Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK) and L-arginine treatment both alone and in combination on blood pressure (BP), and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+ALSK (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+ALSK+L-arginine (ALSK+L-arg) treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

Electric paralyzation and reduction of weight loss in the processing of round-cooked spiny lobsters

This study proposes alternatives to the current methods of processing round-cooked lobster. The paralyzation of lobsters with direct electric shock consumes 10.526 x 10-3 kWh, which is significantly less than the 11 kWh required by the traditional thermal-shock method (based on 60 kg of lobsters). A better weight gain was obtained by immersion of paralyzed lobsters in brine before cooking. Systematic trials combining 3, 6, or 9% brine concentrations with immersion periods of 15, 30, or 45 minutes were performed in order to determine the best combinations. A mathematical model was designed to predict the weight gain of lobsters of different sizes in any combination of treatments. For small lobsters, a 45 minutes immersion in 6% brine gave the best response in terms of weight gain (4.7%) and cooking produced a weight loss of only 1.34% in relation to fresh lobster weight. For medium-sized lobsters, a 45 minutes immersion in 9% brine produced a weight gain of 2.64%, and cooking a weight gain of 1.08%. For large lobsters, a 45 minutes immersion in 6% brine produced a weight gain of 3.87%, and cooking a weight gain of 1.62%.

Variance reduction properties of dynamic hedging models - empirical evidence from BRICS countries

This Master’s Thesis analyses the effectiveness of different hedging models on BRICS (Brazil, Russia, India, China, and South Africa) countries. Hedging performance is examined by comparing two different dynamic hedging models to conventional OLS regression based model. The dynamic hedging models being employed are Constant Conditional Correlation (CCC) GARCH(1,1) and Dynamic Conditional Correlation (DCC) GARCH(1,1) with Student’s t-distribution. In order to capture the period of both Great Moderation and the latest financial crisis, the sample period extends from 2003 to 2014. To determine whether dynamic models outperform the conventional one, the reduction of portfolio variance for in-sample data with contemporaneous hedge ratios is first determined and then the holding period of the portfolios is extended to one and two days. In addition, the accuracy of hedge ratio forecasts is examined on the basis of out-of-sample variance reduction. The results are mixed and suggest that dynamic hedging models may not provide enough benefits to justify harder estimation and daily portfolio adjustment. In this sense, the results are consistent with the existing literature.

The investigation of the reduction mechanism of the 5a-reductase enzyme of Penicillium decumbens /

The 5a-reductase of Penicillium decumbens ATCC 10436 was used as a model for the mammalian enzyme to investigate the mechanism of reduction of testosterone to 5adihydrotestosterone . The purpose of this study was to search for specific 5a-reductase inhibitors which antagonize prostate cancer . In a whole-cell biotransformation mode, this organism reduced testosterone (1) to 5a-dihydrosteroids (8) and 5aandrostane- 3, 17-dione (9) in yields of 28% and 37% respectively. Control experiments have shown that 5aandrostane- 3, 17-dione (9) can be produced from the corresponding alcohol (8) in a subsequent reaction separate from that catalysed by the 5a-reductase enzyme . Androst-4- ene-3, 17-dione (2) is reduced to give only (9) with a recovery of 80% The stereochemistry of the reduction was determined by 500 MHz ^H NMR analysis of the products resulting from the deuterium labelled substrates. The results were obtained by an analysis of the NOE difference spectra, double-quantum filtered phase sensitive COSY 2-D spectra, and ^^c-Ir 2-D shift correlation spectra of deuterium labelled products. According to the unambiguous assignment of the signals due to H-4a and H-4Ii in 5a-dihydro steroids, the NMR data show clearly that addition of hydrogen to the 4{5)K bond has occurred in a trans manner at positions 413 and 5a. To Study the reduction mechanism of this enzyme, several substrates were prepared as following; 3-methyleneandrost-4-en- 17fi-ol(3), androst-4-en-17i5-ol(5) , androst-4-en-3ii, 17fi-diol (6) and 4, 5ii-epoxyandrostane-3, 17-dione (7) . Results suggest that this enzyme system requires an oxygen atom at the 3-position of the steroid in order to bind the substrate. Furthermore, the mechanism of this 5a-reductase may proceed via direct addition of hydrogen at the 4,5 position without involvement of a carbonyl group as an intermediate.

Participants' perceptions of their involvement in a cardiovascular disease risk factor reduction program

A cardiovascular disease risk factor reduction program was implemented in the Niagara region. To gain an understanding of this program from the participants ' perspective, 10 participants of the program were interviewed to document their perceptions of what they learned in the program, their perceptions of their behaviour change and their perceptions of factors that facilitated or impeded any behaviour change. The learning style inventory and PET test were also given to the participants to further understand their perceptions. Findings unique to this study highlighted aspects of the andragogical model, self-directed learning theory, learning style preference and psychological type that were prominent in the participants' comments and perspectives. Implications for practice, theory development and further research are suggested.

Deletion of the RNR4 gene causes hyperresistance to the carcinogen 4-NQO in the yeast model

La stabilité génomique, qui est essentielle à la vie, est possible grâce à la réplication et la réparation de l’ADN. Une des enzymes responsables de la réplication et de la réparation de l’ADN est la ribonucleotide reductase (RNR), qui est retrouvée chez la levure et chez l’humain. Cette enzyme catalyse la formation de déoxyribonucléotides et maintien le pool de dNTP requis pour la réparation et la réplication de l’ADN. L’enzyme RNR est un tétramère α2β2 constitué d’une grande (R1, α2) et d’une petite (R2, β2) sous-unité. Chez S. cerevisiae, les gènes RNR1 et RNR3 encodent la sous-unité α2 (R1). L’activité catalytique de RNR dépend d’une interaction avec le fer et de la formation d’un complexe entre R1 et R2. L’expression de toutes les sous-unités est inductible par les dommages causés à l’ADN. Dans cette étude, nous démontrons que des cellules qui n’expriment pas une des sous-unités, Rnr4, du complexe RNR sont sensibles à divers agents endommageant l’ADN, tels que le méthyl méthane sulfonate, la bléomycine, le péroxyde d’hydrogène et les rayons ultraviolets (UVC 254 nm). Au contraire, le mutant est résistant au 4-nitroquinoline-1- oxide (4-NQO), un composé qui engendre des lésions encombrantes. Par conséquent, le mutant rnr4Δ démontre une réduction marquée en mutations induites par le 4-NQO comparativement à la souche parentale. Nous voulions identifier la voie de réparation de l’ADN qui conférait cette résistance au 4-NQO ainsi que les protéines impliquées. Les voies BER, NER et MMR n’ont pas aboli la résistance au 4-NQO de la souche rnr4Δ. La protéine recombinante Rad51 ne joue pas un rôle critique dans la réparation de l’ADN et dans la résistance au 4-NQO. La délétion du gène REV3, qui encode une polymérase de contournement, impliquée dans la réparation post-réplication, a partiellement aboli la résistance au 4-NQO dans rnr4Δ. Ces résultats suggèrent que la polymérase Rev3 et possiblement d’autres polymérases translésion (Rev1, Rev7, Rad30) pourraient être impliquées dans la réparation de lésions encombrantes dans l’ADN dans des conditions de carence en dNTP. La réparation de l’ADN, un mécanisme complexe chez la levure, implique une vaste gamme de protéines, dont certaines encore inconnues. Nos résultats indiquent qu’il y aurait plus qu’une protéine impliquée dans la résistance au 4-NQO. Des investigations plus approfondies seront nécessaires afin de comprendre la recombinaison et la réparation post-réplication.

Evaluation of mitochondrial function in a model of developmental programming of hypertension associated with transient neonatal oxygen exposure

UNE EXPOSITION NÉONATALE À L’OXYGÈNE MÈNE À DES MODIFICATIONS DE LA FONCTION MITOCHONDRIALE CHEZ LE RAT ADULTE Introduction: L’exposition à l’oxygène (O2) des ratons nouveau-nés a des conséquences à l’âge adulte dont une hypertension artérielle (HTA), une dysfonction vasculaire, une néphropénie et des indices de stress oxydant. En considérant que les reins sont encore en développement actif lors des premiers jours après la naissance chez les rats, jouent un rôle clé dans le développement de l’hypertension et qu’une dysfonction mitochondriale est associé à une augmentation du stress oxydant, nous postulons que les conditions délétères néonatales peuvent avoir un impact significatif au niveau rénal sur la modulation de l’expression de protéines clés du fonctionnement mitochondrial et une production mitochondriale excessive d’espèces réactives de l’ O2. Méthodes: Des ratons Sprague-Dawley sont exposés à 80% d’O2 (H) ou 21% O2 (Ctrl) du 3e au 10e jr de vie. En considérant que plusieurs organes des rats sont encore en développement actif à la naissance, ces rongeurs sont un modèle reconnu pour étudier les complications d’une hyperoxie néonatale, comme celles liées à une naissance prématurée chez l’homme. À 4 et à 16 semaines, les reins sont prélevés et les mitochondries sont extraites suivant une méthode d’extraction standard, avec un tampon contenant du sucrose 0.32 M et différentes centrifugations. L’expression des protéines mitochondriales a été mesurée par Western blot, tandis que la production d’ H202 et les activités des enzymes clés du cycle de Krebs ont été évaluées par spectrophotométrie. Les résultats sont exprimés par la moyenne ± SD. Résultats: Les rats mâles H de 16 semaines (n=6) présentent une activité de citrate synthase (considéré standard interne de l’expression protéique et de l’abondance mitochondriales) augmentée (12.4 ± 8.4 vs 4.1 ± 0.5 μmole/mL/min), une diminution de l’activité d’aconitase (enzyme sensible au redox mitochondrial) (0.11 ± 0.05 vs 0.20 ± 0.04 μmoles/min/mg mitochondrie), ainsi qu’une augmentation dans la production de H202 (7.0 ± 1.3 vs 5.4 ± 0.8 ρmoles/mg protéines mitochondriales) comparativement au groupe Ctrl (n=6 mâles et 4 femelles). Le groupe H (vs Ctrl) présente également une diminution dans l’expression de peroxiredoxin-3 (Prx3) (H 0.61±0.06 vs. Ctrl 0.78±0.02 unité relative, -23%; p<0.05), une protéine impliquée dans l’élimination d’ H202, de l’expression du cytochrome C oxidase (Complexe IV) (H 1.02±0.04 vs. Ctrl 1.20±0.02 unité relative, -15%; p<0.05), une protéine de la chaine de respiration mitochondriale, tandis que l’expression de la protéine de découplage (uncoupling protein)-2 (UCP2), impliquée dans la dispersion du gradient proton, est significativement augmentée (H 1.05±0.02 vs. Ctrl 0.90±0.03 unité relative, +17%; p<0.05). Les femelles H (n=6) (vs Ctrl, n=6) de 16 semaines démontrent une augmentation significative de l’activité de l’aconitase (0.33±0.03 vs 0.17±0.02 μmoles/min/mg mitochondrie), de l’expression de l’ATP synthase sous unité β (H 0.73±0.02 vs. Ctrl 0.59±0.02 unité relative, +25%; p<0.05) et de l’expression de MnSOD (H 0.89±0.02 vs. Ctrl 0.74±0.03 unité relative, +20%; p<0.05) (superoxide dismutase mitochondriale, important antioxidant), tandis que l’expression de Prx3 est significativement réduite (H 1.1±0.07 vs. Ctrl 0.85±0.01 unité relative, -24%; p<0.05). À 4 semaines, les mâles H (vs Ctrl) présentent une augmentation significative de l’expression de Prx3 (H 0.72±0.03 vs. Ctrl 0.56±0.04 unité relative, +31%; p<0.05) et les femelles présentent une augmentation significative de l’expression d’UCP2 (H 1.22±0.05 vs. Ctrl 1.03±0.04 unité relative, +18%; p<0.05) et de l’expression de MnSOD (H 1.36±0.01 vs. 1.19±0.06 unité relative, +14%; p<0.05). Conclusions: Une exposition néonatale à l’O2 chez le rat adulte mène à des indices de dysfonction mitochondriale dans les reins adultes, associée à une augmentation dans la production d’espèces réactives de l’oxygène, suggérant que ces modifications mitochondriales pourraient jouer un rôle dans l’hypertension artérielle et d’un stress oxydant, et par conséquent, être un facteur possible dans la progression vers des maladies cardiovasculaires. Mots-clés: Mitochondries, Reins, Hypertension, Oxygène, Stress Oxydant, Programmation

Statistical model based 3D shape prediction of postoperative trunks for non-invasive scoliosis surgery planning

One of the major concerns of scoliosis patients undergoing surgical treatment is the aesthetic aspect of the surgery outcome. It would be useful to predict the postoperative appearance of the patient trunk in the course of a surgery planning process in order to take into account the expectations of the patient. In this paper, we propose to use least squares support vector regression for the prediction of the postoperative trunk 3D shape after spine surgery for adolescent idiopathic scoliosis. Five dimensionality reduction techniques used in conjunction with the support vector machine are compared. The methods are evaluated in terms of their accuracy, based on the leave-one-out cross-validation performed on a database of 141 cases. The results indicate that the 3D shape predictions using a dimensionality reduction obtained by simultaneous decomposition of the predictors and response variables have the best accuracy.

Extension schemes for the Alignment Model of English-Malayalam Statistical Machine Translator

In Statistical Machine Translation from English to Malayalam, an unseen English sentence is translated into its equivalent Malayalam sentence using statistical models. A parallel corpus of English-Malayalam is used in the training phase. Word to word alignments has to be set among the sentence pairs of the source and target language before subjecting them for training. This paper deals with certain techniques which can be adopted for improving the alignment model of SMT. Methods to incorporate the parts of speech information into the bilingual corpus has resulted in eliminating many of the insignificant alignments. Also identifying the name entities and cognates present in the sentence pairs has proved to be advantageous while setting up the alignments. Presence of Malayalam words with predictable translations has also contributed in reducing the insignificant alignments. Moreover, reduction of the unwanted alignments has brought in better training results. Experiments conducted on a sample corpus have generated reasonably good Malayalam translations and the results are verified with F measure, BLEU and WER evaluation metrics.

Model Calculations and Implementation of Filters and Hybrid Green VCSELs based on Optical Thin Film Stacks

This work introduced the novel conception of complex coupled hybrid VCSELs for the first time. Alternating organic and inorganic layers in the lasers provide periodic variation of refractive index and optical gain, which enable single mode operation and low threshold of the VCSELs. Model calculations revealed great reduction of the lasing threshold with factors over 30, in comparison with the existing micro-cavity lasers. Tunable green VCSEL has been also designed, implemented and analyzed taking advantage of the broad photoluminescence spectra of the organics. Free standing optical thin films without compressive stress are technologically implemented. Multiple membrane stacks with air gap in between have been fabricated for the implementation of complex coupled VCSEL structures. Complex coupled hybrid VCSEL is a very promising approach to fill the gaps in the green spectral range of the semiconductor lasers.

Understanding Subsystems in Biology through Dimensionality Reduction, Graph Partitioning and Analytical Modeling

Biological systems exhibit rich and complex behavior through the orchestrated interplay of a large array of components. It is hypothesized that separable subsystems with some degree of functional autonomy exist; deciphering their independent behavior and functionality would greatly facilitate understanding the system as a whole. Discovering and analyzing such subsystems are hence pivotal problems in the quest to gain a quantitative understanding of complex biological systems. In this work, using approaches from machine learning, physics and graph theory, methods for the identification and analysis of such subsystems were developed. A novel methodology, based on a recent machine learning algorithm known as non-negative matrix factorization (NMF), was developed to discover such subsystems in a set of large-scale gene expression data. This set of subsystems was then used to predict functional relationships between genes, and this approach was shown to score significantly higher than conventional methods when benchmarking them against existing databases. Moreover, a mathematical treatment was developed to treat simple network subsystems based only on their topology (independent of particular parameter values). Application to a problem of experimental interest demonstrated the need for extentions to the conventional model to fully explain the experimental data. Finally, the notion of a subsystem was evaluated from a topological perspective. A number of different protein networks were examined to analyze their topological properties with respect to separability, seeking to find separable subsystems. These networks were shown to exhibit separability in a nonintuitive fashion, while the separable subsystems were of strong biological significance. It was demonstrated that the separability property found was not due to incomplete or biased data, but is likely to reflect biological structure.

Crop yield reduction in the tropics under climate change: Processes and uncertainties

Many modelling studies examine the impacts of climate change on crop yield, but few explore either the underlying bio-physical processes, or the uncertainty inherent in the parameterisation of crop growth and development. We used a perturbed-parameter crop modelling method together with a regional climate model (PRECIS) driven by the 2071-2100 SRES A2 emissions scenario in order to examine processes and uncertainties in yield simulation. Crop simulations used the groundnut (i.e. peanut; Arachis hypogaea L.) version of the General Large-Area Model for annual crops (GLAM). Two sets of GLAM simulations were carried out: control simulations and fixed-duration simulations, where the impact of mean temperature on crop development rate was removed. Model results were compared to sensitivity tests using two other crop models of differing levels of complexity: CROPGRO, and the groundnut model of Hammer et al. [Hammer, G.L., Sinclair, T.R., Boote, K.J., Wright, G.C., Meinke, H., and Bell, M.J., 1995, A peanut simulation model: I. Model development and testing. Agron. J. 87, 1085-1093]. GLAM simulations were particularly sensitive to two processes. First, elevated vapour pressure deficit (VPD) consistently reduced yield. The same result was seen in some simulations using both other crop models. Second, GLAM crop duration was longer, and yield greater, when the optimal temperature for the rate of development was exceeded. Yield increases were also seen in one other crop model. Overall, the models differed in their response to super-optimal temperatures, and that difference increased with mean temperature; percentage changes in yield between current and future climates were as diverse as -50% and over +30% for the same input data. The first process has been observed in many crop experiments, whilst the second has not. Thus, we conclude that there is a need for: (i) more process-based modelling studies of the impact of VPD on assimilation, and (ii) more experimental studies at super-optimal temperatures. Using the GLAM results, central values and uncertainty ranges were projected for mean 2071-2100 crop yields in India. In the fixed-duration simulations, ensemble mean yields mostly rose by 10-30%. The full ensemble range was greater than this mean change (20-60% over most of India). In the control simulations, yield stimulation by elevated CO2 was more than offset by other processes-principally accelerated crop development rates at elevated, but sub-optimal, mean temperatures. Hence, the quantification of uncertainty can facilitate relatively robust indications of the likely sign of crop yield changes in future climates. (C) 2007 Elsevier B.V. All rights reserved.

Examining the interaction of growing crops with local climate using a coupled crop-climate model

This paper examines to what extent crops and their environment should be viewed as a coupled system. Crop impact assessments currently use climate model output offline to drive process-based crop models. However, in regions where local climate is sensitive to land surface conditions more consistent assessments may be produced with the crop model embedded within the land surface scheme of the climate model. Using a recently developed coupled crop–climate model, the sensitivity of local climate, in particular climate variability, to climatically forced variations in crop growth throughout the tropics is examined by comparing climates simulated with dynamic and prescribed seasonal growth of croplands. Interannual variations in land surface properties associated with variations in crop growth and development were found to have significant impacts on near-surface fluxes and climate; for example, growing season temperature variability was increased by up to 40% by the inclusion of dynamic crops. The impact was greatest in dry years where the response of crop growth to soil moisture deficits enhanced the associated warming via a reduction in evaporation. Parts of the Sahel, India, Brazil, and southern Africa were identified where local climate variability is sensitive to variations in crop growth, and where crop yield is sensitive to variations in surface temperature. Therefore, offline seasonal forecasting methodologies in these regions may underestimate crop yield variability. The inclusion of dynamic crops also altered the mean climate of the humid tropics, highlighting the importance of including dynamical vegetation within climate models.

The Wheal Jane wetlands model for bioremediation of acid mine drainage

Acid mine drainage (AMD) is a widespread environmental problem associated with both working and abandoned mining operations. As part of an overall strategy to determine a long-term treatment option for AMD, a pilot passive treatment plant was constructed in 1994 at Wheal Jane Mine in Cornwall, UK. The plant consists of three separate systems, each containing aerobic reed beds, anaerobic cell and rock filters, and represents the largest European experimental facility of its kind. The systems only differ by the type of pretreatment utilised to increase the pH of the influent minewater (pH <4): lime dosed (LD), anoxic limestone drain (ALD) and lime free (LF), which receives no form of pretreatment. Historical data (1994-1997) indicate median Fe reduction between 55% and 92%, sulphate removal in the range of 3-38% and removal of target metals (cadmium, copper and zinc) below detection limits, depending on pretreatment and flow rates through the system. A new model to simulate the processes and dynamics of the wetlands systems is described, as well as the application of the model to experimental data collected at the pilot plant. The model is process based, and utilises reaction kinetic approaches based on experimental microbial techniques rather than an equilibrium approach to metal precipitation. The model is dynamic and utilises numerical integration routines to solve a set of differential equations that describe the behaviour of 20 variables over the 17 pilot plant cells on a daily basis. The model outputs at each cell boundary are evaluated and compared with the measured data, and the model is demonstrated to provide a good representation of the complex behaviour of the wetland system for a wide range of variables. (C) 2004 Elsevier B.V/ All rights reserved.

Impacts of forestry on nitrogen in upland and lowland catchments: a comparison of the River Severn at Plynlimon in mid-Wales and the Bedford Ouse in south-east England using the INCA Model

The impacts of afforestation at Plynlimon in the Severn catchment, mid-Wales. and in the Bedford Ouse catchment in south-east England are evaluated using the INCA model to simulate Nitrogen (N) fluxes and concentrations. The INCA model represents the key hydrological and N processes operating in catchments and simulates the daily dynamic behaviour as well as the annual fluxes. INCA has been applied to five years of data front the Hafren and Hore headwater sub-catchments (6.8 km(2) area in total) of the River Severn at Plytilimon and the model was calibrated and validated against field data. Simulation of afforestation is achieved by altering the uptake rate parameters in the model. INCA simulates the daily N behaviour in the catchments with good accuracy as well as reconstructing the annual budgets for N release following clearfelling a four-fold increase in N fluxes was followed by a slow recovery after re-afforestation. For comparison, INCA has been applied to the large (8380 km(2)) Bedford Ouse catchment to investigate the impact of replacing 20% arable land with forestry. The reduction in fertiliser inputs from arable farming and the N uptake by the forest are predicted to reduce the N flux reaching the main river system, leading to a 33% reduction in N-Nitrate concentrations in the river water.