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Role of ion channels in gastrointestinal cancer

World journal of Gastroenterology 2019年第38期25卷 5732-5772页

作者： kyle j anderson Robert T Cormier Patricia M Scott Department of Biomedical Sciences University of Minnesota Medical School

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer *** functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of *** this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and *** members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon ***-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle *** VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC *** have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer ***2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal *** distinct types of K+channels are found dysregulated in the GI *** are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CR

关键词： Ion channels Gastrointestinal cancer Colorectal cancer Gastric cancer Pancreatic cancer Esophageal cancer Hepatocellular carcinoma Prognostic biomarker Novel therapies Clinical targets

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Disaster Awareness and Preparedness Among Older Adults in Canada Regarding Floods, Wildfires, and Earthquakes

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International journal of Disaster Risk Science 2024年第2期15卷 198-212页

作者： Evalyna Bogdan Rachel Krueger julie Wright kyle Woods Shaieree Cottar School of Administrative Studies Disaster and Emergency Management ProgramYork UniversityTorontoOntario M3J 1P3Canada Department of Geography and Environmental Management University of WaterlooWaterlooOntario N2L 3G1Canada Partners for Action Faculty of EnvironmentUniversity of WaterlooWaterlooOntario N2L 3G1Canada

Older adults are significantly impacted by natural hazards and disasters that are exacerbated by climate change. Understanding their awareness and preparedness is essential for enhancing disaster resilience. This study investigated the attitudes, actions, and recommendations of older adults regarding natural hazards that pose risks in their geographic area—specifically floods, wildfires, and/or earthquakes in Canada. Methods for this study included survey and focus groups with older adults(n = 161 and n = 10, respectively) and other high-risk groups from across Canada, that are vulnerable to these natural hazards. The main findings from this study are that current awareness and preparedness among older adults is low, though stronger perceptions of risks are associated with risks specific to geographic locations where respondents live. Several barriers, such as hazard vulnerability misperceptions, cost-related reasons, and lack of hazard awareness have resulted in low awareness and preparedness among these populations. The two main recommendations arising from this research are:(1) improve awareness and preparedness with tailor-made emergency preparedness materials for older adults;and(2) adopt community-based approaches to disaster preparedness through existing community groups to strengthen social connections with a focus on locally specific hazards. The findings from this research can be applied to other hazards, including heatwaves and pandemics.

关键词： Canada Community-based disaster risk management Disaster awareness and preparedness Disaster resilience Natural hazards Older adults

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Promoting Older Adults' Engagement in Disaster Settings: An Introduction to the Special Issue

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International journal of Disaster Risk Science 2024年第2期15卷 181-185页

作者： Haorui Wu Christine AWalsh julie LDrolet kyle Breen Faculty of Health School of Social WorkDalhousie UniversityHalifaxNS B3H 4R2Canada Faculty of Social Work University of CalgaryCalgaryAB T2N 1N4Canada Faculty of Social Work Central&Northern Alberta RegionUniversity of CalgaryEdmontonAB T5J 4P6Canada

1 Introduction Globally, surging extreme events and the escalating aging population present ongoing and severe challenges to the full spectrum of international community development(for example, social, health, and ec... 详细信息

关键词： extreme challenges economic

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Opposite latitudinal gradients for species richness and phylogenetic diversity of endemic snakes in the Atlantic Forest

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Current Zoology 2024年第4期70卷 522-530页

作者： joséThales da Motta Portillo josuéanderson Rēgo Azevedo Fausto Erritto Barbo Ricardo j.Sawaya Programa de Pos-Graduacao em Biologia Animal Instituto de BiocienciasLetras e Ciencias ExatasUniversidade Estadual Paulista"Julio de Mesquita Filho"Rua Cristovao Colombo2265Sao Josédo Rio PretoSao Paulo 15054-000Brazil Programa de Colecoes Cientificas Biologicas Coordenagao de BiodiversidadeInstituto Nacional de Pesquisas da AmazoniaAvenida AndréAraujo2936ManausAmazonas 69067-375Brazil Gothenburg Global Biodiversity Centre University of GothenburgBox 461GothenburgVastra Gotaland SE-40530Sweden Instituto Federal de Educacao Ciencia e Tecnologia de Minas GeraisRodovia Machado-Paraguacukm 3MachadoMinas Gerais 37750-000Rraizil Centro de Ciencias Naturais e Humanas UniversidadeFederaldo ABCRua Arcturus03Sao Bernardo do CampoSao Paulo09606-070Brazil

The decrease in species richness toward higher latitudes is an expected biogeographical *** pattern could be related to particular envi-ronmental constraints and the evolutionary history of ***,species richness does not fully represent the evolutionary history of the clades behind their *** diversity better clarifies the role of historical factors in biogeographical *** analyzed envi-ronmental and historical drivers related to latitudinal variation in species richness and phylogenetic diversity of Atlantic Forest endemic *** implemented species distribution models,from voucherbased locality points,to map the snake ranges and *** used generalized additive mixed models to evaluate the relationships among the diversity metrics and area,topographical roughness,and past climate change velocity since the Last Maximum Glacial in the Atlantic Forest latitudinal *** to the expected general pattern,species richness was higher toward higher latitudes,being positively related to past climatic *** richness also increased with total area and higher topographical *** diversity,on the other hand,showed opposite relationships related to the same *** diversity increased with lower climatic stability in lower ***,dimensions of diversity were affected in different ways by historical and environmental constraints in this unique and threatened biodiversity hotspot.

关键词： biodiversity latitudinal gradient neotropical region phylogenetic diversity serpents species richness.

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Academic productivity correlates with industry earnings in foot and ankle fellowship programs in the United States:A retrospective analysis

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World journal of Orthopedics 2024年第2期15卷 129-138页

作者： Albert T Anastasio Anthony N Baumann Kempland C Walley kyle j Hitchman Conor O’Neill jonathan Kaplan Samuel B Adams Department of Orthopedic Surgery Duke University HospitalDurhamNC 27710United States College of Medicine Northeast Ohio Medical UniversityRootstownOH 44272United States Department of Orthopedic Surgery University of MichiganAnn ArborMI 48109United States School of Osteopathic Medicine Campbell UniversityLillingtonNC 27546United States

BACKGROUND The study investigates the connection between academic productivity and industry earnings in foot and ankle orthopedic surgery *** metrics like the H-index and Open Payments Database(OPD)data,it addresses a gap in understanding the relationship between scholarly achievements and financial outcomes,providing a basis for further exploration in this specialized medical *** To elucidate the trends between academic productivity and industry earnings across foot and ankle orthopedic surgery fellowship programs in the United *** This study is a retrospective analysis of the relationship between academic productivity and industry earnings of foot and ankle orthopedic surgery fellowships at an individual faculty and fellowship *** productivity was defined via H-index and recorded from the Scopus *** earnings were recorded from the *** Forty-eight foot and ankle orthopedic surgery fellowships(100%of fellowships)in the United States with a combined total of 165 physicians(95.9%of physicians)were *** individual physician(n=165)total life-time earnings reported on the OPD website was United States Dollar(USD)451430.30±1851084.89(range:USD 25.16-21269249.85;median:USD 27839.80).Mean physician(n=165)H-index as reported on Scopus is 14.24±12.39(range:0-63;median:11).There was a significant but weak correlation between individual physician H-index and individual physician total life-time earnings(P<0.001;Spearman’s rho=0.334)and a significant and moderate positive correlation between combined fellowship H-index and total life-time earnings per fellowship(P=0.004,Spearman’s rho=0.409).CONCLUSION There is a significant and positive correlation between academic productivity and industry earnings at foot and ankle orthopedic surgery fellowships in the United *** observation is true on an individual physician level as well as on a fellowship level.

关键词： Sunshine act Foot and ankle Orthopedic surgery Orthopedic fellowship Industry earnings

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Epidemiologic investigation of pediatric distal humerus fractures: An American insurance claims database study

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World journal of Orthopedics 2024年第1期15卷 52-60页

作者： kyle jay Klahs jake E Dertinger Grant T Mello Kevin Thapa Alexis B Sandler E'Stephan j jesus Garcia Nata Parnes Department of Orthopaedic Surgery Texas Tech University Health Sciences-El PasoEl PasoTX 79905United States Medical School California Health Sciences University College of Osteopathic MedicineClovisCA 93611United States Undergraduate School Binghampton UniversityVestalNY 13902United States Department of Orthopaedic Surgery William Beaumont Army Medical CenterFort BlissTX 79918United States Department of Orthopaedic Surgery Carthage Area HospitalCarthageNY 13619United States

BACKGROUND Distal humerus elbow fractures are one of the most common traumatic fractures seen in pediatric patients and present as three main types:Supracondylar(SC),lateral condyle(LC),and medial epicondyle(ME)*** To evaluate the epidemiology of pediatric distal humerus fractures(SC,LC,and ME)from an American insurance claims *** A retrospective review was performed on patients 17 years and younger with the ICD 9 and 10 codes for SC,LC and ME fractures based on the IBM Truven MarketScan®Commercial and IBM Truven MarketScan Medicare Supplemental *** from 2015 to 2020 were queried for treatments,patient age,sex,length of hospitalization,and *** A total of 1133 SC,154 LC,and 124 ME fractures were *** fractures had the highest percentage of operation at 83%,followed by LC(78%)and ME fractures(41%).Male patients were,on average,older than female patients for both SC and ME *** In the insurance claims databases used,SC fractures were the most reported,followed by LC fractures,and finally ME *** was identified to be a factor for how a pediatric distal humerus fractures,with patients with SC and LC fractures being younger than those with ME *** peak age per injury per sex was similar to reported historic central tendencies,despite reported trends for younger physiologic development.

关键词： Supracondylar humerus fracture Lateral condyle fracture Medial epicondyle fracture Pediatric elbow Truven Epidemiology

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COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： kyle A.Smith Tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.Gustafson Emmanuel Katsanis Richard j.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory Medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of Medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： jason Philip Appleton Lisa j Woodhouse Craig S anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy j England Kailash Krishnan Grant Mair Keith W Muir john Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical Research 2024年第4期11卷 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim jennifer E.kyle Kelly G.Stratton Carrie D.Nicora Nathalie Munoz Kathleen M.Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus Kent j.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.Clark Grant Tietje justin Teeguarden Kristin E.Burnum-johnson Biological Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Environmental and Molecular Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics Division Pacific Northwest National LaboratoryRichlandWA 99352USA National Security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA Environmental and Molecular Toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism Immunity

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Detailed characterization of kHz-rate laser-driven fusion at a thin liquid sheet with a neutron detection suite

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High Power Laser Science and Engineering 2024年第1期12卷 13-23页

作者： Benjamin M.Knight Connor M.Gautam Colton R.Stoner Bryan V.Egner joseph R.Smith Chris M.Orban juan j.Manfredi kyle D.Frische Michael L.Dexter Enam A.Chowdhury Anil K.Patnaik Department of Engineering Physics Air Force Institute of TechnologyWPAFBOHUSA Physics Department Marietta CollegeMariettaOHUSA Department of Physics The Ohio State UniversityColumbusOHUSA Department of Materials Science and Engineering and Department of Electrical and Computer ScienceThe Ohio State UniversityColumbusOHUSA Intense Energy Solutions LLCPlain CityOHUSA

We present detailed characterization of laser-driven fusion and neutron production(-10^(5)/second) using 8 mj, 40 fs laser pulses on a thin(<1 μm) D_2O liquid sheet employing a measurement suite. At relativistic inte... 详细信息

We present detailed characterization of laser-driven fusion and neutron production(-10^(5)/second) using 8 mj, 40 fs laser pulses on a thin(j-309 organic scintillator with pulse-shape discrimination, a ~3He proportional counter and a set of 36 bubble detectors. Time-of-flight analysis of the scintillator data shows the energy of the produced neutrons to be consistent with 2.45 MeV. Particle-in-cell simulations using the WarpX code support significant neutron production from D-D fusion events in the laser±target interaction region. This high-repetition-rate laser-driven neutron source could provide a low-cost, on-demand test bed for radiation hardening and imaging applications.

关键词： high-repetition-rate laser-driven fusion laser-plasma interaction liquid target neutron detectors

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