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Stroma-targeting strategies in pancreatic cancer:Past lessons,challenges and prospects

World journal of Gastroenterology 2021年第18期27卷 2105-2121页

作者： Faran Polani patrick M Grierson Kian-Huat Lim Division of Oncology Department of Internal MedicineBarnes-Jewish Hospital and The Alvin J.Siteman Comprehensive Cancer CenterWashington University School of MedicineSaint LouisMO 63110United States

Pancreatic ductal adenocarcinoma(PDAC)is projected to emerge as the second leading cause of cancer-related death after *** treatment resistance is perhaps the most significant factor that underlies the poor prognosis of *** date,combination chemotherapy remains the mainstay of treatment for most PDAC *** to other cancer types,treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and *** from typically harboring genetic alterations that to date remain undruggable and are drivers of treatment resistance,PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting cancer progression and treatment ***,emerging evidence also suggests that indiscriminate targeting and near complete depletion of stroma may promote PDAC aggressiveness and lead to detrimental *** conflicting results undoubtedly warrant the need for a more in-depth understanding of the heterogeneity of tumor stroma in order to develop modulatory strategies in favor of tumor *** advent of novel techniques including single cell RNA sequencing and multiplex immunohistochemistry have further illuminated the complex heterogeneity of tumor cells,stromal fibroblasts,and immune *** new knowledge is instrumental for development of more refined therapeutic strategies that can ultimately defeat this ***,we provide a concise review on lessons learned from past stromatargeting strategies,new challenges revealed from recent preclinical and clinical studies,as well as new prospects in the treatment of PDAC.

关键词： Stroma Pancreatic cancer Treatment resistance Cancer-associated fibroblasts Clinical trials

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The Role and Effectiveness of Local Institutions in the Management of Forest Biodiversity in New Dabaga-Ulongambi Forest Reserve,Iringa Region-Tanzania

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Chinese journal of Population,Resources and Environment 2012年第1期10卷 111-115页

作者： Richard A.Giliba Zacharia j.Lupala Canisius j.Kayombo Yobu M.Kiungo patrick Mwendwa Forestry Training Institute Tanzania Kilolo District Natural Resources Office Iringa jomo Kenyatta University of Agriculture and Technology Kenya

This paper examines the role and effectiveness of locacal institutions in the management of forest biodiversity in New Dabaga-Ulongambi Forest Reserve, Tanzania. Data were obtained through questionnaires, interviews, focus group discussions, participatory rural appraisal and field observations. The study revealed that the most remarkable local institutions connected to forest biodiversity management include： Village Natural Resources Man- agement Committee （92%）, tree nursery group （79.4%）, beekeep- ing groups （61.1%）, fish fanning （43.3%）, livestock rearing group （33.9%）. Main activities carried out by local institutions which directly contribute to the sustainability Of forest reserve include： forest patrols, fire extinguish, preparation of fire breaks, plant- ing of trees along the forest boundaries, creation of awareness, arresting of forest defaulters, participation in income generation activities. For the purpose of realization that local communities are capable of managing forest biodiversity through their traditional institutions, the policy should provide tangible opportunity for local communities to meet their needs as they manage the forests.

关键词： local institution participatory forest management forest biodiversity

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Bayesian inference of atomistic structure in functional materials

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npj Computational Materials 2019年第1期5卷 836-842页

作者： Milica Todorović Michael U.Gutmann jukka Corander patrick Rinke Department of Applied Physics Aalto UniversityP.O.Box 11100Aalto FI-00076Finland School of Informatics University of Edinburgh10 Crichton StreetEdinburgh EH89ABUK Institute of Basic Medical Sciences University of OsloSognsvannsveien 90372 OsloNorway Department of Mathematics and Statistics University of HelsinkiP.O.Box 68Helsinki FI-00014Finland

Tailoring the functional properties of advanced organic/inorganic heterogeneous devices to their intended technological applications requires knowledge and control of the microscopic structure inside the *** quantum mechanical simulation methods deliver accurate energies and properties for individual configurations,however,finding the most favourable configurations remains computationally *** propose a‘building block’-based Bayesian Optimisation Structure Search(BOSS)approach for addressing extended organic/inorganic interface problems and demonstrate its feasibility in a molecular surface adsorption *** BOSS,a Bayesian model identifies material energy landscapes in an accelerated fashion from atomistic configurations sampled during active *** allowed us to identify several most favourable molecular adsorption configurations for C_(60) on the(101)surface of TiO_(2) anatase and clarify the key molecule-surface interactions governing structural *** structures were in good agreement with detailed experimental images of this surface adsorbate,demonstrating good predictive power of BOSS and opening the route towards large-scale surface adsorption studies of molecular aggregates and films.

关键词： adsorption functional inorganic

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Temporal changes in physiological and performance responses across game-specific simulated basketball activity

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journal of Sport and Health Science 2018年第2期7卷 176-182页

作者： Aaron T.Scanlan jordan L.Fox Nattai R.Borges patrick S.Tucker Vincent j.Dalbo Human Exercise and Training Laboratory Central Queensland University Clinical Biochemistry Laboratory Central Queensland University School of Medical and Applied Sciences Central Queensland University

Purpose: The aims of this study were to:(1) provide a comprehensive physiological profile of simulated basketball activity and(2) identify temporal changes in player responses in controlled ***: State-level male basketball players(n = 10) completed 4 × 10 min simulated quarters of basketball activity using a reliable and valid courtbased test. A range of physiological(ratings of perceived exertion, blood lactate concentration([BLa~—]), blood glucose concentration([BGlu]), heart rate(HR), and hydration) and physical(performance and fatigue indicators for sprint, circuit, and jump activity) measures were collected across ***: Significantly reduced [BLa~—](6.19 ± 2.30 vs. 4.57 ± 2.33 mmol/L; p = 0.016) and [BGlu](6.91 ± 1.57 vs. 5.25 ± 0.81 mmol/L;p = 0.009) were evident in the second half. A mean HR of 180.1 ± 5.7 beats/min(90.8% ± 4.0% HR max) was observed, with a significant increase in vigorous activity(77%—95% HR max)(11.31 ± 6.91 vs. 13.50 ± 6.75 min; p = 0.024) and moderate decrease in near-maximal activity(>95% HR_(max))(7.24 ± 7.45 vs. 5.01 ± 7.20 min) in the second half. Small increases in performance times accompanied by a significantly lower circuit decrement(11.67% ± 5.55% vs. 7.30% ± 2.16%; p = 0.032) were apparent in the second ***: These data indicate basketball activity imposes higher physiological demands than previously thought and temporal changes in responses might be due to adapted pacing strategies as well as fatigue-mediated mechanisms.

关键词： Cardiovascular Game-play Hydration Rating of perceived exertion Simulation Team sports

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Neoadjuvant chemoradiation changes podoplanin expression in esophageal cancer patients

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World journal of Gastroenterology 2020年第23期26卷 3236-3248页

作者： Ute Warnecke-Eberz patrick Plum Viola Schweinsberg Uta Drebber Christiane j Bruns Dolores T Müller Arnulf H Holscher Elfriede Bollschweiler Department of General Visceral and Cancer SurgeryUniversity Hospital of CologneCologne 50937Germany Department of Dermatology University Hospital of CologneCologne 50937Germany Institute of Pathology University Hospital of CologneCologne 50937Germany Agaplesion Markus Hospital Frankfurt 60431Germany

BACKGROUND Locally advanced adenocarcinoma of the esophagus(EAC) and squamous cell carcinoma(ESCC) result in a worse prognosis. Neoadjuvant treatment improves survival, however, only for responders. The transmembrane glycoprotein podoplanin is overexpressed in squamous cell carcinomas, mi RNA-363 is associated to its regulation in head and neck *** To predict therapy response and prognosis markers, and targets for novel therapies would individualize treatments leading to more favourable *** Expression of podoplanin protein has been visualized by immunohistochemistry in surgical specimens of 195 esophageal cancer patients who underwent transthoracic esophagectomy: 90 ESCC and 105 EAC with clinical T2-3, Nx, *** hundred and six patients received neoadjuvant chemoradiation. RNA was extracted from paraffin-embedded tissue, and mi RNA-363 quantified by realtime Taq Man-real-time-PCR. D2-40 mab staining of > 5% was scored as high podoplanin expression(HPE). We related podoplanin and mi RNA-363 expression to histopathologic response after neoadjuvant treatment and clinicopathological characteristics, such as histological tumor type, survival rate or clinical tumor *** confirmed expression of membrane-bound podoplanin in 90 ESCC patients.26% showed HPE of > 5%. In addition, absence in EAC patients(only 2% with HPE) was shown. Lower podoplanin expression has been detected in resectionspecimen of 58 ESCC patients after neoadjuvant(RTx/CTx) treatment, only 11% with HPE, compared to 50% HPE of 32 non-pretreated primary surgery patients,P = 0.0001. This difference of podoplanin expression was confirmed comparing pre-treatment biopsies with matching post-treatment surgical specimens, P juvant treatment. Low(0-5%)podoplanin expression was associated with better prognosis compared to patients with HPE, P = 0.013. Podoplanin e

关键词： Esophageal cancer Response prediction Prognosis D2-40 Posttranscriptional regulation miRNA-363

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Assessing the USLE Crop and Management Factor C for Soil Erosion Modeling in a Large Mountainous Watershed in Central China

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journal of Earth Science 2010年第6期21卷 835-845页

作者： Sarah Schnbrodt patrick Saumer Thorsten Behrens Christoph Seeber Thomas Scholten Institute of Geography Department of Physical Geography and Soil Science University of Tübingen Science Strategy Coordination and Planning Office European Space Agency-ESRIN Center for International Development and Environmental Research Giessen University

Due to the impoundment of the Yangtze River, the Three Gorges Dam in China fosters high land-use dynamics. Soil erosion is expected to increase dramatically. One of the key factors in soil erosion control is the vegetation cover and crop type. However, determining these factors adequately for the use in soil erosion modeling is very time-consuming especially for large mountainous areas, such as the Xiangxi （香溪） catchment in the Three Gorges area. In our study, the crop and management factor C was calculated using the fractional vegetation cover （CFvc） based on Landsat-TM images from 2005, 2006, and 2007 and on literature studies （CLIT）. In 2007, the values of CFvc range between 0.001 and 0.98 in the Xiangxi catchment. The mean CFVC value is 0.05. CLIT values are distinctly higher, ranging from 0.08 to 0.46 with a mean value of 0.32 in the Xiangxi catchment. The mean potential soil loss amounts to 120.62 t/ha/a in the Xiangxi catchment when using CLIT for modeling. Based on CFVC, the predicted mean soil loss in the Xiangxi catchment is 11.50 t/ha/a. Therefore, CLIT appears to bemore reliable than the C factor based on the fractional vegetation cover.

关键词： C factor soil erosion modeling Universal Soil Loss Equation fractional vegetation cover Three Gorges Dam Yangtze River.

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Pseudocholinesterase Deficiency: A Case Report and Literature Review

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Open journal of Anesthesiology 2012年第4期2卷 188-194页

作者： patrick j. Hackett Tetsuro Sakai Department of Anesthesiology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

A 72-year-old male underwent neck dissection and parotidectomy with facial nerve preservation. Endotracheal intubation was facilitated with succinylcholine. Prolonged muscle paralysis which was first detected after failure to stimulate the facial nerve with electrocautery, lasted five hours. Laboratory tests indicated pseudocholinesterase (PChE) deficiency. A thyroidectomy one month later was performed uneventfully using rocuronium as a muscle relaxant. Literature review revealed a total of 40 PChE deficiency cases being reported since 1956.

关键词： Prolonged Paralysis Succinylcholine Pseudocholinesterase Deficiency Dibucaine Number Case Review

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Age structure in neutral theory resolves inconsistencies related to reproductive-size threshold

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journal of Plant Ecology 2012年第1期5卷 64-71页

作者： james Rosindell patrick A.jansen Rampal S.Etienne Institute of Integrative and Comparative Biology Faculty of Biological SciencesUniversity of LeedsLeeds LS29JTWest YorkshireUK Institute of Bioinformatics and Evolutionary Studies University of IdahoMoscowID 83844USA Center for Tropical Forest Science Smithsonian Tropical Research InstitutePO Box 0843-03092BalboaAnconRepublic of Panama Centre of Ecosystem Studies Wageningen UniversityPO Box 476700 AA Wageningenthe Netherlands Community and Conservation Ecology Centre for Ecological and Evolutionary StudiesUniversity of GroningenPO Box 111039700 CC Groningenthe Netherlands

Aims Neutral theory consists of a suite of models that assume ecological equivalence among individual *** have been most commonly applied to tropical forest tree communities either as null models or as *** models typically only include reproductive adults;therefore,fitting to empirical tree community data requires defining a reproductive-size threshold,which for trees is usually set arbitrarily to a diameter at breast height(DBH)of 100 *** inevitable exclusion of some reproductive adults and inclusion of some saplings cause a non-random sampling bias in neutral model ***,we investigate this problem and resolve it by introducing simple age structure into a neutral *** We compared the performance and sensitivity of DBH threshold of three variants of a spatially explicit neutral model:the traditional model,a model incorporating random sampling and a model with two distinct age classes—reproductive adults and *** the age-structured model,saplings are offspring from adults that disperse according to a Gaussian dispersal kernel around the *** only extra parameter is the ratio of adults to saplings,which is not a free parameter but directly *** used species–area relationships(SARs)to explore the predicted effect of saplings on the species richness at different scales in our *** then evaluated the three model variations to find the parameters required to maintain the observed level of species richness in the 50-ha plot on Barro Colorado Island(BCI).We repeated our analysis filtering the data at different minimum tree-size thresholds in order to find the effect this threshold has on our ***,we used empirical species–individual relationships(SIRs)to test the pre-existing hypothesis that environmental filtering is the primary cause of differences between the assemblage of saplings and that of adults on *** Findings Our age-structured neutral model was characterized by SARs that

关键词： neutral theory age structure sampling DBH

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Sustainable Ammonia Synthesis from Nitrogen and Water by One-Step Plasma Catalysis

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Energy & Environmental Materials 2023年第2期6卷 284-292页

作者： Tianqi Zhang Renwu Zhou Shuai Zhang Rusen Zhou jia Ding Fengwang Li jungmi Hong Liguang Dou Tao Shao Anthony B.Murphy Kostya(Ken)Ostrikov patrick j.Cullen School of Chemical and Biomolecular Engineering University of SydneyDarlingtonNSW 2008Australia Beijing International S&T Cooperation Base for Plasma Science and Energy Conversion Institute of Electrical EngineeringChinese Academy of SciencesBeijing 100190China School of Chemistry and Physics and Centre for Materials Science Queensland University of TechnologyBrisbaneQld 4000Australia State Key Laboratory of Electrical Insulation and Power EquipmentCenter for Plasma BiomedicineXi’an Jiaotong UniversityXi’an 710049China CSIRO Manufacturing LindfieldNSW 2070Australia

Sustainable ammonia synthesis at ambient conditions that relies on renewable sources of energy and feedstocks is globally sought to replace the Haber-Bosch ***,using nitrogen and water as raw materials,a nonthermal plasma catalysis approach is demonstrated as an effective powerto-chemicals conversion strategy for ammonia *** sustaining a highly reactive environment,successful plasma-catalytic production of NH_(3) was achieved from the dissociation of N_(2) and H_(2)O under mild ***-induced vibrational excitation is found to decrease the N_(2) and H_(2)O dissociation barriers,with the presence of matched catalysts in the nonthermal plasma discharge reactor contributing significantly to molecular dissociation on the catalyst *** functional theory calculations for the activation energy barrier for the dissociation suggest that ruthenium catalysts supported on magnesium oxide exhibit superior performance over other catalysts in NH_(3) production by lowering the activation energy for the dissociative adsorption of N_(2) down to 1.07 *** highest production rate,2.67 mmol gcat.^(-1) h^(-1),was obtained using ruthenium catalyst supported on magnesium *** work highlights the potential of nonthermal plasma catalysis for the activation of renewable sources to serve as a new platform for sustainable ammonia production.

关键词： Haber-Bosch plasma catalysis ruthenium catalyst sustainability sustainable ammonia

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Practical Aspects for Designing Statistically Optimal Experiments

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journal of Statistical Science and Application 2014年第3期2卷 85-92页

作者： Mark j. Anderson patrick j. Whitcomb Stat-Ease Inc. Minneapolis MN USA

Due to operational or physical considerations, standard factorial and response surface method （RSM） design of experiments （DOE） often prove to be unsuitable. In such cases a computer-generated statistically-optimal design fills the breech. This article explores vital mathematical properties for evaluating alternative designs with a focus on what is really important for industrial experimenters. To assess ＂goodness of design＂ such evaluations must consider the model choice, specific optimality criteria （in particular D and I）, precision of estimation based on the fraction of design space （FDS）, the number of runs to achieve required precision, lack-of-fit testing, and so forth. With a focus on RSM, all these issues are considered at a practical level, keeping engineers and scientists in mind. This brings to the forefront such considerations as subject-matter knowledge from first principles and experience, factor choice and the feasibility of the experiment design.

关键词： design of experiments optimal design response surface methods fraction of design space.

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