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| 1 | Expression and reconstitution of the bioluminescent Ca2+reporter aequorin in human embryonic stem cells,and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes显示文摘In order to develop a novel method of visualizing possible Ca^(2+) signaling during the early differentiation of h ESCs into cardiomyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the bioluminescent Ca^(2+) reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation with f-coelenterazine. The temporal nature of the Ca^(2+) signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca^(2+) transients(generated by release from intracellular stores) were detected in 1–12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KCl or Ca Cl_2, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor(IP_3R) agonist, small Ca^(2+) transients were generated from day 1 onward. That ATP was inducing Ca^(2+) release from functional IP_3 Rs was demonstrated by treatment with 2-APB, a known IP_3 R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor(Ry R) agonist, a minimal Ca^(2+) response was observed at day 8 of differentiation only. Thus, our data indicate that unlike Ry Rs, IP_3 Rs are present and continually functional at these early stages of cardiomyocyte differentiation. | Harvey Y.S.Chan Man Chun Cheung Yi Gao Andrew L.Miller Sarah E.Webb | 2016 | Science China(Life Sciences)2016，59，8： | 5 |
| 2 | Identification of Ca2+ signaling components in neural stem/progenitor cells during differentiation into neurons and glia in intact and dissociated zebrafish neurospheres显示文摘The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells(NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3 r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor(IP3 R) type-1 and ryanodine receptor(RyR) type-2 are differentially expressed in cells with neuron-or radial glial-like properties. Furthermore, ATP but not caffeine(IP3 R and RyR agonists, respectively), induced the generation of Ca^(2+) transients in cells exhibiting neuron-or glial-like morphology. These results indicate the differential expression of components of the Ca^(2+) -signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca^(2+) signaling as a read-out. | Man Kit Tse Ting Shing Hung Ching Man Chan Tiffany Wong Mike Dorothea Catherine Leclerc Marc Moreau Andrew L.Miller Sarah E.Webb | 2018 | Science China(Life Sciences)2018，61，11： | 4 |
| 3 | 汽车发动机用粉末冶金主轴承盖显示文摘粉末冶金主轴承盖(MBC)于1993年第一次用于GM的3100与3800V6发动机。该零件一年消耗粉末5 000多t,是北美粉末冶金零件中应用量最大者。选择粉末冶金材料替代传统的铸铁,是因为其有利于零件的功能,而且因为粉末冶金工艺能成形为最终形状,从而使GM可节省下对主轴承盖的切削加工生产线的大部分投资。由于灰铸铁强度不够高,球墨铸铁的价格高又难切削加工,因此,为这种零件开发了一种强度高、成本低的粉末冶金合金钢。这篇论文说明了主轴承盖的功能要求,比较了铸铁与粉末冶金的材料和生产工艺,说明了粉末冶金的设计利益;此外,还讨论了粉末冶金主轴承盖要求的强度、一致性、完善性(无缺陷)及切削性,其中包括试验与试验验证。 | Terry M.Cadle Mark A.Jarrett William L.Miller 韩凤麟 | 2009 | 粉末冶金技术2009，27，5： | 3 |
| 4 | YPED: An Integrated Bioinformatics Suite and Database for Mass Spectrometry-based Proteomics Research显示文摘We report a significantly-enhanced bioinformatics suite and database for proteomics research called Yale Protein Expression Database(YPED) that is used by investigators at more than 300 institutions worldwide. YPED meets the data management, archival, and analysis needs of a high-throughput mass spectrometry-based proteomics research ranging from a singlelaboratory, group of laboratories within and beyond an institution, to the entire proteomics community. The current version is a significant improvement over the first version in that it contains new modules for liquid chromatography–tandem mass spectrometry(LC–MS/MS) database search results, label and label-free quantitative proteomic analysis, and several scoring outputs for phosphopeptide site localization. In addition, we have added both peptide and protein comparative analysis tools to enable pairwise analysis of distinct peptides/proteins in each sample and of overlapping peptides/proteins between all samples in multiple datasets. We have also implemented a targeted proteomics module for automated multiple reaction monitoring(MRM)/selective reaction monitoring(SRM) assay development. We have linked YPED's database search results and both label-based and label-free fold-change analysis to the Skyline Panorama repository for online spectra visualization. In addition, we have built enhanced functionality to curate peptide identifications into an MS/MS peptide spectral library for all of our protein database search identification results. | Christopher M.Colangelo Mark Shifman Kei-Hoi Cheung Kathryn L.Stone Nicholas J.Carriero Erol E.Gulcicek TuKiet T.Lam Terence Wu Robert D.Bjornson Can Bruce Angus C.Nairn Jesse Rinehart Perry L.Miller Kenneth R.Williams | 2015 | Genomics, Proteomics & Bioinformatics2015，13，1： | 3 |
| 5 | The teaching of academic listening comprehension and the question of authenticity显示文摘 | Flowerdew J L.Miller | | 0，，01： | 1 |
| 6 | Development of gemcitabine-resistant patient-derived xenograft models of pancreatic ductal adenocarcinoma显示文摘Aim:Gemcitabine is a frontline agent for locally-advanced and metastatic pancreatic ductal adenocarcinoma(PDAC),but neither gemcitabine alone nor in combination produces durable remissions of this tumor type.We developed three PDAC patient-derived xenograft(PDX)models with gemcitabine resistance(gemR)acquired in vivo,with which to identify mechanisms of resistance relevant to drug exposure in vivo and to evaluate novel therapies.Methods:Mice bearing independently-derived PDXs received 100 mg/kg gemcitabine once or twice weekly.Tumors initially responded,but regrew on treatment and were designated gemR.We used immunohistochemistry to compare expression of proteins previously associated with gemcitabine resistance[ribonucleotide reductase subunit M1(RRM1),RRM2,human concentrative nucleoside transporter 1(hCNT1),human equilibrative nucleoside transporter 1(hENT1),cytidine deaminase(CDA),and deoxycytidine kinase(dCK)]in gemR and respective gemcitabine-naïve parental tumors.Results:Parental and gemR tumors did not differ in tumor cell morphology,amount of tumor-associated stroma,or expression of stem cell markers.No consistent pattern of expression of the six gemR marker proteins was observed among the models.Increases in RRM1 and CDA were consistent with in vitro-derived gemR models.However,rather than the expected decreases of hCNT1,hENT1,and dCK,gemR tumors expressed no change in or higher levels of these gemR marker proteins than parental tumors.Conclusion:These models are the first PDAC PDX models with gemcitabine resistance acquired in vivo.The data indicate that mechanisms identified in models with resistance acquired in vitro are unlikely to be the predominant mechanisms when resistance is acquired in vivo.Ongoing work focuses on characterizing unidentified mechanisms of gemR and on identifying agents with anti-tumor efficacy in these gemR models。 | Aubrey L.Miller Patrick L.Garcia Tracy L.Gamblin Rebecca B.Vance Karina J.Yoon | 2020 | Cancer Drug Resistance2020，3，3： | 1 |
| 7 | English teacher preference:The case of China's non-English-major students显示文摘 | He D L.Miller | | 0，，03： | 1 |
| 8 | Calcium signaling during the early meroblastic cleavages of zebrafish and medaka embryos显示文摘The regulation of cytokinesis in“giant”embryonic cells(i.e.,>500μm in diameter)presents exacting challenges that include long-range signaling with respect to time and space;the transport and assembly,followed by disassembly,of an extensive contractile apparatus;and the remodeling and addition of new surface membrane to the resulting daughter cells. | Andrew L.MILLER | 2010 | Frontiers in Biology2010，5，4： | 0 |
| 9 | Rational design of oral drugs targeting mucosa delivery with gut organoid platforms显示文摘Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads(i.e.,immunogens)against gastric damage.In this study,hollowed nanocarriers(NCs:silica nanospheres and gold nanocages)with poly-l-lysine(PLL)coating and mammalian orthoreovirus cell attachment proteinσ1 functionalization(NC-PLL-σ1)were explored as functional oral drug delivery vehicles(ODDVs).The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells(M-cells)mediated transcytosis(viaσ1-α2–3-linked sialic acids adherence)across gastrointestinal epithelia.PLL coating provided protection and slow-release of rhodamine 6 G(R6G),a model payload.The transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in vitro.When compared with other experimental groups,the fully functionalized ODDV system(with PLL-σ1)demonstrated two significant advantages:a significantly higher transport efficiency(198%over blank control at 48 h);and protection of payloads which led to both better transport efficiency and extended-release of payloads(61%over uncoated carriers at 48 h).In addition,it was shown that the M cell presence in intestinal organoid monolayers(modulated by Rank L stimulation)was a determining factor on the transport efficiency of the ODDVs:more M-cells(induced by higher Rank L)in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload(R6G).The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines. | Tianjian Tong Yijun Qi Derrick Rollins Luke D.Bussiere Debarpan Dhar Cathy L.Miller Chenxu Yu Qun Wang | 2023 | Bioactive Materials2023，，12： | 0 |
| 10 | Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review显示文摘There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted. | Avery L.Miller Nathan K.Evanson J.Michael Taylor | 2024 | Neural Regeneration Research2024，19，8： | 0 |
| 11 | The Effects of 5 Weeks of Leg-Drive Training on Bench Press Performance in Recreationally-Trained,College-Age Men显示文摘Introduction The bench press is commonly used to measure upper-body strength.While much emphasis has been placed on the upper-body,little is known about how the lower-body can play a role in bench press performance.Leg-drive is a technique that includes flexing the knee so the feet line up posterior to the knee joint,while simultaneously contracting the knee extensors isometrically during the lift.The purpose of this study was to compare strength characteristics of lifters in a standard bench press versus a leg-drive bench press over the course of 5-weeks of training.Methods Twenty-three recreationally active males(age:22.4±2.1 years,height:175.0±5.9 cm,mass:78.4±9.5 kg)were randomized into a standard bench or leg-drive bench press group.Participants performed four sets to failure,two times per week for five weeks.Variables of interests were training volume and 1-repetition maximum(1RM)strength.For training volume,a 2×5(group×week)repeated measures analysis of variance(RMANOVA)was used.For the 1RM’s,a 2×2×2(group×press type×time)RMANOVA was used.A priori alpha levels were set to 0.05.Results Over time,both groups showed an approximate 6%increase in 1RM strength.Training volume for week 4 was 5.6%less than week 5,but was not different from weeks 1 through 3.No between-group differences were observed for 1RM strength or training volume.Conclusion This results of this work indicates that 5 weeks of leg-drive training is effective in increasing 1RM strength,but was not more effective than standard bench press training.Practically,lifters should choose either lifting style based on personal preference. | Jacob K.Gardner Justin T.Chia Brent M.Peterson Kelsey L.Miller | 2022 | Journal of Science in Sport and Exercise2022，4，3： | 0 |
| 12 | 垂直对流与倾斜对流相互作用的数值试验显示文摘1.引言对称不稳定性('倾斜对流')在大气中起一定作用的看法是有道理的.除理论研究外,Emanuel和他的同事已观测到部分中纬度斜压系统对于倾斜对流来说是中性的,即θ_e(相当位温)和M(总动量)面相互平行.认为在水平温度梯度存在的情况下只要有垂直对流作用就能使大气稳定到倾斜对流,这是没有道理的,其实倾斜对流本身必定出现,并在垂直对流消失之处取而代之.较为合理的观点是认为这些并不是两种互不相关的现象,而是一种较普遍现象的两种情况. | Timothy L.Miller Shih-Hung Chou 吕越华 | 1992 | 气象科技1992，20，6： | 0 |
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