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Co-delivery of PARP and PI3K inhibitors by nanoscale metal-organic frameworks for enhanced tumor chemoradiation

Nano Research 2019年第12期12卷 3003-3017页

作者： Megan j.Neufeld allison N.DuRoss Madeleine R.Landry Hayden Winter Andrea M.Goforth Conroy Sun Department of Pharmaceutical Sciences College of PharmacyOregon State UniversityPortlandOregon 97201USA Department of Chemistry Portland State University1719 SW 10th AvePortlandOregon 97201USA Department of Radiation Medicine Oregon Health&Science University3181 S.W.Sam Jackson Park RdPortlandOregon 97239USA

Due to their complementary activity,the use of DNA damage repair(DDR)inhibitors during radiotherapy(RT)has yielded promising ***,this approach is often hindered by toxicity and poor in vivo stability of the DDR in *** scale metal-organic frameworks(nMOFs)represent an emerging class of crystalline materials which exhibit advantageous properties over traditional nanomaterials and demonstrate great potential in ***,a unique,synergistic treatment strategy for enhancing the therapeutic efficacy of RT vianMOF-mediated drug delivery and RT enhancement was evaluated.A nMOF containing the high-Zelement Hf and the ligand 1,4-dicarboxybenzene(Hf-BDC)was synthesized and loaded with the two DDR inhibitor drugs,talazoparib and buparlisib(TB@Hf-BDC-PEG).TB@Hf-BDC-PEGaugmented RT by increasing reactive oxygen species generation and thus DNA damage of which repair was inhibited *** enhancement was demonstrated in vivo where the combination of concurrent radiation with in travenous TB@Hf-BDC-PEG administration resulted in improved tumor control and increased ***,no apparent toxicity was observed with nMOF treatment,supporting its potential as an attractive candidate over traditional nano *** work provides the first report of nMOFs employed to enhance thetherapeutic response to RT through DDR inhibitor delivery and physical radiation dose enhancement.

关键词： nano scale metal-organic frameworks chemoradiotherapy DNA damage repair inhibitors drug delivery radiation dose enhancement

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Traumatic brain injury induced by exposure to blast overpressure via ear canal

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Neural Regeneration Research 2022年第1期17卷 115-121页

作者： Yang Ou Brad AClifton jinghui Li David Sandlin Na Li Li Wu Chunming Zhang Tianwen Chen jun Huang Yue Yu jerome allison Fan Fan Richard jRoman james Shaffery Wu Zhou Yi Pang Hong Zhu Departmant of Otolaryngology and Head Neck Surgery Department of Neurobiology and Anatomical Sciences MD Program School of Medicine Graduate Program in Neuroscience Department of Pediatrics Department of Pharmacology and Toxicology Department of Psychiatry and Human Behavior University of Mississippi Medical CenterJacksonMSUSA Kunming Medical University KunmingYunnan ProvinceChina Department of Otolaryngology First Affiliated HospitalShanxi Medical UniversityTaiyuanShanxi ProvinceChina

Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian *** ears are most often damaged following exposure to *** there is an association between tympanic membrane perforation and TBI in blast exposure victims,little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear *** present study investigated whether exposure to blasts directed through the ear canal causes brain injury in LongEvans *** were exposed to a single blast(0–30 pounds per square inch(psi))through the ear canal,and brain injury was evaluated by histological and behavioral outcomes at multiple *** exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain,including increased expression of c-Fos,induction of a profound chronic neuroinflammatory response,and apoptosis of *** blast-induced injury was not limited only to the brainstem most proximal to the source of the blast,but also affected the forebrain including the hippocampus,amygdala and the habenula,which are all involved in cognitive ***,the animals exhibited long-term neurological deficits,including signs of anxiety in open field tests 2 months following blast exposure,and impaired learning and memory in an 8-arm maze 12 months following blast *** results suggest that the unprotected ear canal provides a locus for blast waves to cause *** study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center(Animal protocol#0932 E,approval date:September 30,2016 and 0932 F,approval date:September 27,2019).

关键词： anxiety blast ear ear protection learning memory microglia neuroinflammation neuron rat traumatic brain injury

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Current applications of artificial intelligence for intraoperative decision support in surgery allison

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Frontiers of Medicine 2020年第4期14卷 369-381页

作者： j.Navarrete-Welton Daniel A.Hashimoto Surgical Artificial Intelligence and Innovation Laboratory Massachusetts General HospitalBostonMA 02114USA Harvard Medical School BostonMA 02114USA

Research into medical artificial intelligence(AI)has made significant advances in recent years,including surgical *** scoping review investigated AI-based decision support systems targeted at the intraoperative phase of surgery and found a wide range of technological approaches applied across several surgical *** the twenty-one(n=21)included papers,three main categories of motivations were identified for developing such technologies:(1)augmenting the information available to surgeons,(2)accelerating intraoperative pathology,and(3)recommending surgical *** many of the proposals hold promise for improving patient outcomes,important methodological shortcomings were observed in most of the reviewed papers that made it difficult to assess the clinical significance of the reported performance *** limitations,the current state of this field suggests that a number of opportunities exist for future researchers and clinicians to work on AI for surgical decision support with exciting implications for improving surgical care.

关键词： artificial intelligence decision support clinical decision support systems intraoperative deep learning computer vision machine learning surgery

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Accuracy of biometric formulae for intraocular lens power calculation in a teaching hospital

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International journal of Ophthalmology(English edition) 2020年第1期13卷 61-65页

作者： Kevin S Tang Elaine M Tran allison j Chen David R Rivera jorge j Rivera Paul B Greenberg Division of Ophthalmology Alpert Medical SchoolBrown UniversityProvidence 02903Rhode IslandUSA Section of Ophthalmology Providence VA Medical CenterProvidence 02908Rhode IslandUSA Shiley Eye Institute and Department of Ophthalmology University of California San DiegoLa Jolla 92093CaliforniaUSA

AIM: To evaluate the accuracy of three commonly used biometric formulae across different axial lengths(ALs) at one United States Veterans Affairs teaching ***: A retrospective chart review was conducted from November 2013 to May 2018. One eye of each patient who underwent cataract surgery with a monofocal intraocular lens(IOL) was included. The range of postoperative follow-up period was from 3 wk to 4 mo. The Holladay 2, Barrett Universal II, and Hill-Radial Basis Function(Hill-RBF) formulae were used to predict the postoperative refraction for all cataract surgeries. For each formula, we calculated the prediction errors [including mean absolute prediction error(MAE)] and the percentage of eyes within ±0.25 diopter(D) and ±0.5 D of predicted refraction. We performed subgroup analyses for short(AL25.0 mm).RESULTS: A total of 1131 patients were screened, and 909 met the inclusion criteria. Resident ophthalmologists were the primary surgeons in 710(78.1%) cases. We found no statistically significant difference in predictive accuracy among the three formulae over the entire AL range or in the short, medium, and long eye subgroups. Across the entire AL range, the Hill-RBF formula resulted in the lowest MAE(0.384 D) and the highest percentage of eyes with postoperative refraction within ±0.25 D(42.7%) and ±0.5 D(75.5%) of predicted. All three formulae had the highest MAEs(>0.5 D) and lowest percentage within ±0.5 D of predicted refraction(<55%) in short ***: In cataract surgery patients at our teaching hospital, three commonly used biometric formulae demonstrate similar refractive accuracy across all ALs. Short eyes pose the greatest challenge to predicting postoperative refractive error.

关键词： cataract surgery biometry intraocular lens power calculation

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Models to predict injury, physical fitness failure and attrition in recruit training: a retrospective cohort study

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Military Medical Research 2020年第4期7卷 391-400页

作者： Robin M.Orr Bruce S.Cohen Stephen C.allison Lakmini Bulathsinhala Edward j.Zambraski Mark jaffrey Tactical Research Unit Bond University2 Promethean WayGold CoastRobinaQLD 4226Australia United States Army Research Institute for Environmental Medicine NatickMA 01760USA Defence Science and Technology Group Port MelbourneVIC 3207Australia

Background:Attrition rate in new army recruits is higher than in incumbent *** the current study,we identified the risk factors for attrition due to injuries and physical fitness failure in recruit training.A variety of predictive models were ***:This retrospective cohort included 19,769 Army soldiers of the Australian Defence Force receiving recruit training during a period from 2006 to *** them,7692 reserve soldiers received a 28-day training course,and the remaining 12,077 full-time soldiers received an 80-day training *** data included anthropometric measures,course-specific variables,injury,and physical fitness *** regression was used to develop a variety of models to predict the rate of attrition due to injuries and physical fitness *** area under the receiver operating characteristic curve was used to compare the performance of the ***:In the overall analysis that included both the 28-day and 80-day courses,the incidence of injury of any type was 27.8%.The 80-day course had a higher rate of injury if calculated per course(34.3%vs.17.6%in the 28-day course),but lower number of injuries per person-year(1.56 vs.2.29).Fitness test failure rate was significantly higher in the 28-day course(30.0%vs.12.1%).The overall attrition rate was 5.2%and 5.0%in the 28-day and 80-day courses,*** fracture was common in the 80-day course(n=44)and rare in the 28-day course(n=1).The areas under the receiver operating characteristic curves for the course-specific predictive models were relatively low(ranging from 0.51 to 0.69),consistent with"failed"to"poor"predictive *** course-combined models performed somewhat better than the course-specific models,with two models having AUC of 0.70 and 0.78,which are considered"fair"predictive ***:Attrition rate was similar between 28-day and 80-day *** comparison to the 80-day full course,the 28-day course had a lower rat

关键词： Military training Predictive modelling Risk management Soldier

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Nitrogen fertilization and potassium requirement for cereal crops under a continuous no-till system

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Pedosphere 2020年第6期30卷 747-758页

作者： allison j.FORNARI Eduardo F.CAIRES Angelo R.BINI Adriano HALISKI Lucas TZASKOS Helio A.W.jORIS State University of Ponta Grossa Avenida Carlos Cavalcanti 4748Ponta Grossa 84030-900Brazil

Nitrogen(N)and potassium(K)are the most required nutrients for corn and wheat *** the N application rate usually boosts crop ***,many uncertainties remain for K *** deficiency results in yield losses,but K application rate based on the percentage of K+in the cation exchange capacity(CEC)is doubtful,especially in soil with high CEC.A field trial was conducted to examine the effects of KCl application before sowing corn and wheat,by raising the percentage of K+in CEC at pH 7.0(CECpH7.0)to approximately 2.5%,3.5%,and 4.5%,and adding N as a topdressing(75,150,and 225 kg ha-1 to corn and 40,80,and 120 kg ha-1 to wheat)on the nutrition and yield of corn and wheat under a continuous no-till system(30 years).Exchangeable K+content increased in the topsoil(0–20 cm depth)up to 7.2 mmolc dm-3 after K application at the highest rate,which,however,did not result in significant increases in nutrient uptake and yields for both corn and *** N application rate positively affected the uptake and removal of all macronutrients by corn and *** N as a topdressing increased yields of corn and wheat by up to 83%and 22%,*** results suggest that in the soil with a high CECpH7.0(162.1 mmolc dm-3),the recommendation for K application made by considering the percentage of K+in the CECpH7.0 may result in excessive application of K fertilizer to crops with high K-recycling potential grown under a continuous no-till system.

关键词： cation exchange capacity crop K demand K recycling N requirement Triticum aestivum L. Zea mays L.

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Cold adaptation does not alter ATP homeostasis during cold exposure in Drosophila melanogaster

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Integrative Zoology 2018年第4期13卷 471-481页

作者： Caroline M.WILLIAMS james R.ROCCA Arthur S.EDISON David B.allison Theodore j.MORGAN Daniel A.HAHN Department of Integrative Biology University of CaliforniaBerkeleyCaliforniaUSA Departments of Entomology and Nematology University of FloridaGainesvilleFloridaUSA Biochemistry University of FloridaGainesvilleFloridaUSA Advanced Magnetic Resonance Imaging and Spectroscopy Facility McKnight Brain InstituteUniversity of FloridaGainesvilleFloridaUSA Departments of Genetics and Biochemistry Complex Carbohydrate Research CenterUniversity of GeorgiaAthensGeorgiaUSA Department of Epidemiology and Biostatistics School of Public HealthIndiana University BloomingtonBloomingtonIndianaUSA Division of Biology Kansas State UniversityManhattanKansasUSA

In insects and other ectotherms,cold temperatures cause a coma resulting from loss of neuromuscular function,during which ionic and metabolic homeostasis are progressively *** adaptation improves homeostasis during cold exposure,but the ultimate targets of selection are still an open *** acclimation and adaptation remodels mitochondrial metabolism in insects,suggesting that aerobic energy production during cold exposure could be a target of ***,we test the hypothesis that cold adaptation improves the ability to maintain rates of aerobic energy production during cold exposure by using^(31)P NMR on live *** lines of Drosophila melanogaster artificially selected for fast and slow recovery from a cold coma,we show that cold exposure does not lower ATP levels and that cold adaptation does not alter aerobic ATP production during cold ***-hardy and cold-susceptible lines both experienced a brief transition to anaerobic metabolism during cooling,but this was rapidly reversed during cold exposure,suggesting that oxidative phosphorylation was sufficient to meet energy demands below the critical thermal minimum,even in cold-susceptible *** thus reject the hypothesis that performance under mild low temperatures is set by aerobic ATP supply limitations in ***,excluding oxygen and capacity limitation as a weak link in energy *** work suggests that the modulations to mitochondrial metabolism resulting from cold acclimation or adaptation may arise from selection on a biosynthetic product(s)of those pathways rather than selection on ATP supply during cold exposure.

关键词： chill coma energetics insect oxygen limitation thermal tolerance

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Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for ***

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Synthetic and Systems Biotechnology 2017年第1期2卷 49-58页

作者： allison E.B.Turner jonas E.Gerson Helen Y.So Daniel j.Krasznai Adrienne j.St.Hilaire Donald F.Gerson Vaccine Research and Development PnuVax Incorporated Headquarters134 Albert St.KingstonOntarioK7L 3V2Canada Vaccine Research and Development PnuVax Incorporated Laboratories6000 Royalmount Ave.MontrealQuebecH4P 2T1Canada

Pneumonia remains the single leading cause of childhood death *** the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing *** current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine *** 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and *** polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation *** vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free *** vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 ***-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were *** serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose *** a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV *** in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

关键词： Pneumonia Vaccine development PCV Pneumococcal conjugate vaccine Polysaccharide Carrier protein In vacuo glycation

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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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压铸过程中铸件-铸型界面换热系数与铸件凝固速率的关系

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金属学报 2009年第1期45卷 102-106页

作者：郭志鹏熊守美 Mei Li john allison 清华大学机械工程系先进成形制造教育部重点实验室北京100084 Research ＆ Advanced Engineering Department Scientific Research Laboratory Ford Motor Company Dearborn MI 48121 USA

在实际压铸实验的基础上,求解了铸件-铸型界面换热系数h与铸件凝固速率v的关系.结果表明,二者呈线性变化关系:h=k_(h-v)·v+ω(其中,斜率k_(h-v)为铸型初始表面温度及铸件厚度的函数,ω为常数);通过线性拟合确定k_(h-v)和ω值,从而确立... 详细信息

在实际压铸实验的基础上,求解了铸件-铸型界面换热系数h与铸件凝固速率v的关系.结果表明,二者呈线性变化关系:h=k_(h-v)·v+ω(其中,斜率k_(h-v)为铸型初始表面温度及铸件厚度的函数,ω为常数);通过线性拟合确定k_(h-v)和ω值,从而确立换热系数与铸件凝固速率的关系.这种关系同时适用于镁合金AM50和铝合金ADC12.

关键词：压铸界面换热系数凝固速率镁合金AM50 铝合金ADC12

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