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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： j.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman jangKeun Kim alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor julian C.Schmidt Michael A.Schmidt Kelly Blease juan Moreno Andrew Boddicker junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton jaime Mateus Christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Development and first evaluation of an attractant impregnated adhesive tape against blood-sucking flies

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Insect Science 2022年第2期29卷 603-612页

作者： junwei j.Zhu Gwang-Hyun Roh Yosuke Asamoto Kujtim Bizati jen-Chieh Liu alexander Lehmann Kyle Harrison David BTaylor Hironao Otake Agroecosystem Management Research Unit US Department of AgricultureAgricultural Research ServiceLincolnNebraskaUSA US Pacific Basin Agricultural Research Center US Department of AgricultureAgricultural Research ServiceHiloHawaiiUSA Oak Ridge Institute for Science and Education Oak RidgeTennesseeUSA Nitto Inc. TeaneckNew JerseyUSA Department of Entomology University of NebraskaLincolnNebraskaUSA

Stable flies are one of the most important arthropod pests of livestock that reduce cattle weight gain and milk production leading to annual economic losses in excess of$2 billion to the US cattle *** host-seeking behavior is primarily mediated by associated odors from stable fly larval development environments and host *** present paper reports the development and evaluation of attractant-impregnated adhesive tapes to reduce stable fly attacks on *** bioassays showed that only m-cresol impregnated adhesive tapes caught significantly more stable flies(16±1)than the control tape without attractant added(7±1),with a 77%fly recapture ***-impregnated adhesive tapes deployed in cattle feedlots showed significant impacts in reducing fly population,with a total of one million stable flies captured over a period of three weeks(mean catches from 57596 to 102088 stable flies per trap per week).It further relieved cattle stress with a significant reduction of biting fly avoidance behavior,(6±0.4 cows observed with tail wagging in control vs.3±0.4 from the trap-deployed).The efficacy of the developed tapes lasted up to 1-week longevity,although 70%of m-cresol was released starting from the second *** m-cresol impregnated adhesive tape provided an 80%reduction in cattle stress due to stable fly *** is the first report of a technology developed by integrating an attractant compound into an adhesive material on a plastic film with demonstrated effectiveness in trapping biting flies that attack livestock animals.

关键词： cattle stress reduction mass trapping m-cresol-impregnated adhesive tapes Stomoxys calcitrans

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Current clinical approach to achalasia

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World journal of Gastroenterology 2009年第32期15卷 3969-3975页

作者： alexander j Eckardt Volker F Eckardt Central Interdisciplinary Endoscopy Unit Department of Gastroenterology and HepatologyCharité University Hospitals BerlinCampus VirchowD-13353 BerlinGermany Department of Gastroenterology Deutsche Klinik für DiagnostikD-65191 WiesbadenGermany

Idiopathic achalasia is a rare primary motility disorder of the esophagus. The classical features are incomplete relaxation of a frequently hypertensive lower esophageal sphincter (LES) and a lack of peristalsis in the tubular esophagus. These motor abnormalities lead to dysphagia, stasis, regurgitation, weight loss, or secondary respiratory complications. Although major strides have been made in understanding the pathogenesis of this rare disorder, including a probable autoimmune mediated destruction of inhibitory neurons in response to an unknown insult in genetically susceptible individuals, a definite trigger has not been identified. The diagnosis of achalasia is suggested by clinical features and conf irmed by further diagnostic tests, such as esophagogastroduodenoscopy (EGD), manometry or barium swallow. These studies are not only used to exclude pseudoachalasia, but also might help to categorize the disease by severity or clinical subtype. Recent advances in diagnostic methods, including high resolution manometry (HRM), might allow prediction of treatment responses. The primary treatments for achieving long-term symptom relief are surgery and endoscopic methods. Although limited high-quality data exist, it appears that laparoscopic Heller myotomy with partial fundoplication is superior to endoscopic methods in achieving long-term relief of symptoms in the majority of patients. However, the current clinical approach to achalasia will depend not only on patients' characteristics and clinical subtypes of the disease, but also on local expertise and patient preferences.

关键词：弛缓临床医学诊断 LES

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Measuring user preferences and behaviour in a topographic immersive virtual environment(TopoIVE)of 2D and 3D urban topographic data

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International journal of Digital Earth 2021年第12期14卷 1835-1867页

作者： Łukasz Halik alexander j.Kent Department of Cartography and Geomatics Adam Mickiewicz UniversityPoznańPoland School of Psychology and Life Sciences Canterbury Christ Church UniversityCanterburyUK

This paper investigates user preferences and behaviour associated with 2D and 3D modes of urban representation within a novel Topographic Immersive Virtual Environment(TopoIVE)created from official 1:10,000 *** participants were divided into two groups:the first were given a navigational task within a simulated city and the second were given the freedom to explore it.A Head-Mounted Display(HMD)Virtual Reality(VR)app allowed participants to switch between 2D and 3D representations of buildings with a remote controller and their use of these modes during the experiment was *** performed mental rotation tests before entering the TopoIVE and were interviewed afterwards about their experiences using the *** results indicate that participants preferred the 3D mode of representation overall,although preference for the 2D mode was slightly higher amongst those undertaking the navigational task,and reveal that different wayfinding solutions were adopted by participants according to their ***,the findings suggest that users exploit different aspects of 2D and 3D modes of visualization in their wayfinding strategy,regardless of their *** potential to combine the functionality of 2D and 3D modes therefore offers substantial opportunities for the development of immersive virtual reality products derived from topographic datasets.

关键词： Virtual reality(VR) immersive virtual environment(IVE) 2D versus 3D wayfinding topographic data

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Microarchitectural mimicking of stroma-induced vasculature compression in pancreatic tumors using a 3D engineered model

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Bioactive Materials 2023年第4期22卷 18-33页

作者： Marcel alexander Heinrich Irene Uboldi Praneeth Reddy Kuninty Marc j.K.Ankone joop van Baarlen Yu Shrike Zhang Kartik jain jai Prakash Department of Advanced Organ Bioengineering and Therapeutics Engineered Therapeutics SectionTechnical Medical CentreUniversity of Twente7500AEEnschedethe Netherlands Laboratorium Pathologie Oost-Nederland(LabPON) 7550 AMHengelothe Netherlands Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical School65 Landsdowne StCambridgeMA02139USA Department of Thermal and Fluid Engineering Biofluid Dynamics SectionUniversity of Twente7500 AE Enschedethe Netherlands

Fibrotic tumors,such as pancreatic ductal adenocarcinoma(PDAC),are characterized for high desmoplastic reaction,which results in high intra-tumoral solid stress leading to the compression of blood *** microarchitectural alterations cause loss of blood flow and poor intra-tumoral delivery of ***,there is a lack of relevant in vitro models capable of replicating these mechanical characteristics and to test anti-desmoplastic ***,a multi-layered vascularized 3D PDAC model consisting of primary human pancreatic stellate cells(PSCs)embedded in collagen/fibrinogen(Col/Fib),mimicking tumor tissue within adjunct healthy tissue,is presented to study the fibrosis-induced compression of vasculature in *** is demonstrated how the mechanical and biological stimulation induce PSC activation,extracellular matrix production and eventually vessel *** clinical relevance is confirmed by correlating with patient transcriptomic ***,the effects of gradual vessel compression on the fluid dynamics occurring within the channel is evaluated in ***,it is demonstrated how cancer-associated fibroblast(CAF)-modulatory therapeutics can inhibit the cell-mediated compression of blood vessels in PDAC in vitro,in silico and in *** is envisioned that this 3D model is used to improve the understanding of mechanical characteristics in tumors and for evaluating novel anti-desmoplastic therapeutics.

关键词： Pancreatic ductal adenocarcinoma Cancer-associated fibroblasts Collagen Fibrinogen Computational flow dynamics 3D in vitro model

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Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

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Cell Research 2005年第6期15卷 465-473页

作者： Francois MA PUjOL,alexander j KASTANIOTIS,j Kalervo HILTUNEN Biocenter Oulu and Department of Biochemistry University of Oulu P.O. Box 3000 FIN-90014 University of Oulu Finland Biocenter Oulu and Department of Biochemistry University of Oulu P.O. Box 3000 FIN-90014 University of Oulu Finland Biocenter Oulu and Department of Biochemistry University of Oulu P.O. Box 3000 FIN-90014 University of Oulu Finland

Genes encoding enzymes involved in biosynthesis of very long chain fatty acids were significantly up-regulatedduring early cotton fiber development. Two cDNAs, GhKCR1 and GhKCR2 encoding putative cotton 3-ketoacyl-CoAreductases that catalyze the second step in fatty acid elongation, were isolated from developing cotton fibers. GhKCR1and 2 contain open reading frames of 963 bp and 924 bp encoding proteins of 320 and 307 amino acid residues,respectively. Quantatitive RT-PCR analysis showed that both these genes were highly preferentially expressed duringthe cotton fiber elongation period with much lower levels recovered from roots, stems and leaves. GhKCR1 and 2showed 30%-32% identity to Saccharomyces cerevisiae Ybr159p at the deduced amino acid level. These cotton cDNAswere cloned and expressed in yeast haploid ybr159w? mutant that was deficient in 3-ketoacyl-CoA reductase ***-type growth rate was restored in ybr159w? cells that expressed either GhKCR1 or 2. Further analysis showed thatGhKCR1 and 2 were co-sedimented within the membranous pellet fraction after high-speed centrifugation, similar to theyeast endoplasmic reticulum marker ScKar2p. Both GhKCR(s) showed NADPH-dependent 3-ketoacyl-CoA reductaseactivity in an in vitro assay system using palmitoyl-CoA and malonyl-CoA as substrates. Our results suggest thatGhKCR1 and 2 are functional orthologues of ScYbr159p.

关键词： very-long-chain fatty acids endoplasmic reticulum fatty acid elongation system 3-ketoacyl-CoA reductase Gossypium hirsutum short-chain alcohol dehydrogenase/reductase protein family.

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Fifth-Order A-WENO Schemes Based on the Adaptive Diffusion Central-Upwind Rankine-Hugoniot Fluxes

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Communications on Applied Mathematics and Computation 2023年第1期5卷 295-314页

作者： Bao-Shan Wang Wai Sun Don alexander Kurganov Yongle Liu School of Mathematical Sciences Ocean University of ChinaQingdao 266100ShandongChina Department of Mathematics SUSTech International Center for Mathematics and Guangdong Provincial Key Laboratory of Computational Science and Material DesignSouthern University of Science and TechnologyShenzhen 518055GuangdongChina Department of Mathematics Harbin Institute of TechnologyHarbin 150001HeilongjiangChina Department of Mathematics Southern University of Science and TechnologyShenzhen 518055GuangdongChina

We construct new fifth-order alternative WENO(A-WENO)schemes for the Euler equations of gas *** new scheme is based on a new adaptive diffusion centralupwind Rankine-Hugoniot(CURH)numerical *** CURH numerical fluxes have been recently proposed in[Garg et al.j Comput Phys 428,2021]in the context of secondorder semi-discrete finite-volume *** proposed adaptive diffusion CURH flux contains a smaller amount of numerical dissipation compared with the adaptive diffusion central numerical flux,which was also developed with the help of the discrete RankineHugoniot conditions and used in the fifth-order A-WENO scheme recently introduced in[Wang et *** j Sci Comput 42,2020].As in that work,we here use the fifth-order characteristic-wise WENO-Z interpolations to evaluate the fifth-order point values required by the numerical *** resulting one-and two-dimensional schemes are tested on a number of numerical examples,which clearly demonstrate that the new schemes outperform the existing fifth-order A-WENO schemes without compromising the robustness.

关键词： A-WENO schemes Central-upwind schemes Discrete Rankine-Hugoniot conditions Numerical dissipation switch Local speeds of propagation Euler equations of gas dynamics

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Forces and energetics of intermittent swimming

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Acta Mechanica Sinica 2017年第4期33卷 725-732页

作者： Daniel Floryan Tyler Van Buren alexander j.Smits Department of Mechanical and Aerospace Engineering Princeton University Princeton NJ 08544 USA

Experiments are reported on intermittent swimming motions. Water tunnel experiments on a nominally two-dimensional pitching foil show that the mean thrust and power scale linearly with the duty cycle, from a value of 0.2 all the way up to continuous motions, indicating that individual bursts of activity in intermittent motions are independent of each other. This conclusion is corroborated by particle image velocimetry（PIV） flow visualizations, which show that the main vortical structures in the wake do not change with duty cycle. The experimental data also demonstrate that intermittent motions are generally energetically advantageous over continuous motions. When metabolic energy losses are taken into account, this conclusion is maintained for metabolic power fractions less than 1.

关键词： intermittent swimming maintained conclusion cycle thrust favorable producing aquatic circles

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Are Off-Field Activities an Underestimated Risk for Hamstring Injuries in Dutch Male Amateur Soccer Players?An Exploratory Analysis of a Prospective Cohort Study

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journal of Science in Sport and Exercise 2022年第1期4卷 28-36页

作者： jur j.Brauers Peter alexander van de Hoef Maarten van Smeden Frank j.G.Backx Michel S.Brink Department of Rehabilitation Physical Therapy Science and SportsUtrecht UniversityUniversity Medical Center UtrechtBrain CenterUtrechtThe Netherlands julius Center for Health Sciences and Primary Care University Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands Center for Human Movement Sciences University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands

Purpose The purpose of this study was to explore what extent male amateur soccer players participate in off-field activities and whether these off-field activities are associated with the development of hamstring *** Amateur soccer players(n=399)from first-class selection teams(n=32)filled out a baseline screening question-naire concerning off-field activities(i.e.,work and study type and hours,traveling time,sleep,energy costs,and time spent on other activities)and their history of hamstring injury as a part of a cluster-randomized controlled *** one competition,the players reported weekly their hamstring injuries,which were verified by medical/technical ***-able Firth corrected logistic regression models were used to explore associations between off-field activities and hamstring *** Sixty-five hamstring injuries were *** injury was significantly associated with hamstring injuries(OR ranging from 1.94[95%CI 1.45-2.61]to 2.02[95%CI 1.49-2.73]),but off-field activities were *** Although amateur soccer players spent a relatively large amount of time on off-field activities,we did not find off-field activities measured at baseline to be associated with hamstring injuries in the subsequent competitive soccer *** contrast,previous hamstring injury was found to be strongly associated with(recurrent)hamstring injuries.

关键词： Risk factors Activities of daily living Psychosocial factors Football Athletic injuries

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Update in the treatment of intracranial atherosclerotic disease

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Stroke & Vascular Neurology 2020年第1期5卷 59-64页

作者： Zachary R Barnard Michael j alexander Neurosurgery Cedars-Sinai Medical CenterLos AngelesCaliforniaUSA

This review highlights the recent evolution of the imaging,medical management,surgical options and endovascular therapies for symptomatic intracranial atherosclerotic disease(ICAD).Recent imaging developments including optical coherence tomography and other modalities to assess the intracranial arteries for symptomatic ICAD are reviewed,not only to diagnose ICAD but to determine if ICAD plaques have any high-risk features for *** future developments in the treatment of ICAD are discussed,including the development of trackable drug-coated balloons for the cerebral circulation to treat primary or restenotic arteries,new iterations of self-expanding intracranial stents with easier delivery systems,and the re-examination of indirect surgical bypass techniques for *** addition to these important technological developments,however,is the evolving evidence regarding the best treatment window for these techniques and additional factors in medical management which can improve patient outcomes in this devastating pathology.

关键词： intracranial balloon arteries

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