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Sarcoma stratification by combined pH2AX and MAP17(PDZK1IP1)levels for a better outcome on doxorubicin plus olaparib treatment

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Signal Transduction and Targeted Therapy 2020年第1期5卷 697-709页

作者： Marco Perez JoséManuel García-Heredia Blanca Felipe-Abrio Sandra Muñoz-Galván Javier Martín-Broto Amancio Carnero Instituto de Biomedicina de Sevilla(IBIS) Hospital Universitario Virgen del RocíoUniversidad de SevillaConsejo Superior de Investigaciones CientíficasSevillaSpain Ciber de Cancer IS Carlos IIIMadridSpain Departamento de Bioquímica Vegetal y Biología Molecular Universidad de SevillaSevillaSpain Departamento de Anatomía Patológica Hospital Universitario Virgen del RocíoSevillaSpain

Sarcomas constitute a rare heterogeneous group of tumors,including a wide variety of histological subtypes.Despite advances in our understanding of the pathophysiology of the disease,first-line sarcoma treatment options are still limited and new treatment approaches are needed.Histone H2AX phosphorylation is a sensitive marker for double strand breaks and has recently emerged as biomarker of DNA damage for new drug development.In this study,we explored the role of H2AX phosphorylation at Ser139 alone or in combination with MAP17 protein,an inducer of DNA damage through ROS increase,as prognostic biomarkers in sarcoma tumors.Next,we proposed doxorubicin and olaparib combination as potential therapeutic strategies against sarcomas displaying high level of both markers.We evaluate retrospectively the levels of pH2AX(Ser139)and MAP17 in a cohort of 69 patients with different sarcoma types and its relationship with clinical and pathological features.We found that the levels of pH2AX and MAP17 were related to clinical features and poor survival.Next,we pursued PARP1 inhibition with olaparib to potentiate the antitumor effect of DNA damaging effect of the DNA damaging agent doxorubicin to achieve an optimal synergy in sarcoma.We demonstrated that the combination of olaparib and doxorubicin was synergistic in vitro,inhibiting cell proliferation and enhancing pH2AX intranuclear accumulation,as a result of DNA damage.The synergism was corroborated in patient-derived xenografts(PDX)where the combination was effective in tumors with high levels of pH2AX and MAP17,suggesting that both biomarkers might potentially identify patients who better benefit from this combined therapy.

关键词： H2AX doxorubicin treatment

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Spatial heterogeneity of factors influencing forest fires size in northern Mexico

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Journal of Forestry Research 2014年第2期25卷 291-300页

作者： Gustavo perez-Verdin marco Antonio Marquez-Linares Maricela Salmeron-Macias Instituto Politecnico Nacional CIIDIR–DGODurangoDgoMexico34220

In Mexico, forest fires are strongly influenced by environmental, topographic, and anthropogenic factors. A government-based database covering the period 2000-2011 was used to analyze the spatial heterogeneity of the factors influencing forest fire size in the state of Durango, Mexico. Ordinary least squares and geographically weighted regression models were fit to identify the main factors as well as their spatial influence on fire size. Results indicate that fire size is greatly affected by distance to roads, distance to towns, precipitation, temperature, and a population gravity index. The geographically weighted model was better than the ordinary least squares model. The improvement of the former is due to the influence of factors that were found to be non-stationary. These results suggest that geographic location determines the influence of a factor on fire size. While the models can be greatly improved with additional information, the study suggests the need to adopt fire management policies to more efficiently reduce the effect of anthropogenic factors. These policies may include more training for landowners who use fire for clearing, closure of roads, application of thinning, prescribed burning, and fire breaks in perimeters adjacent to roads.

关键词： Durango Mexico geographically weighted regression ordinary least squares stationarity

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Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

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Journal of Sport and Health Science 2024年第3期13卷 419-427页

作者： Andres Marmol-perez Jose J.Gil-Cosano Esther Ubago-Guisado Francisco J.Llorente-Cantarero Juan Francisco Pascual-Gázquez Kirsten K.Ness Vicente Martinez-Vizcaino Jonatan R.Ruiz Luis Gracia-marco Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18011Spain Department of Epidemiology and Cancer Control St.Jude Children's Research HospitalMemphisTN 38105USA Department of Communication and Education Loyola University AndalusiaSeville 41704Spain Biosanitary Research Institute ibs.GranadaGranada 18012Spain Maimonides Biomedical Research Institute of Cordoba(IMIBIC) Cordoba 14004Spain CIBEROBN Biomedical Research Networking Center for Physiopathology of Obesity and NutritionCarlos III Health InstituteMadrid 28029Spain Department of Specific Didactics Faculty of EducationUniversity of CordobaCordoba 14071Spain Pediatric and adolescent hematology and oncology service Pediatrics and Pediatric Surgery Clinical Management UnitVirgen de las Nieves University HospitalGranada 18014Spain Health and Social Research Center Universidad de Castilla-La ManchaCuenca 13001Spain

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added ben

关键词： Bone health Childhood cancer DXA Lean mass Resistance training

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A technical and socioeconomic approach to estimate forest residues as a feedstock for bioenergy in northern Mexico

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Forest Ecosystems 2019年第4期6卷 312-322页

作者： Guadalupe Carrasco-Diaz Gustavo perez-Verdin Jonathan Escobar-Flores marco Antonio Marquez-Linares Instituto Politecnico Nacional CIIDIR Dgo.

Background: Forest residues can be a feasible alternative for converting energy into fuels, electricity, or heat.Compared to other second-generation bioenergy sources, they do not compete for food, are relatively cheap,abundant in forest-rich areas, and more importantly their energy balance is close to zero. Biomass estimations can help design energy strategies to reduce fossil fuels dependency. Because of the land property distribution in Mexico,biomass estimations should consider not only the physical availability, but also the willingness of landowners to extract such raw materials.Methods: This study presents a methodological approach for evaluating the potential use of forest residues as a feedstock to generate bioenergy in northern Mexico. Remote sensing and field forest inventory were used to estimate the quantity and distribution of forest residues. In addition, a discrete choice analysis evaluated landowners’ preferences towards bioenergy development, including the most important factors that influence their willingness to extract their products and the expected price.Results and conclusions: Considering both physical and socio-economic aspects, results showed that about59,000 metric tons per year could be available in the study area. The vast majority of landowners surveyed are willing to extract forest residues, as long as they are presented with extraction plans with the highest income. However, many showed concerns about the environmental impacts this activity can have on soils,plants, and fauna. These results can help evaluate the potential of these resources for bioenergy development.

关键词： Bioenergy Choice experiments Forest landowners Forest residues Remote sensing

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Evaluation of an educational telephone intervention strategy to improve non-screening colonoscopy attendance:A randomized controlled trial

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World Journal of Gastroenterology 2020年第47期26卷 7568-7583页

作者： Agustin Seoane Xenia Font Juan C perez Rocio perez Carlos F Enriquez Miriam Parrilla Faust Riu Josep M Dedeu Luis E Barranco Xavier Duran Ines A Ibanez marco A Alvarez Digestive Department Endoscopy UnitHospital del MarParc de Salut MarBarcelona 08003Spain Colorectal Cancer Research Group IMIM(Hospital del Mar Medical Research Institute)Barcelona 08003Spain Department of Medicine Autonomous University of BarcelonaBarcelona 08003Spain Consulting Service on Methodology for Biomedical Research IMIM(Hospital del Mar Medical Research Institute)Barcelona 08003Spain

BACKGROUND Colonoscopy attendance is a key quality parameter in colorectal cancer population screening programmes.Within these programmes,educative interventions with bidirectional contact carried out by trained personnel have been proved to be an important tool for colonoscopy attendance improvement,and because of its huge clinical and economic impact,they have been widely implemented.However,outside of this population programmes,educative measures to improve colonoscopy attendance have been poorly studied and no navigation interventions are usually performed.AIM To investigate the clinical and economic impacts of an educational telephone intervention on colonoscopy attendance outside colorectal cancer screening programmes.METHODS This randomized controlled trial included consecutive patients referred to colonoscopy from primary care centres from November 2017 to May 2018.The intervention group(IG)received a telephone intervention,while the control group(CG)did not.Patients assigned to the IG received an educational telephone call 7 d before the colonoscopy appointment.The intervention was carried out by two nurses with deep endoscopic knowledge who were previously trained for a telephone educational intervention for colonoscopy.The impact on patient compliance with preparedness protocols related to bowel cleansing,antithrombotic management,and sedation scheduling was also evaluated.A second call was conducted to assess patient satisfaction.Intention-to-treat(ITT)and perprotocol(PP)analyses were performed.RESULTS A total of 738 and 746 patients were finally included in the IG and CG respectively.Six hundred thirteen(83%)patients were contacted in the IG.The non-attendance rate was lower in the IG,both in the ITT analysis(IG 8.4%vs CG 14.3%,P<0.001)and in the PP analysis(4.4%vs 14.3%,P<0.001).In a multivariable analysis,belonging to the control group increased the risk of nonattendance in both,the ITT analysis(OR 1.81,95%CI:1.27 to 2.58,P=0.001)and the PP analysis(OR 3.56,95%CI:2.25 to 5.64,P<0.001).There was als

关键词： Colonoscopy Quality improvement No-show patients Nursing education Patient compliance Telephone intervention

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TRPA1 Is Expressed in Central But Not in Peripheral Glia

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Journal of Biomedical Science and Engineering 2016年第11期9卷 515-531页

作者： Vittorio Vellani Carolina Gomis-perez Marcello Pinti Massimiliano Prandini Giorgia Pavesi Chiara Giacomoni marco Caprini Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Modena Italy Department of Pharmacy and Biotechnology University of Bologna Bologna Italy Department of Life Sciences University of Modena and Reggio Modena Italy Department of Economy and Technology University of San Marino Città di San Marino Republic of San Marino

TRPA1 are cation channels expressed in sensory neurons and in several other cell types. This channel is specifically activated by ally isothiocyanate (AITC), the pungent component of mustard oil, as well as by other electrophilic compounds. Although TRPA1 expression in central glia has been reported, its subcellular localization and its expression in peripheral glia have not been investigated before. In this paper we report the molecular and functional expression of TRPA1 in rat cortical astrocytes. Real-time RT-PCR identified low but significant amounts of TRPA1 mRNA in cortical astrocytes while no signal was seen in peripheral glia isolated from dorsal root ganglia (DRG) or in a glial cell line (DITNC-1). Calcium imaging showed AITC-induced signals in astro-cytes while no response in peripheral glia. AITC induced calcium signals in astrocytes in the presence and in the absence of extracellular calcium, suggesting an intracellular localization of TRPA1 channels. Whole cell electrophysiological recordings were performed in astrocytes, in peripheral glia and in DITNC-1 cells transfected with TRPA1 during AITC application. In TRPA1-transfected DITNC-1 cells typical TRPA1 currents were recorded with a reversal potential near 0 mV, consistent with the opening of a non-selective cation channel. No such currents were recorded in untransfected DITNC-1 cells, in astrocytes and in peripheral glial cells, where even high concentrations of AITC (up to 10 mM) induced no significant outward current. In astrocytes AITC transiently induced an outward rectifying current with the reversal potential near ?90 mV, consistent with K channel activation, likely activated by intracellular release of calcium. Our results suggest that TRPA1 channels are molecularly and functionally expressed in calcium-containing organelles of rat cortical astrocytes, with no expression in the plasma membrane.

关键词： Astrocytes Intracellular TRPA1 DITNC-1 Ensheathing Schwann Cells

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A Parallel Implementation of Multiple Secret Image Sharing Based on Cellular Automata

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通讯和计算机（中英文版） 2013年第5期10卷 649-660页

作者： Adrian Hernandez-Becerril Mariko Nakano-Miyatake marco Ramirez-Tachiquin Hector perez-Meana Postgraduate Section National Polytechnic Institute of Mexico Mexico City Mexico Department of Engineering La Salle University Mexico City Mexico

Recently, a multisecret sharing scheme for secret color images among a set of users was proposed, which allows that each participant to share secret color images with the rest of participants in such way that all of them can recover all secret color images only if all participants pool their shares. In this work a parallel implementation of the cellular automata-based multisecret sharing scheme is proposed, in which the technology of CUDA (Compute Unified Device Architecture) is used in parallelization, taking advantage that each cell of cellular automata can be processed independently. The processing time of the proposed scheme is analyzed and it is proved that the proposed parallel algorithm using the CUDA structure is more than 12 times faster than the conventional sequential algorithm. This reduction of temporal complexity allows the practical use of the secret sharing scheme in many information security fields.

关键词：元胞自动机并行实现秘密共享方案时间复杂度影像多机彩色图像顺序算法

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Aggregation properties of a therapeutic peptide for rheumatoid arthritis:A spectroscopic and molecular dynamics study

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ChemPhysMater 2022年第1期1卷 62-70页

作者： Rita Cimino marco Savioli Noemi Ferrante Carrante Ernesto Placidi Hilda Garay-perez Matilde López-Abad Alexis Musacchio Lasa Maria Del Carmen Domínguez-Horta Emanuela Gatto Francesca Cavalieri Gianfranco Bocchinfuso Mariano Venanzi PEPSA-LAB Department of Chemical Sciences and TechnologyUniversity of Rome Tor VergataVia della Ricerca Scientifica 100133RomeItaly Department of Physics University of Rome‘Sapienza’P.le A.Moro 500185 RomeItaly Centre for Genetic Engineering and Biotechnology PO Box 616210600HavanaCuba School of Science RMIT UniversityMelbourneVIC 3001Australia

The biological properties of therapeutic peptides,such as their pharmacokinetics and pharmacodynamics,are correlated with their structure and aggregation properties.Herein,we studied the aggregation properties of a therapeutic peptide(CIGB-814),currently in phase 2 clinical trial,for the treatment of rheumatoid arthritis over a wide range of concentrations(μM-mM).We applied spectroscopic techniques(fluorescence,circular dichro-ism,resonance,and dynamic light scattering),atomic force microscopy,and molecular dynamics simulations to determine the aggregation mechanism of CIGB-814.We found that the hierarchical aggregation of CIGB-814 at micromolar concentrations was initiated by the formation of peptide oligomers.Subsequently,the peptide oligomers trigger the nucleation and growth of peptide nanostructures(cac=123μM),ultimately leading to the fibrillization of CIGB-814(cac’=508μM).These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.

关键词： Molecular dynamics of peptide oligomers Peptide aggregation Peptide fibrils Peptide nanostructures Therapeutic peptides Treatment of rheumatoid arthritis

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墨尔本“Southbank by Beulah”国际竞赛概念方案

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现代装饰 2018年第10期 126-129页

作者：李存皓孙守泉 marco Gastoldl Jennifer perez-Rojas 王心逸 Thoufeeq Ahamed 雷蕾 Jaime Cadarso Reinier Simons MAD

7月27日,马岩松带领的MAD建筑事务所在墨尔本公布了“Southbank by Beulah”超高层国际竞赛的概念方案,该项目是Beulah International位于墨尔本Southbank的一块基地面积为6000平方米的场地,包括酒店、住宅、办公、商业的超高层综合体。... 详细信息

7月27日,马岩松带领的MAD建筑事务所在墨尔本公布了“Southbank by Beulah”超高层国际竞赛的概念方案,该项目是Beulah International位于墨尔本Southbank的一块基地面积为6000平方米的场地,包括酒店、住宅、办公、商业的超高层综合体。MAD尝试将墨尔本丰富的自然环境垂直延展于高层设计中,在高密度城市环境中营造“云端、高山、丛林”的自然意境,消除传统高密度城市所带有的隔阂感,以更亲切的尺度拉近市民与社区、自然的距离,并以自然的形态点缀墨尔本的城市天际线,成为墨尔本未来独一无二的城市地标。

关键词：墨尔本竞赛国际高密度城市自然环境城市环境建筑事务所高层综合体

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Inhibition Mechanism in Concrete by Organic Substances： An Experimental and Theoretical Study

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材料科学与工程（中英文版） 2010年第10期4卷 66-77页

作者： marco Ormellese Elmer Augusto perez Giuseppina Raffaini Fabio Ganazzoli Luciano Lazzari Department of Chemistry Materials and Chemical Engineering Politecnico di Milano Via Mancinelli Milano 7-20131 Italy

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