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Predictive biomarkers in precision medicine and drug development against lung cancer

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Chinese journal of Cancer 2015年第7期34卷 295-309页

作者： Bingliang Fang Reza j Mehran john V Heymach Stephen G Swisher Department of Thoracic and Cardiovascular Surgery The University of Texas MD Anderson Cancer Center Department of Thoracic and Head/Neck Medical Oncology The University of Texas MD Anderson Cancer Center

The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been *** agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer ***,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted ***,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug *** review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug *** identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition ***,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.

关键词：生物标志物药物开发预测肺癌医学受体酪氨酸激酶表皮生长因子受体治疗药物

Vibration induced flow in hoppers:DEM 2D polygon model

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Particuology 2008年第6期6卷 455-466页

作者： Feras Y. Fraige Paul A. Langston Andrew j. Matchett john Dodds Faculty of Mining and Environmental Engineering Al-Hussein Bin Talal University Jordan Chemical and Environmental Engineering Nottingham University University Park Chemical Engineering University of Teesside Centre RAPSODEE Ecole Des Mines

A two-dimensional discrete element model （DEM） simulation of cohesive polygonal particles has been developed to assess the benefit of point source vibration to induce flow in wedge-shaped hoppers. The particle-particle interaction model used is based on a multi-contact principle. The first part of the study investigated particle discharge under gravity without vibration to determine the critical orifice size （Bc） to just sustain flow as a function of particle shape. It is shown that polygonal-shaped particles need a larger orifice than circular particles. It is also shown that Bc decreases as the number of particle vertices increases. Addition of circular particles promotes flow of polygons in a linear manner. The second part of the study showed that vibration could enhance flow, effectively reducing Bc. The model demonstrated the importance of vibrator location （height）, consistent with previous continuum model results, and vibration amplitude in enhancing flow.

关键词： Bulk solids Vibration DEM Hoppers Materials handling Polygon

Aseismic smart building isolation systems under multi-level earthquake excitations： Part II, energy-dissipation and damage reduction

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Frontiers of Structural and Civil Engineering 2015年第3期9卷 297-306页

作者： Min-Ho CHEY j. Geoffrey CHASE john B. MANDER Athol j. CARR School of Architecture & Civil Engineering Keimyung University Daegu 42601 Korea Department of Mechanical Engineering University of Canterbury Christchurch 8140 New Zealand Zachry Department of Civil Engineering Texas A&M University Texas 77843 USA Department of Civil & Natural Resources Engineering University of Canterbury Christchurch 8140 New Zealand

Based on the performance results of the previously suggested smart building isolation systems （lst companion paper）, this following study verifies the control effects of the systems from the view point of energy dissipation and damage level metrics. Several different model cases of the strategically isolated multi-story building structures utilizing passive dampers and semi-active resettable devices are analyzed and the energy-based target indices are compared. Performance comparisons are conducted on statistically calculated story/structural hysteretic energy and story/structural damage demands over realistic suites of earthquake ground motion records, representing seismic excitations of specific return period probability. Again, the semi-active solutions show significant promise for applications ofresettable device, offering advantages over passive systems in the consistent damage reductions. The specific results of this study include the identification of differences in the mechanisms by which smart building isolation systems remove energy, based on the differences in the devices used. Less variability is also seen for the semi-active isolation systems, indicating an increased robustness.

关键词： smart building isolation story and structural energy-dissipation damage assessment

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Demographic histories of three predatory lady beetles reveal complex patterns of diversity and population size change in the United States

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Insect Science 2018年第6期25卷 1065-1079页

作者： Arun Sethuraman Fredric j.janzen Michael A.Rubio Yumary Vasquez john j.Obrycki Department of Biological Sciences Cafifomia State University San MarcosSan MarcosCaliforniaUSA Department of Ecology Evolution and Organismal BiologyIowa State UniversityAmesIowaUSA Department of Entomology University of KentuckyLexingtonKentuckyUSA

Predatory lady beetles (Coccinellidae)contribute to biological control of agri- cultural pests,however,multiple species frequently compete for similar resources in the same *** studies have examined ecological interactions among the native North American convergent lady beetle (Hippodamia convergens)and two intro- duced species,the seven-spotted lady beetle (Coccinella septempunctata)and the Asian lady beetle (Harmonia axyridis),in agricultural fields and described multiyear population ***,the evolutionary dynamics of these interacting species of predatory beetles are *** utilize publicly available multilocus genotype data from geographically disjunct populations of these three species to estimate demography across North American *** analyses reveal (1)a recent (4-5years)decline (>12 fold)in microsatellite effective population size ***,while expanding (mutation scaled growth rate in 1/u generations =2910,SD =362)over evolutionary time scales,(2)a massive (>150 fold),and very recent,effective population size decline in Ha. axyridis,and (3)population size growth (mutation scaled growth rate =997,SD =60)over recent and evolutionary time scales in *** these estimates are based on genetic data with different mutation rates and patterns of inheritance (mitochondrial versus nuclear),these dynamic and differing population size histories are striking. Further studies of the interactions of these predatory lady beetles in the field are thus warranted to explore the consequences of population size change and biological control activities for evolutionary trajectories in North America.

关键词： biological control bottleneck demography effective population size inva- siveness predatory lady beetles

Effects of resistance training performed to repetition failure or non-failure on muscular strength and hypertrophy:A systematic review and meta-analysis

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journal of Sport and Health Science 2022年第2期11卷 202-211页

作者： jozo Grgic Brad j.Schoenfeld john Orazem Filip Sabol Institute for Health and Sport(IHES) Victoria UniversityMelbourneVIC 3011Australia Department of Health Sciences Lehman CollegeBronxNY 10468USA School of Health Sciences Human Services and NursingLehman CollegeBronxNY 10468USA Fitness Academy Zagreb 10000Croatia Faculty of Kinesiology University of ZagrebZagreb 10000Croatia

Purpose:We aimed to perform a systematic review and meta-analysis of the effects of training to muscle failure or non-failure on muscular strength and ***:Meta-analyses of effect sizes(ESs)explored the effects of training to failure ***-failure on strength and *** meta-analyses explored potential moderating effects of variables such as training status(trained ***),training volume(volume equated *** non-equated),body region(upper ***),exercise selection(***-joint exercises(only for strength)),and study design(independent *** groups).Results:Fifteen studies were included in the *** studies included young adults as ***-analysis indicated no significant difference between the training conditions for muscular strength(ES=-0.09,95%confidence interval(95%CI):-0.22 to 0.05)and for hypertrophy(ES=0.22,95%CI:-0.11 to 0.55).Subgroup analyses that stratified the studies according to body region,exercise selection,or study design showed no significant differences between training *** studies that did not equate training volume between the groups,the analysis showed significant favoring of non-failure training on strength gains(ES=-0.32,95%CI:-0.57 to-0.07).In the subgroup analysis for resistance-trained individuals,the analysis showed a significant effect of training to failure for muscle hypertrophy(ES=0.15,95%CI:0.03-0.26).Conclusion:Training to muscle failure does not seem to be required for gains in strength and muscle ***,training in this manner does not seem to have detrimental effects on these adaptations,*** studies should be conducted among older adults and highly trained individuals to improve the generalizability of these findings.

关键词： IRM Cross-sectional area Data synthesis Muscle size

Two decades of variable retention in British Columbia: a review of its implementation and effectiveness for biodiversity conservation

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Ecological Processes 2019年第1期8卷 402-423页

作者： William j.Beese john Deal B.Glen Dunsworth Stephen j.Mitchell Timothy j.Philpott Vancouver Island University 900 Fifth StreetNanaimoBC V9R 5S5Canada Western Forest Products 118–1334 Island Hwy.Campbell RiverBC V9W 8C9Canada Glen Dunsworth Ecological Consulting 7857 Shangri-La Rd.LantzvilleBC V0R 2H0Canada University of British Columbia 2424 Main MallVancouverBC V6T 1Z4Canada BC Min.of Forests Lands and Nat.Res.Oper400–640 Borland St.Williams LakeBC V2G 4T1Canada

Stand-level retention is an important component of sustainable forest management which aims to balance ecological,social and economic ***-term retention of mature forest structures at the time of harvesting(variable retention)is intended to produce future forest stands that more closely resemble conditions that develop after natural disturbances,thereby maintaining greater diversity of habitats for a variety of *** includes features such as live and dead trees representing multiple canopy layers,undisturbed understory vegetation and coarse woody *** the past two decades,variable retention has become common on forest lands in the temperate rainforests of coastal British Columbia(BC)and has been applied to a lesser extent in inland forest *** review of studies in BC and in similar forest types in our region indicates that both aggregated and dispersed retention can contribute to biodiversity conservation by providing short-term‘life-boating’habitat for some species and by enhancing the structural characteristics of future *** example,greater abundance of species present in the pre-harvest forest have been documented for vegetation,birds,carabid beetles,gastropods,ectomycorrhizal fungi and soil fauna in retention cutblocks compared to *** are,however,some negative consequences for timber production such as wind damage to retained trees and reduced growth rates of tree regeneration compared to *** authors suggest an adaptive management approach for balancing competing objectives when faced with *** includes monitoring the implementation and effectiveness of various strategies for achieving *** two decades of experience applying variable retention harvesting to industrial-scale management of forest lands in BC suggests that it is possible to balance production of wood with biodiversity conservation.

关键词： Alternative silvicultural systems Clearcutting Biological legacies Forest biodiversity Old-growth Variable retention British Columbia

Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems

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Hepatobiliary & Pancreatic Diseases International 2018年第2期17卷 169-175页

作者： Nikolaos Benetatos james Hodson Ravi Marudanayagam Robert P Sutcliffe john R Isaac john Ayuk Tahir Shah Keith j Roberts The HPB Unit Queen Elizabeth Hospital Birmingham University Hospitals Birmingham NHS Foundation Trust Institute of Translational Medicine Queen Elizabeth Hospital Birmingham University Hospitals Birmingham Endocrinology Queen Elizabeth Hospital Birmingham University Hospitals Birmingham Liver Unit Queen Elizabeth Hospital Birmingham University Hospital of Birmingham NHS Foundation Trust

Background: Pancreatic neuroendocrine tumors(PNETs) display wide heterogeneity with highly variable prognosis. This study aimed to identify variables related to survival after surgical resection of ***: A total of 143 patients were identified from a prospectively maintained database. Patient characteristics were analyzed and prognostic factors for overall survival and progression-free survival were evaluated. The WHO, ENETS and AjCC scoring systems were applied to the cohort, and their ability to predict patient outcomes were ***: Multivariate analysis found that female gender, lymph node metastases and increasing WHO2010 grade to be independently associated with reduced overall survival(P jCC scoring systems to be similarly predictive of 5-year overall survival. Modified Ki67 significantly improved its accuracy in predicting 5-year overall survival(AUROC: 0.699 vs 0.605;P < 0.01).Conclusions: Multi-visceral or debulking surgery is associated with poor outcomes. There seems to be no significant difference between enucleation and anatomical segmental resection. Available scoring systems have reasonable accuracy in stratifying disease severity, with no system identified as being *** stratification with modified grading systems needs further validation before applied in clinical practice.

关键词： Pancreatic neuroendocrine tumors Prognostic factors Validation of staging systems

The effects of growth hormone on therapy resistance in cancer

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Cancer Drug Resistance 2019年第3期2卷 827-846页

作者： Reetobrata Basu john j.Kopchick Ohio University Heritage College of Osteopathic Medicine(OU-HCOM) Ohio UniversityAthensOH 45701USA Edison Biotechnology Institute Ohio UniversityAthensOH 45701USA.

Pituitary derived and peripherally produced growth hormone(GH)is a crucial mediator of longitudinal growth,organ development,metabolic regulation with tissue specific,sex specific,and age-dependent *** and its cognate receptor(GHR)are expressed in several forms of cancer and have been validated as an anti-cancer target through a large body of in vitro,in vivo and epidemiological ***,the underlying molecular mechanisms of GH action in cancer prognosis and therapeutic response had been sparse until *** review assimilates the critical details of GH-GHR mediated therapy resistance across different cancer types,distilling the therapeutic implications based on our current understanding of these effects.

关键词： Growth hormone receptor growth hormone therapy resistance chemoresistance

Magnetic resonance studies of a gas-solids fluidised bed:jet-jet and jet-wall interactions

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Particuology 2010年第6期8卷 617-622页

作者： Meenal Pore Daniel j.Holland Thusara C.Chandrasekera Christoph R.Müller Andrew j.Sederman john S.Dennis Lynn F.Gladden john F.Davidson Department of Chemical Engineering and Biotechnology University of CambridgePembroke StreetCambridgeCB2 3RAUK Department of Mechanical and Process Engineering ETH ZurichSonneggstrasse 38092 ZurichSwitzerland

Magnetic resonance imaging （MRI） gave images of air jets from orifices in the distributor plate of a bed of poppy seeds. Attention focused on two features：（1） The interaction between nearby vertical jets from two, three or four orifices; （2） Wall effects, where one or more orifices created vertical jets near the vertical wall of the cylinder containing the particle bed. The results show that nearby jets are mutually attracted. Likewise a jet near a wall bends out of the vertical, towards the wall, For multiple adjacent jets, the jet lengths show dependence on orifice layout： the lengths are in reasonable agreement with published measurements, by other methods, for single jets. The MRI gives three-dimensional images of the single jets and of multiple jets, separate or merging.

关键词： Fluidised bed MRI jets Distributor design