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Secular change in earth processes： Preface

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Geoscience Frontiers 2018年第4期9卷 965-966页

作者： Richard M.Palin christopher j.Spencer Department of Geology and Geological Engineering Colorado School of Mines Golden CO 80401 USA The Institute of Geoscience Research (TIGER) School of Earth and Planetary Sciences Curtin University WA 6102 Australia

*** Uniformitarianism is a traditional approach used in many areas of geoscience that assumes the geologic processes observed today operated similarly throughout all of Earth history（Hutton,1788;Windley,1993）,with such an ideology commonly encapsulated by the maxim＂the present is the key to the past＂.This concept is closely associated with the philosophical principle of Occam’s razor.

关键词： Secular change in earth processes Preface

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Diagnosis of autoimmune gastritis by high resolution magnification endoscopy

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World journal of Gastroenterology 2006年第28期12卷 4586-4587页

作者： George K Anagnostopoulos Krish Ragunath Anthony Shonde christopher j Hawkey Wolfson Digestive Diseases Centre University HospitalNottinghamUnited Kingdom

Endoscopic visualisation of gastric atrophy is usually not feasible with *** endoscopy. Magnifying endoscopy is helpful to analyze the subepithelial microvascular architecture as well as the mucosal surface microstructure without tissue biopsy. Using this technique we were able to describe the normal gastric microvasculature pattern and we also identified characteristic patterns in two cases of autoimmune atrophic gastritis.

关键词： Magnification endoscopy Autoimmune gastritis Collecting venules Subepithelial capillary network

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Thulium：YAG VapoEnucleation of the prostate in large glands： a prospective comparison using 70- and 120-W 2-μm lasers

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Asian journal of Andrology 2012年第2期14卷 325-329页

作者： christopher Netsch Thorsten Bach Thomas RW Herrmann Andreas j Gross Department of Urology Asklepios Hospital BarmbekHamburg 22291Germany Department of Urology MHH Medical School of HannoverHannover 30625Germany

This study compared the efficacy of 70- and 120-w 2-μm thulium：YAG VapoEnucleation of the prostate （ThuVEP） for patients with benign prostatic obstruction （BPO）. A prospective analysis of 84 patients with symptomatic BPO and prostatic enlargement （t〉 60 ml） who underwent either 70-w （n=44） or 120-w ThuVEP （n=40） non-randomly was carried out. Patient demographics and perioperative and 12-month follow-up data were analysed. The mean prostate volume was 79.90---27.49 ml in patients who had received 70-w ThuVEP, which was less than in those who had received 120-w ThuVEP （88.53＋-25.10; P=0.033）. The mean enucleation （resected weight/laser time, 2.16±1.21 g min-1 vs. 1.23±0.60 g min-1; P=-0.013）, operation efficiency （resected weight/total operation time, 0.76±0.35 g min-1 vs. 0.42＋-0.27 g min-1; P=-0.000） and percentage of resected tissue （66.93%±22.79% vs. 45.41%±23.33%; P=-0.000） were higher with 120-w treatment compared to 70-w ThuVEP. One patient （1.2% of total patients）（in the 120-w group） required a blood transfusion postoperatively. Sixty-one patients （73%） were available for review at the 12-month follow-up time point. The quality of life （QoL）, International Prostate Symptom Score （IPSS）, maximum urinary flow rate （Qmax）, postvoiding residual urine （PVR） and prostate volume improved significantly after treatment （P≤ 0.035） and were not significantly different between those treated with the different devices （70- and 120-w）. The median prostate volume reduction was 81.70% and 82.19% with 70- and 120-w ThuVEP, respectively. The incidence of complications was low and did not differ between groups treated with the different devices. Two patients （2.4%）（one per group） had a bladder neck contracture at the follow-up. ThuVEP is a safe and efficacious procedure for the treatment of symptomatic BPO. The incidence of complications was low with both devices. The 120-w thulium：YAG device enhances the effectiveness of Th,VEP with reeard to the oercentaee of resected tissue

关键词： benign prostatic obstruction laser prostate Revolix Tm:YAG ThuVEP VapoEnucleation

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High–Speed electron beam curing of thick electrode for high energy density Li-ion batteries

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Green Energy & Environment 2019年第4期4卷 375-381页

作者： Zhijia Du christopher j.janke jianlin Li David L.Wood III Energy and Transportation Science Division Oak Ridge National LaboratoryOak RidgeTN 37831USA Chemical Sciences Division Oak Ridge National LaboratoryOak RidgeTN 37831USA

Electron beam curing is demonstrated as a promising method for high speed,low cost and environmentally friendly battery electrode *** work reports transfer of this process to pilot scale equipment and evaluation of electrochemical performance in prototype 1.5 Ah pouch *** LiNi0.5Mn0.3Co0.2O2(NMC532)composite electrodes with an areal loading of 25 mg cm^-2(~4 mAh cm^-2)are successfully cured at a line speed of 500 feet per minute at 275 *** to the NMC532 cathode processed via a conventional coating method,the electron beam cured electrodes show higher capacity fade in the first 100 cycles,but similar fade rate *** improvement strategies are proposed and *** work demonstrates that electron beam curing is a promising method for manufacturing thick battery electrodes at high speeds and low capital/operation cost.

关键词： Electron beam curing Li-ion batteries Thick electrode

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