This is done taking into account the material self-heating during

This is done taking into account the material self-heating during such unusually high strain rates. Two regimes for the dynamic process of strain induced crystallization are evidenced. For the NR tested,

the obtained characteristic time is around 20 ms when the material average elongation during the cyclic test is above a critical elongation value lambda(c). lambda(c) is the minimum elongation needed to induce crystallization during low strain rate tensile tests. Moreover, a rapid increase of this characteristic time is found when the average elongation decreases below this critical value. (c) 2012 Elsevier Ltd. All rights reserved.”
“Peanut allergy is one of the most common food allergies. Allergen-specific oral immunotherapy (OIT) and sublingual Selleck Alvocidib immunotherapy (SLIT) for peanut allergy aim to induce desensitization and then tolerance to peanuts. However, there is still considerable uncertainty about the safety of these two approaches and if the risk is justified by the benefit of the therapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of OIT and

Saracatinib mouse SLIT in patients with peanut allergy. We performed searches of the MEDLINE, CINAHL, EMBASE, ISI Web of Science, and Cochrane databases (through March 18, 2013) for randomized controlled trials (RCTs) that compared OIT or SLIT with a placebo in patients with peanut allergy. The study selection and data extraction were independently performed by two reviewers. The primary outcome was the proportion of patients whose condition improved. We also analyzed immunologic changes and adverse events. A meta-analysis was performed using a random effects model. Three RCTs that comprised a total of 86 subjects

were analyzed. OIT or SLIT had a significantly positive effect on peanut allergy (odds ratio [OR], 38.44; 95% confidential interval [CI] 6.01-245.81). Several immunologic changes associated with the induction of tolerance were improvements. There is no difference between the OIT or SLIT group and placebo group in the number of patients who required epinephrine during the study (OR, 0.51; 95% CI, 0.03-10.20). This study showed a statistically significant benefit of peanut immunotherapy in patients with peanut allergy. However, these findings are based on an analysis of a small number of RCTs. Additional learn more larger, well-designed and double-blind RCTs are needed.”
“Objective: We studied the effects of soy consumption on oxidative stress, blood homocysteine, coagulation factors, and phosphorus in peritoneal dialysis patients.\n\nDesign: This was an unblinded, randomized clinical trial.\n\nSetting: This study involved peritoneal dialysis centers in Tehran, Iran.\n\nPatients: We included 40 peritoneal dialysis patients (20 males and 20 females).\n\nIntervention: Peritoneal dialysis patients were randomly assigned to either a soy or control group.

Pedicle screw fixation with additional transpedicular fusion has

Pedicle screw fixation with additional transpedicular fusion has remained controversial because of inconsistent reports.\n\nA retrospective single surgeon cohort study was performed. Between October 2001 and May 2007, 30 consecutive patients with 31 acute traumatic burst fractures of the thoracolumbar spine (D12-L5) were treated operatively. The mean age of the patients was 45.7 years (range : 19-78). There were 23 men and 7 women. Nineteen thoracolumbar fractures were sustained in falls from

a height; the other fractures were the result of motor vehicle accidents.\n\nThe vertebrae most often involved were L1 in 13 patients and L2 in 8 patients. According to check details the Magerl classification, 25 patients sustained Type A1, 4 Type A2 and 2 Type A3 fractures. The mean time from injury to surgery was 6 days (range 2-14 days).\n\nTwo postoperative complications were observed : one superficial and one deep infection.\n\nMean Cobb’s angle improved from +7.16 degrees (SD 12.44) preoperatively to -5.48 degrees (SD 11.44) immediately after operation, with a mean loss of correction of 1.00 degrees (SD 3.04) at two years.\n\nReconstruction of the anterior column is important to prevent loss of correction.\n\nIn our experience, the use of transpedicular bone grafting has efficiently restored the anterior column and

has preserved the post-operative correction of kyphosis until healing of the fracture.”
“Recent advances in Synthetic Biology have yielded standardized Ferroptosis inhibitor and automatable

DNA assembly protocols that enable a broad range of biotechnological research and development. Unfortunately, the experimental design required for modem scar-less multipart DNA assembly methods is frequently laborious, time-consuming, and error-prone. Here, we report Etomoxir inhibitor the development and deployment of a web-based software tool, j5, which automates the design of scar-less multipart DNA assembly protocols including SLIC, Gibson, CPEC, and Golden Gate. The key innovations of the j5 design process include cost optimization, leveraging DNA synthesis when cost-effective to do so, the enforcement of design specification rules, hierarchical assembly strategies to mitigate likely assembly errors, and the instruction of manual or automated construction of scar-less combinatorial DNA libraries. Using a GFP expression testbed, we demonstrate that j5 designs can be executed with the SLIC, Gibson, or CPEC assembly methods, used to build combinatorial libraries with the Golden Gate assembly method, and applied to the preparation of linear gene deletion cassettes for E. coil. The DNA assembly design algorithms reported here are generally applicable to broad classes of DNA construction methodologies and could be implemented to supplement other DNA assembly design tools.

Conclusion: PMN functional impairment in AD patients could repres

Conclusion: PMN functional impairment in AD patients could represent an additional cause of skin infections, coupled with other known defects in the innate immune system. The increased MFI of adhesion molecules and TLRs is rather a consequence of the increased skin barrier permeability to bacterial molecules

Compound C datasheet capable of stimulating immunological reactions. Copyright (C) 2012 S. Karger AG, Basel”
“Salt marshes are among the most productive systems of the world, with plant primary production limited by soil oxygen deficiency and nutrient availability. Nevertheless, root adaptations to anoxia and nutrient acquisition are different and often incompatible. The SW Atlantic salt marshes are characterized by high densities of the deep (up to 1 m) burrowing crab Neohelice granulata (Dana, 1851) that may change soil physical and chemical characteristics by burrow construction. In this work, we experimentally evaluated the hypothesis that crab burrowing can enhance soil oxygenation, causing changes in Spartina densiflora Brongniart below ground tissues from structures adapted to anoxia

to systems adapted for nutrient acquisition. This response, in turn, would enhance plant productivity. Results from field observations PI3K inhibitor show that oxygen availability is higher in zones with high burrow densities. As burrow densities increased, the plant root distribution changed from shallow (associated to low oxygen availability) to deeper and vertically homogeneous, with a positive correlation between burrow density and plant aboveground biomass. Experimental exclusion of crabs shows that they induce changes of root strategies from anoxia toleration to nutrient efficient acquisition, with increasing plant productivity. The invasive success that this plant shows in other parts of the world is likely to be due to their ability to tolerate harsh environmental conditions. Our results

suggest that the morphological find more plasticity of S. densiflora is also important in their native zone given the characteristics of their specific habitat. (C) 2009 Elsevier B.V. All rights reserved.”
“Rationale, aims and objectivesThis article conducts a literature review about the cost-effectiveness of pharmacotherapy for chronic obstructive pulmonary disease (COPD) in ambulatory care.\n\nMethodsRelevant economic evaluations were identified by searching Medline (PubMed) and the National Health Service (NHS) Economic Evaluation Database. The search strategy focused on literature reviews and primary economic evaluations. Economic evaluations were included, which compared pharmacotherapy for COPD, chronic bronchitis or pulmonary emphysema with an alternative in terms of costs and health outcomes.\n\nResultsThe majority of economic evaluations show that pharmacotherapy for COPD in ambulatory care is cost-effective.


“Objective: This study aimed to estimate the incidence and


“Objective: This study aimed to estimate the incidence and relative risk of stroke and post-stroke all-cause mortality in patients with schizophrenia.\n\nMethods: This study identified a study population from the National Health Insurance Research Database (NHIRD) between 1999 and 2003 that included 80,569 patients with schizophrenia

and 241,707 age- and sex-matched control participants without schizophrenia. The participants were randomly selected from the 23,981,020-participant NHIRD, which consists of 96% Taiwanese SRT2104 molecular weight participants. Participants who had experienced a stroke between 1999 and 2003 were excluded. Using data from the NHIRD between 2004 and 2008, the incidence of stroke (ICD-9-CM code 430-438) and patient survival

SIS3 solubility dmso after stroke were calculated for both groups. After adjusting for confounding risk factors, a Cox proportional-hazards model was used to compare the five-year stroke-free survival rate to the all-cause mortality rate across the two cohorts.\n\nResults: Over five years, 1380 (1.71%) patients with schizophrenia and 2954 (1.22%) controls suffered from strokes. After adjusting for demographic characteristics and comorbid medical conditions, patients with schizophrenia were 1.13 times more likely to have a stroke (95% CI=1.05-1.22; P=0.0006). In addition, 1039 (24%) patients who had a stroke died during the follow-up period. After adjusting for patient, physician and hospital variables, the all-cause mortality hazard ratio for patients with schizophrenia was 1.23 (95%

CI=1.06-1.41; P=0.0052).\n\nConclusions: During a five-year follow-up, the likelihood of developing a stroke and the all-cause mortality rate Androgen Receptor screening were greater among patients with schizophrenia as compared with the control group. (C) 2012 Elsevier B.V. All rights reserved.”
“Over 25 years ago Francis reported an association between blood transfusion and worsened cancer prognosis. Subsequently there has been much debate over whether there is in fact such an association, and if so, what is its underlying mechanism. Allogeneic blood transfusion is the most frequent allo-transplantation procedure performed on a routine basis with no prior HLA-typing. 50% of the recipients of unprocessed red cells and platelets become allo-immunised. It is our proposition that as result of normal physiological ageing and metabolic processes (with depletion of ATP and reduction of active membrane processes), there is leaching of biologically active substances from the cells into stored blood products. These leached bioactive substances have immuno-modulatory effects, which may in part explain the increased likelihood of postoperative sepsis and adult respiratory distress syndrome in transfusion recipients.

5-mm LCP

Reconstruction Plate; 3 5-mm LCP Superior Clavic

5-mm LCP

Reconstruction Plate; 3.5-mm LCP Superior Clavicle Plate; 3.5-mm LCP Superior Anterior Clavicle Plate; Synthes, Inc, West Chester, Pennsylvania). Specimens were tested for stiffness in axial torsion and cantilever bending and then loaded to failure in 3-point bending. Data were analyzed using 2-way analysis of variance and Tukey’s test (P smaller than .05). No significant Smoothened inhibitor differences were found between unicortical and bicortical fixation in failure load, cantilever bending, and cross body stiffness. Bicortical fixation was significantly stiffer than unicortical fixation in torsion only for the same plates. Significant differences also existed between plates in torsion. Unicortical locked plate fixation may be a reasonable option in the treatment of displaced midshaft clavicle fracture fixation to avoid complications associated with posteroinferior hardware penetration following clavicle fracture fixation based on the biomechanical performance of these constructs. However, it remains unclear whether these differences will be clinically significant.”
“To

investigate the expression of TSPAN1 (Gene ID: 10103), Ki67 and CD34 in gastric carcinomas and the clinicopathological ZD1839 molecular weight significance, the expression of TSPAN1, Ki67 and CD34 was detected in 86 cases of gastric carcinoma, paraffin-embedded

sections using an immunohistochernical method. The rates of overexpression of TSPAN1, Ki67 and CD34 in gastric carcinomas were 56.98%, 74.42%, and 62.79%, respectively. The overexpression of these markers was positively correlated with clinical stage and negatively correlated with survival rates (at 3 and 5 years). The overexpression of TSPAN1 and Ki67 was negatively Rabusertib supplier correlated with carcinoma differentiation, and the overexpression of TSPAN1 and CD34 was positively correlated with infiltration and lymph node status of the tumor. Thus, overexpression of TSPAN1, Ki67 and CD34 in gastric cancer tissues is associated with development of the cancer. The detection of expression of TSPAN1, Ki67 and CD34 in gastric cancer may provide useful prognostic information for patients with the disease.”
“Both the monophyly and inter-relationships of the major annelid groups have remained uncertain, despite intensive research on both morphology and molecular sequences. Morphological cladistic analyses indicate that Annelida is monophyletic and consists of two monophyletic groups, the clitellates and polychaetes, whereas molecular phylogenetic analyses suggest that polychaetes are paraphyletic and that sipunculans are crown-group annelids.

Results: In vivo, insulin decreased

\n\nResults: In vivo, insulin decreased Panobinostat clinical trial TLW, enchanced AFC, increased

the expressions of alpha-, beta-, and gamma-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of alpha-, beta-, and gamma-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway.\n\nConclusions: Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression CYT387 of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.”
“Type 2 diabetes is associated with significant cardiovascular morbidity

and mortality. Although low-density lipoprotein cholesterol levels may be normal in patients with type 2 diabetes, insulin resistance drives a number of changes in lipid metabolism and lipoprotein composition that render low-density lipoprotein cholesterol and other lipoproteins more pathogenic than species found in patients without type 2 diabetes. Dyslipidemia, which affects almost 50% of patients with type 2 diabetes, is a cardiovascular risk factor characterized by elevated triglyceride levels, low high-density lipoprotein cholesterol levels, and a preponderance of small, dense, low-density lipoprotein particles. Early, aggressive pharmacological management is advocated to reduce low-density lipoprotein cholesterol levels, regardless of baseline YH25448 levels. A number of lipid-lowering agents, including

statins, fibrates, niacin, and bile acid sequestrants, are available to target normalization of the entire lipid profile. Despite use of combination and high-dose lipid-lowering agents, many patients with type 2 diabetes do not achieve lipid targets. This review outlines the characteristics and prevalence of dyslipidemia in patients with type 2 diabetes and discusses strategies that may reduce the risk of cardiovascular disease in this population.”
“Data on the burden of acute kidney injury (AKI) in resource-poor countries such as Tanzania are minimal because of a lack of nephrology services and an inability to recognize and diagnose AKI with any certainty. In the few published studies, high morbidity and mortality are reported. Improved nephrology care and dialysis may lower the mortality from AKI in these settings. Hemodialysis is expensive and technically challenging in resource-limited settings.

(C) 2013 Elsevier Inc All rights reserved “
“A group of aci

(C) 2013 Elsevier Inc. All rights reserved.”
“A group of acidic nucleosides were synthesized to develop a new class of ribonuclease A (RNase A) inhibitors. Our

recent study on carboxymethylsulfonyl-modified nucleosides revealed some interesting results in RNase A inhibition. This positive outcome triggered an investigation of the role played by secondary sugar hydroxy groups in inhibiting RNase A activity. Uri-dines and cytidines modified with -SO2CH2COOH groups at the 2′-and 3′-positions show good inhibitory properties with low inhibition constant (Ki) values in VX 770 the range of 109-17 mm. The present work resulted in a set of inhibitors that undergo more effective interactions with the RNase A active site, as visualized by docking studies.”
“IntroductionImmune response probably changes during human life, being influenced by cumulative exposure to environmental factors and individual genetic background. MethodsPatients investigated for suspected interstitial lung disease were prospectively enrolled. After completing the diagnostic process, 121 patients were diagnosed extrinsic allergic alveolitis (EAA) and 136 sarcoidosis. Three groups LY2606368 cost according to age were established ( smaller than 30 years, 30-60 years, bigger than 60 years), clinical manifestation, vital capacity (VC), forced expired volume in 1s (FEV1), lung diffusing capacity for carbon monoxide-transfer factor (TLCO) and bronchoalveolar

AZD7762 lavage fluid (BALF) differential cell count were compared among the groups. ResultsAge subgroups of EAA patients did not significantly differ in lung functions. In the group above 60 years, non-significantly higher neutrophils and eosinophils counts and CD4/CD8 ratio were observed. Sarcoidosis patients were significantly younger than EAA group and had significantly better lung functions

(VC, FEV1, TLCO). Patients with sarcoidosis above 60 years of age had significantly higher percentages of neutrophils in BALF compared with younger patients. BALF percentage of neutrophils positively correlated with age. ConclusionsPresented results may support the hypothesis that reactivity of immune system changes during the life, which may result in different manifestation of interstitial lung diseases according to age.”
“Background: Production of L-sorbose from D-sorbitol by Gluconobacter oxydans is the first step to produce L-ascorbic acid on industrial scale. The sldhAB gene, which encodes the sorbitol dehydrogenase (SLDH), was overexpressed in an industrial strain G. oxydans WSH-003 with a strong promoter, P-tufB. To enhance the mRNA abundance, a series of artificial poly(A/T) tails were added to the 3′-terminal of sldhAB gene. Besides, their role in sldhAB overexpression and their subsequent effects on L-sorbose production were investigated. Results: The mRNA abundance of the sldhAB gene could be enhanced in G. oxydans by suitable poly(A/T) tails.

There is a need for methodologically rigorous research to determi

There is a need for methodologically rigorous research to determine the most effective timing and method of delivery of preparatory GANT61 order information to improve patient outcomes.”
“Within

cells, lipids are stored in the form of lipid droplets (LDs), consisting of a neutral lipid core, surrounded by a phospholipid monolayer and an outer layer of protein. LDs typically accumulate either triacylglycerol (TAG) and diacylglycerol or cholesteryl ester (CE), depending on the type of tissue. Recently, there has been an increased interest in the proteins that surround LDs. LD proteins have been found to be quite diverse, from structural proteins to metabolic enzymes, proteins involved in vesicular transport, and proteins that may play a role in LD formation. Previous proteomics analyses have focused on TAG-enriched LDs, whereas CE-enriched LDs have been largely ignored. Our study has compared the LD proteins from CE-enriched LDs to TAG-enriched LDs in steroidogenic cells. In Rabusertib primary rat granulosa cells loaded with either HDL to produce CE-enriched LDs or fatty acids to produce TAG-enriched LDs, 61 proteins were found to be elevated in CE-enriched LDs and 40 proteins elevated in TAG-enriched LDs with 278 proteins in similar amounts. Protein expression was further validated by selected reaction monitoring (SRM) mass spectrometry (MS). SRM verified expression

of 25 of 27 peptides that were previously detected by tandem mass tagging MS. Several proteins were confirmed to be elevated in CE-enriched selleck kinase inhibitor LDs by SRM including the intermediate filament vimentin. This study is the first to compare the proteins found on CE-enriched LDs with TAG-enriched LDs and constitutes the first step in creating a better understanding of the proteins found on CE-enriched LDs in steroidogenic cells.”
“Background/Aims: Endoscopic ultrasonography (EUS) is helpful for evaluating the depth of tumor invasion and lymph node metastasis of rectal neuroendocrine tumors (NETs). The aim of this study was to clarify the clinical impact

of EUS for rectal NETs less than 10 mm in diameter. Materials and Methods: : A total of 76 rectal NETs treated at our hospital between June 2006 and March 2013 were reviewed retrospectively. All lesions were analyzed with EUS to evaluate the depth of tumor invasion. The lesions were resected by endoscopic submucosal resection with band ligation (ESMR-L) or endoscopic submucosal dissection (ESD) and examined histologically. Results: Endoscopic ultrasonography findings showed that all lesions were confined to the submucosa and revealed no adjacent lymph node metastasis. Seventy-five of the 76 lesions were completely resected by ESMR-L. One lesion was resected by ESD and the resected deep margin of the lesion was histologically positive. Only one lesion exhibited lymphatic invasion. Conclusion: EUS may not be essential for diagnosis and treatment planning for rectal NETs less than 10 mm in size.

DESIGN Adult and adolescent dosing and drug clearance data we

\n\nDESIGN Adult and adolescent dosing and drug clearance data were obtained from FDA-approved drug labels and publicly available databases containing LCL161 mouse reviews of pediatric trials submitted to the FDA. Dosing information was compared for products with concordant indications for adolescent and adult patients. Adolescent drug clearance was predicted from adult pharmacokinetic data by using allometric scaling and compared with observed values.\n\nMAIN OUTCOMES AND MEASURES Adolescent and adult dosing information and drug clearance.\n\nRESULTS There were 126 unique products with pediatric studies

submitted to the FDA since the FDA Amendments Act of 2007, of which 92 had at least 1 selleck screening library adolescent indication concordant

with an adult indication. Of these 92 products, 87 (94.5%) have equivalent dosing for adults and adolescent patients. For 18 of these 92 products, a minimum weight or body surface area threshold is recommended for adolescents to receive adult dosing. Allometric scaling predicted adolescent drug clearance with an overall mean absolute percentage error of 17.0%.\n\nCONCLUSIONS AND RELEVANCE Approved adult and adolescent drug dosing is equivalent for 94.5% of products with an adolescent indication studied since the FDA Amendments Act of 2007. Allometric scaling may be a useful tool to avoid unnecessary dedicated pharmacokinetic studies in the adolescent population during pediatric drug development, although each development program in adolescents requires a full discussion of drug dosing with the FDA.”
“To clarify the significance find more of post-transplant serum ferritin (SF), we retrospectively assessed pre- and post-transplant SF. Among 256 patients undergoing allogeneic stem cell transplant (SCT) for hematologic malignancies between 2000 and 2011, those who had relapsed within 1 year were excluded, and 110 patients surviving for more than 1

year were included in the analysis. The cut-off value of SF was 1000 ng/mL, and four pre- and post-SF groups were defined: low-low (n = 62), low-high (n = 12), high-low (n = 13) and high-high (n = 23). Outcomes at 5 years for each group were as follows: overall survival (OS) 88.2, 38.1, 92.3 and 76.7%, respectively, p = 0.004, and non-relapse mortality (NRM) 11.3, 53.6, 7.7 and 18.9%, respectively, p = 0.037. Patients receiving larger transfusion volumes or developing chronic graft-versus-host disease (GVHD) demonstrated higher 1-year SF values. In multivariate analysis for OS and NRM, low-high SF remained a significant predictor of OS (hazard ratio [HR] = 3.49, 95% confidence interval [CI]: 1.10-11.0, p = 0.032) and NRM (HR = 2.95, 95% CI: 1.04-8.36, p = 0.041). These results suggest that the elevation of SF at 1 year after SCT, which may reflect transfusion and the development of chronic GVHD, may have an aggravating influence on outcomes after SCT.

Some members of this family have largely resisted structural char

Some members of this family have largely resisted structural characterization as a result of challenges associated with their inherent flexibility. Small-angle scattering (SAS) is often the method of choice for check details their structural study. An extensive set of simulated data for both flexible and rigid multidomain systems was analyzed and modeled using standard protocols. This study clearly shows that SAXS profiles obtained from highly flexible proteins can be wrongly interpreted as arising from a rigid structure. In this context, it would be important to identify features from the SAXS data or from the derived structural models that

indicate interdomain motions to differentiate between these two scenarios. Features of SAXS data that identify

flexible proteins are: (1) general attenuation of fine structure in the scattering profiles, which becomes more dramatic in Kratky representations, and (2) a reduced number of interdomain correlation peaks in p(r) functions that also present large D (max) values and a smooth decrease to 0. When modeling this dynamically averaged SAXS data, the structures obtained present characteristic trends: (1) ab initio models display a decrease in resolution, and (2) rigid-body models present highly extended conformations this website with a lack of interdomain contacts. The ensemble optimization method represents an excellent strategy to identify interdomain motions unambiguously. This study provides information that should help researchers to select the best modeling strategy for the structural interpretation of SAS experiments of multidomain proteins.”
“In this report a textile azo dye Remazol orange was degraded and detoxified by bacterium Pseudomonas aeruginosa BCH

in plain distilled water. This bacterial selleck products decolorization performance was found to be pH and temperature dependent with maximum decolorization observed at pH 8 and temperature 30 A degrees C. Bacterium tolerated higher dye concentrations up to 400 mg l(-1). Effect of initial cell mass showed that higher cell mass concentration can accelerate decolorization process with maximum of 92 % decolorization observed at 2.5 g l(-1) cell mass within 6.5 h. Effect of various metal ions showed Mn has inducing effect whereas Zn strongly inhibited the decolorization process at 5 mM concentration. Analysis of biodegradation products carried out with UV-vis spectroscopy, HPTLC and FTIR confirmed the decolorization and degradation of Remazol orange. Possible route for the degradation of dye was proposed based on GC-MS analysis. During toxicological scrutiny in Allium cepa root cells, induction in the activities of superoxide dismutase (SOD), guaiacol peroxidase (GPX) and inhibition of catalase (CAT) along with raised levels of lipid peroxidation and protein oxidation in dye treated samples were detected which conclusively indicated the generation of oxidative stress.