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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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Operation of the GTS-LHc Source for the Hadron Injector at cERN

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chinese Physics c 2007年第S1期31卷 51-54页

作者： L.Dumas c.hill D.Hitz D.Küchler c.Mastrostefano M.O'Neil R.Scrivens cERN AB/ABP/HSL1211 Geneva 23Switzerland cEA DRFMC/SBT.17 rue des Martyrs38054 Grenoble Cedex 9France

The GTS-LHc ion source,designed and build by cEA Grenoble,was installed and commissioned at cERN in *** than the source has delivered oxygen and lead ion beams(O^(4+) and Pb^(27+) from the source,Pb^(54+) from the linac)for the commissioning of the Low Energy Ion Ring(LEIR).Results of this operation and attempts to improve the source performance and reliability,and the linac performance will be presented in this paper.

关键词： operation linear accelerator metal ions bias disk

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Framework for atomic-level characterisation of quantum computer arrays by machine learning

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npj computational Materials 2020年第1期6卷 1513-1520页

作者： Muhammad Usman Yi Zheng Wong charles D.hill Lloyd c.L.Hollenberg center for Quantum computation and communication Technology University of MelbourneParkvilleVIC 3010Australia School of Physics University of MelbourneParkvilleVIC 3010Australia School of computing and Information Systems Melbourne School of EngineeringUniversity of MelbourneParkvilleVIC 3010Australia School of Mathematics and Statistics University of MelbourneParkvilleVIC 3010Australia

Atomic-level qubits in silicon are attractive candidates for large-scale quantum computing;however,their quantum properties and controllability are sensitive to details such as the number of donor atoms comprising a qubit and their precise *** work combines machine learning techniques with million-atom simulations of scanning tunnelling microscopic(STM)images of dopants to formulate a theoretical framework capable of determining the number of dopants at a particular qubit location and their positions with exact lattice site precision.A convolutional neural network(cNN)was trained on 100,000 simulated STM images,acquiring a characterisation fidelity(number and absolute donor positions)of>98% over a set of 17,600 test images including planar and blurring noise commensurate with experimental *** formalism is based on a systematic symmetry analysis and feature-detection processing of the STM images to optimise the computational *** technique is demonstrated for qubits formed by single and pairs of closely spaced donor atoms,with the potential to generalise it for larger donor *** method established here will enable a high-precision post-fabrication characterisation of dopant qubits in silicon,with high-throughput potentially alleviating the requirements on the level of resources required for quantum-based characterisation,which will otherwise be a challenge in the context of large qubit arrays for universal quantum computing.

关键词： quantum character donor

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AN/APG-67多功能雷达性能鉴定

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现代雷达 1989年第6期11卷 1-16页

作者： Robert L.Nevin Jerome c.hill 杨楠黄淪中

概述 AN/APG-67多功能雷达是一种采用现代技术的相参数字式火控雷达,它是为诺斯罗普公司F-20“虎鲨”式飞机研制的。从1983年初开始对这种雷达进行了飞行试验和鉴定。本报告提出了鉴定的主要结论。 AN/APG-67雷达能够帮助F-20飞机完成... 详细信息

概述 AN/APG-67多功能雷达是一种采用现代技术的相参数字式火控雷达,它是为诺斯罗普公司F-20“虎鲨”式飞机研制的。从1983年初开始对这种雷达进行了飞行试验和鉴定。本报告提出了鉴定的主要结论。 AN/APG-67雷达能够帮助F-20飞机完成空对空和空对地任务。空对空搜索和跟踪工作方式具有上视、下视和边扫描边跟踪方式,以及人工或自动截获转入单目标跟踪的能力。在完成空对地任务时,雷达能对地面和海面动目标进行探测和跟踪,并且有真波束和多卜勒锐化地图测绘和空对地测距功能。

关键词：火控雷达多功能雷达机载雷达

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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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A simple umbelliferone based fluorescent probe for the detection of nitroreductase

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Frontiers of chemical Science and Engineering 2018年第2期12卷 311-314页

作者： Adam c. Sedgwick Alex Hayden Barry hill Steven D. Bull Robert B. P. Elmes Tony D. James Department of chemistry University of Bath Bath BA2 7AY UK Department of chemistry Maynooth University Maynooth Co. Kildare Ireland

A simple nitrobenzyl-umbelliferone （NcOU1） was synthesised containing a nitroreductase （NTR） trigger moiety. The presence of NTR, resulted in the fragmentation of the parent molecule and release of the highly emissive fluorophore umbelliferone via an NTR-catalyzed reduction of the nitro group. In the presence of the NTR enzyme, NcOU1 gave rise to a 5-fold increase in fluorescence intensity at 455 nm and was selective for NTR over other reductive enzymes. These results indicate that NcOU1 can be used as a simple assay for the detection of NTR.

关键词： Fluorescence

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Semi-transparent,flexible,and electrically conductive silicon mesh by capillarity-driven welding of vapor-liquid-solid-grown nanowires over large areas

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Nano Research 2020年第5期13卷 1465-1471页

作者： Thomas A.celano Seokhyoung Kim David J.hill James F.cahoon Department of chemistry University of North Carolina at Chapel HillChapel HillNC 27599-3290USA

Bottom-up synthesis of semiconductor nanowires(NWs)by the vapor-liquid-solid(VLS)mechanism has enabled diverse technological applications for these *** metallic NWs,however,it has been challenging to form large-area interconnected NW ***,we generate centimeter-scale meshes of mechanically and electrically interconnected Si NWs by sequentially growing,collapsing,and joining the NWs using a capillarity-driven welding *** fabricate meshes from VLS-grown NWs ranging in diameter from 20 to 100 nm and find that the meshes are three-dimensional with a thickness ranging from^1 to^10 microns depending on the NW *** extinction measurements reveal that the networks are semi-transparent with a color that depends on the absorption and scattering characteristics of individual ***,active voltage contrast imaging of both centimeter-and micron-scale meshes reveals widespread electrical *** a sacrificial layer,we demonstrate that the mesh can be liberated from the growth substrate,yielding a highly flexible and transparent *** transport measurements both on the growth substrate and on liberated,flexible films reveal electrical conduction across a centimeter scale with a sheet resistance of^160-180 kΩ/square that does not change significantly upon *** the ability to encode complex functionality in semiconductor NWs through the VLS process,we believe these meshes of networked NWs could find application as neuromorphic memory,electrode scaffolds,and bioelectronic interfaces.

关键词： semiconductor nanowire conductive network flexible electronics welding thermal annealing active-voltage contrast

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Evaluating the Impacts of Using Different Digital Surface Models to Estimate Forest Height with TanDEM-X Interferometric coherence Data

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雷达学报（中英文） 2020年第2期9卷 386-398页

作者： cHEN Hao hill David A. WHITE Joanne c. cLOUDE Shane R. canadian Forest Service 506 Burnside Road WestVictoriaBritish ColumbiaV8Z 1M5Canada Applied Electromagnetics consultants 26 Westfield AvenueCuparFifeKY155AAUK

In our previous studies, we demonstrated the usefulness of TanDEM-X interferometric bistatic mode with single polarization to obtain forest heights for the purposes of large area mapping. A key feature of our approach has been the use of a simplified Random Volume Over Ground(RVOG) model that locally estimates forest height. The model takes TanDEM-X interferometric coherence amplitude as an input and uses an external Digital Surface Model(DSM) to account for local slope variations due to terrain topography in order to achieve accurate forest height estimation. The selection of DSM for use as a local slope reference is essential, as an inaccurate DSM will result in less accurate terrain-correction and forest height estimation. In this paper, we assessed TanDEM-X height estimates associated with scale variations in different DSMs used in the model over a remote sensing supersite in Petawawa, canada. The DSMs used for assessments and comparisons included ASTER GDEM, ALOS GDSM, airborne DRAPE DSM, canadian DSM and TanDEM-X DSM. Airborne Laser Scanning(ALS) data were used as reference for terrain slope and forest height comparisons. The results showed that, with the exception of the ASTER GDEM, all DSMs were sufficiently accurate for the simplified RVOG model to provide a satisfactory estimate of stand-level forest height. When compared to the ALS 95th height percentile, the modeled forest heights had R2 values greater than 80% and Root-Mean-Square Errors(RMSE)less than 2 m. For a close similarity in slope estimation with the ALS reference, coverage across canada and open data access, the 0.75 arc-second(20 m) resolution canadian DSM was selected as a preferred choice for the simplified RVOG model to provide TanDEM-X height estimation in canada.

关键词： Interferometric cOA Digital surface model Forest height

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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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Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability

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Neural Regeneration Research 2017年第12期12卷 2045-2049页

作者： Allison H.Payne Gregory W.Hawryluk Yoshimi Anzai Henrik Odéen Megan A.Ostlie ethan c.Reichert Amanda J.Stump Satoshi Minoshima Donna J.cross Department of Radiology and Imaging Sciences University of Utah Salt Lake City UT USA Department of Neurosurgery University of Utah Salt Lake City UT USA

Spinal cord injury（ScI） affects thousands of people every year in the USA, and most patients are left with some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, we used magnetic resonance imaging-guided focused ultrasound（MRg FUS） as a non-invasive approach to increase permeability in the blood-spinal cord barrier（BScB）. We hypothesize that localized, controlled sonoporation of the BScB by MRg FUS will aid delivery of therapeutics to the injury. Here, we report our preliminary findings for the ability of MRg FUS to increase BScB permeability in the thoracic spinal cord of a normal rat model. First, an excised portion of normal rat spinal column was used to characterize the acoustic field and to estimate the insertion losses that could be expected in an MRg FUS blood spinal cord barrier opening. Then, in normal rats, MRg FUS was applied in combination with intravenously administered microbubbles to the spinal cord region. Permeability of the BScB was indicated as signal enhancement by contrast administered prior to T1-weighted magnetic resonance imaging and verified by Evans blue dye. Neurological testing using the Basso, Beattie, and Breshnahan scale and the ladder walk was normal in 8 of 10 rats tested. Two rats showed minor impairment indicating need for further refinement of parameters. No gross tissue damage was evident by histology. In this study, we have opened successfully the blood spinal cord barrier in the thoracic region of the normal rat spine using magnetic resonance-guided focused ultrasound combined with microbubbles.

关键词： focused ultrasound spinal cord magnetic resonance imaging contrast-enhanced blood-spinalcord barrier

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