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Involvement of substance P and the NK-1 receptor in pancreatic cancer

world Journal of Gastroenterology 2014年第9期20卷 2321-2334页

作者： Miguel Muoz rafael Coveas Virgen del Rocío University Hospital Research Laboratory on Neuropeptides (IBIS) 41013 Seville Spain Institute of Neurosciences of Castilla y León (INCYL) Laboratory of Neuroanatomy of the Peptidergic Systems (Lab 14) University of Salamanca 37007 Salamanca Spain

Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,***,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer *** peptide substance P(SP)has a widespread distribution throughout the *** binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor *** is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer *** these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.

关键词： Pancreas Substance P Neurokinin-1 receptor antagonists Apoptosis Antitumor Angiogenesis Metastasis Pancreatic cancer

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Quercetin prevents spinal motor neuron degeneration induced by chronic excitotoxic stimulus by a sirtuin 1-dependent mechanism

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Translational Neurodegeneration 2017年第1期6卷 310-323页

作者： rafael Lazo-Gomez Ricardo Tapia División de Neurociencias Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoCircuito exterior s/nCiudad UniversitariaCoyoacán04510 Ciudad de MéxicoMexico

Background:Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron *** therapeutic strategies are an unmet need for these ***,such as quercetin and resveratrol,are plant-derived compounds that activate sirtuins(SIRTs)and have shown promising results in some models of neuronal death,although their effects have been scarcely tested in models of motor neuron ***:In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA)into the rat spinal cord *** and resveratrol were co-infused with AMPA and motor behavior and muscle strength were assessed daily for up to ten ***,animals were fixed and lumbar spinal cord tissue was analyzed by histological and immunocytological ***:we found that the chronic infusion of AMPA[1 mM]caused a progressive motor neuron degeneration,accompanied by astrogliosis and microgliosis,and motor deficits and paralysis of the rear *** infusion ameliorated AMPA-induced paralysis,rescued motor neurons,and prevented both astrogliosis and microgliosis,and these protective effects were prevented by EX527,a very selective SIRT1 *** contrast,neither resveratrol nor EX527 alone improved motor behavior deficits or reduced motor neuron degeneration,albeit both reduced ***:These results suggest that quercetin exerts its beneficial effects through a SIRT1-mediated mechanism,and thus SIRT1 plays an important role in excitotoxic neurodegeneration and therefore its pharmacological modulation might provide opportunities for therapy in motor neuron disorders.

关键词： Motor neuron disorder Quercetin Resveratrol Sirtuin Excitotoxicity

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Influence of Rare-Earth Substitution for Iron in FeCrMoCB Bulk Metallic Glasses

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Chinese Physics Letters 2010年第7期27卷 192-194页

作者： Abderrezak Bouchareb Badis Bendjemil rafael Piccin Marcello Baricco Dipartimento di Chimica I.F.M/NIS/CNISM/INSTM Universita di Torino Via Giuria 9 10125 Torino Italy Laboratoire d'Etude et la Recherche de l'Etat Condensd (LEREC) University of Badji Mokhtar P.O. Box 12 23000 Annaba Algeria University of Guelma P.O. Box 12 24000 Guelma Algeria

The effects of rare earth addition on the glass forming ability of Fe50-xCr15Mo14C15B6Mx （x =0, 2 and M=Y, Gd） bulks and ribbons are studied. The thermal and structural properties of the samples are measured by a combination of differential scanning calorimetry （DSC）, x-ray diffraction and scanning electron microscopy. Chemical compositions are checked by energy dispersive spectroscopy analysis. The copper mold casting technique leads to a fully amorphous structure up to 2mm only for compositions containing Y or Gd. In the case of ribbons, a fully amorphous phase is observed for all the compositions. The roles of Y and Gd are discussed on the basis of melting behavior analyzed by high-temperature DSC. Such elements act as oxygen scavengers, avoiding heterogeneous nucleation.

关键词： Dispersants Measurement Microscopy

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The Role of Chilean Mountain Areas in Time of Drought and Energy Crisis:New Pressures and Challenges for Vulnerable Ecosystems

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Journal of Mountain Science 2012年第4期9卷 451-462页

作者： rafael SáNCHEZ Carla MARCHANT Axel BoRSDoRF Institute for Geography Pontifical University Catholic of ChileAvenida Vicu a Mackenna 4860MaculSantiago de Chile Institute for Geography University of InnsbruckInnrain 526020 InnsbruckAustria Institute for Mountain Research:Man and Environment Austrian Academy of SciencesTechnikerstr.21a6020 InnsbruckAustria

In the summer of 2010/2011 Chile suffered the third most severe energy and water supply crisis in only one decade. This may be surprising as the Andes which accompany the country along 4,200 km are a water tower and could provide more electricity and water than needed. on top of that, it has to be mentioned that Chile also counts with sunny and windy climates and with excellent geothermal energy resources and thus has a huge potential as far as renewable energies are concerned. After analyzing the existing natural conditions, the infrastructure and the present challenges of climate change, it has to be asked in which way Chile can make use of this potential in the near future, considering the legal and political situation and the technological opportunities. It seems that the resources are still hidden in the Andes, and only the key is missing to realize the country＇s natural potential. This research has been based on the analysis of existing literature, media, quantitative data from government institutions and other antecedents obtained by the authors in field work done in the South of Chile in 2oLo. The added value of this compilation lies in the comprehensive perspective, linking the knowledge of climatologists, hydrologists, mountain researchers and energy experts in order to support a sustainable energy and water supply for the future in Chile. From this present research, it can be concluded that Chile necessarilyhas to adopt new energy-related strategies, particularly those aimed at diminishing the strong dependence on traditional sources of energy and establishing new techniques and technologies for generating electrieity and utilizing the vast potential that the country is ready to offer, such as that provided by the Andes along 4,200 kilometers.

关键词： Mountain region Andes Energy supply Chile

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Nylon 6-cellulose composite hosted in a hypodermic needle: Biofluid extraction and analysis by ambient mass spectrometry in a single device

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Journal of Pharmaceutical Analysis 2023年第11期13卷 1346-1352页

作者： Jaime Millan-Santiago rafael Lucena Soledad Cardenas Affordable and Sustainable Sample Preparation(AS2P)Research Group Analytical Chemistry DepartmentChemical Institute for Energy and Environment(IQUEMA)University of CordobaE-14071CordobaSpain

This study proposes a hypodermic needle(HN)as a sorbent holder and an electrospray(ESI)emitter,thus combining extraction and analysis in a single device.A novel nylon 6-cellulose(N6-Cel)composite sorbent is proposed to extract methadone from oral fluid *** cellulosic substrate provides the composite with high porosity,permitting the flow-through of the sample,while the polyamide contributes to the extraction of the *** low price of the devices(considering the holder and the sorbent)contributes to the affordability of the method,and their small size allows easy transportation,opening the door to on-site *** the optimum conditions,the analyte can be determined by high-resolution ambient ionization mass spectrometry at a limit of detection(LoD)as low as 0.3 mg/L and precision(expressed as relative standard deviation,RSD)better than 9.3%.The trueness,expressed as relative recovery(RR),ranged from 90%to 109%.As high-resolution mass spectrometers are not available in many laboratories,the method was also adapted to low-resolution *** this sense,the direct infusion of the eluates in a triple quadrupole-mass spectrometry provided an LoD of 2.2 mg/*** RSD was better than 5.3%,and the RR ranged from 96%to 121%.

关键词： ESI emitter Mass spectrometry Hypodermic needle Composite Methadone

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Fuzzy C-means Rule Generation for Fuzzy Entry Temperature Prediction in a Hot Strip Mill

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Journal of Iron and Steel Research International 2016年第2期23卷 116-123页

作者： Jose Angel BARRIoS Cesar VILLANUEVA Alberto CAVAZoS rafael CoLAS Mechanical and Electrical Engineering Faculty Autonomous University of Nuevo LeonSan Nicolas de los Garza 66451Nuevo LeonMexico Hot Rolling Department Ternium ChurubuscoMonterrey 64000Nuevo LeonMexico

Variable estimation for finishing mill set-up in hot rolling is greatly affected by measurement uncertainties, variations in the incoming bar conditions and product changes. The fuzzy C-means algorithm was evaluated for rule base generation for fuzzy and fuzzy grey-box temperature estimation. Experimental data were collected from a real- life mill and three different sets were randomly drawn. The first set was used for rule-generation, the second set was used for training those systems with learning capabilities, while the third one was used for validation. The perform- ance of the developed systems was evaluated by five performance measures applied over the prediction error with the validation set and was compared with that of the empirical rule-base fuzzy systems and the physical model used in plant. The results show that the fuzzy C-means generated rule-bases improve temperature estimation; however, the best results are obtained when fuzzy C-means algorithm, grey-box modeling and learning functions are combined. Application of fuzzy C-means rule generation brings improvement on performance of up to 72%.

关键词： gray-box modeling ANFIS hot rolling temperature estimation fuzzy C-means rule base generation

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Sampling lattices in semi-grand canonical ensemble with autoregressive machine learning

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npj Computational Materials 2022年第1期8卷 588-597页

作者： James Damewood Daniel Schwalbe-Koda rafael Gómez-Bombarelli Department of Materials Science and Engineering Massachusetts Institute of Technology77 Massachusetts AvenueCambridgeMA02319USA

Calculating thermodynamic potentials and observables efficiently and accurately is key for the application of statistical mechanics simulations to materials ***,naive Monte Carlo approaches,on which such calculations are often dependent,struggle to scale to complex materials in many state-of-the-art disciplines such as the design of high entropy alloys or multi-component *** address this issue,we adapt sampling tools built upon machine learning-based generative modeling to the materials space by transforming them into the semi-grand canonical ***,we show that the resulting models are transferable across wide ranges of thermodynamic conditions and can be implemented with any internal energy model U,allowing integration into many existing materials *** demonstrate the applicability of this approach to the simulation of benchmark systems (AgPd,CuAu) that exhibit diverse thermodynamic behavior in their phase ***,we discuss remaining challenges in model development and promising research directions for future improvements.

关键词： canonical thermodynamic directions

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Systemic treatment in EGFR-ALK NSCLC patients:second line therapy and beyond

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Cancer Biology & Medicine 2014年第3期11卷 173-181页

作者： Niki Karachaliou rafael Rosell Translational Research Unit Dr Rosell Oncology InstituteQuirón Dexeus University Hospital08028 BarcelonaSpain Cancer Biology and Precision Medicine Program Catalan Institute of Oncology Hospital Germans Trias i PujolCtra Canyet s/n08916 BadalonaBarcelonaSpain Fundación Molecular oncology Research (MoRe) Sabino Arana 5-1908028 BarcelonaSpain

Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer(NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to influence response to targeted therapies. The principle goal of precision medicine is to define those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few "mountains" [representing the most commonly mutated genes like KRAS, epidermal growth factor(EGFR), and anaplastic lymphoma kinase(ALK)] and a vast number of "hills"(representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected.

关键词： Lung cancer epidermal growth factor(EGFR) anaplastic lymphoma kinase fusions(ALK fusions) tyrosine kinase inhibitors(TKIs) TKI resistance

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Elastography-based screening for esophageal varices in patients with advanced chronic liver disease

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world Journal of Gastroenterology 2019年第3期25卷 308-329页

作者： rafael Paternostro Thomas Reiberger Theresa Bucsics Department of Medicine Ⅲ Division of Gastroenterology and Hepatology Medical University of Vienna

Elastography-based liver stiffness measurement(LSM) is a non-invasive tool for estimating liver fibrosis but also provides an estimate for the severity of portal hypertension in patients with advanced chronic liver disease(ACLD). The presence of varices and especially of varices needing treatment(VNT) indicates distinct prognostic stages in patients with compensated ACLD(cACLD). The Baveno VI guidelines suggested a simple algorithm based on LSM ography, TE) and platelet count > 150 G/L for ruling-out VNT in patients with cACLD. These(and other) TE-based LSM cut-offs have been evaluated for VNT screening in different liver disease etiologies. Novel point shear-wave elastography(pSwE) and two-dimensional shear wave elastography(2D-SwE) methodologies for LSM have also been evaluated for their ability to screen for "any" varices and for VNT. Finally, the measurement of spleen stiffness(SSM) by elastography(mainly by pSwE and 2D-SwE) may represent another valuable screening tool for varices. Here, we summarize the current literature on elastography-based prediction of "any" varices and VNT. Finally,we have summarized the published LSM and SSM cut-offs in clinically useful scale cards.

关键词： Elastography Liver stiffness Spleen stiffness Shear wave Magnetic resonance elastography Varices Portal hypertension Cirrhosis Advanced chronic liver disease

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Disturbance and forest recovery in the Monarch Butterfly Biosphere Reserve,Mexico

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Journal of Forestry Research 2020年第5期31卷 1551-1566页

作者： Jose Lopez-Garcıa rafael M.Navarro-Cerrillo Instituto de Geografıa Universidad Nacional Autonoma de MexicoCiudad UniversitariaC.P.04510 CoyoacanDFMexico Departamento de Ingenierıa Forestal Universidad de CordobaCampus de RabanalesCarretera Nacional IV km 39614014 CordobaSpain

Analysis of the change in forest cover is important to determine stand dynamics and the processes involved in disturbance and *** of the core zone of the Monarch Butterfly Biosphere Reserve were studied using photo interpretation techniques,considering biennial changes between 1999 and 2013 and changes over the whole period of study 1999–*** matrices were elaborated to determine the processes of change involved in both recovery and *** biennial changes for the whole period amounted to 2274 ha;343 ha accounted as degraded in more than one biennial *** total changes in forest cover between 1999 and 2013 involved 4902 ha,out of which,2912 ha were affected by disturbance,and 1990 ha were *** density and 2013 vegetation cover maps,the overall accuracy was 95.6%and 90.2%,*** combining both maps,gradual processes were revealed that were not evident in separate *** methodology is useful for the management and conservation of natural protected areas.

关键词： Illegal logging Forest density change Forest recovery Conifer forests Monarch Butterfly Biosphere Reserve

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