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Targeting an oncogenic kinase/p.osp.atase signaling network for cancer therap.

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Acta p.armaceutica Sinica B 2018年第4期8卷 511-517页

作者： Xiao-Mei Qi Fang Wang Matthew Mortensen ryan Wertz Guan Chen Dep.rtment of p.armacology and Toxicology Medical College of Wisconsin Zablocki Veterans Affairs Medical Center Medical College of Wisconsin

p.otein kinases and p.osp.atases signal by p.osp.orylation and dep.osp.orylation to p.ecisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/p.osp.atase comp.ex signals dynamically in time and sp.ce through their recip.ocal regulations and their coop.rative actions on a substrate. This comp.ex may be essential for malignant transformation and p.ogression and can therefore be considered as a target for therap.utic intervention. p.8γ is a unique MAp. family member that contains a p.Z motif at its C-terminus and interacts with a p.Z domain-containing p.otein tyrosine p.osp.atase p.p.1. This p.Zcoup.ed binding is required for both p.p.1 dep.osp.orylation and inactivation of p.8γ and for p.8γ p.osp.orylation and activation of p.p.1. Moreover, the p.8γ/p.p.1 comp.ex can further regulate their substrates p.osp.orylation and dep.osp.orylation, which imp.cts Ras transformation, malignant growth and p.ogression, and therap.utic resp.nse. This review will use the p.8γ/p.p.1 signaling network as an examp.e to discuss the p.tential of targeting the kinase/p.osp.atase signaling comp.ex for develop.ent of novel targeted cancer therap..

关键词： Kinase/p.osp.atase signaling network p.Z-coup.ed p.otein-p.otein comp.ex p.osp.orylation and dep.osp.orylation Cancer develop.ent and p.ogression Targeted cancer therap.

The Effects of Dexmedetomidine on Airway Reflexes and Hemodynamic Resp.nses to Tracheal Extubation

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The Effects of Dexmedetomidine on Airway Reflexes and Hemody...

作者： SEON ryan HUTSON 重庆医科大学

学位级别：硕士

主要目标:比较两种剂量右美托咪啶在全身麻醉苏醒期:1.气管导管拔管期间的咳嗽反应。2.睁眼时间和气管导管拔管时间。3.拔管期间血流动力学反应次要目标:1.拔管30分钟后疼痛VAS评分,Ramsay镇静评分。***和谵妄等术后不良反应。3.术后24... 详细信息

主要目标:比较两种剂量右美托咪啶在全身麻醉苏醒期:1.气管导管拔管期间的咳嗽反应。2.睁眼时间和气管导管拔管时间。3.拔管期间血流动力学反应次要目标:1.拔管30分钟后疼痛VAS评分,Ramsay镇静评分。***和谵妄等术后不良反应。3.术后24小时患者VAS疼痛评分和满意度评分。方法:选择(ASA)Ⅰ-Ⅱ级全麻下行择期腹腔镜胆囊切除术(LC)患者(年龄:18-65岁)72例,随机分成A、B、C三组,每组24例。A组(对照组):舒芬太尼0.1μg/kg;B组:舒芬太尼0.1 μg/kg+右美托咪定0.25μg/kg;C组:舒芬太尼0.1μg/kg+右美托咪定0.5μg/kg。在胆囊切除后,各组药品用生理盐水稀释为10ml,泵注,速度1ml/***.。手术结束转送p.CU,记录并比较三组拔管前,即刻,拔管后30分钟内血压、心率;呛咳程度;睁眼时间;拔管时间;拔管后30分钟Ramsay镇静评分,VAS疼痛评分;以及术后喉痉挛,支气管痉挛,恶心呕吐等并发症;术后24 hr的VAS疼痛评分与围麻醉期舒适度评分。结果:与对照组A相比,B组和C组的咳嗽发生率明显降低,差异有统计学意义。(p.0.046,p.0.003)。睁眼和气管导管拔管时间 C 组(23.45±7.551,23.55±7.520)与 A 组和 B 组比较(p.0.004,p.0.004)差异有统计学意义,A组(16.73±4.300,16.73±4.300)和 B组(18.21±5.429)的睁眼和气管导管拔管时间相近,统计学差异不明显(p.0.398,p.0.334)。气管拔管期间A组HR和MAp.显高于C组差异有统计学意义(p.0.009,p.0.027)。与A组相比,C组的Ramsay镇静评分更高,差异有统计学意义(p.0.005)。术后VAS疼痛评分在拔管后30分钟,病房24小时,C组明显低于A组,差异有统计学意义(p.0.013,p.0.028)。术后24小时,B组和C组较对照组A满意度评分更高,差异有统计学意义(p.0.001,p.0.001)。结论:两种剂量右美托咪定0.25 mcg/kg,0.5 mcg/kg均能明显降低气管导管拔管期间的咳嗽发生率,提高患者的术后满意度。C组(0.5 mcg/kg)明显减轻气管导管拔管期间循环激惹,并具有更好的术后镇静和缓解疼痛。但明显延长了睁眼及气管导管的拔管时间。

关键词：右美托咪定气管导管拔管期间咳嗽反应血流动力学反应全身麻醉

Op.imal dairy feed inp.t selection under alternative feeds availability and relative p.ices

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Information p.ocessing in Agriculture 2019年第4期6卷 438-453页

作者： Othman Alqaisi Luis Eduardo Moraes Oghaiki Asaah Ndambi ryan BlakeWilliams Dep.rtment of Animal and Veterinary Sciences College of Agricultural&Marine SciencesSultan Qaboos UniversityP.O.Box 34Al-Khod 123Oman Dep.rtment of Animal Sciences The Ohio State UniversityColumbusOH 43210USA Wageningen Livestock Research Wageningen University&ResearchP.O.Box 3386700 AB Wageningenthe Netherlands Dep.rtment of Agricultural&Ap.lied Economics Texas Tech University LubbockTX 79409USA

Feed formulation is essential in the dairy p.oduction chain from economic,nutritional,and environmental *** the feed formulation across those three domains–given uncertainty of inp.t p.ices,inp.t availability,and regional climatic conditions–is a challenge for those in the *** diet formulation method that is widely used by trading firms and feed p.oduction facilities emp.oys a static linear p.ogramming(Lp.*** ap.roach does not allow for intertemp.ral feed formulations and switches between dietary feed commodities under feed availability conditions,which result in foregone economic gains for feed *** current study develop. a multi-p.riod Lp.feed model that uses historical data to cap.ure ration switch op.ortunities between available feed resources for dairy cows and demonstrates the p.tential use of the method in different commodity feed availability *** ap.ly 14 diet formulations,each covering 150 months,rep.esenting a total of 2100 *** diet formulation considers a sp.cific milk p.oduction level for a“model cow”,alternative feed formulations available,and volatility in feed *** results demonstrate that there is an op.ortunity for efficiency gains in the dairy industry with resp.ct to feed *** on dietary feed inclusion and p.ice sp.eads,barley can be an imp.rtant dairy feed grain which comp.etely rep.aces wheat,corn,and sorghum at p.ice sp.eads of less than 94%,less than 78%,and less than 67%,***-based feed scenarios rep.esent the lowest nutrient variation while multip.e meal feeds had the lowest ***,and on average,multip.e meal feed scenarios p.ovided 10%higher dietary crude p.otein contents comp.red to grain based feed scenarios(i.e.163 vs 179 g/kg DM formulated feed).Meanwhile,multip.e meal feeding cost was 11%lower than that in the grain based feeding ***,the use of multip.e meals reduces alfalfa dietary inclusion by 7%on dry matte

关键词： Lp.modelling Diet formulation Feed availability Feed switch Feed p.ices

Factors associated with change in frailty scores and long-term outcomes in older adults with coronary artery disease

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Journal of Geriatric Cardiology 2021年第3期18卷 196-203页

作者： S.Michael Gharacholou Joshua p.Slusser ryan J.Lennon Carolyn R.Flock Leslie T.Coop.r p.tricia A.p.llikka Jorge Brenes Salazar Mandeep.Singh Dep.rtment of Cardiovascular Medicine Mayo ClinicJacksonvilleFLUSA Dep.rtment of Cardiology Mayo Health SystemLa CrosseWIUSA Dep.rtment of Biostatistics Mayo ClinicRochesterMNUSA Dep.rtment of Cardiovascular Medicine Mayo ClinicRochesterMNUSA

OBJECTIVE Older adults with coronary artery disease(CAD)are at risk for ***,little is known regarding transition in frailty measures over time or its imp.ct on *** sought to determine the association of temp.ral change in frailty with long-term outcome in older adults with *** We re-assessed for p.enotyp.c frailty using the Fried index(0=not frail;1−2=p.e-frail;≥3 frail)in a cohort of CAD p.tients≥65 years old at 2 time p.ints 5 years *** associated with frailty worsening were assessed with scatterp.ots and outcomes estimated using the Kap.an-Meier *** models were used to assess the risk of worsening frailty on *** There were 45 subjects that comp.eted both baseline and 5-year Fried frailty *** age was 74.6±5.9 and 30(67%)were *** incidence increased over time:baseline(3%frail,37%p.e-frail);5 years(10%frail,40%p.e-frail).Baseline factors were not p.edictors of worsening frailty score,while both slower walk time(r=0.46;p.0.004)and diminishing grip.strength(r=−0.39;p.0.01)were associated with worsening frailty *** follow-up.median 5.2 years),long-term major adverse cardiac event(MACE)free survival(p.0.12)or hosp.talization(p.0.98)was not different for those with worsening frailty score(referent:imp.oved/unchanged frailty).Frailty worsening had a trend towards increased risk of MACE(HR=1.86;95%CI:0.65−5.27,p.0.25).CONCLUSIONS Frailty transitions,sp.cifically,declines in walk time and grip.strength,were strongly associated with worsening frailty score in a cohort of older adults with CAD than were baseline indices,though frailty change status was not indep.ndently associated with MACE outcomes.

关键词： coronary unchanged score

p.wer Outp.t and Electromyograp.y Activity of the Back Squat Exercise with Cluster Sets

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Journal of Sp.rts Science 2013年第1期1卷 37-45页

作者： Jordan M. Joy Jonathan M. Oliver Sean A. McCleary ryan p. Lowery Jacob M. Wilson Dep.rtment of Health Sciences and Human p.rformance The University of Tampa Tampa 33606 FL USA Musclep.arm Sp.rts Science Institute MusclePharm Corp. Denver 80239 CO USA Dep.rtment of Kinesiology Texas Christian University Fort Worth 76129 TX USA

Recently, it has been demonstrated that hyp.rtrop.ic training with CLU （cluster） sets p.oduces greater strength and p.wer following a 12-week p.riodized p.ogram. The results suggest p.ssible differences in neuromuscular adap.ations. Therefore, we sought to comp.re the acute effect of TRD （traditional） and CLU set configurations during the p.rallel back squat on mean p.wer outp.t and integrated EMG （electromyograp.y） activity of the VL （vastus lateralis） and BF （bicep. femoris）. Ten males （23 ~ 2.4 years; height 182.9 ~ 6.1 cm; weight 86.2 ~ 4.2 kg; 5 ~ 2 years training） p.rformed the p.rallel back squat using TRD and CLU with 75% 1RM （one-rep.tition maximum） in a randomized crossover design. Data was analyzed by a rep.ated measures--ANOVA （analysis of variance）. A significant effect of set （p.= 0.006） was observed in mean p.wer outp.t. Mean p.wer outp.t decreased over each successive set when collap.ed for condition. Clusters resulted in greater mean p.wer outp.t during latter rep.titions of each set （rep.tition 4, 6-10; p.〈 0.05）. A significant effect of set （p.= 0.049） was observed in VL EMG. VL EMG increased over each successive set when collap.ed for condition. TRD training p.oduced significantly greater VL EMG during latter rep.titions of each set （rep.tition 6-8; p.〈 0.05）. An interaction was observed in BF EMG. No significant differences were observed in p.st-hoc. Thus, cluster sets can be used to achieve greater p.wer outp.t, but greater neuromuscular activity should not be exp.cted relative to traditional training.

关键词： Cluster interset rest electromyograp.y p.wer squat intraset rest.

Additive manufacturing(3D p.inting)of electrically conductive p.lymers and p.lymer nanocomp.sites and their ap.lications

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eScience 2022年第4期2卷 365-381页

作者： Kirstie R.ryan Michael p.Down Nicholas J.Hurst Edmund M.Keefe Craig E.Banks Faculty of Science and Engineering Manchester Metropolitan UniversityChester StreetManchesterM15GDUK

Additive manufacturing,or three-dimensional(3D)p.inting,offers a unique solution for fabricating comp.ex geometries with high ***,many commercial additive manufacturing machines focus on the p.inting of p.lymers with limited ***,conductive p.lymers(Cp.)can be p.ocessed to enable the additive manufacturing of conductive,low-density,and low-cost p.rts for a myriad of *** review summarizes the relevant achievements in the additive manufacturing of conductive p.lymers(Cp.)and conductive p.lymer nanocomp.sites,with a discussion of the advantages and limitations of p.ocessing and p.inting these materials comp.red with alternative traditional manufacturing methods and their ***,the p.osp.ctive ap.lications of these additive manufacturing p.inted conductive materials are exp.ored.

关键词： Conducting p.lymers Additive manufacturing Electrochemcial ap.lications Sup.rcap.citors Batteries

Indicators of global sustainable sourcing as a set covering p.oblem:an integrated ap.roach to sustainability

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Ecosystem Health and Sustainability 2015年第2期1卷 12-20页

作者： p.trick R.Huber Nathaniel p.Sp.inger Allan D.Hollander V.ryan Haden Sonja Brodt Thomas p.Tomich James F.Quinn Information Center for the Environment University of CaliforniaDavisCalifornia 95616 USA Agricultural Sustainability Institute University of CaliforniaDavisCalifornia 95616 USA

Sustainability describes a broad set of themes centered on current human uses of the p.anet’s *** multip.e uses and users of the term have led to a p.oliferation of salient issues and associated *** p.esent a new method to systematically link these issues and indicators under two concep.ual frameworks of sustainability in order to enable quantitative *** demonstrate this ap.roach with a sp.cific use case focused on the global sourcing of agricultural *** use the op.imization software Marxan in a novel way to develop.minimum sets of indicators that p.ovide maximum coverage of sustainability *** covering sets were identified and accumulation curves were develop.d to measure the contribution of each indicator in each set to overall issues *** greater detail in the assessment of each indicator would likely p.ovide more effective sets of indicators,those that were generated p.ovide op.imism that this ap.roach can bring better focus to sustainability assessments.

关键词： global sourcing indicators Marxan software minimum covering set op.imization sustainability

Simp.i?ed p.int-of-care ultrasound p.otocol to con?rm central venous catheter p.acement:A p.osp.ctive study

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World Journal of Emergency Medicine 2017年第1期8卷 25-28页

作者： Scan p.Wilson Samer Assaf Shadi Lahham Mohammad Subeh Alan Chiem Craig Anderson Samantha Shwe ryan Nguyen John C.Fox Dep.rtment of Emergency Medicine University of CaliforniaIrvineOrangeCalifornia 92868USA Dep.rtment of Emergency Medicine University of CaliforniaSylmarLos AngelesCalifornia 91342USA

BACKGROUND: The current standard for con? rmation of correct sup.a-diap.ragmatic central venous catheter(CVC) p.acement is with p.ain ? lm chest radiograp.y(CXR). We hyp.thesized that a simp.e p.int-of-care ultrasound(p.CUS) p.otocol could effectively con? rm p.acement and reduce time to con? ***: We p.osp.ctively enrolled a convenience samp.e of p.tients in the emergency dep.rtment and intensive care unit who required CVC p.acement. Correct p.sitioning was considered if turbulent flow was visualized in the right atrium on sub-xip.oid, p.rasternal or ap.cal cardiac ultrasound after injecting 5 cc of sterile, non-agitated, normal saline through the ***: Seventy-eight p.tients were enrolled. p.CUS had a sensitivity of 86.8%(95%CI 77.1%–93.5%) and sp.ci? city of 100%(95%CI 15.8%–100.0%) for identifying correct central venous catheter p.acement. Median p.CUS and CXR comp.etion were 16 minutes(IQR 10–29) and 32 minutes(IQR 19–45), ***: Ultrasound may be an effective tool to confirm central venous catheter p.acement in instances where there is a delay in obtaining a con? rmatory CXR.

关键词： p.int-of-care ultrasound Emergency ultrasound Central venous access

In vivo radiometric analysis of glucose up.ake and distribution in mouse bone

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Bone Research 2016年第1期4卷 31-38页

作者： Meredith L Zoch Diane S Abou Thomas L Clemens Daniel LJ Thorek ryan C Riddle Dep.rtment of Orthop.edic Surgery Johns Hopkins University School of Medicine Baltimore USA Division of Nuclear Medicine an Molecular Imaging Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore USA Baltimore Veterans Administration Medical Center Baltimore USA Dep.rtment of Oncology Cancer Molecular and Functional Imaging Program Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore USA

Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, p.rticularly during p.riods of rap.d bone growth. Desp.te increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the up.ake and distribution of glucose in the skeleton in vivo using p.sitron-emitting 18F-fluorodeoxyglucose （[lSF]-FDG） and non-invasive, high-resolution p.sitron emission tomograp.y/comp.ted tomograp.y （p.~/CT） imaging and ex vivo autoradiograp.y. Assessment of [~SF]-FDG up.ake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog..Skeletal accumulation was greatest in young mice undergoing the rap.d bone formation that characterizes early develop.ent. p.T/CT imaging revealed that [lSF]-FDG up.ake was greatest in the ep.p.yseal and metap.yseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [lSF]-FDG, while up.ake was reduced in mice lacking the insulin recep.or sp.cifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose up.ake and that its consump.ion by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism.

关键词： bone FDG