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Hitting a moving target:inhibition of the nuclear export receptor XPO1/CRM1 as a therapeutic approach in cancer

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Cancer Drug Resistance 2018年第3期1卷 139-163页

作者： Maria Sendino Miren Josu Omaetxebarria jose antonio Rodríguez Department of Genetics Physical Anthropology and Animal PhysiologyUniversity of the Basque Country(UPV/EHU)Leioa48940Spain. Department of Biochemistry and Molecular Biology University of the Basque Country(UPV/EHU)Leioa 48940Spain

Cellular homeostasis crucially relies on the correct nucleocytoplasmic distribution of a vast number of proteins and RNA molecules,which are shuttled in and out of the nucleus by specialized transport *** nuclear export receptor XPO1,also called CRM1,mediates the translocation of hundreds of proteins and several classes of RNA to the cytoplasm,and thus regulates critical signaling pathways and cellular *** normal function of XPO1 appears to be often disrupted in malignant cells due to gene mutations or,most commonly,aberrant *** to its important physiological roles and its frequent alteration in human tumors,XPO1 is a promising target for cancer ***1 inhibitors have undergone extensive testing as therapeutic agents in preclinical models of cancer,with promising *** of these inhibitors,Selinexor,is currently being evaluated in multiple clinical trials of different types of solid tumors and hematological ***,we review several key aspects of XPO1 function,as well as the mechanisms that may lead to its alteration in cancer,and provide an update on the status of XPO1 inhibitors being developed as drugs for cancer therapy,including the definitive results of the first clinical trials with Selinexor that have been recently published.

关键词： XPO1 CRM1 nucleocytoplasmic transport Selinexor

Pacemaker therapy in the elderly patients

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Journal of Geriatric Cardiology 2007年第2期4卷 127-128页

作者： jose antonio Lapuerta-Irigoyen Santiago Herrero Pacemaker and Coronary Unit Intensive Care Service Cabuees Hospital Gijon Spain

　　The treatment of choice in symptomatic cases of patients with severe bradycardia remains the implantation of a pacemaker.……

关键词： Pacemaker therapy in the elderly patients

Immediate post-operative complications(I):Post-operative bleeding;vascular origin:Thrombosis pancreatitis

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World Journal of Transplantation 2020年第12期10卷 415-421页

作者： jose antonio Perez Daga Rosa Perez Rodriguez Julio Santoyo Department of Surgery Hospital Regional de MálagaMalaga 29010Spain

Simultaneous pancreas-kidney transplantation is the treatment of choice forinsulin-dependent diabetes that associates end-stage diabetic nephropathy, sinceit achieves not only a clear improvement in the quality of life, but also provides along-term survival advantage over isolated kidney transplant. However, pancreastransplantation still has the highest rate of surgical complications among organtransplants. More than 70% of early graft losses are attributed to technical failures,that is, to a non-immunological cause. The so-called technical failures includegraft thrombosis, bleeding, infection, pancreatitis, anastomotic leak and pancreaticfistula. Pancreatic graft thrombosis leads these technical complications as the mostfrequent cause of early graft loss. Currently most recipients receive postoperativeanticoagulation with the aim of reducing the rate of thrombosis. Hemoperitoneumin the early postoperative period is a frequent cause of relaparotomy, but it is notusually associated with graft loss. The incidence of hemoperitoneum is clearlyrelated to the use of anticoagulation in the postoperative period. Post-transplantpancreatitis is another cause of early postoperative complications, less frequentthan the previous. In this review, we analyze the most common surgicalcomplications that determine pancreatic graft losses.

关键词： Pancreas transplantation Vascular graft thrombosis Postoperative hemorrhage Graft pancreatitis Reperfusion injury Tissue donors Risk factors

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

HVEM,a cosignaling molecular switch,and its interactions with BTLA,CD160 and LIGHT

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Cellular & Molecular Immunology 2019年第7期16卷 679-682页

作者： jose Ignacio Rodriguez-Barbosa Pascal Schneider Andreas Weigert Kyung-Mi Lee Tae-Jin Kim jose-antonio Perez-Simon Maria-Luisa del Rio Transplantation Immunobiology Section Research Institutes of the University of LeonCampus of Vegazana s/n24071 LeonSpain Leon Regional Transplantation Coordination Center Leon University HospitalLeonSpain Acción Estratégica en Salud Consorcio CIBER-ONCSevilleSpain Department of Biochemistry University of Lausanne1066 EpalingesSwitzerland Institute of Biochemistry I Faculty of MedicineGoethe-University Frankfurt60590 FrankfurtGermany Department of Biochemistry and Molecular Biology Korea University College of MedicineSeoul 02841Republic of Korea Department of Biomedical Engineering Center for Bio-Integrated ElectronicsSimpson Querrey Institute for BioNanotechnologyNorthwestern UniversityEvanstonIL 60208USA Department of Hematology Virgen del Rocio University HospitalBiomedical Institute of SevillaSevillaSpain

Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T *** the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T *** expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.

关键词： stimulation homeostasis inflammation

Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

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Journal of Pharmaceutical Analysis 2020年第6期10卷 532-545页

作者： Natalia Navas Jesús Hermosilla Anabel Torrente-Lopez jose Hernandez-Jimenez jose Cabeza Raquel Perez-Roblesa antonio Salmeron-García Department of Analytical Chemistry Science Faculty/Biomedical Research Institute ibs.GranadaUniversity of GranadaGranadaE-18071Spain UGC Farmacia Hospitalaria Biomedical Research Institute ibs.Granada.Hospital Universitario San Cecilio de GranadaGranadaE-18012Spain

COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many *** studies suggest that cytokine storms(interleukins)may play an important role in severe cases of *** key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality ***(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS *** investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical *** has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug ***,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of *** is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.

关键词： COVID-19 Tocilizumab Critical quality attributes IV and SC medicines

Optimal Coordinated Operation of Distributed Static Series Compensators for Wide-area Network Congestion Relief

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Journal of Modern Power Systems and Clean Energy 2022年第5期10卷 1374-1384页

作者： Camilo Andres Ordonez M antonio Gomez-Exposito Guillermo EVinasco M jose Maria Maza-Ortega IEEE Smart Wires Union CityUSA Department of Electrical Engineering University of SevilleSevillaSpain Interconexion Electrica SA Intercolombia Sevilla Spain

Relieving network congestions is a critical goal for the safe and flexible operation of modern power systems, especially in the presence of intermittent renewables or distributed generation. This paper deals with the real-time coordinated operation of distributed static series compensators(DSSCs) to remove network congestions by suitable modifications of the branch reactance. Several objective functions are considered and discussed to minimize the number of the devices involved in the control actions, the total losses or the total reactive power exchanged, leading to a non-convex mixed-integer non-linear programming problem. Then, a heuristic methodology combining the solution of a regular NLP with k-means clustering algorithm is proposed to get rid of the binary variables, in an attempt to reduce the computational cost. The proposed coordinated operation strategy of the DSSCs is tested on several benchmark systems, providing feasible and sufficiently optimal solutions in a reasonable time frame for practical systems.

关键词： Distributed static series compensation(DSSC) flexible AC transmission system(FACTS) mixed-integer non-linear programming(MINLP) wide-area network control

Development and test verification of air temperature model for Chinese solar and Spainish Almeria-type greenhouses

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International Journal of Agricultural and Biological Engineering 2017年第4期10卷 66-76页

作者： Jorge antonio Sanchez-Molina Li Ming Francisco Rodriguez jose Luis Guzman Wang Hui Yang Xinting The Automatic Control Robotics and Mechatronics Research GroupDepartment of InformaticsceiA3CIESOLUniversity of AlmeriaAlmeria 04120Spain Beijing Research Center for Information Technology in Agriculture/National Engineering Research Center for Information Technology in Agriculture/National Engineering Laboratory for Agri-product Quality Traceability/Key Laboratory for Information Technologies in Agriculture Ministry of AgricultureBeijing 100097China

Growth can be defined as an increment in biomass or an increment in weight or height of the organs of the plant influenced by physiological *** of these processes have their limits genetically determined,but climate and irrigation play an important *** of its importance,microclimate has been extensively studied in the modeling as a surrounding condition which is imposed by the exterior *** main objective of this work was to develop a temperature model based on the energy balance dynamics at two different greenhouse locations-South-eastern Spain and Northern China,and the traditional structures of Chinese solar greenhouse and Almería-type multi-span greenhouse were taken into *** final model was developed by combining the external conditions,the actuator influence and the crop growth,where the temperature is influenced by soil,crop,cover,actuators,back wall and greenhouse *** model took into account the energy lost by convective and conductive fluxes,as well as the energy supplied by solar radiation and heating *** soil and the back wall are the main media for energy *** temperature dynamic was determined by a physical model,which considered the energy balance from a holistic point of view-as a sub-model for a customizable interface among the external climate,the plant and the greenhouse *** influences of different subsystems included in the temperature model were analyzed and *** results showed a high R^(2)value of 0.94 for Beijing and 0.95 for Almeria,and the average error was low,of which the MAE and RMSE were 0.71 and 1.365 for Almeria and 0.62 and 1.102 for Beijing,***,the model can be considered as a powerful tool for control design purposes in microclimate systems.

关键词： air temperature model Chinese solar greenhouse Spanish Almería-type greenhouse energy balance dynamics microclimate

Thermal analysis of olive tree pruning and the by-products obtained by its gasification and pyrolysis: The effect of some heavy metals on their devolatilization behavior

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Journal of Energy Chemistry 2019年第5期28卷 105-117页

作者： Irene lanez-Rodriguez Maria Angeles Martin-Lara Gabriel Blazquez Oscar Osegueda Monica calero Department of Chemical Engineering Faculty of SciencesUniversity of GranadaAvda.Fuentenuevas/n 18071 GranadaSpain Department of Process Engineering and Environmental Sciences Jose Simeon Canas Central American UniversityBulevar Los ProceresSan SalvadorEl Salvador

In this work, the effect of the presence of nickel and lead in thermal decomposition of olive tree pruning (OTP), OTP-char and OTP-ashes was studied by thermogravimetry. Experiments were conducted in two kinds of atmosphere (nitrogen atmosphere and oxidizing atmosphere with 20% of O2) at a heating rate of 10 ℃/min. This investigation describes the chemical, physical and fuel properties of the OTP, which shows a similar composition to other lignocellulosic materials such as hazelnut husk and wood sawdust. In addition, SEM analysis indicated that OTP-char surface is higher than OTP surface with plenty of holes and channels. It makes the char an ideal support for metal retention specially for Pb metal (OTP retained 8.55 mg/g whereas OTP char retained 11.57 mg/g). On the other hand, metal retention occurred by adsorption or ion exchange, according to the IR spectrum of the samples. The results of thermogravimetric tests proved that the presence of lead did not have a strong effect on the decomposition of the samples, since TG and DTG curves were very similar. However, nickel increased the mass loss rate, accelerating the decomposition process, showing higher peaks in DTG curves. Additionally, for temperatures higher than 360 ℃, the volatilization of the samples was improved in the nickel-polluted sample, achieving a higher mass loss, getting more energy from the biomass and reducing the quantity of residues left after the process.

关键词： Biosorption Lead Metal-polluted biomass Nickel Thermal decomposition Thermogravimetric analysis