94 research outputs found

    Verification of the Coupled Code PARCS/TWOPORFLOW with Rod Ejection Accident Calculations for Small Modular Reactors

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    Research on small modular reactors (SMRs) is gaining importance since they are key for addressing energy challenges in various sectors. These types of reactors integrate novel technologies that rely heavily on passive safety systems. Among the most developed light water reactors, SMR designs are SMART and NuScale. This work analyzes the academic boron-free Karlsruhe Small Modular Reactor (KSMR), which may fit in SMART, and a core design resembling NuScale. The research aims to explore the potential of new multiphysics tools under development to predict safety parameters of SMRs during normal operation and transients. For this purpose, the Purdue Advanced Reactor Core Simulator (PARCS) and TWOPORFLOW (TPF) codes have been coupled using the Interface for Code Coupling (ICoCo), orchestrating code execution through a C++ Supervisor program. In this work, a nodewise rod ejection accident (REA) has been analyzed for two different scenarios. The first is a hot-zero-power scenario for the KSMR core, and the second is initiated at 75% of nominal power for the NuScale core. Verification of results has been done though code-to-code comparison. Comparison of the PARCS/TPF results obtained for both KSMR and NuScale with reference cases shows acceptable differences. Key safety parameters predicted by the codes for the REA analysis of both cores have also been evaluated against the latest U.S. Nuclear Regulatory Commission regulation for reactivity initiated accidents showing that all parameters fulfill core coolability acceptance criteria and fuel rod cladding failure thresholds. The presented work highlights the transition from the coupling of PARCS with a mixture model code, such as SCF, to a coupling with a two-phase model code, such as TPF. These findings contribute to a better understanding of SMR phenomenology during accidental sequences and demonstrate the capabilities of the coupled codes

    Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells.

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    The nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis. By using multiple particle tracking (MPT) technique on chromatin granules, we designed a SURF (Speeded Up Robust Features)-based algorithm to study the mechanical properties of isolated nuclei and in living cells. We have determined the apparent shear stiffness, viscosity and optical density of the nucleus, and how the chromatin structure influences on these biophysical values. Moreover, we used our MPT-SURF analysis to study the apparent mechanical properties of isolated nuclei from patients of acute lymphoblastic leukemia. We found that leukemia cells exhibited mechanical differences compared to normal lymphocytes. Interestingly, isolated nuclei from high-risk leukemia cells showed increased viscosity than their counterparts from normal lymphocytes, whilst nuclei from relapsed-patient's cells presented higher density than those from normal lymphocytes or standard- and high-risk leukemia cells. Taken together, here we presented how MPT-SURF analysis of nuclear chromatin granules defines nuclear mechanical phenotypic features, which might be clinically relevant.post-print1994 K

    Stereoselective synthesis of oxime containing Pd(II) compounds: Highly effective, selective and stereo-regulated cytotoxicity against carcinogenic PC-3 cells

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    New palladium compounds [Pd{(1S,4R)-NOHNH(R)}Cl-2] (R = Ph 1a or Bn 1b), [Pd{(1S,4R)-NOHNH(R)}{(1S,4R)-NONH(R)}][Cl] (R = Ph 2a or Bn 2b) and corresponding [Pd{(1R,4S)-NOHNH(R)}Cl-2] (R = Ph 1a' or Bn 1b') and [Pd{(1R,4S)-NOHNH(R)}{(1R,4S)-NONH(R)}][Cl] (R = Ph 2a' or Bn 2b') have been synthesized. Novel compounds 1a, 1b, and 2b (and 1a', 1b', and 2b') were obtained in solution as a mixture of diastereomers whose relative ratios depend on the solvent and the nature of the amino substituent. In contrast, the synthetic reactions of derivatives 2a and 2a' were stereospecific, and afforded single enantiomers of absolute configuration (S-N,1S(C),4R(C))-(R-N,1S(C),4R(C)) and (R-N,1R(C),4S(C))-(S-N,1R(C),4S(C)), respectively. All compounds have been fully characterized by NMR and IR spectroscopy, time-dependent UV-spectroscopy, ESI-HR-MS in water, and CHN elemental analysis. Absolute configurations of the major epimers of 1a and 1a', both epimers of 1b and enantiomer 2a', were determined by single crystal X-ray crystallography, and confirmed by 2D NOESY NMR experiments in solution. Additionally, the pH-dependent stability of 2b in water was assessed by H-1-NMR spectroscopy. Metal derivatives have been tested in vitro against three human cancer (prostate PC-3, cervical HeLa, and breast MCF-7) cell lines. The highest anticancer activities were shown by palladium compound 2a' in all cancer cells, with IC50 values up to 80 times lower than those found for cisplatin. The cytotoxicity of 2a and 2a '' is stereo-dependent, with IC50 values that differ significantly for each enantiomer in all the cell lines tested. The cytotoxic activity of 2a and 2a' was further evaluated against the non-tumorigenic human prostate RWPE-1 cell line, revealing a selectivity index (SI) of ca. 30 for derivative 2a'. DNA interactions have been investigated by equilibrium dialysis, fluorescence resonance energy transfer (FRET) DNA melting assays, and viscometric titrations, pointing to groove and/or external binding. Cell cycle assay on PC-3 cells after treatment with 2a or 2a' shows cell cycle arrest in the S and G2/M phases, especially when the cells are treated with compound 2a'.Ministerio de Ciencia e InnovaciónMinisterio de Economía, Industria y CompetitividadUniversidad de AlcaláComunidad de Madri

    Low Phase Angle Values Are Associated with Malnutrition according to the Global Leadership Initiative on Malnutrition Criteria in Kidney Transplant Candidates : Preliminary Assessment of Diagnostic Accuracy in the FRAILMar Study

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    Malnutrition has a negative impact on patients with chronic diseases and its early identification is a priority. The primary objective of this diagnostic accuracy study was to assess the performance of the phase angle (PhA), a bioimpedance analysis (BIA)-derived parameter, for malnutrition screening using the Global Leadership Initiative for Malnutrition (GLIM) criteria as the reference standard in patients with advanced chronic kidney disease (CKD) waiting for kidney transplantation (KT); criteria associated with low PhA in this population were also analyzed. Sensitivity, specificity, accuracy, positive and negative likelihood ratios, predictive values, and area under the receiver operating characteristic curve were calculated for PhA (index test) and compared with GLIM criteria (reference standard). Of 63 patients (62.9 years old; 76.2% men), 22 (34.9%) had malnutrition. The PhA threshold with the highest accuracy was ≤4.85° (sensitivity 72.7%, specificity 65.9%, and positive and negative likelihood ratios 2.13 and 0.41, respectively). A PhA ≤ 4.85° was associated with a 3.5-fold higher malnutrition risk (OR = 3.53 (CI95% 1.0-12.1)). Considering the GLIM criteria as the reference standard, a PhA ≤ 4.85° showed only fair validity for detecting malnutrition, and thus cannot be recommended as a stand-alone screening tool in this population

    The diacylglycerol kinase α/Atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

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    Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells

    Breast feeding, parity and breast cancer subtypes in a Spanish cohort

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    Background: Differences in the incidence and outcome of breast cancer among Hispanic women compared with white women are well documented and are likely explained by ethnic differences in genetic composition, lifestyle, or environmental exposures. METHODOLGY/PRINCIPAL FINDINGS: A population-based study was conducted in Galicia, Spain. A total of 510 women diagnosed with operable invasive breast cancer between 1997 and 2010 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics were collected. The different breast cancer tumor subtypes were compared on their clinico-pathological characteristics and risk factor profiles, particularly reproductive variables and breastfeeding. Among the 501 breast cancer patients (with known ER and PR receptors), 85% were ER+/PR+ and 15% were ER-&PR-. Among the 405 breast cancer with known ER, PR and HER2 status, 71% were ER+/PR+/HER2- (luminal A), 14% were ER+/PR+/HER2+ (luminal B), 10% were ER-/PR-/HER2- (triple negative breast cancer, TNBC), and 5% were ER-/PR-/HER2+ (non-luminal). A lifetime breastfeeding period equal to or longer than 7 months was less frequent in case patients with TNBC (OR = 0.25, 95% CI = 0.08-0.68) compared to luminal A breast cancers. Both a low (2 or fewer pregnancies) and a high (3-4 pregnancies) number of pregnancies combined with a long breastfeeding period were associated with reduced odds of TNBC compared with luminal A breast cancer, although the association seemed to be slightly more pronounced among women with a low number of pregnancies (OR = 0.09, 95% CI = 0.005-0.54). Conclusions/significance: In case-case analyses with the luminal A cases as the reference group, we observed a lower proportion of TNBC among women who breastfed 7 or more months. The combination of longer breastfeeding duration and lower parity seemed to further reduce the odds of having a TNBC compared to a luminal A breast cancer

    Breast feeding, parity and breast cancer subtypes in a Spanish cohort

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    Background: Differences in the incidence and outcome of breast cancer among Hispanic women compared with white women are well documented and are likely explained by ethnic differences in genetic composition, lifestyle, or environmental exposures. METHODOLGY/PRINCIPAL FINDINGS: A population-based study was conducted in Galicia, Spain. A total of 510 women diagnosed with operable invasive breast cancer between 1997 and 2010 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics were collected. The different breast cancer tumor subtypes were compared on their clinico-pathological characteristics and risk factor profiles, particularly reproductive variables and breastfeeding. Among the 501 breast cancer patients (with known ER and PR receptors), 85% were ER+/PR+ and 15% were ER-&PR-. Among the 405 breast cancer with known ER, PR and HER2 status, 71% were ER+/PR+/HER2- (luminal A), 14% were ER+/PR+/HER2+ (luminal B), 10% were ER-/PR-/HER2- (triple negative breast cancer, TNBC), and 5% were ER-/PR-/HER2+ (non-luminal). A lifetime breastfeeding period equal to or longer than 7 months was less frequent in case patients with TNBC (OR = 0.25, 95% CI = 0.08-0.68) compared to luminal A breast cancers. Both a low (2 or fewer pregnancies) and a high (3-4 pregnancies) number of pregnancies combined with a long breastfeeding period were associated with reduced odds of TNBC compared with luminal A breast cancer, although the association seemed to be slightly more pronounced among women with a low number of pregnancies (OR = 0.09, 95% CI = 0.005-0.54). Conclusions/significance: In case-case analyses with the luminal A cases as the reference group, we observed a lower proportion of TNBC among women who breastfed 7 or more months. The combination of longer breastfeeding duration and lower parity seemed to further reduce the odds of having a TNBC compared to a luminal A breast cancer

    Collagen XIX Alpha 1 improves prognosis in amyotrophic lateral sclerosis

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    The identification of more reliable diagnostic or prognostic biomarkers in age-related neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), is urgently needed. The objective in this study was to identify more reliable prognostic biomarkers of ALS mirroring neurodegeneration that could be of help in clinical trials. A total of 268 participants from three cohorts were included in this study. The muscle and blood cohorts were analyzed in two cross-sectional studies, while the serial blood cohort was analyzed in a longitudinal study at 6-monthly intervals. Fifteen target genes and fourteen proteins involved in muscle physiology and differentiation, metabolic processes and neuromuscular junction dismantlement were studied in the three cohorts. In the muscle biopsy cohort, the risk for a higher mortality in an ALS patient that showed high Collagen type XIX, alpha 1 (COL19A1) protein levels and a fast progression of the disease was 70.5% (P < 0.05), while in the blood cohort, this risk was 20% (P < 0.01). In the serial blood cohort, the linear mixed model analysis showed a significant association between increasing COL19A1 gene levels along disease progression and a faster progression during the follow-up period of 24 months (P < 0.05). Additionally, higher COL19A1 levels and a faster progression increased 17.9% the mortality risk (P < 0.01). We provide new evidence that COL19A1 can be considered a prognostic biomarker that could help the selection of homogeneous groups of patients for upcoming clinical trial and may be pointed out as a promising therapeutic target in ALS

    BiblioMadSalud, cooperando en un espacio común

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    BiblioMadSalud (BMS) surge en 2015, como una red informal de profesionales de bibliotecas en activo que tienen como denominador común la temática (ciencias de la salud) y la ubicación geográfica (Comunidad de Madrid) pero pertenecientes a distintas administraciones (estatal y autonómica), contextos (Administración, hospitales, organizaciones profesionales, universidades y organismos públicosde investigación) y ámbitos (público y privado) con el objetivo de promover la coordinación y colaboración entre sus instituciones, en un formato organizativo innovador a nivel regional y nacional. Material y método: análisis descriptivo del proceso y desarrollo de BiblioMadSalud.Resultados: BibliomadSalud se ha desarrollado a partir de sucesivas etapas: 1. Génesis: diseño y planificación de su identidad, funcionalidades y estructura; 2. Organización: creación de sus órganos competentes como Comité Ejecutivo, Grupos de Trabajo y Asamblea; e. Puesta en marcha: elaboración de un directorio geolocalizado de bibliotecas, organización de tres jornadas de participación asamblearia, constitución de 10 grupos de trabajo (BiblioBaremo, BiblioMOOCsalud, Estadísticas, Contribuyendo al OA, Callejeando, Recursos de aprendizaje, #BiblioRRHH, BiblioEvalúa, BiblioEstructura y BiblioVisibilidad), organización de actividades formativas trimestrales y difusión en redes sociales.Conclusiones: la colaboración entre instituciones de distintas administraciones, contextos y ámbitos, siempre resulta enriquecedora; trabajar organizados en Grupos de Trabajo con objetivos concretos facilita la visibilización de resultados; las actividades formativas periódicas han contribuido a una mayor cohesión del colectivo; la constitución como red informal, aunque útil en el momento de arranque, dará paso a alguna estructura asociativa más estable para la continuidad de BMS.BiblioMadSalud (BMS) emerges in 2015 as an informal network for library professsionalsin active service that have as common denominator their discipline (Health Sciences) and geographical location (Comunidad de Madrid), bur separated by their dependence of different government bodies (Central State or Autonomous Communities), contexts (Administration, Hospitals, Professional Organizations, Universities and Public Research Organizations) or sector (publico r private). Its goa lis to promote coordination and collaboration between their instituions through an innovative organizational model that Works at regional an national level.Methods: Descriptive análisis of the genesis and development of BiblioMadSalud.Results: BiblioMadSalud has evolved over successive stages: 1: Genesis: design and planning of its identity, functionalities and structure; 2.Organization: creation of thir competent bodies, such as the Executive Committee, task groups or Assembly; 3. Impelentation: creation of a geolocated directory of libraries, organization of three anual meeting of participation in the Assemby, formation of 10 task groups (BiblioBaremo, BiblioMOOCsalud, Estadísticas, Contribuyendo al OA, Callejeando, Recursos de aprendiaaje, #BiblioRRHH, BiblioEvalúa, BiblioEstructura y BiblioVisibilidad), organization of quarterly education activities and disseminationon social networks.Conclusion: cooperation betwwwn institutions from different administrations, contexts and sectors is always rewarding; working in task groups with particular objetives helps to make the results visible; periodic educational activities contribute to a better cohesiono f the collective; the constitution as an informal network, though useful at firt, Will give way to a more stable associative structure for the continuity of BMS

    Bibliomadsalud, cooperating in a common space

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    XVI Jornadas Nacionales de Información y Documentación en Ciencias de la Salud. Oviedo, 4-5 de abril de 2019. Contiene presentación, comunicación y vídeo de comunicaciones en formato exprés.BiblioMadSalud surge, en 2015, como una red informal de profesionales de bibliotecas en activo, que tienen como denominador común la temática (ciencias de la salud) y la ubicación geográfica (Comunidad de Madrid) pero pertenecientes a distintas administraciones (estatal y autonómica), contextos (Administración, hospitales, organizaciones profesionales, universidades y Organismos públicos de investigación) y ámbitos (público y privado) con el objetivo de promover la coordinación y colaboración entre sus instituciones, en un formato organizativo innovador a nivel regional y nacional.BiblioMadSalud emerges in 2015 as an informal network for library professionals in active service that that have as common denominator their discipline (Health Sciences) and geographical location (Comunidad de Madrid), but separated by their dependence of different government bodies (Central State or Autonomous Communities), contexts (Administration, Hospitals, Professional Organizations, Universities and Public Research Organizations) or sectors (public or private). Its goal is to promote coordination and collaboration between their institutions through an innovative organizational model that works at regional and national level.N
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