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A Novel Ensemble Learning System for Cyberattack Classification

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Intelligent Automation & Soft Computing 2023年第8期37卷 1691-1709页

作者： óscar Mogollón-Gutiérrez Josécarlos sancho Nunez Marávila Vegas Andrés Caro Lindo Department of Computer and Telematic Systems Engineering Universidad de ExtremaduraSchool of TechnologyCáceres10005Spain

Nowadays,IT systems rely mainly on artificial intelligence(AI)algorithms to process *** is generally used to extract knowledge from stored information and,depending on the nature of data,it may be necessary to apply different AI *** this article,a novel perspective on the use of AI to ensure the cybersecurity through the study of network traffic is *** is done through the construction of a two-stage cyberattack classification ensemble model addressing class imbalance following a one-vs-rest(OvR)*** the growing trend of cyberattacks,it is essential to implement techniques that ensure legitimate access to *** address this issue,this work proposes a network traffic classification system for different categories based on several AI *** the first task,binary models are generated to clearly differentiate each type of traffic from the *** binary models generated,an ensemble model is developed in two phases,which allows the separation of legitimate and illegitimate traffic(phase 1)while also identifying the type of illegitimate traffic(phase 2).In this way,the proposed system allows a complete multiclass classification of network *** estimation of global performance is done using a modern dataset(UNSW-NB15),evaluated using two approaches and compared with other state-of-art *** proposal,based on the construction of a two-step model,reaches an F1 of 0.912 for the first level of binary classification and 0.7754 for the multiclass *** results show that the proposed system outperforms other state-of-the-art approaches(+0.75%and+3.54%for binary and multiclass classification,respectively)in terms of F1,as demon-strated through comparison together with other relevant classification metrics.

关键词： Intrusion detection ensemble learning two-phase model UNSW-NB15 cybersecurity

The labyrinth of nuclear reprogramming

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Journal of Molecular Cell Biology 2011年第6期3卷 327-329页

作者： Ignacio sancho-Martinez Emmanuel Nivet Juan carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Center for Regenerative Medicine in Barcelona Dr Aiguader 88Barcelona 08003Spain

Human embryonic stem cells(ESCs)have the capability to differentiate into all somatic cell types,a process that recapitu-lates the early stages of human ***,the use of ESCs raises several controversies,particularly concern-ing the ethical dilemma regarding the use of human embryonic material and the need for embryo *** discov-ery of induced pluripotent stem cell(iPSC)technology in 2006(Takahashi and Yamanaka,2006)opened the door for possible application of pluripotent stem-cell-related therapies in the clinic as well as for the generation of patient-derived pluripotent stem cells suitable for disease modeling in vitro.

关键词： programming destruction opened

Mitochondrial determinants of chemoresistance

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Cancer Drug Resistance 2019年第3期2卷 634-646页

作者： Ansooya Bokil Patricia sancho IIS Aragon Hospital Universitario Miguel ServetZaragoza 50009Spain

Chemoresistance constitute nowadays the major contributor to therapy failure in most *** are main factors that mitigate cell response to therapy,such as target organ,inherent sensitivity to the administered compound,its metabolism,drug efflux and influx or alterations on specific cellular targets,among *** now know that intrinsic properties of cancer cells,including metabolic features,substantially contribute to *** fact,during the last years,numerous reports indicate that cancer cells resistant to chemotherapy demonstrate significant alterations in mitochondrial metabolism,membrane polarization and *** activity and expression of several mitochondrial proteins are modulated under treatment to cope with stress,making these organelles central players in the development of resistance to ***,we review the role of mitochondria in chemoresistant cells in terms of metabolic rewiring and function of key mitochondria-related proteins.

关键词： Mitochondria chemoresistance oxidative phosphorylation fatty acid oxidation metabolism uncoupling proteins ABC transporters

Metabolism of tissue macrophages in homeostasis and pathology

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Cellular & Molecular Immunology 2022年第3期19卷 384-408页

作者： Stefanie K.Wculek Gillian Dunphy Ignacio Heras-Murillo Annalaura Mastrangelo David sancho Immunobiology Laboratory Centro Nacional de Investigaciones Cardiovasculares(CNIC)Melchor Fernández Almagro 3Madrid28029Spain

Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy and structural *** emerging field of immunometabolism highlights the importance of cellular metabolism for the maintenance and activities of immune *** are embryo-or adult bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome,atherosclerosis,fibrosis or *** metabolism has largely been studied in ***,different organs contain diverse macrophage populations that specialize in distinct and often tissue-specific *** context specificity creates diverging metabolic challenges for tissue macrophage populations to fulfill their homeostatic roles in their particular microenvironment and conditions their response in pathological ***,we outline current knowledge on the metabolic requirements and adaptations of macrophages located in tissues during homeostasis and selected diseases.

关键词： Tissue macrophages metabolism homeostasis pathology tissue regeneration

Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells

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World Journal of Stem Cells 2020年第11期12卷 1410-1428页

作者： Petra Jagust Sonia Alcala Bruno Sainz Jr Christopher Heeschen Patricia sancho Molecular Pathology Programme Spanish National Cancer Research Centre(CNIO)Madrid 28029Spain Department of Biochemistry Autónoma University of MadridInstituto de Investigaciones Biomédicas"Alberto Sols"CSIC-UAMMadrid 28029Spain Center for Single-Cell Omics&Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai Jiao Tong University School of MedicineShanghai 200025China Hospital Universitario Miguel Servet IIS AragonZaragoza 50009Spain

BACKGROUND Cellular metabolism regulates stemness in health and disease.A reduced redox state is essential for self-renewal of normal and cancer stem cells(CSCs).However,while stem cells rely on glycolysis,different CSCs,including pancreatic CSCs,favor mitochondrial metabolism as their dominant energy-producing *** suggests that powerful antioxidant networks must be in place to detoxify mitochondrial reactive oxygen species(ROS)and maintain stemness in oxidative *** glutathione metabolism is critical for normal stem cell function and CSCs from breast,liver and gastric cancer show increased glutathione content,we hypothesized that pancreatic CSCs also rely on this pathway for ROS *** To investigate the role of glutathione metabolism in pancreatic *** Primary pancreatic cancer cells of patient-derived xenografts(PDXs)were cultured in adherent or CSC-enriching sphere conditions to determine the role of glutathione metabolism in ***-time polymerase chain reaction(PCR)was used to validate RNAseq results involving glutathione metabolism genes in adherent vs spheres,as well as the expression of pluripotency-related genes following *** TCGA and GTEx RNAseq data from pancreatic cancer vs normal tissue samples were analyzed using the webserver *** glutathione-sensitive fluorescent probe monochlorobimane was used to determine glutathione content by fluorimetry or flow *** inhibitors of glutathione synthesis and recycling[buthionine-sulfoximine(BSO)and 6-Aminonicotinamide(6-AN),respectively]were used to investigate the impact of glutathione depletion on CSC-enriched *** with propidium iodide(cell cycle),Annexin-V(apoptosis)and CD133(CSC content)were determined by flow ***-renewal was assessed by sphere formation assay and response to gemcitabine treatment was used as a readout for *** Analysis of our previously published RNAseq dataset E-MTAB-

关键词： Pancreatic cancer Cancer stem cells Glutathione Self-renewal Chemoresistance Redox

Morphometry and subpopulation structure of Holstein bull spermatozoa： variations in ejaculates and cryopreservation straws

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Asian Journal of Andrology 2016年第6期18卷 851-857页

作者： Anthony Valverde Hector Arenan Maria sancho Jesus Contell Jesus Yaniz Alejandro Fernandez Caries Soler Technological Institute of Costa Rica San Carlos Campus S Xenetica Fontao Fontao-Esperante 27210 Lugo Spain R+D Department Proiser R+D Scientific Park University of Valencia 46980 Paterna Spain Department of Animal Production and Food Science Politechnical School of Huesca University of Zaragoza 22071 Huesca Spain Department of Functional Biology and Physical Anthropology University of Valencia 46100 Burjassot Spain

Sperm quality is evaluated for the calculation of sperm dosage in artificial reproductive programs. The most common parameter used is motility, but morphology has a higher potential as a predictor of genetic quality. Morphometry calculations from CASA-Morph technology improve morphological evaluation and allow mathematical approaches to the problem. Semen from 28 Holstein bulls was collected by artificial vagina, and several ejaculates were studied. After general evaluation, samples were diluted, packaged in 0.25 ml straws, and stored in liquid nitrogen. Two straws per sample were thawed, and slides were processed and stained with Diff-Quik. Samples were analyzed by a CASA-Morph system for eight morphometric parameters. In addition to the ＂classical＂ statistical approach, based on variance analysis （revealing differences between animals, ejaculates, and straws）, principal component （PC） analysis showed that the variables were grouped into PC1, related to size, and PC2 to shape. Subpopulation structure analysis showed four groups, namely, big, small, short, and narrow from their dominant characteristics, representing 31.0%, 27.3%, 24.1%, and 17.7% of the total population, respectively. The distributions varied between animals and ejaculates, but between straws, there were no differences in only four animals. This modern approach of considering an ejaculate sperm population as divided into subpopulations reflecting quantifiable parameters generated by CASA-Morph systems technology opens a new view on sperm function. This is the first study applying this approach to evaluate different ejaculates and straws from the same individual. More work must be done to improve seminal dose calculations in assisted reproductive programs.

关键词： cryopreservation Holstein bull sperm morphometry subpopulations

Sperm kinematic, head morphometric and kinetic- morphometric subpopulations in the blue fox （Alopex lagopus）

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Asian Journal of Andrology 2017年第2期19卷 154-159页

作者： Caries Soler Jesus Contell Lorena Bori Maria sancho Almudena Garcia-Molina Anthony Valverde Jan Segarvall Department of Functional Biology and Physical Anthropology University of Valencia 46100 Burjassot Spain R+D Department Proiser R+D Scientific Park University of Valencia 46980 Paterna Spain Technological Institute of Costa Rica San Carlos Campus School of Agronomy 223-21001 Alajuela Costa Rica Finnish Fur Breeders Association ProFur 65101 Vaasa Finland

This work provides information on the blue fox ejaculated sperm quality needed for seminal dose calculations. Twenty semen samples, obtained by masturbation, were analyzed for kinematic and morphometric parameters by using CASA-Mot and CASA-Morph system and principal component （PC） analysis. For motility, eight kinematic parameters were evaluated, which were reduced to PC1, related to linear variables, and PC2, related to oscillatory movement. The whole population was divided into three independent subpopulations： SP1, fast cells with linear movement; SP2, slow cells and nonoscillatory motility; and SP3, medium speed cells and oscillatory movement. In almost all cases, the subpopulation distribution by animal was significantly different. Head morphology analysis generated four size and four shape parameters, which were reduced to PC 1, related to size, and PC2, related to shape of the cells. Three morphometric subpopulations existed. SPI： large oval cells; SP2： medium size elongated cells; and SP3. small and short cells. The subpopulation distribution differed between animals. Combining the kinematic and morphometric datasets produced PC1, related to morphometric parameters, and PC2, related to kinematics, which generated four sperm subpopulations - SPI.. high oscillatory motility, large and short heads; SP2; medium velocity with small and short heads; SP3. slow motion small and elongated cells; and SP4. high linear speed and large elongated cells. Subpopulation distribution was different in all animals. The establishment of sperm subpopulations from kinematic, morphometric, and combined variables not only improves the well-defined fox semen characteristics and offers a good conceptual basis for fertility and sperm preservation techniques in this species, but also opens the door to use this approach in other species, included humans.

关键词： integration of motility and morphology principal component analysis sperm morphometry subpopulation

Lipid droplets as metabolic determinants for stemness and chemoresistance in cancer

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World Journal of Stem Cells 2021年第9期13卷 1307-1317页

作者： Alba Royo-Garcia Sarah Courtois Beatriz Parejo-Alonso Pilar Espiau-Romera Patricia sancho Hospital Universitario Miguel Servet IIS AragónZaragoza 50009Spain

Previously regarded as simple fat storage particles,new evidence suggests thatlipid droplets(LDs)are dynamic and functional organelles involved in keycellular processes such as membrane biosynthesis,lipid metabolism,cellsignalling and ***,an increased LD content is one of the mostapparent features resulting from lipid metabolism reprogramming necessary tosupport the basic functions of cancer *** have been associated to differentcellular processes involved in cancer progression and aggressiveness,such astumorigenicity,invasion and metastasis,as well as ***,all of these processes are controlled by a subpopulation of highly aggressivetumoral cells named cancer stem cells(CSCs),suggesting that LDs may befundamental elements for stemness in *** the key role of CSCs onchemoresistance and disease relapse,main factors of therapy failure,the design ofnovel therapeutic approaches targeting these cells may be the only chance forlong-term survival in cancer *** this sense,their biology and functionalproperties render LDs excellent candidates for target discovery and design ofcombined therapeutic *** this review,we summarise the currentknowledge identifying LDs and CSCs as main contributors to cancer aggressiveness,metastasis and chemoresistance.

关键词： Lipids Lipid droplets Lipid metabolism Stemness Cancer stem cells Chemoresistance

The WAK-like protein RFO1 acts as a sensor of the pectin methylation status in Arabidopsis cell walls to modulate root growth and defense

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Molecular Plant 2023年第5期16卷 865-881页

作者： Apolonio I.Huerta Gloria sancho-Andre´s Juan carlos Montesinos Javier Silva-Navas Sole`ne Bassard Corinne Pau-Roblot Christopher Kesten Rudolf Schlechter Susanne Dora Temurkhan Ayupov Je´rome Pelloux^ Julia Santiago Clara Sa´nchez-Rodrı´guez ETH Zurich Institute of Molecular Plant Biology(D-BIOL)ZurichSwitzerland University of Lausanne Department of Plant Molecular BiologyLausanneSwitzerland UMRT INRAE 1158 BioEcoAgro–BIOPI Biologie des Plantes et Innovation Universite´de Picardie33 Rue St Leu80039 AmiensFrance Present address:Lonza AG VispVisSwitzerland Present address:Institute of Microbiology Freie Universitat BerlinBerlinGermany Present address:Institute of Molecular and Clinical Ophthalmology-Basel BaselSwitzerland Present address:Centro de Biotecnologı´a y Geno´mica de Plantas Universidad Polite´cnica de Madrid(UPM)–Instituto Nacional de Investigacio´n y Tecnologı´a Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPM28223 Pozuelo de Alarco´nSpain

Most organisms adjust their development according to the environmental *** the majority,this implies the sensing of alterations to cell walls caused by different *** the relevance of this process,few molecular players involved in cell wall sensing are known and ***,we show that the wall-associated kinase-like protein RESISTANCE TO FUSARIUM OXYSPORUM 1(RFO1)is required for plant growth and early defense against Fusarium oxysporum and functions by sensing changes in the pectin methylation levels in the cell *** RFO1 dwell time at the plasma membrane is affected by the pectin methylation status at the cell wall,regulating MITOGEN-ACTIVATED PROTEIN KINASE and gene *** show that the extracellular domain of RFO1 binds de-methylated pectin in vitro,whose distribution in the cell wall is altered during *** *** analyses also indicate that RFO1 is required for the BR-dependent plant growth alteration in response to inhibition of pectin de-methyl-esterase activity at the cell ***,our work demonstrates that RFO1 is a sensor of the pectin methylation status that plays a unique dual role in plant growth and defense against vascular pathogens.

关键词： alterations walls pectin