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Phase Ⅱ trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/CDKN2A

Signal Transduction and Targeted Therapy 2023年第11期8卷 5518-5527页

作者： Javier Martin-Broto Jeronimo Martinez-Garcia David SMoura Andres Redondo antonio Gutierrez antonio lopez-pousa Javier Martinez-Trufero Isabel Sevilla Roberto Diaz-Beveridge Maria Pilar Solis-Hernandez Amancio Carnero Marco Perez David Marcilla Jesus Garcia-Foncillas Pablo Romero Javier Fernandez-Jara Daniel lopez-lopez Ivan Arribas Nadia Hindi Health Research Institute-Fundación Jiménez Díaz University Hospital Universidad Autónoma de Madrid(IIS-FJDUAM)28040MadridSpain Medical Oncology Department Fundación Jimenez Diaz University Hospital28040MadridSpain General de Villalba University Hospital 28400MadridSpain Medical Oncology Department University Hospital Virgen de la Arrixaca30120MurciaSpain Department of Medical Oncology Hospital Universitario La Paz-IdiPAZP.Castellana26128046MadridSpain Hematology Department University Hospital Son Espases07120MallorcaSpain Medical Oncology Department Sant Pau Hospital08025BarcelonaSpain Medical Oncology Department University Hospital Miguel Servet50009ZaragozaSpain Investigación Clínica y Traslacional en Cáncer/Instituto de Investigaciones Biomédicas de Malaga(IBIMA)/Hospitales Universitarios Regional y Virgen de la Victoria de Malaga MalagaSpain Medical Oncology Department Hospital Universitari i Politècnic La Fe46026ValenciaSpain Medical Oncology Department Central University Hospital of Asturias33011OviedoSpain Instituto de Biomedicina de Sevilla(IBiS HUVRCSICUS)41013SevillaSpain Pathology Department Virgen del Rocio University Hospital41013SevillaSpain Radiology Department Fundación Jimenez Diaz University Hospital28040MadridSpain Computational Medicine Platform Fundación progreso y salud(FPS)Hospital Virgen del Rocío41013SevilleSpain Bioinformatics in Rare Diseases(BiER).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER) FPSHospital Virgen del RocioSevillaSpain Universitat de València-ERI-CES 46010ValenciaSpain

Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 ***4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK *** investigators of this study found that CDK4 overexpression,while not of CDKN2A,was the most consistent predictive factor for palbociclib efficacy in *** adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed CDK4,but not CDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudraCT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this *** was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at *** 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%CI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 *** median PFS and overall survival were 4.2(95%CI 3.6–4.8)and 12(95%CI 8.7–15.4)months,*** research showed a significant correlation between CDK4 mRNA and protein *** was active in a variety of sarcoma subtypes,selected by CDK4/CDKN2A,and deserves further investigation in the sarcoma context.

关键词： CDKN2A sarcoma CDK4

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Building an interoperable space for smart agriculture

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Digital Communications and Networks 2023年第1期9卷 183-193页

作者： Ioanna Roussaki Kevin Doolin antonio Skarmeta George Routis Juan antonio lopez-Morales Ethel Claffey Manuel Mora Juan antonio Martinez Institute of Communications and Computer Systems AthensGreece Walton Institute WaterfordIreland Department of Information and Communications Engineering University of MurciaMurciaSpain School of Business Waterford Institute of TechnologyWaterfordIreland R&D Department Odin SolutionsMurciaSpain

The digital transformation in agriculture introduces new challenges in terms of data,knowledge and technology adoption due to critical interoperability issues,and also challenges regarding the identification of the most suitable data sources to be exploited and the information models that must be ***(Building an Interoperable,Data-Driven,Innovative and Sustainable European Agri-Food Sector)addresses these challenges by providing an overarching solution that integrates various heterogeneous hardware and software resources(e.g.,devices,networks,platforms)and enables the seamless sharing of data and knowledge throughout the agri-food *** paper introduces the main concepts of DEMETER and its reference architecture to address the data sharing and interoperability needs of farmers,which is validated via two rounds of 20 large-scale pilots along the DEMETER *** paper elaborates on the two pilots carried out in region of Murcia in Spain,which target the arable crops sector and demonstrate the benefits of the deployed DEMETER reference architecture.

关键词： Smart agriculture Internet of things(IoT) DEMETER Reference architecture Interoperability Agricultural information model(AIM) Pilot validation

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Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2013年第1期19卷 17-25页

作者： Elena Garrido Elisa Carrera Rebeca Manzano antonio lopez-Sanroman Inflammatory Bowel Disease Clinic Department of GastroenterologyUniversity Hospital Ramón y Cajal28034 MadridSpain Department of Gastroenterology University Hospital of Guadalajara19002 GuadalajaraSpain Department of Gastroenterology Hospital Sureste28500 MadridSpain

Cytomegalovirus(CMV) infection is common in *** virus then enters a "latency phase" and can reactivate to different stimuli such as *** clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of ***,CMV reactivation is frequent in severe or steroid-resistant *** is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe *** methods are used to diagnose CMV *** is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being *** chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic *** endoscopic features have not been described in active UC and CMV *** colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive *** antiviral drugs may be *** controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.

关键词： Cytomegalovirus Inflammatory bowel disease Crohn’s disease Ulcerative colitis Hematoxylin and eosin Immunohistochemical Polymerase chain reaction Ganciclovir Infectious colitis

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Unsupervised full-color cellular image reconstruction through disordered optical fiber

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Light(Science & Applications) 2023年第6期12卷 1091-1102页

作者： Xiaowen Hu Jian Zhao Jose Enrique antonio-lopez Rodrigo Amezcua Correa Axel Schülzgen CREOL The College of Optics and PhotonicsUniversity of Central FloridaOrlandoFL 32816USA The Picower Institute for Learning and Memory Massachusetts Institute of TechnologyCambridgeMA 02139USA

Recent years have witnessed the tremendous development of fusing fiber-optic imaging with supervised deep learning to enable high-quality imaging of hard-to-reach ***,the supervised deep learning method imposes strict constraints on fiber-optic imaging systems,where the input objects and the fiber outputs have to be collected in *** unleash the full potential of fiber-optic imaging,unsupervised image reconstruction is in ***,neither optical fiber bundles nor multimode fibers can achieve a point-to-point transmission of the object with a high sampling density,as is a prerequisite for unsupervised image *** recently proposed disordered fibers offer a new solution based on the transverse Anderson ***,we demonstrate unsupervised full-color imaging with a cellular resolution through a meter-long disordered fiber in both transmission and reflection *** unsupervised image reconstruction consists of two *** the first stage,we perform a pixel-wise standardization on the fiber outputs using the statistics of the *** the second stage,we recover the fine details of the reconstructions through a generative adversarial *** image reconstruction does not need paired images,enabling a much more flexible calibration under various *** new solution achieves full-color high-fidelity cell imaging within a working distance of at least 4 mm by only collecting the fiber outputs after an initial *** imaging robustness is also demonstrated when the disordered fiber is bent with a central angle of 60°.Moreover,the cross-domain generality on unseen objects is shown to be enhanced with a diversified object set.

关键词： fiber optical image

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MXene multi-functionalization of polyrotaxane based PCMs and the applications in electronic devices thermal management

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Nano Materials Science 2024年第5期6卷 495-503页

作者： Guangzhong Yin Alba Marta lopez Ignacio Collado antonio Vazquez-lopez Xiang Ao Jose Hobson Silvia G.Prolongo Deyi Wang Escuela Politecnica Superior Universidad Francisco de VitoriaCtra.Pozuelo-Majadahonda Km 1.80028223 Pozuelo de AlarconMadridSpain IMDEA Materials Institute C/Eric Kandel228906GetafeMadridSpain Materials Science and Engineering Area Escuela Superior de Ciencias Experimentales y TecnologíaUniversidad Rey Juan CarlosC/Tulipan s/n28933MadridSpain Universidad Carlos III de Madrid Departamento de Ciencia e Ingeniería de Materiales e Ingeniería QuímicaIAAB.Avda.Universidad3028911LeganesMadridSpain Instituto de Tecnologías para la Sostenibilidad Universidad Rey Juan CarlosC/Tulipan s/n28933MadridSpain

The aim of this work was to improve the thermal conductivity and electromagnetic shielding of the leakage proof phase change materials(PCMs),in which a polyrotaxane(PLR)was used as a support material to encapsulate PEG 1k or PEG 6k and MXene as multi-functional *** PCMs can be processed conveniently by a hot press and the PEG 1k containing samples showed excellent *** conducted a systematic evaluation of the phase transition behavior of the material,thermal conductivity and electromagnetic shielding performance ***,the PCMs achieved a high enthalpy values(123.9–159.6 J/g).The PCMs exhibited an increase of 44.3%,and 137.5%in thermal conductivity values with higher MXene content(5 wt%)for PLR-PEG6k and PLR-PEG1k,respectively,and show high shape stability and no leakage during and after phase *** introduction of MXene can significantly improve the electromagnetic shielding performance of PCM ***,higher conductive samples(samples which contain high MXene contents)offer a higher EMI SE shielding,reaching a maximum of 4.67 dB at 5.6 GHz for *** improvements solve the main problems of organic PEG based PCMs,thus making PLR-PEG-MXene based PCMs good candidates for thermoregulators of both solid-state disks and smart *** is worth pointing out that the sample PLR-1k-MX5 can decrease 4.3C of the reference temperature during cellphone ***,the temperature of the protecting sheet in the simulated solid state disk with PCM was significantly lower(showing a decreasing of 7.9℃)compared with the blank sample.

关键词： Phase change materials Thermal regulation MXene Polyrotaxane Nanocomposites

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Endosomal escape of protein nanoparticles engineered through humanized histidine-rich peptides

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Science China Materials 2020年第4期63卷 644-653页

作者： Hector lopez-Laguna Rafael Cubarsi Ugutz Unzueta Ramon Mangues Esther Vazquez antonio Villaverde Institut de Biotecnologia i de Biomedicina Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingenieria Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Departament de Matematiques Universitat Politecnica de Catalunya08034BarcelonaSpain Institut d'Investigacions Biomediques Sant Pau Hospital de la Santa Creu i Sant Pau08025 BarcelonaSpain

Poly-histidine peptides such as H6(HHHHHH)are used in protein biotechnologies as purification tags,protein-assembling agents and endosomal-escape *** pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or drug delivery to be produced in form of recombinant ***,the clinical applicability of H6-tagged proteins is restricted by the potential immunogenicity of these *** this study,we have explored several humanized histidine-rich peptides in tumor-targeted modular proteins,which can specifically bind and be internalized by the target cells through the tumoral marker *** were particularly interested in exploring how protein purification,self-assembling and endosomal escape perform in proteins containing the variant histidine-rich *** the tested candidates,the peptide H5 E(HEHEHEHEH)is promising as a good promoter of endosomal escape of the associated fulllength protein upon endosomal *** numerical modelling of cell penetration and endosomal escape of the tested proteins has revealed a negative relationship between the amount of protein internalized into target cells and the efficiency of cytoplasmic *** fact demonstrates that the His-mediated,proton sponge-based endosomal escape saturates at moderate amounts of internalized protein,a fact that might be critical for the design of protein materials for cytosolic molecular delivery.

关键词： protein materials nanoparticles genetic design endosomal escape poly-histidines

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Recent Advances on Early-Stage Fire-Warning Systems: Mechanism, Performance, and Perspective

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Nano-Micro Letters 2022年第12期14卷 106-136页

作者： Xiaolu Li antonio Vazquez-lopez Jose Sanchez del Rio Saez De-Yi Wang IMDEA Materials Institute C/Eric Kandel228906 GetafeMadridSpain E.T.S.de Ingenieros de Caminos Universidad Politecnica de MadridCalle Profesor Aranguren 328040 MadridSpain Departamento de Ingenieria Electrica Electronica Automatica y Fisica AplicadaETSIDIUniversidad Politecnica de MadridRonda de Valencia 328012 MadridSpain

Early-stage fire-warning systems(EFWSs)have attracted significant attention owing to their superiority in detecting fire situations occurring in the pre-combustion *** progress on EFWSs has been achieved recently,and they have presented a considerable possibility for more evacuation time to control constant unintentional fire hazards in our daily *** review mainly makes a comprehensive summary of the current EFWSs,including the working mechanisms and their *** to the different working mechanisms,fire alarms can be classified into graphene oxide-based fire alarms,semiconductor-based fire alarms,thermoelectric-based fire alarms,and fire alarms on other working ***,the challenge and prospect for EFWSs are briefly provided by comparing the art of state of fire *** work can propose a more comprehensive understanding of EFWSs and a guideline for the cutting-edge development direction of EFWSs for readers.

关键词： Smart thermosensitive fire sensors Working mechanism Response time Signal conversion

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Complete polarization control in multimode fibers with polarization and mode coupling

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Light(Science & Applications) 2018年第1期7卷 603-612页

作者： Wen Xiong Chia Wei Hsu Yaron Bromberg Jose Enrique antonio-lopez Rodrigo Amezcua Correa Hui Cao Department of Applied Physics Yale UniversityNew HavenCT 06520USA Racah Institute of Physics Hebrew University of JerusalemJerusalem 91904Israel CREOL The College of Optics and PhotonicsUniversity of Central FloridaOrlandoFL 32816USA

Multimode optical fibers have seen increasing applications in communication,imaging,high-power lasers,and ***,inherent imperfections and environmental perturbations cause random polarization and mode mixing,causing the output polarization states to be different from the input polarization *** difference poses a serious issue for employing polarization-sensitive techniques to control light–matter interactions or nonlinear optical processes at the distal end of a fiber ***,we demonstrate complete control of polarization states for all output channels by only manipulating the spatial wavefront of a laser beam into the *** polarization states for individual output channels are generated by wavefront shaping without constraining the input *** strong coupling between the spatial and polarization degrees of freedom in a multimode fiber enables full polarization control with the spatial degrees of freedom alone;thus,wavefront shaping can transform a multimode fiber into a highly efficient reconfigurable matrix of waveplates for imaging and communication applications.

关键词： polarization fiber multimode

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Recent advances in bird sperm morphometric analysis and its role in male gamete characterization and reproduction technologies

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Asian Journal of Andrology 2016年第6期18卷 882-888页

作者： Julian Santiago-Moreno Milagros Cristina Esteso Silvia Villaverde-Morcillo Adolfo Toledano-Diaz Cristina Castafio Rosario Velazquez antonio lopez-Sebastian Agustin lopez Goya Javier Gimeno Martinez Department of Animal Reproduction INIA 28040 Madrid Spain Veterinary Clinical and Research Services Fieb Foundation 28760 Tres Cantos Madrid Spain FAUNIA 28032 Madrid Spain

Postcopulatory sexual selection through sperm competition may be an important evolutionary force affecting many reproductive traits, including sperm morphometrics. Environmental factors such as pollutants, pesticides, and climate change may affect different sperm traits, and thus reproduction, in sensitive bird species. Many sperm-handling processes used in assisted reproductive techniques may also affect the size of sperm cells. The accurately measured dimensions of sperm cell structures （especially the head） can thus be used as indicators of environmental influences, in improving our understanding of reproductive and evolutionary strategies, and for optimizing assisted reproductive techniques （e.g., sperm cryopreservation） for use with birds. Computer-assisted sperm morphometry analysis （CASA-Morph） provides an accurate and reliable method for assessing sperm morphometry, reducing the problem of subjectivity associated with human visual assessment. Computerized systems have been standardized for use with semen from different mammalian species. Avian spermatozoa, however, are filiform, limiting their analysis with such systems, which were developed to examine the approximately spherical heads of mammalian sperm cells. To help overcome this, the standardization of staining techniques to be used in compute^-assessed light microscopical methods is a priority. The present review discusses these points and describes the sperm morphometric characteristics of several wild and domestic bird species.

关键词： avian computer-assisted assay morphometry spermatozoa

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Simulation Tools for a Fiber-Optic Based Structural Health Monitoring System

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Transactions of Nanjing University of Aeronautics and Astronautics 2018年第2期35卷 219-225页

作者： Alfredo Güemes antonio Fernandez-lopez Jaime García-Ramírez Maria Eugenia Reyes-Perez Flor Criado Zurita Laboratory for Composites & Smart Structures Department of AeronauticsPolytechnic University of Madrid

Probability of detection(POD)graphics allow for a change from qualitative to quantitative assessment for every damage detection system,and as such it is a main request for conventional non-destructive testing(NDT)*** availability can greatly help towards the industrialization of the corresponding Structural health monitoring(SHM)*** having in mind that for SHM systems the sensors are at fixed positions,and the location of a potential damage would change its *** robust simulation tools are required to obtain the model assisted probability of detection(MAPOD)which is needed to validate the SHM *** tool may also help for the optimization of the sensor distribution,and finally will allow a probabilistic risk ***,simulation of ultrasonic waves SHM system,was a main milestone in this *** article deals with the simulation tools for a strain based SHM system,using fiber optic sensors(FOS).FOS are essentially strain/temperature sensors,either with multi-point or with distributed *** simulation tool includes the finite element model(FEM)for the original and damaged structure,and algorithms to compare the strain data at the pre-established sensors locations,and from this comparison to extract information about damage occurrence and *** study has been applied to the structure of an all-composite unmanned aircraft vehicle(UAV)now under construction,designed at Universidad Politecnica de Madrid for the inspection of electrical utilities *** sensing optical fibers were internally bonded at the fuselage and *** inspection is planned to be done with the aircraft at the test bench by imposing known *** the acquired strain data,damage occurrence may be calculated as slight deviations from the *** is a fast inspection procedure without requiring trained specialists,and it would allow for detection of hidden *** indicates that stringer par

关键词： damage detection fiber optics distributed sensing finite element models probability of detection(POD) principal component analysis (PCA) fibre bragg gratings (FBG)

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