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CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： alvaro quintanal-villalonga Kenta Kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar Dennis Kinyua Hong Zhong Barbara P.Mello Metamia Ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes Michael C.Haffner Nichlas D.Socci Richard P.Koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.Chan Charles M.Rudin Department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan Kettering Cancer Center New YorkNYUSA Department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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Monoclonal antibodies and aptamers:The future therapeutics for Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2795-2814页

作者： alvaro Barrera-Ocampo Facultad de Ingenierıa Diseno y Ciencias AplicadasDepartamento de Ciencias Farmaceuticas y QuimicasGrupo NaturaUniversidad IcesiCali 760031Colombia

Alzheimer’s disease(AD)is considered the most common and prevalent form of dementia of adult-onset with characteristic progressive impairment in cognition and *** cure for AD has not been found yet and the treatments available until recently were only *** of multidisciplinary approaches and efforts made by pharmaceutical companies,it was only in the past two years that new drugs were approved for the treatment of the *** beta(Aβ)immunotherapy is at the core of this therapy,which is one of the most innovative approaches looking to change the course of *** technology is based on synthetic peptides or monoclonal antibodies(mAb)to reduce Ab levels in the brain and slow down the advance of ***,this article reviews the state of the art about AD neuropathogenesis,the traditional pharmacologic treatment,as well as the modern active and passive immunization describing approved drugs,and drug prototypes currently under investigation in different clinical *** addition,future perspectives on immunotherapeutic strategies for AD and the rise of the aptamer technology as a non-immunogenic alternative to curb the disease progression are discussed.

关键词： Aβ Monoclonal antibody DNA aptamers Cognitive impairment Alzheimer’s disease Clinical trials Immunotherapy Machine learning

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Smoothed particle hydrodynamics based numerical study of hydroplaning considering permeability characteristics of runway surface

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Frontiers of Structural and Civil Engineering 2024年第3期18卷 319-333页

作者： Yang YANG Xingyi ZHU Denis JELAGIN alvaro GUARIN Key Laboratory of Road and Traffic Engineering of Ministry of Education Tongji UniversityShanghai 200092China Auto Engineering Research Institute BYD Auto Industry Company LimitedShenzhen 518118China Department of Civil and Architectural Engineering KTH Royal Institute of TechnologyStockholm 10044Sweden

The presence of water films on a runway surface presents a risk to the landing of *** tire of the aircraft is separated from the runway due to a hydrodynamic force exerted through the water film,a phenomenon called *** a lot of numerical investigations into hydroplaning have been conducted,only a few have considered the impact of the runway ***,computational problems,such as excessive distortion and computing efficiency decay,may arise with such numerical models when dealing with the thin water *** paper presents a numerical model comprising of the tire,water film,and the interaction with the runway,applying a mathematical model using the smoothed particle hydrodynamics and finite element(SPH-FE)*** material properties and geometric features of the tire model were included in the model framework and water film thicknesses from 0.75 mm to 7.5 mm were used in the numerical ***,this work investigated the impacts of both surface texture and the runway *** interaction between tire rubber and the rough runway was analyzed in terms of frictional force between the two *** SPH-FE model was validated with an empirical equation proposed by the National Aeronautics and Space Administration(NASA).Then the computational efficiency of the model was compared with the traditional coupled Eulerian-Lagrangian(CEL)*** on the SPH-FE model,four types of the runway(Flat,SMA-13,AC-13,and OGFC-13)were *** simulation of the asphalt runway shows that the SMA-13,AC-13,and OGFC-13 do not present a hydroplaning risk when the runway permeability coefficient exceeds 6%.

关键词： SPH-FE approach hydroplaning numerical simulation surface texture runway surface reconstruction

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Alkali and Plasma-Treated Guadua angustifolia Bamboo Fibers:A Study on Reinforcement Potential for Polymeric Matrices

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Journal of Renewable Materials 2024年第8期12卷 1399-1416页

作者： Patricia Luna Juan Lizarazo-Marriaga alvaro Mariño Facultad de Ingeniería Universidad Nacional de ColombiaBogotá11001Colombia Facultad de Ciencias Universidad Nacional de ColombiaBogotá11001Colombia

This study focuses on treating Guadua angustifolia bamboo fibers to enhance their properties for reinforcement applications in composite ***(alkali)and physical(dry etching plasma)treatments were used separately to augment compatibility of Guadua angustifolia fibers with various composite *** influence of these treatments on the fibers’performance,chemical composition,and surface morphology were *** analysis indicated that alkali treatments reduced the tensile modulus of elasticity and strength of fibers by up to 40%and 20%,respectively,whereas plasma treatments maintain the fibers’mechanical *** spectroscopy revealed significant alterations in chemical composition due to alkali treatments,while plasma-treated fibers showed minimal *** examination through Scanning Electron Microscopy(SEM)revealed post-treatment modifications in both cases;alkali treatments served as a cleanser,eliminating lignin and hemicellulose from the fiber surface,whereas plasma treatments also produce rough *** results validate the impact of the treatments on the fiber mechanical performance,which opens up possibilities for using Guadua angustifolia fibers as an alternative reinforcement in composite manufacturing.

关键词： Bamboo fibers Guadua angustifolia alkali treatment dry etching plasma treatment composite reinforcement

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Multiple scales method for analyzing a forced damped rotational pendulum oscillatorwithgallows

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Communications in Theoretical Physics 2024年第5期76卷 58-67页

作者： Haifa A Alyousef alvaro H Salas B M Alotaibi S A El-Tantawy Department of Physics College of SciencePrincess Nourah bint Abdulrahman UniversityP.O.Box 84428Riyadh 11671Saudi Arabia Department of Mathematics and Statistics Universidad Nacional de ColombiaFIZMAKO Research GroupColombia Department of Physics Faculty of SciencePort Said UniversityPort Said 42521Egypt Research Center for Physics(RCP) Department of PhysicsFaculty of Science and ArtsAl-MikhwahAl-Baha UniversityAl-Baha 1988Saudi Arabia

This study reports the analytical solution for a generalized rotational pendulum system with gallows and periodic excited *** multiple scales method(MSM)is applied to solve the proposed *** types of rotational pendulum oscillators are studied and talked about in *** include the forced damped rotating pendulum oscillator with gallows,the damped standard simple pendulum oscillator,and the damped rotating pendulum oscillator without *** MSM first-order approximations for all the cases mentioned are derived in *** obtained results are illustrated with concrete numerical *** first-order MSM approximations are compared to the fourth-order Runge-Kutta(RK4)numerical ***,the maximum error is estimated for the first-order approximations obtained through the MSM,compared to the numerical approximations obtained by the RK4 ***,we conducted a comparative analysis of the outcomes obtained by the used method(MSM)and He-MSM to ascertain their respective levels of *** proposed method can be applied to analyze many strong nonlinear oscillatory equations.

关键词： rotational pendulum system multiple scales method approximate solution damped oscillations forced pendulum with gallows he-multiple scales method

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Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1756-1762页

作者： Sergio Hoyos Pablo Posada-Moreno Natalia Guzman-Arango Romario Chanci-Drago Jaime Chavez alvaro Andrés-Duarte Santiago Salazar-Ochoa Hepatobilary and Liver Transplant Unit Hospital Pablo Tobon Uribe and Gastrohepathology Group Universidad de AntioquiaMedellin 050034AntioquiaColombia Department of General Surgery Universidad Pontificia BolivarianaMedellín 050034AntioquiaColombia

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic *** can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related *** diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for ***,it is unclear whether managing these small tumors expectantly is truly *** To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated *** This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,*** assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery *** variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of *** The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),*** involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in *** recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 *** survival was additionally comparable between the two tumor *** Tumor size does not dictate prognosis;lymph node and lymphovascular involvement a

关键词： Neuroendocrine tumor Pancreatic neoplasm Pancreas Pancreatic neuroendocrine neoplasm Pancreatic neuroendocrine tumors

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Quantum-mechanical effects in photoluminescence from thin crystalline gold films

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Light(Science & Applications) 2024年第4期13卷 783-794页

作者： Alan R.Bowman alvaro Rodríguez Echarri Fatemeh Kiani Fadil Iyikanat Ted V.Tsoulos Joel D.Cox Ravishankar Sundararaman F.Javier García de Abajo Giulia Tagliabue Laboratory of Nanoscience for Energy Technologies(LNET) STIÉcole Polytechnique Fédérale de Lausanne(EPFL)LausanneSwitzerland ICFO–Institut de Ciencies Fotoniques The Barcelona Institute of Science and TechnologyCastelldefels(Barcelona)Spain. MBI–Max-Born-Institut BerlinGermany. POLIMA–Center for Polariton-driven Light–Matter Interactions University of Southern DenmarkOdense MDenmark. Danish Institute for Advanced Study University of Southern DenmarkOdense MDenmark. Department of Materials Science&Engineering Rensselaer Polytechnic InstituteTroyNYUSA. Department of Physics Applied Physicsand AstronomyRensselaer Polytechnic InstituteTroyNYUSA. ICREA–Institucio Catalana de Recerca i Estudis Avancats BarcelonaSpain

Luminescence constitutes a unique source of insight into hot carrier processes in metals,including those in plasmonic nanostructures used for sensing and energy ***,being weak in nature,metal luminescence remains poorly understood,its microscopic origin strongly debated,and its potential for unraveling nanoscale carrier dynamics largely ***,we reveal quantum-mechanical effects in the luminescence emanating from thin monocrystalline gold ***,we present experimental evidence,supported by first-principles simulations,to demonstrate its photoluminescence origin(i.e.,radiative emission from electron/hole recombination)when exciting in the interband *** model allows us to identify changes to the measured gold luminescence due to quantum-mechanical effects as the gold film thickness is ***,such effects are observable in the luminescence signal from flakes up to 40 nm in thickness,associated with the out-of-plane discreteness of the electronic band structure near the Fermi *** qualitatively reproduce the observations with first-principles modeling,thus establishing a unified description of luminescence in gold monocrystalline flakes and enabling its widespread application as a probe of carrier dynamics and light-matter interactions in this *** study paves the way for future explorations of hot carriers and charge-transfer dynamics in a multitude of material systems.

关键词： luminescence quantum crystalline

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Potential role of transmembrane 9 superfamily member 1 as a biomarker in urothelial cancer

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World Journal of Clinical Oncology 2024年第8期15卷 965-967页

作者： alvaro Pinto Abrahams Ocanto Felipe Couñago Department of Medical Oncology University Hospital La PazPaseo Castellana 261Madrid 28046Spain Department of Radiation Oncology GenesisCareHospital Universitario San Francisco de AsísMadrid 28002Spain Department of Radiation Oncology GenesisCareVithas La Milagrosa University HospitalMadrid 28010Spain National Director GenesisCare Madrid 28043Spain

Bladder cancer is a urological tumor with high rates of recurrence despite recent advances in novel *** proteins involved in the molecular mechanisms are currently an enigma,especially the transmembrane 9 superfamily member 1 which has an unclear *** et al published the function and mechanism of this protein,and showed that it could participate in the proliferation,migration and invasion of tumor cells in bladder cancer,therefore treatments directed against this protein may be beneficial in avoiding this condition.

关键词： Bladder cancer Transmembrane 9 superfamily member 1 Biomarker Urothelial cancer Protein

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Rainfall Sensitivity to Microphysics and Planetary Boundary Layer Parameterizations in Convection-Permitting Simulations over Northwestern South America

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Journal of Meteorological Research 2024年第4期38卷 805-825页

作者： K.Santiago HERNANDEZ Sebastian GOMEZ-RIOS Juan J.HENAO Vanessa ROBLEDO alvaro RAMiREZ-CARDONA Angela M.RENDON Geolimna Escuela AmbientalFacultad de IngenieriaUniversidad de AntioquiaMedellin 050010Colombia Grupo de Ingenieria y Gestion Ambiental(GIGA) Escuela AmbientalFacultad de IngenieriaUniversidad de AntioquiaMedellin 050010Colombia Division of Atmospheric Sciences Desert Research InstituteRenoNV 89512USA

Convection-permitting modeling allows us to understand mechanisms that influence rainfall in specific ***,microphysics parameterization(MP) and planetary boundary layer(PBL) schemes remain an important source of uncertainty,affecting rainfall intensity,occurrence,duration,and ***,we study the sensitivity of rainfall to three MP [Weather Research and Forecasting(WRF) Single-Moment 6-class(WSM6),Thompson,and Morrison] and two PBL [the Yonsei University(YSU) and Mellor–Yamada Nakanishi Niino(MYNN)] schemes with a convection-permitting resolution(4 km) over northwestern South America(NWSA).Simulations were performed by using the WRF model and the results were evaluated against soundings,rain gauges,and satellite data,considering the spatio-temporal variability of rainfall over diverse regions prone to deep convection in *** and PBL schemes largely influenced simulated rainfall,with better results for the less computationally expensive WSM6 MP and YSU PBL *** rain gauges and satellite estimates,simulations with Morrison MP overestimated rainfall,especially westward of the Andes,whereas the MYNN PBL underestimated precipitation in the Amazon–Savannas *** found that the uncertainty in the rainfall representation is highly dependent on the region,with a higher influence of MP in the Colombian Pacific and PBL in the Amazon–Savannas *** analyzing rainfall-related processes,the selection of both MP and PBL parameterizations exerted a large influence on the simulated lower tropospheric moisture flux and moisture *** schemes significantly influenced the downward shortwave radiation,with MYNN simulating a greater amount of low clouds,which decreased the radiation ***,latent heat fluxes were greater for YSU,favoring moist convection and *** schemes had a marked impact on vertical ***,Morrison MP showed stronger convection and higher precipitation rates,which is assoc

关键词： sensitivity microphysics planetary boundary layer(PBL) Weather Research and Forecasting(WRF) processes

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Motivational and Methodological Factors Involved in the Helping Behavior Test in Laboratory Rodents

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Journal of Behavioral and Brain Science 2024年第8期14卷 240-254页

作者： Gabriela F. Marinho Jaqueline M. Wuo João Paulo Kurita alvaro C. Lima Regina H. Silva Pharmacology Department Federal University of So Paulo So Paulo Brazil

Empathy allows humans and other animals to share the emotional state of another, adopting that individual’s perspective on a given situation. This ability is fundamental for species living in groups. Helping behavior in laboratory animals has been used to study empathy. In this test, subjects are exposed to a conspecific that is trapped and learn to open the cage to release the other animal. However, the interpretation of helping behavior as an emphatically motivated action is still controversial. Here we review the studies that use the helping behavioral test proposed by Ben-Ami Bartal and colleagues in 2011 to better understand motivational factors for this behavior. In addition, we compare methodological aspects of these studies. In conclusion, helping behavior can be driven by empathy, but other factors such as the desire for social contact and learning components cannot be ruled out as motivators. In addition, studies focused on evaluating neurobiological mechanisms underlying helping behavior in laboratory rodents can help elucidate the factors involved in releasing the trapped co-specific.

关键词： Animal Models Empathy Prosocial Behavior Rats

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