Evolutionary dynamics of interlinked public goods traits: an experimental study of siderophore production in Pseudomonas aeruginosa.

Public goods cooperation is common in microbes, and there is much interest in understanding how such traits evolve. Research in recent years has identified several important factors that shape the evolutionary dynamics of such systems, yet few studies have investigated scenarios involving interactions between multiple public goods. Here, we offer general predictions about the evolutionary trajectories of two public goods traits having positive, negative or neutral regulatory influence on one another's expression, and we report on a test of some of our predictions in the context of Pseudomonas aeruginosa's production of two interlinked iron-scavenging siderophores. First, we confirmed that both pyoverdine and pyochelin siderophores do operate as public goods under appropriate environmental conditions. We then tracked their production in lines experimentally evolved under different iron-limitation regimes known to favour different siderophore expression profiles. Under strong iron limitation, where pyoverdine represses pyochelin, we saw a decline in pyoverdine and a concomitant increase in pyochelin - consistent with expansion of pyoverdine-defective cheats derepressed for pyochelin. Under moderate iron limitation, pyochelin declined - again consistent with an expected cheat invasion scenario - but there was no concomitant shift in pyoverdine because cross-suppression between the traits is unidirectional only. Alternating exposure to strong and moderate iron limitation caused qualitatively similar though lesser shifts compared to the constant-environment regimes. Our results confirm that the regulatory interconnections between public goods traits can significantly modulate the course of evolution, yet also suggest how we can start to predict the impacts such complexities will have on phenotypic divergence and community stability.

A support system for evaluating a suitable joining method in the production of sheet metal goods

This report illustrates a comparative study of various joining methods involved in sheet metal production. In this report it shows the selection of joining methods, which includes comparing the advantages and disadvantages of a method over the other ones and choosing the best method for joining. On the basis of various joining process from references, a table is generated containing set of criterion that helps in evaluation of various sheet metal joining processes and in selecting the most suitable process for a particular product. Three products are selected and a comprehensive study of the joining methods is analyzed with the help of various parameters. The table thus is the main part of the analysis process of this study and can be advanced with the beneficial results. It helps in a better and easy understanding and comparing the various methods, which provides the foundation of this study and analysis. The suitability of the joining method for various types of cases of different sheet metal products can be tested with the help of this table. The sections of the created table display the requirements of manufacturing. The important factor has been considered and given focus in the table, as how the usage of these parameters is important in percentages according to particular or individual case. The analysis of the methods can be extended or altered by changing the parameters according to the constraint. The use of this table is demonstrated by pertaining the cases from sheet metal production.

Rapid improvement of canine cognitive dysfunction with immunotherapy designed for Alzheimer's disease

Immunotherapy against amyloid-β(Aβ) may improve rodent cognitive function by reducing amyloid neuropathology and is being validated in clinical trials with positive preliminary results. However, for a complete understanding of the direct and long-term immunization responses in the aged patient, and also to avoid significant side effects, several key aspects remain to be clarified. Thus, to investigate brain Aβ clearance and Th2 responses in the elderly, and the reverse inflammatory events not found in the immunized rodent, better Alzheimer"s disease (AD) models are required. In the aged familiar canine with a Cognitive Dysfunction Syndrome (CDS) we describe the rapid effectiveness and the full safety profile of a new active vaccine candidate for human AD prevention and treatment. In these aged animals, besidesa weak immune system, the antibody response activated a coordinated central and peripheral Aβ clearance, that rapidly improved their cognitive function in absence of any side effects. Our results also confirm the interest to use familiar dogs to develop innovative and reliable therapies for AD.

Effectiveness of antioxidants in preventing oxidation of palm oil enriched with heme iron: A model for iron fortification in baked products

Bakery products such as biscuits, cookies, and pastries represent a good medium for iron fortification in food products, since they are consumed by a large proportion of the population at risk of developing iron deficiency anemia, mainly children. The drawback, however, is that iron fortification can promote oxidation. To assess the extent of this, palm oil added with heme iron and different antioxidants was used as a model for evaluating the oxidative stability of some bakery products, such as baked goods containing chocolate. The palm oil samples were heated at 220°C for 10 min to mimic the conditions found during a typical baking processing. The selected antioxidants were a free radical scavenger (tocopherol extract (TE), 0 and 500 mg/kg), an oxygen scavenger (ascorbyl palmitate (AP), 0 and 500 mg/kg), and a chelating agent (citric acid (CA), 0 and 300 mg/kg). These antioxidants were combined using a factorial design and were compared to a control sample, which was not supplemented with antioxidants. Primary (peroxide value and lipid hydroperoxide content) and secondary oxidation parameters (p-anisidine value, p-AnV) were monitored over a period of 200 days in storage at room temperature. The combination of AP and CA was the most effective treatment in delaying the onset of oxidation. TE was not effective in preventing oxidation. The p-AnV did not increase during the storage period, indicating that this oxidation marker was not suitable for monitoring oxidation in this model.

Effectiveness of antioxidants in preventing oxidation of palm oil enriched with heme iron: A model for iron fortification in baked products

Bakery products such as biscuits, cookies, and pastries represent a good medium for iron fortification in food products, since they are consumed by a large proportion of the population at risk of developing iron deficiency anemia, mainly children. The drawback, however, is that iron fortification can promote oxidation. To assess the extent of this, palm oil added with heme iron and different antioxidants was used as a model for evaluating the oxidative stability of some bakery products, such as baked goods containing chocolate. The palm oil samples were heated at 220°C for 10 min to mimic the conditions found during a typical baking processing. The selected antioxidants were a free radical scavenger (tocopherol extract (TE), 0 and 500 mg/kg), an oxygen scavenger (ascorbyl palmitate (AP), 0 and 500 mg/kg), and a chelating agent (citric acid (CA), 0 and 300 mg/kg). These antioxidants were combined using a factorial design and were compared to a control sample, which was not supplemented with antioxidants. Primary (peroxide value and lipid hydroperoxide content) and secondary oxidation parameters (p-anisidine value, p-AnV) were monitored over a period of 200 days in storage at room temperature. The combination of AP and CA was the most effective treatment in delaying the onset of oxidation. TE was not effective in preventing oxidation. The p-AnV did not increase during the storage period, indicating that this oxidation marker was not suitable for monitoring oxidation in this model.

PRPF mutations are associated with generalized defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa.

Proteins PRPF31, PRPF3 and PRPF8 (RP-PRPFs) are ubiquitously expressed components of the spliceosome, a macromolecular complex that processes nearly all pre-mRNAs. Although these spliceosomal proteins are conserved in eukaryotes and are essential for survival, heterozygous mutations in human RP-PRPF genes lead to retinitis pigmentosa, a hereditary disease restricted to the eye. Using cells from patients with 10 different mutations, we show that all clinically relevant RP-PRPF defects affect the stoichiometry of spliceosomal small nuclear RNAs (snRNAs), the protein composition of tri-small nuclear ribonucleoproteins and the kinetics of spliceosome assembly. These mutations cause inefficient splicing in vitro and affect constitutive splicing ex-vivo by impairing the removal of at least 9% of endogenously expressed introns. Alternative splicing choices are also affected when RP-PRPF defects are present. Furthermore, we show that the steady-state levels of snRNAs and processed pre-mRNAs are highest in the retina, indicating a particularly elevated splicing activity. Our results suggest a role for PRPFs defects in the etiology of PRPF-linked retinitis pigmentosa, which appears to be a truly systemic splicing disease. Although these mutations cause widespread and important splicing defects, they are likely tolerated by the majority of human tissues but are critical for retinal cell survival.

Validation Studies of Thermal-hydraulic Code for Safety Analysis of Nuclear Power Plants

This thesis gives an overview of the validation process for thermal hydraulic system codes and it presents in more detail the assessment and validation of the French code CATHARE for VVER calculations. Three assessment cases are presented: loop seal clearing, core reflooding and flow in a horizontal steam generator. The experience gained during these assessment and validation calculations has been used to analyze the behavior of the horizontal steam generator and the natural circulation in the geometry of the Loviisa nuclear power plant. The cases presented are not exhaustive, but they give a good overview of the work performed by the personnel of Lappeenranta University of Technology (LUT). Large part of the work has been performed in co-operation with the CATHARE-team in Grenoble, France. The design of a Russian type pressurized water reactor, VVER, differs from that of a Western-type PWR. Most of thermal-hydraulic system codes are validated only for the Western-type PWRs. Thus, the codes should be assessed and validated also for VVER design in order to establish any weaknesses in the models. This information is needed before codes can be used for the safety analysis. Theresults of the assessment and validation calculations presented here show that the CATHARE code can be used also for the thermal-hydraulic safety studies for VVER type plants. However, some areas have been indicated which need to be reassessed after further experimental data become available. These areas are mostly connected to the horizontal stem generators, like condensation and phase separation in primary side tubes. The work presented in this thesis covers a large numberof the phenomena included in the CSNI code validation matrices for small and intermediate leaks and for transients. Also some of the phenomena included in the matrix for large break LOCAs are covered. The matrices for code validation for VVER applications should be used when future experimental programs are planned for code validation.

Investigation of interaction between native and impurity defects in ZnSe

Zinc selenide is a prospective material for optoelectronics. The fabrication of ZnSe­based light-emitting diodes is hindered by complexity of p-type doping of the component materials. The interaction between native and impurity defects, the tendency of doping impurity to form associative centres with native defects and the tendency to self-compensation are the main factors impeding effective control of the value and type of conductivity. The thesis is devoted to the study of the processes of interaction between native and impurity defects in zinc selenide. It is established that the Au impurity has the most prominent amphoteric properties in ZnSe among Cu, Ag and Au impurities, as it forms a great number of both Au; donors and Auz„ acceptors. Electrical measurements show that Ag and Au ions introduced into vacant sites of the Zn sublattice form simple single-charged Agz„+ and Auzn+ states with d1° electron configuration, while Cu ions can form both single-charged Cuz„ (d1) and double-charged Cuzr`+ (d`o) centres. Amphoteric properties of Ag and Au transition metals stimulated by time are found for the first time from both electrical and luminescent measurements. A model that explains the changes in electrical and luminescent parameters by displacement of Ag ions into interstitial sites due to lattice deformation forces is proposed. Formation of an Ag;-donor impurity band in ZnSe samples doped with Ag and stored at room temperature is also studied. Thus, the properties of the doped samples are modified due to large lattice relaxation during aging. This fact should be taken into account in optoelectronic applications of doped ZnSe and related compounds.

Analysis of emergency braking performance with particular consideration of temperature effects on brakes

During vehicle deceleration due to braking there is friction between the lining surface and the brake drum or disc. In this process the kinetic energy of vehicle is turned into thermal energy that raises temperature of the components. The heating of the brake system in the course of braking is a great problem, because besides damaging the system, it may also affect the wheel and tire, which can cause accidents. In search of the best configuration that considers the true conditions of use, without passing the safety limits, models and formulations are presented with respect to the brake system, considering different braking conditions and kinds of brakes. Some modeling was analyzed using well-known methods. The flat plate model considering energy conservation was applied to a bus, using for this a computer program. The vehicle is simulated to undergo an emergency braking, considering the change of temperature on the lining-drum. The results include deceleration, braking efficiency, wheel resistance, normal reaction on the tires and the coefficient of adhesion. Some of the results were compared with dynamometer tests made by FRAS-LE and others were compared with track tests made by Mercedes-Benz. The convergence between the results and the tests is sufficient to validate the mathematical model. The computer program makes it possible to simulate the brake system performance in the vehicle. It assists the designer during the development phase and reduces track tests.

Association of Alport's syndrome with HLA-DR2 antigen in a group of unrelated patients

A few family studies have evaluated HLA antigens in Alport's syndrome; however, there are no large population studies. In the present report, we studied 40 unrelated white patients with Alport's syndrome seen at the Unit of Renal Transplantation, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil. HLA-A, -B, -DR and -DQ antigens were typed using a complement-dependent microlymphocytotoxicity assay. A control white population (N = 403) from the same geographical area was also typed for HLA antigens. Although the frequencies of HLA-A and -B antigens of patients were not statistically different from controls, the frequency of HLA-DR2 antigen observed in patients (65%) was significantly increased in relation to controls (26%; P<0.001). The relative risk and etiologic fraction for HLA-DR2 antigen were 5.2 and 0.525, respectively. Although few immunological abnormalities have been shown in Alport's syndrome, in this report we emphasize the association of HLA molecules and Alport's syndrome. Besides the well-known inherited molecular defects encoded by type IV collagen genes in Alport's syndrome, the major histocompatibility alleles may be in linkage disequilibrium with these defective collagen genes

Prevention of contrast induced nephropathy with sodium bicarbonate (the PROMEC study)

Introduction: Contrast-induced nephropathy is a common complication of radiographic procedures. Different measures have been used to avoid this damage, but the evidence is controversial. New investigations are required to clarify it. We investigated the efficacy and safety of sodium bicarbonate solution compared with sodium chloride solution to prevent contrast induced nephropathy in patients with or at risk of renal dysfunction. Methods: A prospective, single-center, randomized clinical trial conducted from May 1, 2007 to February 8, 2008. Inpatients in a tertiary center, scheduled to undergo a procedure with the nonionic radiographic contrast agent iohexol. There were 220 patients with serum creatinine levels of at least 1.2 mg/dL (106.1 µmol/L) and/or type 2 diabetics, who were randomized to receive an infusion of sodium chloride (n = 113) or sodium bicarbonate (n = 107) before and after contrast dye administration. The intervention were "A" group received 1 ml/kg/hour of normal saline solution, starting 12 hours before and continuing 12 hours after iohexol contrast. "B" group received 3 ml/kg of sodium bicarbonate solution (150 mEq/L) one hour prior to procedure and then drip rate was decreased to 1 ml/kg/hour until 6 hours post procedure. Our main outcome measure was change in serum creatinine. Results: The mean creatinine value after the procedure was 1.26 mg/dL in the saline group and 1.22 mg/dL in the bicarbonate group (mean difference: 0.036; CI 95%: -0.16 to 0.23, p = 0.865). The diagnosis of contrast-induced nephropathy, defined by increase in serum creatinine on 25% or more within 2 days after administration of radiographic contrast, was done in twelve patients (12%) in the bicarbonate group and eighth patients (7.1%) in the saline group (RR: 1.68, CI 95%: 0.72 to 3.94). Conclusion: Our investigation showed that there were no differences between normal saline solution (extended infusion) vs. bicarbonate solution for nephroprotection.

Failure modes of passive decay heat removing safety systems of modern nuclear power plants

The purpose of this master’s thesis is to gain an understanding of passive safety systems’ role in modern nuclear reactors projects and to research the failure modes of passive decay heat removal safety systems which use phenomenon of natural circulation. Another purpose is to identify the main physical principles and phenomena which are used to establish passive safety tools in nuclear power plants. The work describes passive decay heat removal systems used in AES-2006 project and focuses on the behavior of SPOT PG system. The descriptions of the main large-scale research facilities of the passive safety systems of the AES-2006 power plant are also included. The work contains the calculations of the SPOT PG system, which was modeled with thermal-hydraulic system code TRACE. The dimensions of the calculation model are set according to the dimensions of the real SPOT PG system. In these calculations three parameters are investigated as a function of decay heat power: the pressure of the system, the natural circulation mass flow rate around the closed loop, and the level of liquid in the downcomer. The purpose of the calculations is to test the ability of the SPOT PG system to remove the decay heat from the primary side of the nuclear reactor in case of failure of one, two, or three loops out of four. The calculations show that three loops of the SPOT PG system have adequate capacity to provide the necessary level of safety. In conclusion, the work supports the view that passive systems could be widely spread in modern nuclear projects.

Criminal liability of canadian corporations for international crimes

Ce mémoire porte sur la responsabilité pénale des entreprises canadiennes pour des crimes internationaux commis en partie ou entièrement à l’étranger. Dans la première partie, nous montrons que les premiers développements sur la reconnaissance de la responsabilité criminelle d’entités collectives devant les tribunaux militaires établis après la deuxième guerre mondiale n’ont pas été retenus par les tribunaux ad hoc des Nations Unies et par la Cour pénale internationale. En effet, la compétence personnelle de ces tribunaux permet uniquement de contraindre des personnes physiques pour des crimes internationaux. Dans la deuxième partie, nous offrons des exemples concrets illustrant que des entreprises canadiennes ont joué dans le passé et peuvent jouer un rôle criminel de soutien lors de guerres civiles et de conflits armés au cours desquels se commettent des crimes internationaux. Nous montrons que le droit pénal canadien permet d’attribuer une responsabilité criminelle à une organisation (compagnie ou groupe non incorporé) pour des crimes de droit commun commis au Canada, comme auteur réel ou comme complice. Nous soutenons qu’il est également possible de poursuivre des entreprises canadiennes devant les tribunaux canadiens pour des crimes internationaux commis à l’extérieur du Canada, en vertu de la Loi canadienne sur les crimes contre l’humanité et les crimes de guerre, du principe de la compétence universelle et des règles de droit commun. Bref, le Canada est doté d’instruments juridiques et judiciaires pour poursuivre des entreprises soupçonnées de crimes internationaux commis à l’étranger et peut ainsi mettre un terme à leur état indésirable d’impunité.