142 research outputs found

    Bounded rationality, capital budgeting decisions and small business

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    Purpose The purpose of this paper is to provide insight into the capital budgeting decision-making of Canadian and Mexican entrepreneurs in small businesses in the food sector. The objective is to understand the capital budgeting decisions through the lens of bounded rationality and how these decisions are affected by different (national) contexts. Design/methodology/approach This is a comparative study in which the use of constructivist grounded theory allowed deep conversations about capital budgeting decisions. Data was collected from forty semi-structured interviews with entrepreneurs/managers in two regions, Mexico and Canada. Findings Insights from this study suggest that entrepreneurs’ capital budgeting decisions are not only taken under conditions of bounded rationality but also suggest a prominent role of context in how bounded rationality is applied differently towards investment decisions. Research limitations/implications While the findings cannot simply be generalized, exploring how capital budgeting decisions are made differently across two regional contexts adds to the understanding of the nexus of context, bounded rationality and capital budgeting decision-making. Practical implications Using a bounded rationality lens, this study contrasts and explains similarities and differences in the entrepreneur’s capital budgeting decision-making within small businesses. The insights add to the body of knowledge and help entrepreneurs to reflect on their approach to decision-making. Originality/value The paper uses a less commonly applied approach to understand two under-researched regional contexts. We use constructivist grounded theory to explore entrepreneurs’ capital budgeting decision-making in small businesses in two regions, Canada and Mexico. The comparative approach and the findings add to the understanding of decision-making, highlight the prominent role of context and also challenge some insights from previous research

    Approximate Preservers on Banach Algebras and C

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    The aim of the present paper is to give approximate versions of Hua’s theorem and other related results for Banach algebras and C*-algebras. We also study linear maps approximately preserving the conorm between unital C*-algebras

    Antiproliferative activity of protein extracts from the black clam (Chione fluctifraga) on human cervical and breast cancer cell lines

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    The wide diversity of the marine environment has been an important resource for the discovery of new bioactive agents from marine organisms. The aim of this study was to obtain protein extracts from the clam Chione fluctifraga and determine its antiproliferative activity against cervical and breast cancer cells. The extracts were obtained by ammonium sulfate fractionation, gel filtration and ion exchange chromatography. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay (MTT). The results showed that 3F3 had antiproliferative effect against HeLa and MDA-MB-231 cell lines with IC50 values of 138.035 and 157.19 μg/ml, respectively, and 2F2 showed IC50 values of 67.46 μg/ml on HeLa cells. These results suggest that protein extracts from C. fluctifraga might be potential anticancer agents.Key words: Protein extracts, clam, antiproliferative activity, breast cancer, cervical cancer

    Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution

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    Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine: glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases.Spanish Ministry of Economy and Competitiveness, MINECO (BIO 2015 66426-R to JMSR, CTQ 2015-64445-R to JLN, ‘Factoría Española de Cristalización’, Consolider-Ingenio 2010 to JAG and SAF2015-69796 to ES), Junta de Andalucia (P11-CTS-07187 to ALP) and FEDER fun

    Análisis de la relevancia y factibilidad de indicadores de calidad en las unidades de nutrición

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    Introducción: La evaluación de la calidad en las actividades sanitarias exige la elección de unos indicadores acordes con los resultados que queremos medir. De todos los posibles, debemos priorizar aquellos que nos permitan obtener la información más relevante sin sobrecargar el trabajo habitual de nuestras Unidades. Objetivo: Conocer la opinión de los socios de SENPE respecto a la relevancia y la viabilidad del uso de una selección de indicadores de calidad para su aplicación en nutrición clínica. Métodos: Encuesta remitida mediante correo electrónico a los socios de SENPE solicitando a los mismos su opinión sobre 12 indicadores de calidad, valorándose cada uno en cuanto a su relevancia y factibilidad de la aplicación en su medio. Resultados: Contestaron 40 encuestados de 40 centros diferentes de 12 comunidades autónomas. En general, los indicadores fueron considerados más relevantes que factibles. Los indicadores mejor puntuados fueron: “identificación en las bolsas de nutrición artificial”, “posición semi-incorporada del paciente con nutrición enteral por sonda nasogástrica” y “protocolos clínicos básicos”. Considerando los indicadores por grupos (de estructura, proceso o resultado) los mejor valorados fueron: “identificación del paciente en las bolsas de nutrición artificial” (estructura), “posición semi-incorporada” y “protocolos clínicos básicos” (proceso), y “cumplimiento del objetivo calórico” (resultado). Conclusión: Los resultados de la encuesta permiten seleccionar indicadores prioritarios para su aplicación en las Unidades de NutriciónIntroduction: The quality assessment in health activities requires the choice of indicators in line with the results we want to measure. Of all possible, we should prioritize those that allow us to obtain the most relevant information without overloading the regular work of our units. Objective: To determine the opinion of the members of SENPE regarding the relevance and feasibility of using a selection of quality indicators designed for use in clinical nutrition. Methods: E-mail survey sent to members of SENPE asking them their views on 12 quality indicators, evaluating each in terms of their relevance and feasibility of implementation in their environment. Results: 40 respondents answered from 40 centers in 12 different regions. In general, the indicators were considered more relevant than feasible. The indicators best rated were: “identification in artificial nutrition bags, “semi-recumbent position in patient with nasogastric tube feeding” and “basic clinical protocols”. Considering the type of indicator: “patient identification in the bags of artificial nutrition (structure),” a semi-incorporated “and” basic clinical protocols (process), and “fulfillment of the caloric goal” (result). Conclusion: The results of the survey can make a selection of indicators that could be considered for first-line introduction in a Nutrition Uni

    Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution

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    Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases

    Multiplex Real-Time PCR Assay Using TaqMan Probes for the Identification of Trypanosoma cruzi DTUs in Biological and Clinical Samples

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    Background: Trypanosoma cruzi has been classified into six Discrete Typing Units (DTUs), designated as TcI–TcVI. In order to effectively use this standardized nomenclature, a reproducible genotyping strategy is imperative. Several typing schemes have been developed with variable levels of complexity, selectivity and analytical sensitivity. Most of them can be only applied to cultured stocks. In this context, we aimed to develop a multiplex Real-Time PCR method to identify the six T. cruzi DTUs using TaqMan probes (MTq-PCR).Methods/Principal Findings: The MTq-PCR has been evaluated in 39 cultured stocks and 307 biological samples from vectors, reservoirs and patients from different geographical regions and transmission cycles in comparison with a multi-locus conventional PCR algorithm. The MTq-PCR was inclusive for laboratory stocks and natural isolates and sensitive for direct typing of different biological samples from vectors, reservoirs and patients with acute, congenital infection or Chagas reactivation. The first round SL-IR MTq-PCR detected 1 fg DNA/reaction tube of TcI, TcII and TcIII and 1 pg DNA/reaction tube of TcIV, TcV and TcVI reference strains. The MTq-PCR was able to characterize DTUs in 83% of triatomine and 96% of reservoir samples that had been typed by conventional PCR methods. Regarding clinical samples, 100% of those derived from acute infected patients, 62.5% from congenitally infected children and 50% from patients with clinical reactivation could be genotyped. Sensitivity for direct typing of blood samples from chronic Chagas disease patients (32.8% from asymptomatic and 22.2% from symptomatic patients) and mixed infections was lower than that of the conventional PCR algorithm.Conclusions/Significance: Typing is resolved after a single or a second round of Real-Time PCR, depending on the DTU. This format reduces carryover contamination and is amenable to quantification, automation and kit production.This work received financial support from the Ministry of Science and Technology of Argentina [PICT 2011-0207 to AGS] and the National Scientific and Technical Research Council in Argentina (CONICET) [PIP 112 2011-010-0974 to AGS]. Work related to evaluation of biological samples was partially sponsored by the Pan-American Health Organization (PAHO) [Small Grants Program PAHO-TDR]; the Drugs and Neglected Diseases Initiative (DNDi, Geneva, Switzerland), Wellcome Trust (London, United Kingdom), SANOFI-AVENTIS (Buenos Aires, Argentina) and the National Council for Science and Technology in Mexico (CONACYT) [FONSEC 161405 to JMR]

    Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome

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    Funding Information: Funding: This work was supported by the Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (ref. PY20_00212, P20_00583), and the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. SAF2016–78722-R, PID2020–120157RB-I00) and the Proyectos I + D + i del Programa Operativo FEDER 2020 (ref. B-CTS-584-UGR20, B-CTS-260-UGR20). FDC was supported by the “Ramón y Cajal” program (ref. RYC-2014–16458), and LBC was supported by the Spanish Ministry of Economy and Competitiveness through the “Juan de la Cierva Incorporación” program (Grant ref. IJC2018– 038026-I, funded by MCIN/AEI/10.13039/501100011033), all of them including FEDER funds. AGJ was funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”(grant ref. FPU20/02926). SGM was funded by a previously mentioned project (ref. PY20_00212). IPATIMUP integrates the i3S Research Unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT), financed by the European Social Funds (COMPETE-FEDER) and National Funds (projects PEstC/SAU/LA0003/2013 and POCI-01–0145-FEDER-007274). AML is funded by the Portuguese Government through FCT (IF/01262/2014). PIM is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European Social Fund, available through the Programa Operacional do Capital Humano. ToxOmics—Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, Nova Medical School, Lisbon, is also partially supported by FCT (Projects: UID/BIM/00009/2013 and UIDB/UIDP/00009/2020). SLarriba received support from Instituto de Salud Carlos III (grant DTS18/00101], co-funded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe), and from “Generalitat de Catalunya” (grant 2017SGR191). SLarriba is sponsored by the “Researchers Consolidation Program” from the SNS-Dpt. Salut Generalitat de Catalunya (Exp. CES09/020). This article is related to the Ph.D. Doctoral Thesis of Miriam Cerván-Martín (grant ref. BES-2017–081222 funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood–testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORaddrs2287839 = 1.85 (1.17–2.93), ORaddrs2233678 = 1.62 (1.11–2.36), ORaddrs62105751 = 1.43 (1.06–1.93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO.publishersversionpublishe

    Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

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    BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients
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