Software development environments and tools in MDE

Abstract. Model-Driven Engineering (MDE) is the notion that we can construct a model of a system that we can then transform into the real thing. The development of software in MDE using Domain-Specific Languages (DSLs) has two phases. First, the development of artifacts such as DSLs and  transformation mechanisms by the modeling experts. Second, people non-technical experts (domain expert or end user) using the artifacts created develop applications simply because of the high level of abstraction allowed by technology. Several factors are considered to limit the use of MDE. One of them,  is the lack of knowledge the tools and the development activities with MDE. To support the MDE initiative, the present work makes a description of the theoretical foundations of MDE, also describes the main activities to build several MDE artifacts with some of the tools most known in this technology

Investigating the Effects of Homocysteine as an Agonist on Invertebrate Glutamatergic Synapses

Hyperhomocysteinemia (HHcy) in mammals can produce neurological deficits, such as memory loss. The cause of the neurological issues is assumed to be due to homocysteine (HCY) binding to glutamatergic receptors in the central nervous system (CNS). High levels of HCY in the CNS are also associated with Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease. Thus, understanding the detailed mechanisms of HCY in model preparations could be useful in developing potential treatments to neurodegenerative diseases with overlapping symptoms to HHcy. The aim of this study is to investigate the efficacy of HCY as an agonist at glutamatergic synapses in invertebrates. The glutamatergic synapses of the larval Drosophila melanogaster (D. melanogaster) and Procambarus clarkii (P. clarkii) neuromuscular junctions (NMJs) were utilized to examine the effects of applying HCY. Measurements of evoked synaptic transmission in both preparations revealed that 100 mM of HCY did not have any consistent effect. The expectation was that the acute action of HCY would have activated the glutamate receptors and then desensitized them so evoked transmission would be blocked. The pharmacological receptor profile of these NMJ receptors are of a quisqualate subtype and not a kainate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate receptor (NMDA) subtype. Consequently, HCY may not have any action on quisqualate glutamate receptor subtypes. The findings of this experiments could provide clinical implications regarding relevant pharmacological treatments in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease

Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes–Memory in Diabetes (ACCORD-MIND) Study

IMPORTANCE African American individuals have higher dementia risk than individuals of white race/ethnicity. They also have higher rates of type 2 diabetes, which may contribute to this elevated risk. This study examined the association of the following 2 classes of alleles at the haptoglobin (Hp) locus that are associated with poor cognition, cardiovascular disease, and mortality: Hp 1-1 (associated with poor cognition and cerebrovascular disease) and Hp 2-1 and Hp 2-2 (associated with greater risk ofmyocardial infarction and mortality). An additional polymorphism in the promoter region of the Hp 2 allele, restricted to individuals of African descent, yields a fourth genotype, Hp 2-1m. African American adults have a higher prevalence of Hp 1-1 (approximately 30%) compared with individuals of white race/ethnicity (approximately 14%), but the potential role of the Hp genotype in cognition among elderly African American individuals with type 2 diabetes is unknown. OBJECTIVE To assess the association of the Hp genotypes with cognitive function and decline in elderly African American adults with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This cohort study used publicly available data and specimens from the Action to Control Cardiovascular Risk in Diabetes–Memory in Diabetes (ACCORD-MIND) study to investigate the association of the Hp genotypes with cognitive function and decline in 466 elderly African American participants with type 2 diabetes. The hypothesis was that the Hp 1-1 genotype compared with the other genotypes would be associated with more cognitive impairment and faster cognitive decline in elderly African American adults with type 2 diabetes. The initial ACCORD trialwas performed from October 28, 1999, to September 15, 2014. This was a multicenter clinical study performed in an academic setting. EXPOSURES The Hp genotypes were determined from serum samples by polyacrylamide gel electrophoresis and by enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURES The Mini-Mental State Examination (MMSE) was used to measure cognitive function and change after 40 months. The MMSE score ranges from 0 to 30 points; higher scores represent better cognition. Associations were examined with analysis of covariance and linear regression, adjusting for age, sex, education, baseline glycated hemoglobin level, systolic blood pressure, diastolic blood pressure, cholesterol level, creatinine level, and treatment arm (intensive vs standard). The cognitive change model adjusted also for the baseline MMSE score. RESULTS Among 466 African American study participants (mean [SD] age, 62.3 [5.7] years), 64.8% were women, and the genotype prevalences were 29.4%(n = 137) for Hp 1-1, 36.1%(n = 168) for Hp 2-1, 10.9%(n = 51) for Hp 2-1m, and 23.6%(n = 110) for Hp 2-2. The groups differed in their baseline MMSE scores (P = .006): Hp 1-1 had the lowest MMSE score (mean [SE], 25.68 [0.23]), and Hp 2-1m had the highest MMSE score (mean [SE], 27.15 [0.36]). Using the least squares method, the 40-month decline was significant for Hp 1-1 (mean [SE], −0.41 [0.19]; P = .04) and for Hp 2-2 (mean [SE], −0.68 [0.21]; P = .001). However, the overall comparison across the 4 groups did not reach statistical significance for the fully adjusted model. The interaction of age with the Hp 1-1 genotype on MMSE score decline estimate per year change was significant (mean [SE], −0.87 [0.37]; P = .005), whereas itwas not significant for Hp 2-1 (mean [SE], 0.06 [0.37]; P = .85), Hp 2-1m (mean [SE], −0.06 [0.51]; P = .89), and Hp 2-2 (mean [SE], −0.44 [0.41]; P = .29), indicating that cognitive decline in Hp 1-1 carrierswas accentuated in older ages, whereas it was not significant for the other Hp genotypes. CONCLUSIONS AND RELEVANCE In this study, the Hp 1-1 genotype, which is 2-fold (approximately 30%) more prevalent among African American individuals than among individuals of white race/ ethnicity, was associated with poorer cognitive function and greater cognitive decline than the other Hp genotypes. The Hp gene polymorphism may explain the elevated dementia risk in African American adults. The neuropathological substrates and mechanisms for these associations merit further investigation

Expert perspectives on global biodiversity loss and its drivers and impacts on people

Despite substantial progress in understanding global biodiversity loss, major taxonomic and geographic knowledge gaps remain. Decision makers often rely on expert judgement to fill knowledge gaps, but are rarely able to engage with sufficiently large and diverse groups of specialists. To improve understanding of the perspectives of thousands of biodiversity experts worldwide, we conducted a survey and asked experts to focus on the taxa and freshwater, terrestrial, or marine ecosystem with which they are most familiar. We found several points of overwhelming consensus (for instance, multiple drivers of biodiversity loss interact synergistically) and important demographic and geographic differences in specialists’ perspectives and estimates. Experts from groups that are underrepresented in biodiversity science, including women and those from the Global South, recommended different priorities for conservation solutions, with less emphasis on acquiring new protected areas, and provided higher estimates of biodiversity loss and its impacts. This may in part be because they disproportionately study the most highly threatened taxa and habitats

The mechanism of formation, structure and physiological relevance of covalent hemoglobin attachment to the erythrocyte membrane

Covalent hemoglobin binding to membranes leads to band 3 (AE1) clustering and the removal of erythrocytes from the circulation; it is also implicated in blood storage lesions. Damaged hemoglobin, with the heme being in a redox and oxygen-binding inactive hemichrome form, has been implicated as the binding species. However, previous studies used strong non-physiological oxidants. In vivo hemoglobin is constantly being oxidised to methemoglobin (ferric), with around 1% of hemoglobin being in this form at any one time. In this study we tested the ability of the natural oxidised form of hemoglobin (methemoglobin) in the presence or absence of the physiological oxidant hydrogen peroxide to initiate membrane binding. The higher the oxidation state of hemoglobin (from Fe(III) to Fe(V)) the more binding was observed, with approximately 50% of this binding requiring reactive sulphydryl groups. The hemoglobin bound was in a high molecular weight complex containing spectrin, ankyrin and band 4.2, which are common to one of the cytoskeletal nodes. Unusually, we showed that hemoglobin bound in this way was redox active and capable of ligand binding. It can initiate lipid peroxidation showing the potential to cause cell damage. In vivo oxidative stress studies using extreme endurance exercise challenges showed an increase in hemoglobin membrane binding, especially in older cells with lower levels of antioxidant enzymes. These are then targeted for destruction. We propose a model where mild oxidative stress initiates the binding of redox active hemoglobin to the membrane. The maximum lifetime of the erythrocyte is thus governed by the redox activity of the cell; from the moment of its release into the circulation the timer is set

Diurnal timing of nonmigratory movement by birds: the importance of foraging spatial scales

Timing of activity can reveal an organism's efforts to optimize foraging either by minimizing energy loss through passive movement or by maximizing energetic gain through foraging. Here, we assess whether signals of either of these strategies are detectable in the timing of activity of daily, local movements by birds. We compare the similarities of timing of movement activity among species using six temporal variables: start of activity relative to sunrise, end of activity relative to sunset, relative speed at midday, number of movement bouts, bout duration and proportion of active daytime hours. We test for the influence of flight mode and foraging habitat on the timing of movement activity across avian guilds. We used 64 570 days of GPS movement data collected between 2002 and 2019 for local (non‐migratory) movements of 991 birds from 49 species, representing 14 orders. Dissimilarity among daily activity patterns was best explained by flight mode. Terrestrial soaring birds began activity later and stopped activity earlier than pelagic soaring or flapping birds. Broad‐scale foraging habitat explained less of the clustering patterns because of divergent timing of active periods of pelagic surface and diving foragers. Among pelagic birds, surface foragers were active throughout all 24 hrs of the day while diving foragers matched their active hours more closely to daylight hours. Pelagic surface foragers also had the greatest daily foraging distances, which was consistent with their daytime activity patterns. This study demonstrates that flight mode and foraging habitat influence temporal patterns of daily movement activity of birds.We thank the Nature Conservancy, the Bailey Wildlife Foundation, the Bluestone Foundation, the Ocean View Foundation, Biodiversity Research Institute, the Maine Outdoor Heritage Fund, the Davis Conservation Foundation and The U.S. Department of Energy (DE‐EE0005362), and the Darwin Initiative (19-026), EDP S.A. ‘Fundação para a Biodiversidade’ and the Portuguese Foundation for Science and Technology (FCT) (DL57/2019/CP 1440/CT 0021), Enterprise St Helena (ESH), Friends of National Zoo Conservation Research Grant Program and Conservation Nation, ConocoPhillips Global Signature Program, Maryland Department of Natural Resources, Cellular Tracking Technologies and Hawk Mountain Sanctuary for providing funding and in-kind support for the GPS data used in our analyses

Experiencias de aprendizaje

Libro de experiencias de aprendizaje del grupo de investigación Giteca y de los semilleros de investigación en la que se visualizan las diferentes experiencias lideradas por instructores y aprendices en las diferentes áreas y líneas de formación.Book of learning experiences of the Giteca research group and the research hotbeds in which the different experiences led by instructors and apprentices in the different areas and lines of training are visualized.Propagación in vitro como un camino de aprendizaje para la formación profesional integral -- Experiencias significativas de aprendizaje, laboratorio de hematología y parasitología animal del Complejo Tecnológico para la Gestión Agroempresarial CTPGA-SENA -- Experiencias significativas adquiridas por aprendices en el área de SENNOVA, Complejo Tecnológico para la Gestión Agroempresarial. Regional – Antioquia -- El papel de la prensa escrita en el desarrollo de la competencia textual -- Aprendiendo a Emprender con un emprendedor -- Ven y te cuento sobre ADSI -- Observaciones fenológicas del cultivo de cacao (Theobroma cacao) en los municipios de Tarazá, El Bagre y Caucasia dentro de la formación del programa SENA emprende rural -- Tejiendo sueños desde la formación -- Forraje verde hidropónico como alternativa para disminuir la expansión de la frontera agrícola en el Putumayo -- La importancia del saber hacer para ser competente en el sector agrícola -- Experiencia significativa de aprendizaje semilleros de investigación -- La investigación como ente transformador de pensamientos -- Piscícola Paraguay; Mi Sueño, Mi Proyecto de Vida! -- Estrategia de aprendizaje a través de la investigación y la empresa aplicando un programa de Responsabilidad Social Empresarial –RSE -- Matemática aplicada para procesos agroindustriales de panificaciónna85 página

The Bacterial Community Structure and Microbial Activity in a Traditional Organic Milpa Farming System Under Different Soil Moisture Conditions

Agricultural practices affect the bacterial community structure, but how they determine the response of the bacterial community to drought, is still largely unknown. Conventional cultivated soil, i.e., inorganic fertilization, tillage, crop residue removal and maize (Zea mays L.) monoculture, and traditional organic farmed soil “milpa,” i.e., minimum tillage, rotation of maize, pumpkin (Cucurbita sp.) and beans (Phaseolus vulgaris L.) and organic fertilization were sampled. Both soils from the central highlands of Mexico were characterized and incubated aerobically at 5% field capacity (5%FC) and 100% field capacity (FC) for 45 days, while the C and N mineralization, enzyme activity and the bacterial community structure were monitored. After applying the different agricultural practices 3 years, the organic C content was 1.8-times larger in the milpa than in the conventional cultivated soil, the microbial biomass C 1.3-times, and C and N mineralization 2.0-times (mean for soil incubated at 5%FC and FC). The dehydrogenase, activity was significantly higher in the conventional cultivated soil than in the milpa soil when incubated at 5%FC, but not when incubated at FC. The relative abundance of Gemmatimonadetes was larger in the conventional cultivated soil than in the milpa soil in soil both at 5%FC and FC, while that of Bacteroidetes showed an opposite trend. The relative abundance of other groups, such as Nitrospirae and Proteobacteria, was affected by cultivation technique, but controlled by soil water content. The relative abundance of other groups, e.g., FBP, Gemmatimonadetes and Proteobacteria, was affected by water content, but the effect depended on agricultural practice. For soil incubated at FC, the xenobiotics biodegradation and metabolism related functions were higher in the milpa soil than in the conventional cultivated soil, and carbohydrate metabolism showed an opposite trend. It was found that agricultural practices and soil water content had a strong effect on soil characteristics, C and N mineralization, enzyme activity, and the bacterial community structure and its functionality. Decreases or increases in the relative abundance of bacterial groups when the soil water content decreased, i.e., from FC to 5%FC, was defined often by the cultivation technique, and the larger organic matter content in the milpa soil did not prevent large changes in the bacterial community structure when the soil was dried

RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA)

Purpose: Two quality controlled inter-laboratory exercises were organized within the EU project ‘Realizing the European Network of Biodosimetry (RENEB)’ to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. Materials and methods: The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants. Results: The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. Conclusions: In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners

A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer

BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. METHODOLOGY: This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1–2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5(m)C content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS: Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy