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A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan cuccia Rachael coates Blake Nassar ethan Littlefield Elizabeth c.Martin Adam T.Melvin cain Department of chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to *** is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause *** this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and *** device provides a platform to evaluate the effects of FSS on McF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the *** of the effects of FSS on McF-7 cells was carried out utilizing two approaches:single cell analysis and bulk *** single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the McF-7 cell line at a single cell *** understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/*** demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were ***,there was no change in p-ERK1/*** is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were *** together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer *** findin

关键词： fluid breast estrogen

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Learning from the 2009 H1N1 pandemic:prospects for more broadly effective influenza vaccines

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分子细胞生物学报:英文版 2011年第3期3卷 144-146页

作者： ethan c.Settembre Philip R.Dormitzer Rino Rappuoli Novartis Vaccines and Diagnostics CambridgeMAUSASienaItaly

calls to develop a universal influenza vaccine have increased in the wake of the 2009 H1N1 influenza *** demand comes at a time when analyses of the human antibody repertoire,informed by structures of complexes between broadly neutralizing antibodies and influenza hemagglutinin,have revealed the target of a class of broadly neutralizing *** studies suggest a path forward to more broadly protective influenza vaccines.

关键词： influenza vaccines protective

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HIDA scan for functional gallbladder disorder： ensure that you know how the scan was done

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Hepatobiliary & Pancreatic Diseases International 2017年第2期16卷 197-201页

作者： Naeem Goussous Hadia Maqsood ethan Spiegler Gopal c Kowdley Steven c cunningham Department of Surgery Saint Agnes Hospital Baltimore USA Department of Nuclear Medicine Saint Agnes Hospital Baltimore USA

BAcKGROUND： Despite the increasing use of fatty meal（FM） as a substitute for cholecystokinin（ccK） in pain reproduction during hepato-imino-diacetic acid（HIDA） scan in functional gallbladder disorder, there are no studies comparing the differences between ccK and FM. The present study was to compare the efficacy of FM in comparison of ccK in FGBD application. METHODS： Patients undergoing HIDA scans from August 2013 to May 2014 were divided into two groups： those undergoing ccK-stimulated HIDA scan versus FM-stimulated HIDA scan. These groups were compared according to demographics and HIDA ***： Of 153 patients, 70 received ccK and 83 FM. There was no difference regarding age, gender, gallstones, gallbladder ejection fraction and time to visualization. However, significantly more of the patients receiving ccK than FM experienced pain reproduction（61% vs 30%, P〈0.01）.cONcLUSIONS： Stimulation of gallbladder contractility with a FM during HIDA is less than half as likely to reproduce biliary symptoms compared to ccK, despite similar ejection fractions and other parameters. It is essential that providers account for this difference when counseling patients regarding cholecystectomy for functional gallbladder disorder.

关键词： gallbladder dysfunction biliary dyskinesia cholecystokinin hepato-imino-diacetic acid

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Reactivity,Regioselectivity,and Synthetic Application of 2-Pyrenyl Units in Scholl Reactions

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ccS chemistry 2023年第9期5卷 2069-2077页

作者： Sai Ho Pun ethan chi Ho Wen Zeming Xia Han chen Felix RFischer Qian Miao Department of chemistry The Chinese University of Hong KongHong Kong Department of chemistry University of CologneCologne Department of chemistry University of CaliforniaBerkeleyCalifornia 94720 Materials Sciences Division Lawrence Berkeley National LaboratoryBerkeleyCalifornia 94720 Kavli Energy NanoScience Institute at the University of california Berkeley and the Lawrence Berkeley National Laboratory BerkeleyCalifornia 94720 Bakar Institute of Digital Materials for the Planet Division of ComputingData Scienceand SocietyUniversity of CaliforniaBerkeleyCalifornia 94720

We herein report the reactivity and regioselectivity of 2-pyrenyl as a coupling unit in Scholl *** the basis of the Scholl reactions of hexaarylbenzene substrates,we have found that pyrenyl units are preferably oxidized over naphthyl and phenyl units under appropriate Scholl reaction conditions,allowing divergent synthesis through a highly controllable intramolecular coupling *** find that the c1 and c3 positions of the 2-pyrenyl unit are the favorable sites for intramolecular coupling while c4 is not reactive to allow further *** reactivity and regioselectivity pattern can be explained by the spin density distribution,which shows that carbon-carbon bonds preferably form at sites with higher positive spin *** by these findings,we successfully synthesized a double helicene and a sextuple helicene through the controlled Scholl reactions of 2-pyrenyl units.

关键词： helicene polycyclic aromatics pyrene Scholl reactions spin density

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Retrospective analysis of eFAST ultrasounds performed on trauma activations at an academic level-1 trauma center

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World Journal of Emergency Medicine 2020年第1期11卷 12-17页

作者： Samantha Shwe Lauren Witchey Shadi Lahham ethan Kunstadt Inna Shniter John c.Fox School of Medicine University of CaliforniaIrvine 92697USA Department of Emergency Medicine University of CaliforniaIrvineOrangeCA 92868USA

BAcKGROUND:Point-of-care ultrasound(POcUS)has become increasingly integrated into the practice of emergency medicine.A common application is the extended focused assessment with sonography in trauma(eFAST)*** American college of Emergency Physicians has guidelines regarding the scope of ultrasound in the emergency department and the appropriate *** objective of this study was to conduct a review of performed,documented and billed eFAST ultrasounds on trauma activation ***:This was a retrospective review of all trauma activation patients during a 10-month period at an academic level-one trauma center.A list comparing all trauma activations was crossreferenced with a list of all billed eFAST *** records were reviewed to determine whether an eFAST was indicated,performed,and appropriately ***:We found that 1,507 of 1,597 trauma patients had indications for eFAST,but 396(27%)of these patients did not have a billed *** these 396 patients,87(22%)had documentation in the provider note that an eFAST was performed but there was no separate procedure *** remaining 309(78%)did not have any documentation of the eFAST in the patient’s chart although an eFAST was recorded and reviewed during ultrasound quality ***:A significant proportion of trauma patients had eFAST exams performed but were not documented or *** of documentation was *** ultrasound programs require appropriate reimbursement to support training,credentialing,equipment,quality assurance,and device *** study demonstrates a significant absence of adequate documentation leading to potential revenue loss for an emergency ultrasound program.

关键词： Point-of-care ultrasound Emergency medicine Focused assessment withsonography in trauma Trauma activation Blunt trauma

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AI缩小了员工之间的差距, 水平越低的员工获益越多?

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中欧商业评论 2024年第2期 84-89页

作者：法布里齐奥·戴阿夸伊森·莫里克凯瑟琳·克洛格富兰希思克·坎德隆渠超男(编译) 哈佛商学院沃顿商学院麻省理工学院斯隆管理学院波士顿咨询不详

人工智能让知识工作者的工作效率平均提高了25.1%,工作质量提高了40%。为什么有的员工使用人工智能后能力提升了43%,可有的员工只提升了17%?2022年底,OpenAI发布了人工智能聊天机器人chatGPT,开启了大模型领域的“速跑”模式,以真实的... 详细信息

人工智能让知识工作者的工作效率平均提高了25.1%,工作质量提高了40%。为什么有的员工使用人工智能后能力提升了43%,可有的员工只提升了17%?2022年底,OpenAI发布了人工智能聊天机器人chatGPT,开启了大模型领域的“速跑”模式,以真实的场景处理自然语言,实现了对话、阅读、翻译、写作、编程、数据分析等功能。2024年伊始,OpenAI再度掀起热潮,视频人工智能模型Sora横空出世,只需要一小段提示文本,Sora可生成长达60秒连续、稳定、高品质的视频,并且提示文本越充分、细节越精确,生成的视频就越真实。

关键词：知识工作者人工智能能力提升数据分析 Open 自然语言 AI 工作效率

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Appropriate extent of surgery for aspirinexacerbated respiratory disease

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2020年第4期6卷 235-240页

作者： ethan G.Muhonen Khodayar Goshtasbi Peter Papagiannopoulos Edward c.Kuan Department of Otolaryngolosy-Head and Neck Sursery University of CaliforniaIrvineUSA Department of Otolaryngolosy-Head and Neck Surgery Rush University Medical CenterChicagoILUSA

The current literature lacks strong guidelines regarding surgical management of patients with aspirin-exacerbated respiratory disease(AERD),who present with the clinical triad of chronic rhinosinusitis with nasal polyposis(cRSwNP),bronchial asthma,and aspirin/nonsteroidal anti-inflammatory drug *** further define the effectiveness of sinus surgery in treating AERD patients,this review article discusses current evidence regarding outcomes associated with more extensive surgery,the benefits of frontal sinus surgery on polyposis,and the role of Draf III *** studies suggest that Draf III frontal sinusotomy may be an efficacious early intervention due to increased neo-ostial patency and subsequent distribution of topical *** studies that further investigate the efficacy and safety of extensive surgery in AERD patients are warranted.

关键词： Endoscopic sinus surgery Draf III Aspirin exacerbated respiratory disease chronic sinusitis Nasal polyps Extent of surgery

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Application of the neuromuscular fatigue threshold treadmill test to muscles of the quadriceps and hamstrings

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Journal of Sport and Health Science 2020年第6期9卷 628-633页

作者： clayton L.camic Attila J.Kovacs Trisha A.VanDusseldorp ethan c.hil. Evan A.Enquist Human Performance Laboratory Exercise and Sport ScienceUniversity of Wisconsin-La CrosseLa CrosseWisconsin 54601USA Department of Exercise Science and Sport Management Kennesaw State UniversityKennesawGeorgia 30144USA Department of Nutrition and Health Sciences University of Nebraska-LincolnLincolnNebraska 68583USA Department of Kinesiology University of AlabamaTuscaloosaAlabama 35487USA

Purpose:The purposes of the present study were:(1)to determine whether the physical working capacity at the fatigue threshold(PWcFT)model that has been used for estimating the onset of neuromuscular fatigue in the vastus lateralis(VL)during incremental treadmill running could also be applied to the vastus medialis(VM),biceps femoris(BF),and semitendinosus(ST)muscles;and(2)if applicable,to compare the running velocities associated with the PWcFT among these ***:Eleven subjects(age 21.7±1.8 years)performed an incremental treadmill test to exhaustion with electromyographic signals recorded from the VL,VM,BF,and ***:The results indicated there were no significant(p>0.05)mean differences in the running velocities associated with the PWcFT for the VL(14.4±2.0 km/h),VM(14.3±1.9 km/h),BF(13.8±1.8 km/h),and ST(14.7±2.3 km/h).In addition,there were significant inter-correlations(r=0.68-0.88)among running velocities associated with the PWcFT of each *** results also indicated that 9 of the 11 subjects exhibited identical PWcFT values for at least 3 of the 4 muscles,but there were no uniform patterns for any intra-individual ***:The findings of the present study suggested that the PWcFT test is a viable method to identify neuromuscular fatigue in the quadriceps and hamstrings during incremental treadmill exercise and results in consistent PWcFT values among these muscles.

关键词： EMG amplitude Muscle activation PWcFT

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Engineered hydrogels for brain tumor culture and therapy

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Bio-Design and Manufacturing 2020年第3期3卷 203-226页

作者： Jai Thakor Samad Ahadian Ali Niakan ethan Banton Fatemeh Nasrollahi Mohammad MHasani‑Sadrabadi Ali Khademhosseini center for Minimally Invasive Therapeutics(c‑MIT) University of California-Los Angeles570 Westwood PlazaLos AngelesCA 90095USA Department of Bioengineering University of California-Los AngelesLos AngelesCA 90095USA Department of Materials Science and Engineering University of California-Los AngelesLos AngelesCA 90095USA Weintraub center for Reconstructive Biotechnology Division of Advanced ProsthodonticsSchool of DentistryUniversity of California-Los AngelesLos AngelesCA 90095USA Department of Radiological Sciences University of California-Los AngelesLos AngelesCA 90095USA Department of chemical and Biomolecular Engineering University of California-Los AngelesLos AngelesCA 90095USA Terasaki Institute for Biomedical Innovation(TIBI) Los AngelesCA 90024USA

Brain tumors’severity ranges from benign to highly aggressive and *** tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral ***,we first describe the physiology and cellular composition of brain ***,we discuss the development of threedimensional tissue models utilizing brain tumor *** particular,we highlight the role of hydrogels in providing a biomimetic support for the cells to grow into defined *** technologies,such as electrospinning and bioprinting,and advanced cellular models aim to mimic the extracellular matrix and natural cellular localization in engineered tumor ***,we review current applications and prospects of hydrogels for therapeutic purposes,such as drug delivery and co-administration with other *** further development,hydrogels can serve as a reliable option for in vitro modeling and treatment of brain tumors for translational medicine.

关键词： Brain tumor Bioengineering cancer cells Drug delivery Hydrogel

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Retinoic acid signaling acts as a rheostat to balance Treg function

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cellular & Molecular Immunology 2022年第7期19卷 820-833页

作者： Govindarajan Thangavelu Gabriela Andrejeva Sara Bolivar-Wagers Sujeong Jin Michael c.Zaiken Michael Loschi ethan G.Aguilar Scott N.Furlan chrysothemis c.Brown Yu-chi Lee cameron McDonald Hyman colby J.Feser Angela Panoskaltsis-Mortari Keli L.Hippen Kelli P.MacDonald William J.Murphy Ivan Maillard Geoffrey R.hill David H.Munn Robert Zeiser Leslie S.Kean Jeffrey c.Rathmell Hongbo chi Randolph J.Noelle Bruce R.Blazar Department of Pediatrics Center for ImmunologyUniversity of MinnesotaMinneapolisMNUSA center for Immunobiology Vanderbilt University Medical CenterNashville TNUSA Department of Pediatrics University of WashingtonSeattleWAUSA Fred Hutchinson cancer Research center SeattleWAUSA Howard Hughes Medical Institute Immunology Program and Ludwig CenterSloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Microbiology and Immunology.Geisel School of Medicine at Dartmouth Norris Cotton Cancer CenterLebanonUSA Department of Immunology Queensland Institute of Medical Research(QIMR)Berghofer Medical Research Institute and School of MedicineUniversity of QueenslandBrisbaneQLDAustralia Departmentof Dermatology School of MedicineUniversity of California DavisSacramentoCAUSA Division of Hematology/Oncology Department of MedicineUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPAUSA Georgia cancer center Augusta UniversityAugustaGAUSA Department of Haematology Oncology and Stem Cell TransplantationFaculty of MedicineFreiburg University Medical CentreFreiburgGermany Boston children's Hospital and the Dana-Farber cancer Institute BostonMAUSA Department of Immunology St.Jude Children's ResearchHospitalMemphisTNUSA

Regulatory T cells(Tregs)promote immune homeostasis by maintaining self-tolerance and regulating inflammatory *** certain inflammatory conditions,Tregs can lose their lineage stability and *** studies have reported that ex vivo exposure to retinoic acid(RA)enhances Treg function and ***,it is unknown how RA receptor signaling in Tregs influences these processes in ***,we employed mouse models in which RA signaling is silenced by the expression of the dominant negative receptor(DN)RARαin all T *** the fact that DNRARαconventional T cells are hypofunctional,Tregs had increased cD25 expression,STAT5 pathway activation,mTORc1 signaling and supersuppressor ***,DNRARαTregs had increased inhibitory molecule expression,amino acid transporter expression,and metabolic fitness and decreased antiapoptotic *** function was observed when wild-type mice were treated with a pharmacologic pan-RAR ***,Treg-specific expression of DNRARαresulted in distinct phenotypes,such that a single allele of DNRARαin Tregs heightened their suppressive function,and biallelic expression led to loss of suppression and *** loss of Treg function was not cell intrinsic,as Tregs that developed in a noninflammatory milieu in chimeric mice reconstituted with DNRARαand wild-type bone marrow maintained the enhanced suppressive *** mapping suggested that maintaining Treg stability in an inflammatory milieu requires RA *** findings indicate that RA signaling acts as a rheostat to balance Treg function in inflammatory and noninflammatory conditions in a dose-dependent manner.

关键词： Retinoic acid Tregulatory cells Autoimmunity Metabolism mTORc1 STAT5

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