145 research outputs found
Pricing perpetual options using Mellin transforms
AbstractWe have derived the expression for the free boundary and price of an American perpetual put as the limit of a finite-lived option
Oleate Potentiates Oxysterol Inhibition of Transcription From Sterol Regulatory Element-1-Regulated Promoters and Maturation of Sterol Regulatory Element-Binding Proteins
Activation of genes containing SRE-1 (sterol regulatory element 1) sequences is known to be under the regulation of sterols through modulation of the proteolytic maturation of SREBPs (SRE-1-binding proteins). Previous work has demonstrated SREBP-mediated transcriptional activation of genes encoding enzymes of sterol and fatty acid biosynthesis. Because synthesis of both sterols and C18 fatty acids are required for cell growth, in the absence of exogenous supplements of these lipids, we examined the hypothesis that fatty acid can also be regulatory in SREBP maturation. Our data indicate that C18 fatty acids can potentiate the biological activities of a typical, regulatory sterol: 25-hydroxycholesterol. Inhibition of C18 fatty acid synthesis in cells cultured in serum-free medium renders them resistant to killing by 25-hydroxycholesterol. Repression of expression of reporter constructs driven by promoters bearing SRE-1 element(s) by 25- hydroxycholesterol is increased by C18 fatty acid supplementation. C18 fatty acids also increase the inhibitory effect of 25-hydroxycholesterol on proteolytic maturation and nuclear localization of SREBPs. Furthermore, we also show that C18 fatty acid supplementation can enhance the inhibitory effect of 25-hydroxycholesterol on sterol and fatty acid biosynthesis. These results demonstrate that maximal down-regulation of SREBP maturation and the consequent repression of SRE-1 promoters occurs in response to both a regulatory sterol and fatty acid
Combined Management of Groundwater Resources and Water Supply Systems at Basin Scale Under Climate Change
Water stress conditions associated with population growth, climate change, and groundwater contamination, represent a significant challenge for all stakeholders in the water sector. Increasing the resilience of Water Supply Systems (WSSs) becomes of fundamental importance: along with an adequate level of service, sustainability targets must be ensured. A long-term management strategy is strictly connected to a holistic approach, based on analyses at different scales. To this end, both groundwater modeling tools and water management models, with different spatial and temporal scales, are routinely and independently employed. Here, we propose a coupled approach combining: i) groundwater models (MODFLOW) to investigate different stress scenarios, involving climate change and anthropic activities; ii) water management models (Aquator), to assess the water resources availability and the best long-term management strategy for large-scale WSS. The management models are implemented starting from input and output flows derived by groundwater models: this leads to establish a comprehensive framework usually not defined in management models and including a quantitative characterization of the aquifer. The proposed methodology, general and applicable to any study area, is here implemented to the WSS of Reggio Emilia Province, and its main groundwater resource, the Enza aquifer, considering three different stress scenarios for groundwater models (BAU, ST1, and ST2), and for management strategies (BAU, BAURV2, ST2). Among the key results, we observe that coupling the two model types: i) allows evaluating water resources availability in connection with management rules; ii) leads to examining more realistic operation choices; iii) permits planning of infrastructures at basin scale
Characterization of marble weathering through pore structure quantitative analysis
Y Stone weathering is strongly controlled by the intrinsic properties of the stone and by its use. Previous studies demonstrate that the response to natural or artificial ageing processes of the rocks seems to be strongly influenced by the pore structure of the stone. A better understanding of this phenomenon is provided by the study and characterization of porosity and of the pore structure at different degrees of alteration. The analysis of the evolution of the decay leads to the evaluation of the durability of marble in facades, and more generally in buildings, as well as for the protection and recovery of artistic and architectural heritage.In this paper, we apply a methodology for the geometrical characterization of the pore structure to quantify alteration induced by natural weathering on marble slabs. The approach is based on the application of a path-finding algorithm to 2D binary images representative of thin sections of marble at different degrees of alteration. Through the identification of the paths within the porous domain, the methodology allows the characterization of the pore structure in terms of pore radius distribution along the identified paths. Analysis of the results demonstrate a good agreement between the degree of alteration of the pore structure and the corresponding variation of the physical and mechanical properties of the rock samples under investigation
Transtornos Neuropsiquiátricos em Idosos Institucionalizados no Sul de Santa Catarina (Brasil)
Contexto: O processo de envelhecimento está associado à s doenças que podem comprometer o bom funcionamento do sistema nervoso central. Objetivo: Avaliar caracterÃstica de declÃnio cognitivo e prevalência de sintomas depressivos e sua associação com dados sociodemográficos de idosos institucionalizados em três instituições de longa permanência do sul de Santa Catarina. Métodos: Estudo transversal, avaliando todos idosos institucionalizados em Tubarão e Laguna/SC. Participaram da presente pesquisa 66 idosos, com idade maior ou igual a sessenta anos, de ambos os gêneros. Para coleta de dados utilizou-se um questionário padronizado abordando dados sociodemográficos, a Escala de Depressão Geriátrica reduzida (EDG-15) e o Mini-Exame do Estado Mental. Resultados: A população estudada era predominantemente feminina, viúva e média de idade 77,3±9,9anos. Sintomas depressivos estiveram presentes em 62,1% dos idosos. PossÃvel déficit cognitivo esteve presente em 37,87% da população. Conclusão: Alta prevalência de sintomas depressivos e déficit cognitivo estiveram presentes nos idosos residentes nas instituições de longa permanência pesquisadas. Diante de tais fatos, o serviço de saúde do Brasil deve estar preparado para avaliar e tratar tais pacientes, a fim de melhorar a qualidade de vida dos idosos institucionalizados.Background: The process of aging is associated with the diseases that may compromise the proper functioning of the central nervous system. Objectives: To evaluate the prevalence of cognitive decline and depressive symptoms and their relationship with sociodemographic characteristics of institutionalized elderly in three long-stay institutions in south of Santa Catarina. Methods: cross-sectional study was carried out with all institutionalized elderly in Tubarão and Laguna (SC). In this study were interviewed 66 individuals, 60 years of age or older, male and female. The data collection was performed through a standardized questionnaire with sociodemographic characteristics, the Geriatric Depression Scale in the reduced form (GDS-15) and Mini-Mental State Examination. Results: The study population was predominantly female, widowed, mean age 77.3±9.9 years old. Depressive symptoms were present in 62.1% of institutionalized elderly. The cognitive decline was present in 37.87% of the institutionalized elderly. Conclusion: High prevalence of depressive symptoms and cognitive deficits were present in the elderly living in long-stay institutions surveyed. Given these facts, the health service in Brazil should be prepared to evaluate and treat institutionalized elderly, improving the quality of life of elderly patients
Pharyngoamygdalitis treatment in San Luis City, Argentina
The aim of this research was to determine and compare the distribution by sex and age of pharyngoamygdalitis cases and analyze quantitatively and qualitatively the applied treatments in Hospitals A (HA) and B (HB) of San Luis city, Argentina. An observational, descriptive, transversal and indication-prescription’s study was carried out. Diagnoses and drugs were classified and the prescriptions were analyzed. Amoxicillin in HA and penicillin G benzathine in HB were mainly prescribed. Antihistamines, mucolytics and antitussives of non-elevated therapeutic value were used. There was widespread use of dipyrone, two NSAIDs were administered simultaneously and non-specific drugs were prescribed. The use of antibiotics in a self-limiting and predominantly viral disease, the high use of injectable drugs, with an inadequate cost/benefit ratio, and of non-elevated therapeutic value are behaviors that lead to the emergence of resistance, adverse reactions and unnecessary expenses. This fact brings to the conclusion that there was a misuse of drugs for pharyngoamygdalitis in San Luis.Colegio de Farmacéuticos de la Provincia de Buenos Aire
A Nanoscale Shape-Discovery Framework Supporting Systematic Investigations of Shape-Dependent Biological Effects and Immunomodulation
Since it is now possible to make, in a controlled fashion, an almost unlimited variety of nanostructure shapes, it is of increasing interest to understand the forms of biological control that nanoscale shape allows. However, a priori rational investigation of such a vast universe of shapes appears to present intractable fundamental and practical challenges. This has limited the useful systematic investigation of their biological interactions and the development of innovative nanoscale shape-dependent therapies. Here, we introduce a concept of biologically relevant inductive nanoscale shape discovery and evaluation that is ideally suited to, and will ultimately become, a vehicle for machine learning discovery. Combining the reproducibility and tunability of microfluidic flow nanochemistry syntheses, quantitative computational shape analysis, and iterative feedback from biological responses in vitro and in vivo, we show that these challenges can be mastered, allowing shape biology to be explored within accepted scientific and biomedical research paradigms. Early applications identify significant forms of shape-induced biological and adjuvant-like immunological control
Costameric integrin and sarcoglycan protein levels are altered in a Drosophila model for Limb-girdle muscular dystrophy type 2H
Mutations in two different domains of the ubiquitously expressed TRIM32 protein give rise to two clinically separate diseases, one of which is Limb-girdle muscular dystrophy type 2H (LGMD2H). Uncovering the muscle-specific role of TRIM32 in LGMD2H pathogenesis has proven difficult, as neurogenic phenotypes, independent of LGMD2H pathology, are present in TRIM32 KO mice. We previously established a platform to study LGMD2H pathogenesis using Drosophila melanogaster as a model. Here we show that LGMD2H disease-causing mutations in the NHL domain are molecularly and structurally conserved between fly and human TRIM32. Furthermore, transgenic expression of a subset of myopathic alleles (R394H, D487N, and 520fs) induce myofibril abnormalities, altered nuclear morphology, and reduced TRIM32 protein levels, mimicking phenotypes in patients afflicted with LGMD2H. Intriguingly, we also report for the first time that the protein levels of βPS integrin and sarcoglycan δ, both core components of costameres, are elevated in TRIM32 disease-causing alleles. Similarly, murine myoblasts overexpressing a catalytically inactive TRIM32 mutant aberrantly accumulate α- and β-dystroglycan and α-sarcoglycan. We speculate that the stoichiometric loss of costamere components disrupts costamere complexes to promote muscle degeneration
Antitumour activity of trabectedin in myelodysplastic/myeloproliferative neoplasms
Background: Juvenile myelomonocytic leukaemia (JMML) and chronic myelomonocytic leukaemia (CMML) are myelodysplastic myeloproliferative (MDS/MPN) neoplasms with unfavourable prognosis and without effective chemotherapy treatment. Trabectedin is a DNA minor groove binder acting as a modulator of transcription and interfering with DNA repair mechanisms; it causes selective depletion of cells of the myelomonocytic lineage. We hypothesised that trabectedin might have an antitumour effect on MDS/MPN. Methods: Malignant CD14+ monocytes and CD34+ haematopoietic progenitor cells were isolated from peripheral blood/bone marrow mononuclear cells. The inhibition of CFU-GM colonies and the apoptotic effect on CD14+ and CD34+ induced by trabectedin were evaluated. Trabectedin's effects were also investigated in vitro on THP-1, and in vitro and in vivo on MV-4-11 cell lines. Results: On CMML/JMML cells, obtained from 20 patients with CMML and 13 patients with JMML, trabectedin - at concentration pharmacologically reasonable, 1-5 nM - strongly induced apoptosis and inhibition of growth of haematopoietic progenitors (CFU-GM). In these leukaemic cells, trabectedin downregulated the expression of genes belonging to the Rho GTPases pathway (RAS superfamily) having a critical role in cell growth and cytoskeletal dynamics. Its selective activity on myelomonocytic malignant cells was confirmed also on in vitro THP-1 cell line and on in vitro and in vivo MV-4-11 cell line models. Conclusions: Trabectedin could be good candidate for clinical studies in JMML/CMML patients
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