Search

Acute myocardial infarction (MI) is one of the leading causes of mortality worldwide. MI is the heart muscle irreversible death secondary to prolonged ischemia. Over the last few decades, medical progress in how and when to restore blood flow to the ischemic area have markedly improved patient survival. Although early heart reperfusion is acknowledged to be the most effective way to limit infarct size, post-ischemic reperfusion is associated with detrimental effects, such as myocardial stunning, ventricular arrhythmias, microvascular dysfunction, and cell death. The molecular mechanisms of these reperfusion injuries remain to be elucidated and their management is very challenging. Among the various therapeutic molecular approaches proposed by experimental studies, nitric oxide (NO) role in protecting heart against MI and reperfusion injuries has been widely assessed and discussed (1–4). NO is a gasotransmitter that is abundantly produced in the cardiovascular system mainly by the NO synthase (NOS) enzymes system. Two isoforms, endothelial NOS (eNOS) and neuronal NOS (nNOS), are constitutively expressed in both myocardium and vessels, whereas inducible NOS (iNOS) is detected only in pathological conditions, such as inflammatory and/or oxidative stress. Both eNOS and nNOS are low-NO output Ca2+-dependent enzymes, while iNOS is a high-NO output Ca2+-independent enzyme. In physiological conditions, NOS form homodimers (“coupled” NOS) that catalyze NO production from l-arginine and O2 through electron transfer from NADPH on the reductase domain of one monomer to the oxidase domain of the second monomer. In pathological conditions, such as in the absence of the essential cofactor tetrahydrobiopterin (BH4), eNOS can be “uncoupled” to produce O2− instead of NO. In stress conditions, NO protects tissues through two distinct pathways. In the first one, NO activates the soluble guanylate cyclase (sGC) that initiates cyclic guanosine monophosphate (cGMP) production, leading to the activation of protein kinase G (PKG). As sGC is the major cell receptor for NO and the NO/sGC/cGMP/PKG pathway plays a critical role in both myocardium excitation–contraction coupling and cardiovascular function regulation (5–8), NO cardioprotective role was first attributed to PKG activation (9–11). However, a second pathway in which proteins are directly modified by NO addition to sulfhydryl residues, a process known as S-nitrosylation (SNO), has recently emerged in the scientific literature. Although PKG activation pathway has been largely involved in NO-mediated cardioprotection (11–13), SNO is now taking the front stage and is considered to be a key player in cardioprotection through (i) the transient modification of protein activity and/or (ii) their protection from irreversible oxidation (14–17). Indeed, Sun et al. (18) showed that reduced heart vulnerability to ischemia–reperfusion (IR) following acute ischemic preconditioning is mainly related to SNO signaling and not to PKG activation through the NO–SGC–cGMP pathway. Accordingly, we found that in exercise training-induced cardioprotection against IR injuries, protein SNO level, but not cGMP level, increased during early reperfusion (19). The same year, Methner et al. (20), using a Cre/loxP approach to selectively ablate type I PKG in cardiomyocytes, demonstrated that ischemic post-conditioning reduced infarct size in these mice like in wild type controls. Moreover, they showed that the cardioprotective effect against IR injury of mitochondria-targeted S-nitrosothiol (MitoSNO), which allows NO and S-nitrosothiol accumulation in mitochondria, was comparable in mice that specifically lack PKG in cardiomyocytes and in controls. This indicates that MitoSNO cardioprotective effect is independent of PKG. The current literature strongly supports NO implication in cardioprotection. However, the mechanism is still debated and whether increased NO availability during IR is cytoprotective remains to be demonstrated. Here, we discuss how NO might contribute to protect heart and particularly the importance of NO (i) localization, (ii) concentration, and (iii) time of availability during IR.

We propose an alternative parameterization of Logistic Regression (LR) for the categorical data, multi-class setting. LR optimizes the conditional log-likelihood over the training data and is based on an iterative optimization procedure to tune this objective function. The optimization procedure employed may be sensitive to scale and hence an effective pre-conditioning method is recommended. Many problems in machine learning involve arbitrary scales or categorical data (where simple standardization of features is not applicable). The problem can be alleviated by using optimization routines that are invariant to scale such as (second-order) Newton methods. However, computing and inverting the Hessian is a costly procedure and not feasible for big data. Thus one must often rely on first-order methods such as gradient descent (GD), stochastic gradient descent (SGD) or approximate second-order such as quasi-Newton (QN) routines, which are not invariant to scale. This paper proposes a simple yet effective pre-conditioner for speeding-up LR based on naive Bayes conditional probability estimates. The idea is to scale each attribute by the log of the conditional probability of that attribute given the class. This formulation substantially speeds-up LR's convergence. It also provides a weighted naive Bayes formulation which yields an effective framework for hybrid generative-discriminative classification. © 2014 IEEE., This research has been supported by the Australian Research Council (ARC) under grant DP140100087 and Asian Office of Aerospace Research and Development, Air Force Office of Scientific Research under contract FA23861214030.

The reduction or cessation of the blood supply to an organ results in tissue ischemia. Ischemia can cause significant tissue damage, and is observed as a result of a thrombosis, as part of a disease process, and during surgery. However, the restoration of the blood supply often causes more damage to the tissue than the ischemic episode itself. Research is therefore focused on identifying the cellular pathways involved in the protection of organs from the damage incurred by this process of ischemia reperfusion (I/R). The hypoxia-inducible factors (HIFs) are a family of heterodimeric transcription factors that are stabilized during ischemia. The genes that are expressed downstream of HIF activity enhance oxygen-independent ATP generation, cell survival, and angiogenesis, amongst other phenotypes. They are, therefore, important factors in the protection of tissues from I/R injury. Interestingly, a number of the mechanisms already known to induce organ protection against I/R injury, including preconditioning, postconditioning, and activation of signaling pathways such as adenosine receptor signaling, converge on the HIF system. This review describes the evidence for HIFs playing a role in I/R protection mediated by these factors, highlights areas that require further study, and discuss whether HIFs themselves are good therapeutic targets for protecting tissues from I/R injury.

Small-conductance Ca(2+)-activated K(+) channel activation is an emerging therapeutic approach for treatment of neurological diseases, including stroke, amyotrophic lateral sclerosis and schizophrenia. Our previous studies showed that activation of SK channels exerted neuroprotective effects through inhibition of NMDAR-mediated excitotoxicity. In this study, we tested the therapeutic potential of SK channel activation of NS309 (25 μM) in cultured human postmitotic dopaminergic neurons in vitro conditionally immortalized and differentiated from human fetal mesencephalic cells. Quantitative RT-PCR and western blotting analysis showed that differentiated dopaminergic neurons expressed low levels of SK2 channels and high levels of SK1 and SK3 channels. Further, protein analysis of subcellular fractions revealed expression of SK2 channel subtype in mitochondrial-enriched fraction. Mitochondrial complex I inhibitor rotenone (0.5 μM) disrupted the dendritic network of human dopaminergic neurons and induced neuronal death. SK channel activation reduced mitochondrial membrane potential, while it preserved the dendritic network, cell viability and ATP levels after rotenone challenge. Mitochondrial dysfunction and delayed dopaminergic cell death were prevented by increasing and/or stabilizing SK channel activity. Overall, our findings show that activation of SK channels provides protective effects in human dopaminergic neurons, likely via activation of both membrane and mitochondrial SK channels. Thus, SK channels are promising therapeutic targets for neurodegenerative disorders such as Parkinson's disease, where dopaminergic cell loss is associated with progression of the disease.

Sobolev descent has long been established as an efficient method for numerically solving boundary value problems, ordinary differential equations and partial differential equations in a small number of iterations. We demonstrate that for any linear ordinary differential equation with initial value conditions sufficient to assure a unique solution, there exists a Hilbert space in which gradient descent will converge to the solution in one iteration. We provide two elementary examples, one initial value problem and one boundary value problem, demonstrating the effectiveness of the theory in numerical settings. As there are ample efficient numerical methods for solving such problems, the significance of the paper is in the approach and the question it raises. Namely, do such spaces exist for wider classes of differential equations?

Despite current treatment options, cardiac failure is associated with significant morbidity and mortality highlighting a compelling clinical need for novel therapeutic approaches. Based on promising pre-clinical data, stem cell therapy has been suggested as a possible therapeutic strategy. Of the candidate cell types evaluated, mesenchymal stromal/stem cells (MSCs) have been widely evaluated due to their ease of isolation and ex vivo expansion, potential allogeneic utility and capacity to promote neo-angiogenesis and endogenous cardiac repair. However, the clinical application of MSCs for mainstream cardiovascular use is currently hindered by several important limitations, including suboptimal retention and engraftment and restricted capacity for bona fide cardiomyocyte regeneration. Consequently, this has prompted intense efforts to advance the therapeutic properties of MSCs for cardiovascular disease. In this review, we consider the scope of benefit from traditional plastic adherence-isolated MSCs and the lessons learned from their conventional use in preclinical and clinical studies. Focus is then given to the evolving strategies aimed at optimizing MSC therapy, including discussion of cell-targeted techniques that encompass the preparation, pre-conditioning and manipulation of these cells ex vivo, methods to improve their delivery to the heart and innovative substrate-directed strategies to support their interaction with the host myocardium. Refereed/Peer-reviewed

Mesenchymal stem cells (MSCs) are an attractive candidate for autologous cell therapy, but their ability to repair damaged myocardium is severely compromised with advanced age. Development of viable autologous cell therapy for treatment of heart failure in the elderly requires the need to address MSC ageing. In this study, MSCs from young (2 months) and aged (24 months) C57BL/6 mice were characterized for gene expression of IGF-1, FGF-2, VEGF, SIRT-1, AKT, p16(INK4a) , p21 and p53 along with measurements of population doubling (PD), superoxide dismutase (SOD) activity and apoptosis. Aged MSCs displayed senescent features compared with cells isolated from young animals and therefore were pre-conditioned with glucose depletion to enhance age affected function. Pre-conditioning of aged MSCs led to an increase in expression of IGF-1, AKT and SIRT-1 concomitant with enhanced viability, proliferation and delayed senescence. To determine the myocardial repair capability of pre-conditioned aged MSCs, myocardial infarction (MI) was induced in 24 months old C57BL/6 wild type mice and GFP expressing untreated and pre-conditioned aged MSCs were transplanted. Hearts transplanted with pre-conditioned aged MSCs showed increased expression of paracrine factors, such as IGF-1, FGF-2, VEGF and SDF-1α. This was associated with significantly improved cardiac performance as measured by dp/dt(max), dp/dt(min), LVEDP and LVDP, declined left ventricle (LV) fibrosis and apoptosis as measured by Masson's Trichrome and TUNEL assays, respectively, after 30 days of transplantation. In conclusion, pre-conditioning of aged MSCs with glucose depletion can enhance proliferation, delay senescence and restore the ability of aged cells to repair senescent infarcted myocardium.

Bu çalışmanın amacı resveratrol'ün miyokardiyal iskemi-reperfüzyonda oluşturduğu koruyucu etkide mitoKATP kanallarının etkisini incelemek. Bunun için 250-300g ağırlığında wistar ratlar ketamin hidroklorür ve ksilazin ile anesteziye edildikten sonra toraks hızla açılarak kalp buzlu Krebs-Heinseleit çözeltisi içerisine alınarak hızlıca Langendorff sistemine asılmıştır. SVGB kalbin sol ventrikülüne yerleştirilmiş lateks balon yardımıyla ölçülmüştür. Deneylerde infarkt alan ve MP35 kayıt sistemiyle hemodinamik parametreler (SVDSB, SVGB, ±dP/dt) ölçülmüştür. Deney hayvanları 3 gruba ayrılmıştır. 1. Grupta (kontrol) grubunda 30 dk'lık dengelenme. 2. grupta resveratrol 20 dk'lık dengelenme ardından 10 dk. resveratrol (10µM) infüzyonu yapılmıştır. 5-HD ve resveratrol'ün kombine kullanıldığı 3. grupta 10. dk'lık dengelenmeden sonra 10 dk. 5-HD (10-1-10-4) ardından 10 dk. resveratrol (10µM) uygulanmıştır. Bütün deney gruplarında 30 dk. iskemi ve 120 dk. reperfüzyon yapılmıştır. Deney sonunda kalpler TTC ile boyanarak infarkt alan tayini yapılmıştır. Resveratrolün infarkt alanda yaptığı azalma 5-HD'nin 10-1ve 10-2 µM konsantrasyonda anlamlı olarak ortadan kalkmıştır. Ayrıca 5-HD'nin 10-1 ve 10-2 µM konsantrasyonda resveratrol'ün SVGB, SVSDB ve ±dP/dt değerlerinde iskemi-reperfüzyon hasarına karşı yaptığı korumayı reperfüzyon süresinde anlamlı olarak ortadan kaldırılmıştır. Bu sonuçlar resveratrolün mitoKATP kanallarını aktive ederek iskemi-reperfüzyon hasarına karşı kalbi koruyabileceğini göstermektedir. The aim of the present study was to investigate the role of mKATP channel at the protective effect of resveratrol in the myocardial ischemia-reperfusion injury. Wistar rats were anesthesia with ketamine+ksilazin and hearts were put into solution after thorax was immediately opened. Finally, the hearts were mounted on the Langendorff system quickly. Left ventricular pressure was measured with a water-filled balloon. In all experiments, the infarct size and hemodynamic parameters (LVDP, LVEDP, ±dP/dt) were measured and evaluated by MP35 recording system. In the first group (control) after isolation of the hearts 10 min stabilization period followed by 20 min normal perfusion was applied. In the 5- hydoxydecanoate (10-1-10-4 µM) and resveratrol (10 µM) group, after 10 min stabilization period, heart was perfused 5-hydroxydecanoate and resveratrol separately 10 min. In the resveratrol group or 5-hydroxydecanoate group, 10 min stabilization, 10 min perfused and 10 min resveratrol or 5-HD perfused. All hearts were subjected to 30 min global ischemia followed by 120 min of reperfusion. The hearts were dyed with TTC for infarct size measurement When resveratrol was applied infarct size significantly decreased against control and 5-HD. 5-HD was significantly decreased this protective effect with dose-dependent. In resveratrol group LVSP, LVEDP and ±dP/dt value during the reperfusion were not change when compared before ischemia values. 5-HD markedly reduced LVSP, LVEDP and ±dP/dt value at during the reperfusion when compared resveratrol. These results show that mKATP channel has potential role in resveratrol protective effect. 69

A newly fabricated polymer electrolyte membrane (PEM) fuel cell usually needs a so-called break-in/conditioning/incubation period to activate it and reach its best performance. Typically, during this activation period the cell performance increases gradually, and then reaches a plateau without further increase. Depending on the membrane electrode assemblies, this process can take hours and even days to complete, which consumes a considerable amount of hydrogen fuel, leading to a higher operating cost. To provide for accelerated conditioning techniques that can complete the process in a short time period, this paper reviews established conditioning protocols and reported methods to condition PEM single cells and stacks, in an attempt to summarize available information on PEM fuel cell conditioning and the underlying mechanisms. Various techniques are arranged into two categories: on-line conditioning and off-line conditioning. For each technique, the experimental procedure and outcomes are outlined. Finally, weaknesses of the currently used conditioning techniques are indicated and further research efforts are proposed.

O objetivo nesse trabalho avaliar o desempenho fisiológico de sementes de cebola após hidrocondicionamento e tratamento com fungicida e recobrimento com polímero. Foram utilizadas sementes de cebola, cv. Bola Precoce, fornecidas pela Hortec, submetidas ao hidrocondicionamento fisiológico em amostras de 5,0 g de sementes embebidas em água destilada entre duas folhas de papel Germitest, com 2,5 vezes o peso seco do papel, durante 24 horas a 25 ºC. Após o hidrocondicionamento efetuou-se a secagem das sementes em estufa com circulação de ar forçado à ±35 ºC por 20 horas, até atingirem a umidade inicial de 7%. Logo após as sementes foram tratadas com o fungicida Captan® na dose de 2 g.kg-1 e recobertas com o polímero Colorseed-Rigran® na dose de 50 mL.kg-1. Os tratamentos foram: 1-testemunha; 2-sementes + fungicida; 3-sementes + polímero; 4-sementes + fungicida + polímero; 5-semente hidrocondicionada; 6-semente hidrocondicionada + fungicida; 7- semente hidrocondicionada + polímero; 8-semente hidrocondicionada + fungicida + polímero. O delineamento experimental foi inteiramente casualizado, com 4 repetições e as médias foram comparadas pelo teste de Scott-Knott no nível de 5% de significância. Pelos resultados verificou-se que o hidrocondicionamento das sementes de cebola favorece a velocidade de emergência e a porcentagem de plântulas emergidas. Sementes hidrocondicionadas originam plântulas maiores e com maior acúmulo de biomassa. O uso de polímero afeta negativamente o vigor das sementes de cebola. The objective of this study was to evaluate the physiological performance of onion seeds after pre-conditioning with water (hydroconditioning), and treatment with fungicide and polymer. Onion seeds cv. Bola Precoce, provided by Hortec, were used and hydroconditioned with distilled water for 5.0 g seed samples between two sheets of Germitest germination paper with 2.5 times the dry weight of the paper, for 24 hours at 25 °C. After hydroconditioning, seeds were dried in an air-forced oven at ±35 °C for 20 hours until they reached 7% moisture content. They were then treated with Captan® fungicide at a dose of 2 g.kg-1 and coated with the polymer Colorseed Rigran® at a dose of 50 mL.kg-1. The treatments were: 1-control; 2-seed + fungicide; 3 seed + polymer; 4-seed + fungicide + polymer; 5-hydroconditioned seed; 6- hydroconditioned seed + fungicide; 7-hydroconditioned seed + polymer; 8- hydroconditioned seed + fungicide+ polymer. The experimental design was completely randomized with 4 replications and averages were compared by the Scott-Knott test at the 5% significance level. Results showed that hydroconditioned onion seeds promote speed of emergence and the percentage of seedlings emerged. Hydroconditioned seeds produced larger seedlings and more biomass. Polymer use adversely affects onion seed vigor.

[EN] A study on the sources of variability in the measurement of particle size distribution using a two-stage dilution system and an engine exhaust particle sizer was conducted to obtain a comprehensive and repeatable methodology that can be used to measure the particle size distribution of aerosols emitted by a light-duty diesel engine under transient operating conditions. The paper includes three experimental phases: an experimental validation of the measurement method; an evaluation of the influence of sampling factors, such as dilution system pre-conditioning; and a study of the effects of the dilution conditions, such as the dilution ratio and the dilution air temperature. An examination of the type and degree of influence of each studied factor is presented, recommendations for reducing variability are given and critical parameter values are identified to develop a highly reliable measurement methodology that could be applied to further studies on the effect of engine operating parameters on exhaust particle size distributions. © 2011 IOP Publishing Ltd., The translation of this paper was funded by the Universidad Politecnica de Valencia, Spain.

Çalışmada; ekmeklik buğdayda (Triticum aestivum L.) ekim öncesi tohum uygulamaları ile farklı azot dozlarının verim ve verime etki eden bazı büyüme özellikleri üzerine etkileri araştırılmıştır. Tarla denemeleri Süleyman Demirel Üniversitesi Tarımsal Araştırma ve Uygulama Merkez Müdürlüğü arazisinde, 2007-08 ve 2008-09 vejetasyon dönemlerinde yürütülmüştür. Araştırma'da Dağdaş-94, Bağcı-2002 ve Karahan-99 ekmeklik buğday çeşitleri kullanılmıştır.Çalışma, Tesadüf Bloklarında Bölünen Bölünmüş Parseller Deneme Desenine göre, 3 tekrarlamalı olarak yürütülmüştür. Araştırmada 4 farklı azot dozlarının (0, 5, 10 ve 15 kg N/da) ve 4 farklı tohum uygulamasının (kontrol, saf su, 100 ve 200 ppm GA3) etkileri incelenmiştir. Tohumlar, ekimden önce 3 saat süreyle ıslatıldıktan sonra oda sıcaklığında kurutularak ekilmiştir. Azot dozlarının yarısı ekimle birlikte, diğer yarısı sapa kalkma döneminde uygulanmıştır.Tohum uygulamalarının kış öncesi büyüme özellikleri üzerine, azot dozlarının hasat döneminde ölçülen parametreler üzerine etkisi belirgin olmuştur. 200 ppm GA3 uygulamaları %50 çıkış süresini kısaltmış, fide uzunluğunu ise %33 oranında artırmıştır. Ancak fide boyunun uzaması fide saplarında sararma, beyazlama ve yatmaya neden olduğu gözlenmiştir. İncelenen özellikler genel olarak değerlendirildiğinde 10 ve 15 kg N/da azot dozlarının olumlu etkileri benzer olmuştur. Gübre maliyetleri de dikkate alınırsa 10 kg N/da dozunun uygun olduğu söylenebilir. Her iki yılın ortalaması dikkate alındığında, en yüksek tane verimi Bağcı-2002 çeşidinde, 15 kg azot dozu ve saf su uygulamasında (415.0 kg/da) elde edilmiştir. En yüksek tane protein oranı ise Karahan-99 çeşidinde, 15 kg azot dozu ve kontrol uygulamasında (%16.5) elde edilmiştir. Ayrıca çalışma sonucunda, çiftçi koşullarında üretim maliyetini artırmayan ön ıslatma uygulamasının önerilebilir olduğu sonucuna varılmıştır. This study was conducted to investigate the effects of seed pre-treatments with gibberellic acid and nitrogen doses on yields of bread wheat cultivars (Triticum aestivum L.) and the effects on some vegetative growth characteristics affecting the yields. The field experiments were conducted at Süleyman Demirel University, Agricultural Research and Experiment Station throughout the growing season of 2007-08 and 2008-09. The winter wheat cultivars, Dagdas-94, Bagci-2002, and Karahan-99 were used in these experiments.The experiment was conducted as split-split plot randomized block design with three replications. The experiment were planned to investigate the effects of 4 different nitrogen dosages (0, 5, 10 and 15 kg/da) and 4 different seed treatments (control, pure water, 100 and 200 ppm GA3). The seeds which had been soaked up for 3 hours before sowing had been air dried at room temperature and then planted. The half of nitrogen dosages was applied with planting and the other half was applied to plots during the bolting.Both the effect of seed pre-treatments on seedling growth traits and the effect of nitrogen doses on maturity periods of wheat were found to be significant. Gibberellic acid treatment (200 ppm) reduced the mean time for 50% germination and increased the length of seedling nearly 33%. Due to increase in the length of seedling, its stems turned out to be yellow and white and lodged. When the characteristics investigated are evaluated generally, the positive effects of the dosages of 10 and 15 kg N/da were the similar. Considering the cost of fertilizers, it can be said that the dosage of 10 kg N/da was appropriate. Considering the average of two years, the highest grain yield (415.0 kg/da) was obtained from Bağcı-2002 cultivar, 15 kg of nitrogen dose, and in pure water treatment plot. The highest grain protein content (%16.5) was obtained from the Karahan-99 cultivar, 15 kg of nitrogen dose, and in control plot. In addition, it was concluded that the pure water treatment that do not increase the cost of production can be considered as recommendable. 160

Üç boyutlu elektromanyetik saçılım ve ışınım problemlerinin çalışılmasında yoğun doğrusal sistemlere yol açan ayrıklaştırılmış yüzey integral denklemlerini çözmek yaygın bir yöntemdir. Çözümün karmaşıklığının azalmasından dolayı, bu doğrusal denklemlerin Krylov altuzayı ve çok seviyeli hızlı çokkutup (ÇSHÇY) yöntemleri kullanılarak iteratif çözümü son derece çekici hale gelmiştir. Fakat bu yaklaşım sadece yakınsama için gereken iterasyon sayısı aşırı derecede yüksek olmadığı sürece işe yaramaktadır. Maalesef, pek çok pratik durumda bu geçerli olmamaktadır. Özellikle, açık yüzey ve karmaşık gerçek hayat problemleri kötü koşullu doğrusal sistemlere yol açmaktadır. Bu tarz problemlerin iteratif çözümleri, kabaca sistem matrislerine yaklaşan tersi alınabilir matrisler olarak tanımlanan öniyileştiriciler olmadan mümkün olmamaktadır.Bu doktora tezinde, büyük ölçekli yüzey integral denklemi problemleri için geliştirdiğimiz etkin öniyileştiricileri sunmaktayız. İlk olarak, en yaygın ve oturmuş bir öniyileştirme yöntemi olan eksik LU (ELU) öniyileştirmesini ele aldık. Bu öniyileştiricilerin nasıl bir kara kutu formunda ve güvenli olarak kullanılabileceklerini gösterdik. Önemli avantajlarına rağmen, ELU öniyileştiricileri temel olarak sıralı bir yapıda oldukları için, paralel çözümlerde kullanılmak üzere bir seyrek yaklaşık ters (SYT) öniyileştiricisi geliştirdik. Paralel ölçeklenebilirlik için önemli olan özgün bir yük dengeleme yöntemi geliştirdik. Daha sonra SYT öniyileştiricilerini, yoğun sistemi bir iç-dış çözümü şeklinde öniyileştiren yakın alan matris sisteminin iteratif çözümünde kullanarak geliştirdik. Mükemmel iletkenler için geliştirdiğimiz son öniyileştirici, benzer bir iç-dış çözümü kullanmakta, ama iç çözümler için ÇSHÇY'nin yaklaşık bir versiyonunu kullanmaktadır. Bu yolla, helikopterler ve metamalzemeler içeren çok sayıda karmaşık gerçek hayat problemini makul iterasyon sayılarında çözmeyi başardık.Son olarak, diyelektrik problemlerinin ayrıklaştırılmasından elde edilen doğrusal sistemlerin öniyileştirilmelerini hedefledik. Mükemmel iletkenlerden farklı olarak, bu sistemler bölünmüş yapıdadırlar.Schur tümleyenine indirgemeyle bu bölünmüş yapıyı öniyileştirme için kullandık. Bu yolla, diyelektrik fotonik kristaller gibi, çözümü zor gerçek hayat problemlerinin makul sürelerde çözümünü mümkün kılan etkin öniyileştiricilerin geliştirilmesi mümkün olmuştur. A popular method to study electromagnetic scattering and radiation of threedimensionalelectromagnetics problems is to solve discretized surface integralequations, which give rise to dense linear systems. Iterative solution of suchlinear systems using Krylov subspace iterative methods and the multilevel fastmultipole algorithm (MLFMA) has been a very attractive approach for largeproblems because of the reduced complexity of the solution. This scheme workswell, however, only if the number of iterations required for convergence of theiterative solver is not too high. Unfortunately, this is not the case for manypractical problems. In particular, discretizations of open-surface problems andcomplex real-life targets yield ill-conditioned linear systems. The iterative solutionsof such problems are not tractable without preconditioners, which can beroughly defined as easily invertible approximations of the system matrices.In this dissertation, we present our efforts to design effective preconditioners forlarge-scale surface-integral-equation problems. We first address incomplete LU(ILU) preconditioning, which is the most commonly used and well-establishedpreconditioning method. We show how to use these preconditioners in a blackboxform and safe manner. Despite their important advantages, ILU preconditionersare inherently sequential. Hence, for parallel solutions, a sparseapproximate-inverse (SAI) preconditioner has been developed. We propose anovel load-balancing scheme for SAI, which is crucial for parallel scalability.Then, we improve the performance of the SAI preconditioner by using it for theiterative solution of the near-field matrix system, which is used to preconditionthe dense linear system in an inner-outer solution scheme. The last preconditionerwe develop for perfectly-electric-conductor (PEC) problems uses the sameinner-outer solution scheme, but employs an approximate version of MLFMA forinner solutions. In this way, we succeed to solve many complex real-life problemsincluding helicopters and metamaterial structures with moderate iteration countsand short solution times. Finally, we consider preconditioning of linear systemsobtained from the discretization of dielectric problems. Unlike the PEC case,those linear systems are in a partitioned structure. We exploit the partitionedstructure for preconditioning by employing Schur complement reduction. In thisway, we develop effective preconditioners, which render the solution of difficultreal-life problems solvable, such as dielectric photonic crystals. 211

Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU). After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM) and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO) and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3%) and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1%) and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 µg/mg protein) and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL) production significantly increased after 15 days of preconditioning compared to G/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed after preconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin. Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina UNIFESP, EPM, Depto. de Medicina SciELO

Heksokinaz (HK), glikoz alımı için temel süreç olan glikoz fosforilasyonundan sorumlu, glikolizin ilk basamağında rol oynayan bir enzimdir.İskemik ön koşullama (IPC), devamlı iskemi/reperfüzyona karşı koruyucu olan kısa sürelerdeki iskemi ve reperfüzyonu içeren bir mekanizmadır. Şimdiye kadar ön koşullama, sağlıklı hayvanlardan elde edilen kalplerde geniş ölçüde çalışılmıştır fakat, hastalıklı (hipertrofik veya miyopatik) kalplerde geçmişte pek fazla çalışılmamıştır. Bu çalışma, diyabetik [Streptozotosin (STZ; 65 mg/kg)] sıçanların kalp dokularında iskemi/reperfüzyonla meydana gelen hasarı önlemede iskemik ön koşullamanın, heksokinaz enzimi ile ilişkisinin belirlenmesi amacıyla yapılmıştır.Çalışmamızda kontrol grubu, diyabet oluşturulan ve ön koşullama uygulanan sıçanlardan elde edilen Langendorff sistemindeki izole kalplere fizyolojik, histolojik, immünohistokimyasal ve biyokimyasal yöntemler uygulanmış, elde edilen veriler istatistiksel olarak değerlendirilmiştir.STZ enjeksiyonundan 4 hafta sonra Langendorff izole kalp sisteminde yaptığımız bu çalışmada, beş dakikalık ve otuz dakikalık reperfüzyon periyodunun sonunda hem normal hem de ön koşullu diyabet gruplarının perfüzyon basınçlarında anlamlı bir azalma, otuz dakikalık reperfüzyon sonunda her iki diyabet grubunda LVDP'de bir artış ve beş dakikalık reperfüzyon sonunda her iki diyabet grubunda kalp vurumlarında azalma gözlenmiştir. Uzun süreli iskemi sonrası uygulanan reperfüzyon, hem kontrol hem de diyabet grubunda doku hasarına yol açmıştır. Kas hücrelerindeki glikojen dağılımının dokunulmamış diyabet grubunda artmış olduğu ve bunun IPC uygulaması ile azaldığı gözlenmiştir. Apoptotik indeks incelendiğinde, uzun süreli iskemi öncesi ile kısa ve uzun süreli reperfüzyon periyotlarında ön koşullu ve ön koşulsuz diyabet gruplarında artış gözlenmiştir. Ön koşullu gruplar karşılaştırıldığında, iskemi uygulamasının apoptozu arttırdığı, beş dakikalık reperfüzyonun bu artışı daha da yükselttiği ve otuz dakikalık reperfüzyon sonucunda beş dakikalık reperfüzyon sonundaki apoptozun azaldığı belirlenmiştir.İskemi uygulaması sonunda ön koşullama yapılan kontrol grubunun laktat dehidrogenaz (LDH) aktivitesinde bir azalma belirlenmiştir. Reperfüzyonun 15. dakikasında ön koşullu diyabet grubunun LDH aktivitesi azalmıştır. Otuz dakikalık reperfüzyon sonunda her iki kontrol grubunda ve ön koşullama uygulanmayan diyabet grubunda artış gözlenmiştir. HK aktivitesi incelendiğinde, iskemi süresince, kontrol kalplerde sitosolik HK aktivitesinde anlamlı bir artış gözlenirken, IPC uygulaması sonrasında bu artış düşmüştür. Kontrollerde mitokondriyal HK aktivitesi bazal durumda ve uzun süreli reperfüzyon periyodunda IPC uygulamasından sonra artmıştır. Diyabetik sıçanlarda ise, kontrol gruplarına göre genel olarak düşük mitokondriyal HK aktivitesi gözlenmiştir. IPC uygulaması, mitokondriyal HK aktivitesini sağlıklı kontrol gruplarındaki kadar yükseltememiştir.Sonuç olarak, bu çalışmada diyabetin iskemi/reperfüzyon hasarına karşı kalbi daha dirençli yaptığı ve uygulanan ön koşullama işleminin ek bir koruma sağlamadığı belirlenmiştir. Hexokinase (HK) is an enzyme that is responsible for the phosphorylation of glucose, which is a fundamental process in glucose metabolism, and that functions in the first step in glycolysis.Ischemic preconditioning (IPC) is a mechanism involving short-term ischemia and reperfusion which protects against long-term ischemia/reperfusion. Preconditioning has been widely studied in the hearts from healthy animals so far, while studies are few with regard to preconditioning in unhealthy hearts (hypertrophic or myopathic). This study was carried out to reveal relation of ischemic preconditioning with hexokinase in preventing ischemia/reperfusion injury in the heart tissue of diabetic rats [Streptozotocin (STZ); 65 mg/kg].In the present study, physiological, histological, immunohistochemical and biochemical techniques were employed for the isolated hearts in Langendorff system from both the control groups rats and the rats rendered diabetic and exposed to preconditioning. Data were statistically evaluated.Four weeks after STZ injection, Langendorff isolated heart system showed a significant decrease in perfusion pressure of both the control group and preconditioned diabetic group after reperfusion period of five and thirty minutes, an increase in LVDP in both diabetic groups after thirty minutes reperfusion, and a decrease in heart rate in both diabetic groups after five minutes reperfusion. Reperfusion after long-term ischemia caused tissue damage both in the control group and diabetic group. Distribution of glycogen in muscle cells was increased when compared with the intact diabetic group, while it was decreased with IPC application. Concerning apoptotic index, it was observed that it increased in short and long-term reperfusion and before long-term ischemia in preconditioned and non-preconditioned diabetic groups. In comparison of preconditioned groups, we found that ischemia resulted in increased apoptosis, being higher with five minutes reperfusion, while apoptosis value of five minutes reperfusion decreased after thirty minutes reperfusion.Preconditioned control group exhibited a decrease in lactate dehydrogenase (LDH) activity after ischemia. LDH activity was decreased in preconditioned diabetic group at 15 minutes of reperfusion, whereas thirty minutes reperfusion resulted in an increase in both control groups and in non-preconditioned diabetic group. As to HK activity, cytosolic HK activity of the control hearts was significantly increased during ischemia, while this elevation was decreased after IPC application. Mitochondrial HK activity was elevated in basal condition and long-term reperfusion after IPC application in the control. Diabetic rats generally showed lower mitochondrial HK activity when compared to the control. However, IPC application could not cause as higher mitochondrial HK activity as in the healthy control groups.In conclusion, the results of the present study demonstrate that diabetes renders heart more resistant against ischemia/reperfusion injury, but preconditioning does not provide an additional protection. 123

A carbonatação, fenômeno físico-químico de reação entre o dióxido de carbono da atmosfera e os produtos da hidratação do cimento, reduz a alcalinidade do concreto, destruindo a película passivadora que envolve o aço, podendo dar condições para a iniciação da corrosão das armaduras. Devido ao tempo requerido para que a reação ocorra em condições naturais, são utilizados ensaios acelerados. No entanto, não há padronização para estes ensaios e existe a dificuldade de se transpor os resultados dessas pesquisas para as condições reais. Este trabalho tem por objetivo estimar a carbonatação natural a partir de ensaios acelerados e de modelos de predição, avaliando possíveis distorções que possam ser causadas pelo processo de aceleração, como pela intervenção dos parâmetros que constituem os modelos, através da comparação com os resultados experimentais. Foram realizados ensaios de carbonatação natural e acelerada, calculados os coeficientes de aceleração a partir dos dados experimentais, e utilizados dois modelos de predição, sendo um complexo e outro simplificado. Para a parte experimental foram empregadas argamassas preparadas com dois tipos de cimento (CP I-S e tipo CP IV) e três relações água/cimento (0,40, 0,55 e 0,70). Para as amostras dos ensaios acelerados de carbonatação foram utilizados dois tempos de cura (7 e 28 dias), dois tipos de precondicionamento (em sala climatizada e conforme recomendações da RILEM) e, dois percentuais de dióxido de carbono (6% e 100% de CO2). Para os ensaios naturais foram adotados três tempos de cura (7, 14 e 28 dias) e três ambientes de exposição ao CO2 atmosférico, sendo um deles um ambiente climatizado (20°C e UR=70%), protegido das intempéries e outros dois externos, não abrigados das chuvas. Os resultados obtidos indicam que o comportamento das amostras precondicionadas em sala climatizada e carbonatadas com 6% de CO2 são as que mais se assemelham às condições naturais de ensaio. O modelo complexo de carbonatação pode substituir os ensaios de carbonatação, mas exige muitos parâmetros de entrada, difíceis de serem medidos e, portanto, difícil de ser utilizado. O modelo simplificado representou bem os resultados acelerados e naturais e foi adaptado para o caso de cimentos pozolânicos. Carbonation, a physicochemical phenomenon with a reaction between atmospheric carbon dioxide and cement hydration products, reduces alkalinity in concrete, and can destroy the passivating film that envelops steel, creating the conditions to begin framework corrosion. Accelerated tests are used due to the time needed for the reaction to occur under natural conditions. However these tests are not standardized and it is difficult to transpose the results of these research studies to real-life conditions. The purpose of this work is to estimate natural carbonation based on accelerated tests and prediction models, verifying whether the tendencies of the natural test are maintained in the accelerated tests and how the parameters that constitute the models intervene in the response, as compared to the experimental results. Natural and accelerated carbonation tests were performed, the acceleration coefficients calculated based on experimental data, and two prediction models were used, one of them complex and the other simplified. For the experimental part, cement mortars prepared with two types of cement (CP I-S and type CP IV) were used, and three water/cement ratios (0.40, 0.55 and 0.70). For the samples of the accelerated carbonation tests, two curing times were used (7 and 28 days), two types of pre-conditioning (in an air conditioned room and according to recommendations from RILEM), and two percentages of carbon dioxide (6% and 100% of CO2). Three curing times (7, 14 and 28 days) were adopted for the natural tests, and three environments of exposure to atmospheric CO2, one of them an air conditioned environment (20°C and UR=70%), protected from the weather, and two other external ones not sheltered from the rain. The results obtained indicate that the behavior of the pre-conditioned samples in an air conditioned room, and carbonated with 6% of CO2 is most similar to the natural testing conditions. The complex carbonation model tested at work can replace the carbonation tests, but requires many input parameters that are difficult to measure, and therefore complicated to use. The simplified carbonation model used provided a good representation of the carbonation results observed in the experimental tests and was adapted to the case of pozzolanic cements.

Synchronized artificial insemination was used to inseminate cows using different types of sire genetics, including low-accuracy, calving-ease, and high-accuracy. These three calf sire groups were compared to calves born to cows bred using natural service. We found substantial production efficiency grains, carcass merit improvement, and economic value to calves born to cows following a synchronized artificial insemination program with high-accuracy semen included. The economic advantage to the high-accuracy calf sire group was computed to be in the neighborhood of $40 to $80/head, relative to the natural service calf sire group.

In recent years, hyperbaric oxygen (HBO) has been used in the treatment of a lot of diseases such as decompression sickness, arterial gas embolism, carbon dioxide poisoning, soft tissue infection, refractory osteomyelitis, and problematic wound, but little is known about its application in liver transplantation. Although several studies have been conducted to investigate the protective effects of HBO on liver transplantation and liver preservation, there are still some controversies on this issue, especially its immunomodulatory effect. In this short review, we briefly summarize the findings supporting the application of HBO during liver transplantation (including donors and recipients).

Made available in DSpace on 2014-08-20T13:44:39Z (GMT). No. of bitstreams: 1 dissertacao_leticia_dos_santos_holbig.pdf: 122179 bytes, checksum: 4242f0c09c55bf484ae980dfebe196bf (MD5) Previous issue date: 2007-03-08 The objective of the study was to evaluate the physiological performance of onion seed after hydroconditioning and coated with polymer and fungicide. Onion seeds cv. Ball early-Hortec ®, Bagé / RS; have been used and subject to hydroconditioning physiological or hydroconditioning samples in 5.0 g of seed pads between two sheets of paper Germitest, with 2.5 times the dry weight of the paper, for 24 hours at 25 ° C. After hydroconditioning made to the drying of the seed in greenhouses with circulation of air forced to ± 35 ° C for 20 hours, until they reach the initial humidity of 7%. Soon after was the coated with polymer-Colorseed Rigran ® in the dose of 50mL.kg-1 and the fungicide Captan ® in the dose of 0.002 g.kg-1. The treatments were to: 1-witness, 2-seed+fungicide, 3 seed+polymer, 4-seed+fungicide +polymer, 5-seed hydroconditioned, 6-seed hidrocondicionada + fungicide, 7-seed hidrocondicionada + polymer, 8 seed+fungicidehidrocondicionada+ polymer. The statistical approach was used 2X4 factorial, with 4 repetitions and averages were compared by Duncan test of the level of significance of 5%. Results showed that the seeds of onion hydroconditioning promoted germination, speed emergency and the percentage of seedlings emerged. Seeds hydroconditioned led seedlings greater and greater accumulation of biomass. Seeds of onion hydroconditioned and covered with polymer-Colorseed Rigran® in the dose of 50mL. Kg-1 and fungicide Captan® at the dose of 0.2%, expressed force that better seeds not conditional. O objetivo do trabalho foi avaliar o desempenho fisiológico de sementes de cebola após hidrocondicionamento e recobrimento com polímero e fungicida. Foram utilizadas sementes de cebola cv. Bola precoce - Hortec®, Bagé/RS; submetidas ao hidrocondicionamento fisiológico ou hidrocondicionamento em amostras de 5,0 g de sementes embebidas entre duas folhas de papel Germitest, com 2,5 vezes o peso seco do papel, durante 24 horas a 25ºC. Após o hidrocondicionamento efetuou-se a secagem das sementes em estufa com circulação de ar forçado à ±35ºC por 20 horas, até atingirem a umidade inicial de 7%. Logo após foi realizado o recobrimento com o polímero Colorseed-Rigran® na dose de 50mL.kg-1 e o fungicida Captan® na dose de 0,002g.kg-1 . Os tratamentos constituíram-se: 1-testemunha, 2-sementes+fungicida, 3- sementes+polímero, 4-sementes+fungicida+polímero, 5- semente hidrocondicionada, 6- semente hidrocondicionada+fungicida, 7- semente hidrocondicionada+polímero, 8- semente hidrocondicionada+fungicida+polímero. O delineamento estatístico utilizado foi fatorial 2X4, com 4 repetições e as médias foram comparadas pelo teste de Duncan ao nível de 5% de significância. Os resultados mostraram que o hidrocondicionamento das sementes de cebola favoreceu a germinação, velocidade de emergência e a porcentagem de plântulas emergidas. Sementes hidrocondicionadas originaram plântulas maiores e com maior acúmulo de biomassa. As sementes de cebola hidrocondicionadas e recobertas com polímero Colorseed-Rigran® na dose de 50mL. kg-1 e fungicida Captan® na dose de 0,2%, expressaram melhor vigor que sementes não condicionadas.

The red alga Mastocarpus stellatus is widely found on the coastline of Brittany (France) and it was previously reported to contain high amounts of floridoside, a well-known glycoside in red algae. Therefore, we aimed at evaluating the potential interest of M. stellatus for industrial purposes. Floridoside extraction was optimized, hydroethanolic mixture being the most efficient extractant compatible with industrial requirements. Floridoside yield was increased significantly through pre-treatment and conditioning of the alga before extraction. Thus, salt stress and drying procedure both resulted in an increase in floridoside concentration. Studies of seasonal variations of floridoside content in this species showed that maximal levels were recovered in autumn. We now propose an optimized procedure for M. stellatus valorization, especially for biomedical applications.

Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) on serine 51 is effected by specific stress-activated protein kinases. eIF2alpha phosphorylation inhibits translation initiation promoting a cytoprotective gene expression program known as the integrated stress response (ISR). Stress-induced activation of GADD34 feeds back negatively on this pathway by promoting eIF2alpha dephosphorylation, however, GADD34 mutant cells retain significant eIF2alpha-directed phosphatase activity. We used a somatic cell genetic approach to identify a gene encoding a novel regulatory subunit of a constitutively active holophosphatase complex that dephosphorylates eIF2alpha. RNAi of this gene, which we named constitutive repressor of eIF2alpha phosphorylation (CReP, or PPP1R15B), repressed the constitutive eIF2alpha-directed phosphatase activity and activated the ISR. CReP RNAi strongly protected mammalian cells against oxidative stress, peroxynitrite stress, and more modestly against accumulation of malfolded proteins in the endoplasmic reticulum. These findings suggest that therapeutic inhibition of eIF2alpha dephosphorylation by targeting the CReP-protein-phosphatase-1 complex may be used to access the salubrious qualities of the ISR.

oz SAYISAL ELEKTROMANYETİK SEYREK MATRİS DENKLEMLERİ İÇİN BİR GRUP YİNELEME VE ÖNKOŞULLAMA ÇÖZÜM ALGORİTMALARINI İÇEREN BİR YAZILIM GELİŞTİRİLMESİ ÜNSOY, Nalan Y.L., Elektrik ve Elektronik Mühendisliği Bölümü Tez Danışmam : Prof. Dr. Mustafa KUZUOĞLU Eylül 2001, 114 Sayfa Sayısal elektromanyetik uygulamalarında, kısmi diferansiyel denklemleri ayrıştırmak için Sonlu Elemanlar ve Sonlu Farklar yöntemleri kullanılır. Bu ayrıştırma sonucunda, Ax = b şeklinde seyrek matris denklemleri elde edilir. Ax = b seyrek matris denklemim çözmek için iki yaklaşım vardır. İlk yaklaşım katsayı matrisi A 'nın çarpanlara ayrılmasına dayalı olan doğrudan yöntemdir. Fakat bu yöntem genellikle fazla sayıda sıfırdan farklı elemanları olan dolu matrislerin oluşmasına yol açar. Diğer yaklaşımda ise yinelemeli yöntemler kullanılır. Bu yöntemlerde gerçek çözüm x 'a yakınsaması umulan bir x(k) dizisi oluşturulur ve bu yöntemde A matrisi sadece matris-vektör çarpımında yer alır. Yineleme yöntemli metodların incelenmesi kaçınılmaz olarak x(k) dizisinin yakınsama hızına odaklanır. Bu tez çalışmasında, Krylov Altuzay Metodları simetrik/simetrik olmayan, reel/kompleks doğrusal sistemlerin yineleme yöntemleri ile çözümleri içinkullanılmıştır. Özellikle eşlenik gradyan yönteminin değişik bir halinin kullanıldığı simetrik kompleks sistemler üzerinde durulmuştur. Önkoşullama teknikleri kullanılarak algoritmaların yakınsama hızı iyileştirilmiştir. Değişik seyrek matris çözüm algoritmalarının performansım değerlendirmek için bir yazılım geliştirilmiştir. Anahtar Sözcükler: Krylov Altuzay Methodlan, Önkoşullama, Seyrek Matris Denklemleri vı ABSTRACT DEVELOPMENT OF A SOFTWARE INVOLVING A GROUP OF ITERATIVE SOLVERS AND PRECONDITIONERS FOR SPARSE MATRIX EQUATIONS OF COMPUTATIONAL ELECTROMAGNETICS ÜNSOY, Nalan M.S., Department of Electrical and Electronics Engineering Supervisor: Prof. Dr. Mustafa KUZUO?LU September 2001, 114 pages The Finite Element Method (FEM) and Finite Difference Method (FDM) are used to discretize the partial differential equations of computational electromagnetics. As a result of this discretization, sparse matrix equations in the form Ax = b are obtained. There are two approaches to solve the sparse matrix equation Ax = b. The first approach is to use a direct method which involves the factorization of the coefficient matrix A. However, this approach usually leads to a dense matrix with several fill-ins. The other approach is to use iterative methods. Iterative methods generate a sequence x(k) (which is supposed to converge to the exact solution x ) and essentially involve the matrix A only in the context of matrix-vector multiplication. The evaluation of an iterative method invariably focuses on the rate of convergence of the iterates x(i). inIn this thesis, Krylov Subspace Methods are used for the iterative solution of syrnmetric/nonsymmetric, real/complex linear equation systems. Special emphasis is given to complex symmetric systems, where a modified version of the conjugate gradient algorithm has been developed. The convergence rate of the algorithms is improved by applying preconditioning techniques. A software has been developed to demonstrate the performance of several sparse matrix solution algorithms. Keywords: Krylov Subspace Methods, Preconditioning, Sparse Matrix Equations IV 114

Background Ischemia is the major cause of acute kidney injury (AKI), associated with high mortality and morbidity. Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can be a potent therapeutic option for the cure of AKI. Methods MSCs were cultured in four groups SNAP (S-nitroso N-acetyl penicillamine), SNAP + Methylene Blue (MB), MB and a control for in vitro analysis. Cultured MSCs were pre-conditioned with either SNAP (100 μM) or MB (1 μM) or both for 6 hours. Renal ischemia was induced in four groups (as in in vitro study) of rats by clamping the left renal padicle for 45 minutes and then different pre-conditioned stem cells were transplanted. Results We report that pre-conditioning of MSCs with SNAP enhances their proliferation, survival and engraftment in ischemic kidney. Rat MSCs pre-conditioned with SNAP decreased cell apoptosis and increased proliferation and cytoprotective genes’ expression in vitro. Our in vivo data showed enhanced survival and engraftment, proliferation, reduction in fibrosis, significant improvement in renal function and higher expression of pro-survival and pro-angiogenic factors in ischemic renal tissue in SNAP pre-conditioned group of animals. Cytoprotective effects of SNAP pre-conditioning were abrogated by MB, an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase. Conclusion The results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury.