Insulin secretion in health and disease: nutrients dictate the pace.

NlmCategory="UNASSIGNED">Insulin is a key hormone controlling metabolic homeostasis. Loss or dysfunction of pancreatic β-cells lead to the release of insufficient insulin to cover the organism needs, promoting diabetes development. Since dietary nutrients influence the activity of β-cells, their inadequate intake, absorption and/or utilisation can be detrimental. This review will highlight the physiological and pathological effects of nutrients on insulin secretion and discuss the underlying mechanisms. Glucose uptake and metabolism in β-cells trigger insulin secretion. This effect of glucose is potentiated by amino acids and fatty acids, as well as by entero-endocrine hormones and neuropeptides released by the digestive tract in response to nutrients. Glucose controls also basal and compensatory β-cell proliferation and, along with fatty acids, regulates insulin biosynthesis. If in the short-term nutrients promote β-cell activities, chronic exposure to nutrients can be detrimental to β-cells and causes reduced insulin transcription, increased basal secretion and impaired insulin release in response to stimulatory glucose concentrations, with a consequent increase in diabetes risk. Likewise, suboptimal early-life nutrition (e.g. parental high-fat or low-protein diet) causes altered β-cell mass and function in adulthood. The mechanisms mediating nutrient-induced β-cell dysfunction include transcriptional, post-transcriptional and translational modifications of genes involved in insulin biosynthesis and secretion, carbohydrate and lipid metabolism, cell differentiation, proliferation and survival. Altered expression of these genes is partly caused by changes in non-coding RNA transcripts induced by unbalanced nutrient uptake. A better understanding of the mechanisms leading to β-cell dysfunction will be critical to improve treatment and find a cure for diabetes.

Mechanisms of protein homeostasis in health, aging and disease.

When emerging from the ribosomes, new polypeptides need to fold properly, eventually translocate, and then assemble into stable, yet functionally flexible complexes. During their lifetime, native proteins are often exposed to stresses that can partially unfold and convert them into stably misfolded and aggregated species, which can in turn cause cellular damage and propagate to other cells. In animal cells, especially in aged neurons, toxic aggregates may accumulate, induce cell death and lead to tissue degeneration via different mechanisms, such as apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The main cellular mechanisms effectively controlling protein homeostasis in youth and healthy adulthood are: (1) the molecular chaperones, acting as aggregate unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate degrading organelles. For unclear reasons, these cellular defences become gradually incapacitated with age, leading to the onset of degenerative diseases. Understanding these mechanisms and the reasons for their incapacitation in late adulthood is key to the design of new therapies against the progression of aging, degenerative diseases and cancers.

Dimensioning DC-voltage capacitor for a DC-distribution system and dynamic analysis

Technical analysis of Low Voltage Direct Current (LVDC) distribution systems shows that in LVDC transmission the customer voltage quality is higher. One of the problems in LVDC distribution networks that converters both ends of the DC line are required. Because of the converters produce not pure DC voltage, but some fluctuations as well, the huge electrolytic capacitors are required to reduce voltage distortions in the DC-side. This thesis master’s thesis is focused on calculating required DC-link capacitance for LVDC transmission and estimation of the influence of different parameters on the voltage quality. The goal is to investigate the methods of the DC-link capacitance estimation and location in the transmission line.

European payment system and monetary union

We make a comparative study of payment systems for E.U. -fifteen countries for the 1996-2002 period. Special attention is paid to the introduction of the new European single currency. The overall trend in payments is for a move from cash to noncash payment instruments, although electronic instruments are not widely used yet. We find a significant impact from the introduction of the new banknotes and coins on card use

Spectrophotometric study of iron oxidation in the iron(II)/thiocyanate/acetone system and some analytical applications

The possibility of using thiocyanate to determine iron(II) and/or iron(III) in water-acetone mixture has been re-examined as part of a systematic and comparative study involving metallic complexes of pseudohalide ligands. Some parameters that affect the complete oxidation of the ferrous cations, their subsequent complexation and the system stability have been studied to optimize the experimental conditions. Our results show the viability and potentiality of this simply methodology as an alternative analytical procedure to determine iron cations with high sensitivity, precision and accuracy. Studies on the calibration, stability, precision, and effect of various different ions have been carried out by using absorbance values measured at 480 nm. The analytical curve for the total iron determination obeys Beer's law (r = 0.9993), showing a higher sensitivity (molar absorptivity of 2.10x10(4) L cm-1 mol-1) when compared with other traditional systems (ligands) or even with the "similar" azide ion [1.53x10(4) L cm-1 mol-1, for iron-III/azide complexes, in 70% (v/v) tetrahydrofuran/water, at 396 nm]. Under such optimized experimental conditions, it is possible to determine iron in the concentration range from 0.5 to 2 ppm (15-65% T for older equipments, quartz cells of 1.00 cm). Analytical applications have been tested for some different materials (iron ores), also including pharmaceutical products for anemia, and results were compared with atomic absorption determinations. Very good agreement was obtained with these two different techniques, showing the potential of the present experimental conditions for the total iron spectrophotometric determinations (errors < 5%). The possibility of iron speciation was made evident by using another specific and auxiliary method for iron(II) or (III).

Researching Manufacturing Planning and Control system and Master Scheduling in a manufacturing firm.

The objective of this thesis is to research Manufacturing Planning and Control (MPC) system and Master Scheduling (MS) in a manufacturing firm. The study is conducted at Ensto Finland Corporation, which operates on a field of electrical systems and supplies. The paper consists of theoretical and empirical parts. The empirical part is based on weekly operating at Ensto and includes inter-firm material analysis, learning and meetings. Master Scheduling is an important module of an MPC system, since it is beneficial on transforming strategic production plans based on demand forecasting into operational schedules. Furthermore, capacity planning tools can remarkably contribute to production planning: by Rough-Cut Capacity Planning (RCCP) tool, a MS plan can be critically analyzed in terms of available key resources in real manufacturing environment. Currently, there are remarkable inefficiencies when it comes to Ensto’s practices: the system is not able to take into consideration seasonal demand and react on market changes on time; This can cause significant lost sales. However, these inefficiencies could be eliminated through the appropriate utilization of MS and RCCP tools. To utilize MS and RCCP tools in Ensto’s production environment, further testing in real production environment is required. Moreover, data accuracy, appropriate commitment to adapting and learning the new tools, and continuous developing of functions closely related to MS, such as sales forecasting, need to be ensured.

REPRODUCTIVE SYSTEM AND POLLEN FLOW IN PROGENIES OF Qualea grandiflora Mart., A TYPICAL SPECIES OF THE BRAZILIAN CERRADO

This study analyzed the reproductive system and the pollen dispersion pattern of Qualea grandiflora progenies. This is a typical species from the Brazilian Cerrado about which there are not too many studies from the genetics point of view. The study was conducted in an area of 2.2 hectares located in the Conservation Unit managed by the Forest Institute of the state of São Paulo, Brazil (Assis State Forest). Total genomic DNA of 300 seeds from 25 plants (12 seeds from each plant) was extracted and amplified using specific primers to obtain microsatellite markers. Results showed that selfing is frequent among adults and progenies, and the species reproduces by outcrossing between related and unrelated individuals (0.913). The single-locus outcrossing rate was 0.632, which indicates that mating between unrelated individuals is more frequent than between related plants. The selfing rate was low (0.087), that is, the species is allogamous and self-fertilization is reduced. About 35% of the plants in the progenies were full-sibs, and about 57%, half-sibs. Besides, about 8% of the progenies were selfing siblings. The genetic differentiation coefficient within progenies was 0.139, whereas the fixation rate was about 27%. The estimate of the effective size revealed that the genetic representativeness of descent was lower than expected in random mating progenies: The analyzed samples corresponded to only 13.2 individuals of an ideal panmictic population. In environmental recovery programs, seeds, preferably from different fruits, should be collected from 95 trees to preserve the genetic diversity of the species.

NON-DESTRUCTIVE ANALYSIS OF THE ROOT SYSTEM AND TREE GROWTH PARAMETERS

ABSTRACT The productivity of Eucalyptus at plantations is increasing and has undergone a variety of research studies. Most research is dealing with simple dendrometric variables like the DBH (diameter at breast height) and tree height, or more complex variables including crown parameters or variables concerning photosynthesis. The root systems, however, have not been well analyzed yet. The objective of the study was to analyze the root system with a non-destructive method and to evaluate possible correlations with dendrometric variables of the tree (DBH, height, crown expansion). A small experimental plantation with 39 even-aged, 6-year-old trees of Eucalyptus grandis x urophylla has been investigated within this study. The results of the study show the highest correlation of the root areas with the crown expansion. In general, the root area shows a significantly bigger expansion in the eucalypt plantation than the tree crown, with a more homogeneous development.

Crop coefficient and water consumption of eggplant in no-tillage system and conventional soil preparation

Under organic management in Seropédica-RJ, Brazil, using a weighing lysimeter, the crop coefficients (kc), the maximum evapotranspiration and the productivity of eggplant cultivation under two cropping systems (no tillage with straw plus soil with conventional preparation) were determined. A whole randomized layout with two treatments (no tillage and conventional) and five replicates during 134 days of cultivation were adopted. There were no significant differences in the eggplant cultivation in the two cropping systems, with a maximum commercial productivity obtained from 47.42 Mg ha-1 for the no-tillage system, and 47.91 Mg ha-1 for the conventional tillage. The accumulated ETc was 285.15 and 323.44 mm for the no-tillage and conventional, respectively. The crop coefficients value for the phases: 1 - transplanting, flowering, 2 - flowering-fruiting, 3 - fruit- first harvesting, 4- first harvesting of the final crop cycle was 0.83, 0.77, 0.90 and 0.97 in no-tillage system for the respective phases and for the conventional one 0.81, 1.14, 1.17 and 1.05 for the same steps described above.

Energy balance in the poultry-shed system and its influence on broiler performance

ABSTRACTThe objective of this study was to determine the energy balance of the poultry-shed system and its effect on broiler performance during the production cycle. The experimental design was completely random with sub-divided blocks. The blocks were composed of five different types of sheds and the sub-blocks of the evaluation times (00:00 h to 23:00 h), allowing an analysis of variance and a comparison between means with the Tukey test. There were no significant differences between the mean values of the exchanges of sensible, latent and total heat between the poultry sheds but the differences for the evaluation times were significant (P<0.05). There was no significant difference between sheds 1 and 4 for broiler productive performance regarding weight gain, feed consumption and feed conversion. Bird performance was significant (P<0.05) for the remaining poultry sheds. The productive indexes remained below the ranges considered ideal for broilers and values in the final weeks were characterized by the poor installation efficiency in controlling temperature variations and, consequently, the energy balance in the system, which adversely affected bird productive performance.

Generation and Characterization of Knockout Mice and Analysis of Patient Material Demonstrates a Role for Tissue Inhibitor of Metalloproteinases 4 (Timp4) in the Cardiovascular System and Tumor Metastasis

This thesis focuses on tissue inhibitor of metalloproteinases 4 (TIMP4) which is the newest member of a small gene and protein family of four closely related endogenous inhibitors of extracellular matrix (ECM) degrading enzymes. Existing data on TIMP4 suggested that it exhibits a more restricted expression pattern than the other TIMPs with high expression levels in heart, brain, ovary and skeletal muscle. These observations and the fact that the ECM is of special importance to provide the cardiovascular system with structural strength combined with elasticity and distensibility, prompted the present molecular biologic investigation on TIMP4. In the first part of the study the murine Timp4 gene was cloned and characterized in detail. The structure of murine Timp4 genomic locus resembles that in other species and of the other Timps. The highest Timp4 expression was detected in heart, ovary and brain. As the expression pattern of Timp4 gives only limited information about its role in physiology and pathology, Timp4 knockout mice were generated next. The analysis of Timp4 knockout mice revealed that Timp4 deficiency has no obvious effect on the development, growth or fertility of mice. Therefore, Timp4 deficient mice were challenged using available cardiovascular models, i.e. experimental cardiac pressure overload and myocardial infarction. In the former model, Timp4 deficiency was found to be compensated by Timp2 overexpression, whereas in the myocardial infarct model, Timp4 deficiency resulted in increased mortality due to increased susceptibility for cardiac rupture. In the wound healing model, Timp4 deficiency was shown to result in transient retardation of re-epithelialization of cutaneous wounds. Melanoma tumor growth was similar in Timp4 deficient and control mice. Despite of this, lung metastasis of melanoma cells was significantly increased in Timp4 null mice. In an attempt to translate the current findings to patient material, TIMP4 expression was studied in human specimens representing different inflammatory cardiovascular pathologies, i.e. giant cell arteritis, atherosclerotic coronary arteries and heart allografts exhibiting signs of chronic rejection. The results showed that cardiovascular expression of TIMP4 is elevated particularly in areas exhibiting inflammation. The results of the present studies suggest that TIMP4 has a special role in the regulation of tissue repair processes in the heart, and also in healing wounds and metastases. Furthermore, evidence is provided suggesting the usefulness of TIMP4 as a novel systemic marker for vascular inflammation.

Health management practices and disease prevalence in dairy sheep systems in Argentina

A cross-sectional survey of 19 dairy sheep farms in Argentina was carried out with the purpose to know farm management, health practices, and occurrence and mortality of diseases. The survey comprised 40% of all sheep milking farms in Argentina. A questionnaire was conducted by way of personal interviews with sheep owners during farm visits. The proportions of farms reporting routine vaccination for clostridial diseases, contagious ecthyma, pneumonia and mineral and vitamin parenteral administration were 63%, 47.3%, 16.6% and 42.1% respectively. Regular treatment against lice was used in 37.5% of the farms, and 89.5% o the farmers treated against gastrointestinal nematodes (GIN). The mean number of GIN drenches per farm was 2.26±1.78 annually. In 68.4% of the milking flocks the California Mastitis Test was regularly done and 55.6% of the farmer managers had sampled their flocks once a year for Brucella ovis antibodies. During the pre-mating period respectively 68.4% and 50% of farmers clinically examined their rams and ewe for general health and teeth condition. The udders of ewes were frequently inspected at the start of each milking period. The most important parasite problems noticed were GIN (reported by 57.9% of farmers), lice (57.9%) and scabies (10.5%) and the most frequent infectious diseases were ecthyma (73.7%), pneumonia and other respiratory problems (57.9%), clinical mastitis (55.6%), clostridial diseases (36.9%) and foot lameness (35.2%). Photosensitivity (47.4%) and ruminal acidosis (42.1%) were reported as other frequent toxic or metabolic disorders. Owners mentioned that the mean lifespan or milk productive time per ewe was 4.5±1.4 years. Perinatal lamb mortality was 8.5% and the total flock mortality rates, above the first 24 h of life was 6.9%. The high rates of lamb mortality during the pre-weaning (10.3%) and post-weaning (5.9%) periods indicate that this problem, as well as the most prevalent diseases, should be the subject of further studies.

Implementing an open data system and showing its benefits

Open data refers to publishing data on the web in machine-readable formats for public access. Using open data, innovative applications can be developed to facilitate people‟s lives. In this thesis, based on the open data cases (discussed in the literature review), Open Data Lappeenranta is suggested, which publishes open data related to opening hours of shops and stores in Lappeenranta City. To prove the possibility of creating Open Data Lappeenranta, the implementation of an open data system is presented in this thesis, which publishes specific data related to shops and stores (including their opening hours) on the web in standard format (JSON). The published open data is used to develop web and mobile applications to demonstrate the benefits of open data in practice. Also, the open data system provides manual and automatic interfaces which make it possible for shops and stores to maintain their own data in the system. Finally in this thesis, the completed version of Open Data Lappeenranta is proposed, which publishes open data related to other fields and businesses in Lappeenranta beyond only stores‟ data.

Algorithm to determine the intersection curves between bezier surfaces by the solution of multivariable polynomial system and the differential marching method

The determination of the intersection curve between Bézier Surfaces may be seen as the composition of two separated problems: determining initial points and tracing the intersection curve from these points. The Bézier Surface is represented by a parametric function (polynomial with two variables) that maps a point in the tridimensional space from the bidimensional parametric space. In this article, it is proposed an algorithm to determine the initial points of the intersection curve of Bézier Surfaces, based on the solution of polynomial systems with the Projected Polyhedral Method, followed by a method for tracing the intersection curves (Marching Method with differential equations). In order to allow the use of the Projected Polyhedral Method, the equations of the system must be represented in terms of the Bernstein basis, and towards this goal it is proposed a robust and reliable algorithm to exactly transform a multivariable polynomial in terms of power basis to a polynomial written in terms of Bernstein basis .

Cytokines as determinants of disease and disease interactions

The immune response to pathogens results in both host resistance and immunopathology. Cytokines and in particular those lymphokines produced by Th1 and Th2 cells play a key role in determining the balance between these two immunologic outcomes. Recent data suggest that interleukin-10, a product of both Th2 cells and macrophages, protects the host against excessive immunopathology. The cytokine environment generated by different pathogens may also influence the course and outcome of infections with unrelated organisms. This relationship may be particularly important in the case of HIV-1 where prior Th1 or Th2 biases established by helminth or intracellular infections may influence either initial viral susceptibility or drive progression to AIDS through immune activation