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neural Regeneration Research 2020年第1期15卷 71-72页

作者： laura Orio Department of Psychobiology and Methods in Behavioural Sciences Complutense University of Madrid

Is there a need for new pharmacotherapies to treat alcohol use disorders(AUDs)?AUD is a highly prevalent condition in the world population that causes medical,psychological,personal,social and economic *** most severe dimension of AUDs is alcohol dependence,a condition in which individuals lose control over alcohol intake despite the negative *** some medications have been approved for this purpose,existing pharmacotherapies are not effective for all people due to the heterogeneity of *** approved medications include:Disulfiram(Antabuse^?),which induces an aversion to drink by increasing alcohol metabolism-derived acetaldehyde;naltrexone(ReVia^?,Vivitrol^?),a competitive opioid antagonist forμ-receptors that decreases heavy drinking and prevents relapse;Acamprosate(Campral^?),an indirect partial agonist at n-methyl-D-aspartic acid glutamate receptors and antagonist at metabotropic glutamate receptors that is used to prevent relapse in detoxified alcoholics.

关键词： metabolism inflammation alcohol

MYC and KRAS cooperation:from historical challenges to therapeutic opportunities in cancer

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Signal Transduction and Targeted Therapy 2024年第9期9卷 3840-3869页

作者： Sílvia Casacuberta-Serra Íñigo González-Larreategui Daniel Capitán-Leo laura Soucek Peptomyc S.L. BarcelonaSpain Models of cancer therapies Laboratory Vall d’Hebron Institute of OncologyCellex CentreHospital University Vall d’Hebron CampusBarcelonaSpain InstitucióCatalana de Recerca i Estudis Avançats BarcelonaSpain Department of Biochemistry and Molecular Biology Universitat Autonoma de BarcelonaBellaterraSpain

RAS and MYC rank amongst the most commonly altered oncogenes in cancer,with RAS being the most frequently mutated and MYC the most *** cooperative interplay between RAS and MYC constitutes a complex and multifaceted phenomenon,profoundly influencing tumor *** and individually,these two oncogenes regulate most,if not all,hallmarks of cancer,including cell death escape,replicative immortality,tumor-associated angiogenesis,cell invasion and metastasis,metabolic adaptation,and immune *** to their frequent alteration and role in tumorigenesis,MYC and RAS emerge as highly appealing targets in cancer ***,due to their complex nature,both oncogenes have been long considered“undruggable”and,until recently,no drugs directly targeting them had reached the *** review aims to shed light on their complex partnership,with special attention to their active collaboration in fostering an immunosuppressive milieu and driving immunotherapeutic resistance in *** this review,we also present an update on the different inhibitors targeting RAS and MYC currently undergoing clinical trials,along with their clinical outcomes and the different combination strategies being explored to overcome drug *** recent clinical development suggests a paradigm shift in the long-standing belief of RAS and MYC“undruggability”,hinting at a new era in their therapeutic targeting.

关键词： therapeutic overcome Together

Galectin-3 prospects as a therapeutic agent for multiple sclerosis

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neural Regeneration Research 2019年第8期14卷 1380-1382页

作者： laura Thomas laura Andrea Pasquini Department of Biological Chemistry School of Pharmacy and Biochemistry Institute of Chemistry Biological Physicochemistry (IQUIFIB) University of Buenos Aires and National Research Council (CONICET)

Galectin-3 (Gal-3) in oligodendrocyte (OLG) differentiation: OLGs are the cells in charge of myelination in the central nervous system (CnS), allowing rapid conduction of the neural action potential and giving trophic support to axons. OLGs undergo a series of changes throughout their life cycle: first, upon neural stem cell comm让ment to the OLG lineage, cells referred to as OLG precursor cells (OPC) present a bipolar morphology, have proliferative and migratory capacity and express molecular markers like platelet-derived growth factor receptor alpha and neural/glial antigen 2.

关键词： multiple sclerosis therapeutic agent Galectin-3 prospects

Corneal and intraocular pressure changes associated to the circadian rhythms:a narrative review

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1921-1928页

作者： laura Barberán-Bernardos MiguelÁngel Ariza-Gracia David P Piñero Department of Optics Pharmacology and AnatomyUniversity of AlicanteSan Vicente del Raspeig 03690AlicanteSpain ARTORG Center for Biomedical Engineering Research University of BernBern 3008Switzerland Department of Ophthalmology(IMQO-Oftalmar) Vithas Medimar International HospitalAlicante 03016Spain

AIM:To synthesize the current body of research regarding the diurnal variations in intraocular pressure(IOP)and corneal biomechanical and morphological parameters,highlighting their significance in various eye ***:A comprehensive review of studies on the diurnal variations of IOP and corneal parameters was *** findings from various studies were assessed,including the Goldmann applanation tonometry(GAT)and non-contact *** on the variations in central corneal thickness(CCT),corneal curvature,and corneal biomechanics measured by the Ocular Response Analyzer system across different population groups was extracted and ***:In both healthy subjects and those with Fuchs dystrophy,IOP and CCT demonstrate marked diurnal *** remains the gold standard for tonometry,with the highest ***,its measurements are influenced by *** patients and those with pseudoexfoliation showed significant diurnal variations in *** biomechanical parameters,especially corneal hysteresis(CH)and the corneal resistance factor(CRF),largely remain stable throughout the day for most of eye conditions,with some ***,the corneal morphology diurnal variation,particularly curvature,yielded mixed conclusions across ***:Circadian rhythms significantly influence various corneal parameters,most notably IOP and *** studies should emphasize standardized approaches larger sample sizes,and delve deeper into less-explored areas,such as the effects of orthokeratology lenses on diurnal biomechanical shifts.

关键词： circadian rhythms intraocular pressure corneal thickness corneal biomechanics corneal curvature

novel Galectin-3 interactions involved in oligodendroglial differentiation make inroads into therapeutic strategies for demyelinating diseases

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neural Regeneration Research 2021年第2期16卷 289-290页

作者： laura Andrea Pasquini Department of Biological Chemistry School of Pharmacy and BiochemistryInstitute of Biological Chemistry and Physicochemistry(IQUIFIB)University of Buenos Aires and National Research Council(CONICET)Buenos AiresArgentina

Galectins(Gals)constitute a 15-member class ofβ-galactoside-binding lectins which recognize *** lacking specific receptors,Gals form multivalent complexes with cell surface glycoconjugates containing suitable oligosaccharides and thus trigger intracellular signals to regulate cell survival and *** are classified into three groups on the basis of their structural architecture:proto,chimera and tandem types。

关键词： spite complexes strategies

Laboratory pull-out tests on fully grouted rock bolts and cable bolts:Results and lessons learned

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Journal of Rock Mechanics and Geotechnical Engineering 2017年第5期9卷 843-855页

作者： Isabelle Thenevin laura Blanco-Martín Faouzi Hadj-Hassen Jacques Schleifer Zbigniew Lubosik Aleksander Wrana MInES ParisTech Department of Geosciences PSL Research University 35 rue Saint Honoré Fontainebleau Cedex 77305 France Department of Extraction Technology and Mining Support Central Mining Institute (GIG) Katowice Poland

Laboratory pull-out tests were conducted on the following rock bolts and cable bolts:steel rebars,smooth steel bars,fiberglass reinforced polymer threaded bolts,flexible cable bolts,IR5/In special cable bolts and Mini-cage cable *** diameter of the tested bolts was between 16 mm and 26 *** bolts were grouted in a sandstone sample using resin or cement *** tests were conducted under either constant radial stiffness or constant confining pressure boundary conditions applied on the outer surface of the rock *** most tests,the rate of displacement was about 0.02 mm/*** tests were performed using a pull-out bench that allows testing a wide range of *** paper provides an extensive database of laboratory pull-out test results and confirms the influence of the confining pressure and the embedment length on the pull-out response(rock bolts and cable bolts).It also highlights the sensitivity of the results to the operating conditions and to the behavior of the sample as a whole,which cannot be neglected when the test results are used to assess the bolt-grout or the grouterock interface.

关键词： Pull-out test Fully grouted bolts Laboratory-scale Confining pressure Embedment length Bolt-grout interface

Development and application of an interface constitutive model for fully grouted rock-bolts and cable-bolts

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Journal of Rock Mechanics and Geotechnical Engineering 2021年第4期13卷 811-819页

作者： Emad Jahangir laura Blanco-Martin Faouzi Hadj-Hassen Michel Tijani MInES ParisTech PSL Research UniversityDepartment of Geosciences35 Rue Saint Honoré77300FontainebleauFrance

This paper proposes a new interface constitutive model for fully grouted rock-bolts and cable-bolts based on pull-out test results.A database was created combining published experimental data with in-house *** means of a comprehensive framework,a Coulomb-type failure criterion accounting for friction mobilization was *** the elastic phase,in which the interface joint is not yet created,the proposed model provides zero radial displacement,and once the interface joint is created,interface dilatancy is modeled using a non-associated plastic potential inspired from the behavior of rock *** results predicted by the proposed model are in good agreement with experimental *** model has been implemented in a finite element method(FEM)code and numerical simulations have been performed at the elementary and the structural *** results obtained provide confidence in the ability of the new model to assist in the design and optimization of bolting patterns.

关键词： Fully grouted bolts Interface constitutive model Dilatancy Pull-out tests Finite element method(FEM)modeling

Some Univalence Conditions for a General Integral Operator

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Chinese Annals of Mathematics,Series B 2012年第6期33卷 801-806页

作者： laura STAnCIU Daniel BREAZ Department of Mathematics University of Pitesti Department of Mathematics University of Alba Iulia

The authors consider the classes of the univalent functions denoted by SH(β),SP and SP(α,β).On these classes,the univalence conditions for a general integral operator are studied.

关键词： Analytic function Integral operator Univalence condition GeneralSchwarz lemma

Hierarchical state-abstracted and socially augmented Q-Learning for reducing complexity in agent-based learning

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控制理论与应用（英文版） 2011年第3期9卷 440-450页

作者： laura RAY Thayer School of Engineering Dartmouth College

A primary challenge of agent-based policy learning in complex and uncertain environments is escalating computational complexity with the size of the task space(action choices and world states) and the number of ***,there is ample evidence in the natural world that high-functioning social mammals learn to solve complex problems with ease,both individually and *** ability to solve computationally intractable problems stems from both brain circuits for hierarchical representation of state and action spaces and learned policies as well as constraints imposed by social *** biologically derived mechanisms for state representation and mammalian social intelligence,we constrain state-action choices in reinforcement learning in order to improve learning *** results bound the reduction in computational complexity due to stateion,hierarchical representation,and socially constrained action selection in agent-based learning problems that can be described as variants of Markov decision *** of two task domains,single-robot herding and multirobot foraging,shows that theoretical bounds hold and that acceptable policies emerge,which reduce task completion time,computational cost,and/or memory resources compared to learning without hierarchical representations and with no social knowledge.

关键词： Decentralized Markov decision process Reinforcement learning Multiagent systems

Genetic predisposition to colorectal cancer:Where we stand and future perspectives

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World Journal of Gastroenterology 2014年第29期20卷 9828-9849页

作者： laura Valle Hereditary Cancer Program Catalan Institute of OncologyIDIBELL08908 BarcelonaSpain

The development of colorectal cancer(CRC)can be influenced by genetic factors in both familial cases and sporadic *** CRC has been associated with genetic changes in high-,moderate-and low-penetrance susceptibility ***,despite the availability of current gene-identification techniques,the genetic causes of a considerable proportion of hereditary cases remain ***-wide association studies of CRC have identified a number of common lowpenetrance alleles associated with a slightly increased or decreased risk of *** accumulation of low-risk variants may partly explain the familial risk of CRC,and some of these variants may modify the risk of cancer in patients with mutations in high-penetrance *** the predisposition to develop CRC will require investigators to address the following challenges:the identification of genes that cause uncharacterized hereditary cases of CRC such as familial CRC type X and serrated polyposis;the classification of variants of unknown significance in known CRC-predisposing genes;and the identification of additional cancer risk modifiers that can be used to perform risk assessments for individual mutation *** performed a comprehensive review of the genetically characterized and uncharacterized hereditary CRC syndromes and of lowand moderate-penetrance loci and variants identified through genome-wide association studies and candidate-gene *** challenges and future perspectives in the field of CRC predisposition are also discussed.

关键词： Hereditary colorectal cancer Familial colorectal cancer High penetrance Low penetrance Cancer syndromes Cancer susceptibility Hereditary cancer genes Risk variants Heritability