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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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Main factors affecting lacertid lizard thermal ecology

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Integrative Zoology 2019年第3期14卷 293-305页

作者： Zaida ORTEGA Francisco javier martÍn-VALLEJO Postgraduate Program in Ecology and Conservation Federal University of Mato Grosso do SulCampo GrandeMato Grosso do SulBrazil Department of Statistics University of SalamancaSpain

The thermal ecology of ectotherms has been studied for almost 2 centuries,but additional attention is currently being paid to it,to understand how organisms deal with the environment in a climate change context.A consensus is still far away due to the large number of factors involved and their complex interactions.In this context,3 analyses in lacertid lizards were carried out:(i)a meta-analysis,to test for differences between body and air temperatures from 71 populations;(ii)a meta-analysis concerning correlations between body and air temperatures from 60 populations;and(iii)a multimodel inference of thermoregulation effectiveness indices from 45 populations.The importance of different factors,including body size,habitat,insularity,altitude,climate and season,was evaluated in all analyses to model the response variables.A strong seasonality effect was observed,with a consistent pattern of less effective thermoregulation in summer compared to other seasons.Altitude was the second most important factor,with a consistent higher thermoregulation effort in populations occurring at high elevations(>1000 m above sea level).Other factors,such as insularity or body size,can also be important,but did not exhibit a clear pattern.Finally,thermoregulation was less affected by climate and habitat type.

关键词： lizards meta-analysis seasonality temperature thermoregulation

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The role of Islet-1 in cell specification,differentiation,and maintenance of phenotypes in the vertebrate neural retina

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neural Regeneration Research 2015年第12期10卷 1951-1952页

作者： Gervasio martín-Partido javier Francisco-Morcillo Departamento de Biología Celular Facultad de CienciasUniversidad de Extremadura

Many blinding diseases,such as retinitis pigmentosa,age-related macular degeneration,and glaucoma involve the permanent loss of retinal neurons,especially photoreceptors or the centrally projecting retinal ganglion ce... 详细信息

关键词： cell RGCs The role of Islet-1 in cell specification,differentiation,and maintenance of phenotypes in the vertebrate neural retina

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Systematic Approach for Web Protection Runtime Tools’Effectiveness Analysis

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Computer Modeling in Engineering & Sciences 2022年第12期133卷 579-599页

作者： Tomás Sureda Riera Juan Ramón Bermejo Higuera javier Bermejo Higuera Juan Antonio Sicilia Montalvo José javier martínez Herráiz Computer Science Department University of AlcaláMadrid28801Spain Escuela Superior de Ingeniería y Tecnología Universidad Internacional de La RiojaLogrono26006Spain

Web applications represent one of the principal vehicles by which attackers gain access to an organization’s network or resources.Thus,different approaches to protect web applications have been proposed to date.Of them,the two major approaches are Web Application Firewalls(WAF)and Runtime Application Self Protection(RASP).It is,thus,essential to understand the differences and relative effectiveness of both these approaches for effective decisionmaking regarding the security of web applications.Here we present a comparative study between WAF and RASP simulated settings,with the aim to compare their effectiveness and efficiency against different categories of attacks.For this,we used computation of different metrics and sorted their results using F-Score index.We found that RASP tools scored better than WAF tools.In this study,we also developed a new experimental methodology for the objective evaluation ofweb protection tools since,to the best of our knowledge,nomethod specifically evaluates web protection tools.

关键词： Web Application Firewall(WAF) Runtime Application Self Protection(RASP) F-Score web attacks experimental methodology

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A Hybrid Statistical-Dynamical Downscaling of Air Temperature over Scandinavia Using the WRF Model

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Advances in Atmospheric Sciences 2020年第1期37卷 57-74页

作者： Jianfeng WAnG Ricardo M.FOnSECA Kendall RUTLEDGE javier martÍn-TORRES Jun YU Department of Mathematics and Mathematical Statistics UmeåUniversitySE 90187UmeåSweden Group of Atmospheric Science Division of Space TechnologyDepartment of Computer ScienceElectrical and Space EngineeringLuleåUniversity of TechnologySE 97187 LuleåSweden novia University of Applied Sciences PO BOX 6FI-65201 VaasaFinland Instituto Andaluz de Ciencias de la Tierra 18100 GranadaSpain The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry Institute for Planetary MaterialsOkayama University at MisasaTottori 682-0193Japan

An accurate simulation of air temperature at local scales is crucial for the vast majority of weather and climate applications.In this work,a hybrid statistical–dynamical downscaling method and a high-resolution dynamical-only downscaling method are applied to daily mean,minimum and maximum air temperatures to investigate the quality of localscale estimates produced by downscaling.These two downscaling approaches are evaluated using station observation data obtained from the Finnish Meteorological Institute over a near-coastal region of western Finland.The dynamical downscaling is performed with the Weather Research and Forecasting(WRF)model,and the statistical downscaling method implemented is the Cumulative Distribution Function-transform(CDF-t).The CDF-t is trained using 20 years of WRF-downscaled Climate Forecast System Reanalysis data over the region at a 3-km spatial resolution for the central month of each season.The performance of the two methods is assessed qualitatively,by inspection of quantile-quantile plots,and quantitatively,through the Cramer-von Mises,mean absolute error,and root-mean-square error diagnostics.The hybrid approach is found to provide significantly more skillful forecasts of the observed daily mean and maximum air temperatures than those of the dynamical-only downscaling(for all seasons).The hybrid method proves to be less computationally expensive,and also to give more skillful temperature forecasts(at least for the Finnish near-coastal region).

关键词： WRF air temperature Cumulative Distribution Function-transform hybrid statistical–dynamical downscaling,model evaluation Scandinavian Peninsula

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Heterogeneous catalysts with programmable topologies generated by reticulation of organocatalysts into metal-organic frameworks:The case of squaramide

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nano Research 2021年第2期14卷 458-465页

作者： Anna broto-Ribas Claudia Vignatti Alicia Jimenez-Almarza javier Luis-Barrera Zahra Dolatkhah Felipe Gandara Inhar Imaz Ruben Mas-Balleste Jose Aleman Daniel Maspoch Catalan Institute of nanoscience and nanotechnology(ICn2) CSIC and The Barcelona Institute of Science and Technology08193 BarcelonaSpain Inorganic Chemistry Department Modulo 7Universidad Autonoma de Madrid28049 MadridSpain Organic Chemistry Department Modulo 1Universidad Autonoma de Madrid28049 MadridSpain Materials Science Factory Instituto de Ciencia de Materiales de Madrid(ICMM)Consejo Superior de Investigaciones Cientificas(CSIC)Calle Sor Juana Ines de la Cruz328049 MadridSpain Institute for Advanced Research in Chemical Sciences(IAdChem) Campus Universidad Autonoma de Madrid28049 MadridSpain Institucio Catalana de Recerca i Estudis Avangats(ICREA) 08100 BarcelonaSpain

A well-established strategy to synthesize heterogeneous,metal-organic framework(MOF)catalysts that exhibit nanoconfinement effects,and specific pores with highly-localized catalytic sites,is to use organic linkers containing organocatalytic centers.Here,we report that by combining this linker approach with reticular chemistry,and exploiting three-dimensioanl(3D)MOF-structural data from the Cambridge Structural Database,we have designed four heterogeneous MOF-based catalysts for standard organic transformations.These programmable MOFs are isoreticular versions of pcu IRMOF-16,feu UiO-68 and pillared-pcu SnU-8X,the three most common topologies of MOFs built from the organic linker p.p'-terphenyldicarboxylic acid(tpdc).To synthesize the four squaramide-based MOFs,we designed and synthesized a linker,4,4’-((3,4-dioxocyclobut-1-ene-1,2-diyl)bis(azanedyil))dibenzoic acid(Sq_tpdc),which is identical in directionality and length to tpdc but which contains organocatalytic squaramide centers.Squaramides were chosen because their immobilization into a framework enhances its reactivity and stability while avoiding any self-quenching phenomena.Therefore,the four MOFs share the same organocatalytic squaramide moiety,but confine it within distinct pore environments.We then evaluated these MOFs as heterogeneous H-bonding catalysts in organic transformations:a Friedel-Crafts alkylation and an epoxide ring-opening.Some of them exhibited good performance in both reactions but all showed distinct catalytic profiles that reflect their structural differences.

关键词： reticular chemistry metal-organic frameworks H-bond catalysis squaramide Friedel-Cratts epoxide ring-opening

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Animal models used to study direct peripheral nerve repair: a systematic review

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neural Regeneration Research 2020年第3期15卷 491-502页

作者： Francisco javier Vela Guadalupe martínez-Chacón Alberto Ballestín JoséLuis Campos Francisco Miguel Sánchez-Margallo Elena Abellán Department of Microsurgery Jesús Usón Minimally Invasive Surgery CentreCáceresSpain Scientific Director Jesús Usón Minimally Invasive Surgery CentreCáceresSpain

Objective:Peripheral nerve repair is required after traumatic injury.This common condition represents a major public health problem worldwide.Recovery after nerve repair depends on several factors,including the severity of the injury,the nerve involved,and the surgeon’s technical skills.Despite the precise microsurgical repair of nerve lesions,adequate functional recovery is not always achieved and,therefore,the regeneration process and surgical techniques are still being studied.Pre-clinical animal models are essential for this research and,for this reason,the focus of the present systematic review(according to the PRISMA statement)was to analyze the different animal models used in pre-clinical peripheral nerve repair studies.Data sources:Original articles,published in English from 2000 to 2018,were collected using the Web of Science,Scopus,and PubMed databases.Data selection:Only preclinical trials on direct nerve repair were included in this review.The articles were evaluated by the first two authors,in accordance with predefined data fields.Outcome measures:The primary outcomes included functional motor abilities,daily activity and regeneration rate.Secondary outcomes included coaptation technique and animal model.Results:This review yielded 267 articles,of which,after completion of the screening,49 studies were analyzed.There were 1425 animals in those 49 studies,being rats,mice,guinea pigs,rabbits,cats and dogs the different pre-clinical models.The nerves used were classified into three groups:head and neck(11),forelimb(8)and hindlimb(30).The techniques used to perform the coaptation were:microsuture(46),glue(12),laser(8)and mechanical(2).The follow-up examinations were histology(43),electrophysiological analysis(24)and behavioral observation(22).Conclusion:The most widely used animal model in the study of peripheral nerve repair is the rat.Other animal models are also used but the cost-benefit of the rat model provides several strengths over the others.Suture techniques are currently the first option for n

关键词： nerve microsurgery peripheral nerve regeneration repair reconstruction direct nerve repair animal model coaptation PRISMA systematic review

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Analysis of naval Ship Evacuation Using Stochastic Simulation Models and Experimental Data Sets

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Computer Modeling in Engineering & Sciences 2020年第3期122卷 971-995页

作者： Roberto Bellas javier martínez Ignacio Rivera Ramón Touza MiguelGómez Rafael Carreño University of Vigo Vigo36310Spain. Spanish navy Madrid28033Spain.

The study of emergency evacuation in public spaces,buildings and large ships may present parallel characteristic in terms of complexity of the layout but there are also significant differences that can hinder passengers to reach muster stations or the lifeboats.There are many hazards on a ship that can cause an emergency evacuation,the most severe result in loss of lives.Providing safe and effective evacuation of passengers from ships in an emergency situation becomes critical.Recently,computer simulation has become an indispensable technology in various fields,among them,the evacuation models that recently evolved incorporating human behavioral factors.In this work,an analysis of evacuation in a Landing Helicopter Dock(LHD)ship was conducted.Escape routes specified by the ship’s procedures were introduced in the model and the six emergency scenarios of the naval Ship Code were simulated.The crew and embarked troops were introduced with their different evacuation behavior,in addition,walking speeds were extracted from data set collected in experiments conducted at other warships.From the results of the simulations,the longest time was chosen and confidence intervals constructed to determine the total evacuation time.Finally,results show that evacuation time meets regulatory requirements and the usefulness and low cost of the evacuation simulation for testing and refining possible ships’layouts and emergency scenarios.

关键词： Evacuation modeling confidence intervals naval ship IMO nATO nSC.

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MMALE—A Methodology for Malware Analysis in Linux Environments

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Computers, Materials & Continua 2021年第5期67卷 1447-1469页

作者： Joséjavier de Vicente Mohino javier Bermejo Higuera Juan Ramón Bermejo Higuera Juan Antonio Sicilia Montalvo Manuel Sánchez Rubio Joséjavier martínez Herraiz Escuela Superior de Ingeniería y Tecnología Universidad Internacional de La RiojaLogroño26006La RiojaSpain Departamento de Ciencias de la Computación de la Escuela Politécnica Superior Universidad de Alcaláde HenaresAlcaláde HenaresMadridSpain

In a computer environment,an operating system is prone to malware,and even the Linux operating system is not an exception.In recent years,malware has evolved,and attackers have become more qualified compared to a few years ago.Furthermore,Linux-based systems have become more attractive to cybercriminals because of the increasing use of the Linux operating system in web servers and Internet of Things(IoT)devices.Windows is the most employed OS,so most of the research efforts have been focused on its malware protection rather than on other operating systems.As a result,hundreds of research articles,documents,and methodologies dedicated to malware analysis have been reported.However,there has not been much literature concerning Linux security and protection from malware.To address all these new challenges,it is necessary to develop a methodology that can standardize the required steps to perform the malware analysis in depth.A systematic analysis process makes the difference between good and ordinary malware analyses.Additionally,a deep malware comprehension can yield a faster and much more efficient malware eradication.In order to address all mentioned challenges,this article proposed a methodology for malware analysis in the Linux operating system,which is a traditionally overlooked field compared to the other operating systems.The proposed methodology is tested by a specific Linux malware,and the obtained test results have high effectiveness in malware detection.

关键词： Malware analysis methodology analysis Linux malware IoT malware

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Two titans fin ally meet each other under nitrogen deficiencies:FEROnIA-TORC1 activation promotes plant growth

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Molecular Plant 2022年第7期15卷 1095-1097页

作者： javier martinez Pacheco Jose M.Estevez Fundación Instituto Leloir and IIBBA-COnICET.Av.Patricias Argentinas 435 Buenos Aires C1405BWEArgentina Centro de Biotecnología Vegetal Facultad de Ciencias de la VidaUniversidad Andres BelloSantiagoChile AnID-Millennium Science Initiative Program-Millennium nucleus for the Development of Super Adaptable Plants(Mn-SAP) SantiagoChile

Plant growth is determined by well-defined developmental processes that integrate cell-intrinsic factors and external environmental cues,and it is largely dependent on the assimilation of macro-and micro-nutrients from the environment.Between the macro-nutrients,the inorganic nitrogen(e.g.,nitrate and ammonium)and amino acids are essential for plant survival and productivity.Beyond acting as macro-nutrients and structural components of macro-molecules,these nitrogen-containing molecules could also act as signaling molecules to orchestrate diverse genetic programs(Wang et al.,2018).

关键词： activation inorganic nitrate

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