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data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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Neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical Neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

Stability of plane-parallel flow of magnetic fluids under external magnetic fields

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Applied Mathematics and Mechanics(English Edition) 2022年第2期43卷 295-310页

作者： P.Z.S.paz F.R.CUNHA Y.d.SOBRAL department of Mathematics University of BrasíliaCampus Universitário Darcy RibeiroBrasília-DF70910-900Brazil Laboratory of Microhydrodynamics and Rheology-Vortex Group Department of Mechanical EngineeringUniversity of BrasíliaCampus Universitário Darcy RibeiroBrasília-DF70910-900Brazil

In this work,we present a theoretical study on the stability of a two-dimensional plane Poiseuille flow of magnetic fluids in the presence of externally applied magnetic *** fluids are assumed to be incompressible,and their magnetization is coupled to the flow through a simple phenomenological *** parameters are defined,and the equations are perturbed around the base *** eigenvalues of the linearized system are computed using a finite difference scheme and studied with respect to the dimensionless parameters of the *** examine the cases of both the horizontal and vertical magnetic *** obtained results indicate that the flow is destabilized in the horizontally applied magnetic field,but stabilized in the vertically applied *** characterize the stability of the flow by computing the stability diagrams in terms of the dimensionless parameters and determine the variation in the critical Reynolds number in terms of the magnetic ***,we show that the superparamagnetic limit,in which the magnetization of the fluids decouples from hydrodynamics,recovers the same purely hydrodynamic critical Reynolds number,regardless of the applied field direction and of the values of the other dimensionless magnetic parameters.

关键词： hydrodynamic stability magnetic fluid Orr-Sommerfeld equation magnetization evolution

An analysis of key process parameters for hybrid manufacturing by material extrusion and CNC machining

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Bio-design and Manufacturing 2018年第4期1卷 237-244页

作者： Ruben paz Javier Santamarta Mario d.Monzon Joshua Garcfa Eujin Pei departamento de Ingenierfa Mecainica Universidad de Las Palmas de Gran CanariaLas Palmas de Gran Canaria 35017 Spain Institute of Materials and Manufacturing Brunel University LondonKingston LaneUxbridge UB83PHUK

Hybrid Manufacturing combines the advantages of Additive Manufacturing (AM)and Subtractive Manufacturing on a single *** previous research has provided a good background of the manufacturing parameters,the analysis is often carried out separately and there is a lack of combined *** purpose of this research is to examine the influence of the main manufacturing parameters involved in AM and subtracfive processes using different ***,the study is focused on the Material Extrusion process concerning the layer height,fill angle and fill density;as well as two factors related to machining,including stepover and pass *** parameters that were examined include the dimension,hardness, flatness,weight and roughness.A mulfifactofial design of Experiments was proposed with a total of 64 ***,a statistical analysis was carried out to assess the influence of the different groups on the response ***,a decision table presented and facilitated the selection of parameters depending on the desired objectives,leading to a framework that was applied to a case study for *** decision guide could enable designers and engineers to select the best strategy for a specific application,leading to a more efficient approach for manufacturing.

关键词： Hybrid manufacturing Material extrusion Additive manufacturing Subtractive manufacturing ~Machining Statistical analysis

distribution of dNA damage in the human sperm nucleus:implications of the architecture of the sperm head

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Asian Journal of Andrology 2020年第4期22卷 401-408页

作者： Silvia González-Rojo Cristina Fernández-díez Marta Lombó María paz Herráez department of Molecular Biology Faculty of BiologyUniversidad de LeónCampus de Vegazana s/n LeónLeón 24071Spain

The sperm nucleus is prone to sustain dNA damage before and after *** of the damage is not homogeneous,and the factors determining differential sensitivity among nuclear regions have not yet been *** sperm chromatin contains three structural domains,two of which are considered the most susceptible to dNA damage:the histone bound domain,harboring developmental related genes,and the domain associated with nuclear matrix *** a quantitative polymerase chain reaction(qPCR)approach,we analyzed the number of lesions in genes homeobox A3(HOXA3),homeobox B5(HOXB 5),sex-determining region Y(SRY)-box 2(SOX2),β-GLOBIN,rdNA 18S,and rdNA 28S in human sperm after ultraviolet irradiation(400μW cm−2,10 min),H2O2treatment(250 mmol l−1,20 min),and cryopreservation,which showed differential susceptibility to genetic *** vulnerability is dependent on the genotoxic agent and independent of the sperm nuclear proteins to which the chromatin is bound and of accessibility to the transcription *** of 8-hydroxy-2'-deoxyguanosine(8-OHdG)showed that the highest level of oxidation was observed after *** distribution of oxidative lesions also differed depending on the genotoxic agent.8-OHdG did not colocalize either with histone 3(H3)or with type IIα+βtopoisomerase(TOPO IIα+β)after H2O2treatment but matched perfectly with peroxiredoxin 6(PRdX6),which is involved in *** study reveals that the characteristics of the sperm head domains are responsible for access of the genotoxicants and cause differential degree of damage to nuclear areas,whereas chromatin packaging has a very limited *** histone-enriched genes analyzed cannot be used as biomarkers of oxidative dNA damage.

关键词： biomarkers dNA damage human sperm oxidative stress sperm chromatin sperm quality

Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

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World Journal of Gastroenterology 2006年第40期12卷 6464-6472页

作者： Alfredo Santana Carlos Medina Maria Cristina paz-Cabrera Federico díaz-Gonzalez Esther Farré Antonio Salas Marek W Radomski Enrique Quintero Gastroenterology department and Research Unit Hospital Universitario de Canarias Tenerife Spain Reumathology department Hospital Universitario de Canrias Tenerife Spain Pathology department Hospital Mutua de Terrassa Barcelona Spain Institute of Molecular Medicine University of Texas Houston-Texas United States

AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (dSS) model of colitis in ***: MMP-9-deficient and wild-type (wt) mice were given 5% dSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P d PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P d to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that dSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by dSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

关键词： Matrix metalloproteinases MMP-9-deficient dextran sodium sulphate Inflammatory bowel disease Experimental colitis

Solving the inverse grating problem by white light interference Fourier scatterometry

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Light(Science & Applications) 2012年第1期1卷 17-23页

作者： Valeriano Ferreras paz Sandy Peterhansel Karsten Frenner Wolfgang Osten Institute of Applied Optics Stuttgart University70569 StuttgartGermany SCoPE—Stuttgart Research Center of Photonic Engineering Stuttgart UniversityStuttgartGermany

Scatterometry is a well-established,fast and precise optical metrology method used for the characterization of sub-lambda periodic *** Fourier scatterometry method,by analyzing the Fourier plane,makes it possible to collect the angle-resolved diffraction spectrum without any mechanical *** improve the depth sensitivity of this method,we combine it with white light *** show the exemplary application of the method on a silicon line *** characterize the sub-lambda features of the grating structures,we apply a model-based reconstruction approach by comparing simulated and measured *** simulations are based on the rigorous coupled-wave analysis method.

关键词： Fourier scatterometry inverse problem optical sub-lambda metrology RCWA white light interference

Cenozoic basin evolution of the Central Patagonian Andes:Evidence from geochronology, stratigraphy, and geochemistry

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Geoscience Frontiers 2019年第3期10卷 1139-1165页

作者： A.Encinas A.Folguera R.Riffo P.Molina L.Fernández paz V.d.Litvak d.A.Colwyn V.A.Valencia M.Carrasco departamento de Ciencias de la Tierra Facultad de Ciencias Químicas Universidad de Concepción Instituto de Estudios Andinos Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales Departamento de Ciencias Geológicas CONICET-Universidad de Buenos Aires Instituto de Estudios Andinos Don Pablo Groeber (IDEAN) department of Geology & Geophysics Yale University School of the Environment Washington State University

The Central Patagonian Andes is a particular segment of the Andean Cordillera that has been subjected to the subduction of two spreading ridges during Eocene and Neogene times. In order to understand the Cenozoic geologic evolution of the Central Patagonian Andes, we carried out geochronologic(U-Pb and^(40)Ar/^(39)Ar), provenance, stratigraphic, sedimentologic, and geochemical studies on the sedimentary and volcanic Cenozoic deposits that crop out in the Meseta Guadal and Chile Chico areas(～47°S). Our data indicate the presence of a nearly complete Cenozoic record, which refutes previous interpretations of a hiatus during the middle Eocene-late Oligocene in the Central Patagonian Andes. Our study suggests that the fluvial strata of the Ligorio Marquez Formation and the flood basalts of the Basaltos Inferiores de la Meseta Chile Chico Formation were deposited in an extensional setting related to the subduction of the Aluk-Farallon spreading ridge during the late Paleocene-Eocene. Geochemical data on volcanic rocks interbedded with fluvial strata of the San Jose Formation suggest that this unit was deposited in an extensional setting during the middle Eocene to late Oligocene. Progressive crustal thinning allowed the transgression of marine waters of Atlantic origin and deposition of the upper Oligocene-lower Miocene Guadal Formation. The fluvial synorogenic strata of the Santa Cruz Formation were deposited as a consequence of an important phase of compressive deformation and Andean uplift during the early-middle Miocene. Finally, alkali flood basalts of the late middle to late Miocene Basaltos Superiores de la Meseta Chile Chico Formation were extruded in the area in response to the suduction of the Chile Ridge under an extensional regime. Our studies indicate that the tectonic evolution of the Central Patagonian Andes is similar to that of the North Patagonian Andes and appears to differ from that of the Southern Patagonian Andes, which is thought to have been the s

关键词： Central Patagonian Andes U-Pb geochronology Ar-Ar geochronology Geochemistry Stratigraphy Sedimentology

通过新型轻量化参数优化方法比较激光选区熔化部件设计的不同细胞结构（英文）

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2019年第2期20卷 117-132页

作者： Rubén paz Mario d.MONZóN Philippe BERTRANd Alexey SOVA Universidad de Las Palmas de Gran Canaria Departamento de Ingeniería Mecánica University of Lyon ENISE

目的:1.提出一种在外型不变的部件内模拟不同细胞结构的方法;2.发展激光选区熔化(SLM)部件轻量化参数设计的新方法;3.利用这一方案实现优化设计并比较不同细胞结构的质量。创新点:1.提出基于拉丁超立方实验设计、遗传算法、克里金元模... 详细信息

目的:1.提出一种在外型不变的部件内模拟不同细胞结构的方法;2.发展激光选区熔化(SLM)部件轻量化参数设计的新方法;3.利用这一方案实现优化设计并比较不同细胞结构的质量。创新点:1.提出基于拉丁超立方实验设计、遗传算法、克里金元模型和有限元方法的轻量化优化方案;2.该方法可通过较少的采样获得良好的结果并能克服几何奇点(内部网格细化算法)的问题。方法:1.进行内部细胞结构的生成和参数化;2.根据输入数据(设计变量和约束条件等)采用拉丁超立方实验设计模拟所选样本;3.利用先前的数据创建克里金元模型并利用预测的元模型来计算遗传算法演化过程中的适应函数;4.将模拟实现的优化结果添加到数据中更新元模型,并通过数次重复迭代提高元模型的准确度直至误差小于5%;5.将这一概念应用于不同的几何结构,然后通过SLM加工制造优化后的几何结构,并在弯曲载荷下进行测试。结论:1.该优化算法通过适当的参数化克服了SLM技术的相关限制,可适用于SLM部件的优化;2.立方单元格在计算机辅助设计定义、参数化和时间优化等方面有一些优势,但和有限元分析的估计结果相比,其存在的缺乏坚实支撑的水平条(悬挂结构)会造成机械性能损失;3.将立方单元结构与用户自定义的参数化增强相结合可以得到更有效的设计结果(更高的比刚度),但更多的设计变量也延长了所需要的优化时间。

关键词：参数优化细胞结构激光选区熔化有限元分析实验设计精细化

Role of lipids in the control of autophagy and primary cilium signaling in neurons

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Neural Regeneration Research 2024年第2期19卷 264-271页

作者： María paz Hernández-Cáceres daniela Pinto-Nuñez Patricia Rivera Paulina Burgos Francisco díaz-Castro Alfredo Criollo Maria Jose Yañez Eugenia Morselli Instituto de Investigación en Ciencias Odontológicas(ICOd) Facultad de OdontologíaUniversidad de ChileSantiagoChile department of Basic Sciences Faculty of Medicine and ScienceUniversidad San SebastiánSantiagoChile Physiology department Faculty of Biological SciencesPontificia Universidad Católica de ChileSantiagoChile Advanced Center for Chronic diseases(ACCdiS) Facultad de Ciencias Químicas y Farmacéuticas&Facultad de MedicinaUniversidad de ChileSantiagoChile Autophagy Research Center SantiagoChile

The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human *** neurons,lipids are involved in signaling pathways controlling autophagy,a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium,a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development.A crosstalk between primary cilia and autophagy has been established;however,its role in the control of neuronal activity and homeostasis is barely *** this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in *** we review the recent literature about specific lipid subclasses in the regulation of autophagy,in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions,specifically focusing on neurons,an area of research that could have major implications in neurodevelopment,energy homeostasis,and neurodegeneration.

关键词： autophagic flux cholesterol fatty acids GPCR lysosomal storage diseases neurons NPC1 phosphoinositides primary cilium