Processing of submicron grain 304 stainless steel

A novel thermomechanical processing technique for the synthesis of bulk submicron grain (grain size approximate to 200 nm) 304 stainless steel is reported. This ingot-metallurgical technique requires a total deformation of only 95%, and the key steps to this processing technique involve (i) formation of ultrafine dislocation cell structure, and (ii) the conversion of dislocation cells into grains with medium to high misorientation by grain boundary sliding

Consolidation of Ti-SiC particle-reinforced metal-matrix composites

Discontinuously-reinforced metal-matrix composites (DMMC) have received an increasing amount of attention in recent years due to their improved strength, stiffness and wear characteristics. These benefits make DMMC quite appealing for many structural applications; however, limited ductility and toughness have prevented their widespread use. Limited ductility and toughness are not unique to this class of advanced materials and are shared by such systems as continuous fiber composites and monolithic ceramics. The introduction of weak microstructural features in these materials has long been known to enhance the overall fracture properties. These features have taken on many forms depending on the system involved; for example, microcracking grain boundaries in ceramics (1) and weakened interracial strengths in continuous fiber composites (2). This approach has proven to be quite effective for a wide variety of materials but remains relatively unexplored for DMMC. It has been assumed that the greatest interracial strength obtainable will produce an optimized mechanical response. This assumption has not been challenged to any significant degree mainly because of the experimental inability to effectively vary the interfacial characteristics using standard processing procedures. The ability to control the evolution of matrix-reinforcement interfaces in DMMC through various processing parameters is of critical importance for both scientific investigations and industrial applications. The extremely short time at the compaction temperature that can be achieved with shock consolidation make it a unique method for the minimization (and subsequent systematic variation) of interracial reactions. Because of the high reactivity of Ti with the readily available reinforcement particles, this system possesses significant potential for gain from improved interfacial control. The fundamental questions concerning the "optimum" interfacial strength for a given DMMC can be systematically investigated with these reactive composite materials. The objective of this study was to produce fully dense DMMC compacts comprised of a reactive particle-matrix combination with little or no interfacial reactions in the as-consolidated condition. This material can provide unique information regarding the role of interfaces in DMMC

Previously Unidentified Changes in Renal Cell Carcinoma Gene Expression Identified by Parametric Analysis of Microarray Data

BACKGROUND. Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated. To better understand this lack of agreement we profiled renal cell tumor gene expression using genome-wide microarrays (45,000 probe sets) and compare our analysis to previous microarray studies. METHODS. We hybridized total RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays. We removed samples with technical defects and removed probesets that failed to exhibit sequence-specific hybridization in any of the samples. We detected differential gene expression in the resulting dataset with parametric methods and identified keywords that are overrepresented in the differentially expressed genes with the Fisher-exact test. RESULTS. We identify 1,234 genes that are more than three-fold changed in renal tumors by t-test, 800 of which have not been previously reported to be altered in renal cell tumors. Of the only 37 genes that have been identified as being differentially expressed in three or more of five previous microarray studies of renal tumor gene expression, our analysis finds 33 of these genes (89%). A key to the sensitivity and power of our analysis is filtering out defective samples and genes that are not reliably detected. CONCLUSIONS. The widespread use of sample-wise voting schemes for detecting differential expression that do not control for false positives likely account for the poor overlap among previous studies. Among the many genes we identified using parametric methods that were not previously reported as being differentially expressed in renal cell tumors are several oncogenes and tumor suppressor genes that likely play important roles in renal cell carcinogenesis. This highlights the need for rigorous statistical approaches in microarray studies.National Institutes of Healt

Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro.

Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I. The application of mechanical strain increased vascular endothelial growth factor A secretion 2-4-fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac extracellular matrix. CPC proliferation was at least 25% higher on fibronectin than that on other matrices, especially for lower strain magnitudes. At 5% strain, connexin43 expression was highest on fibronectin. With increasing strain magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on collagen I and a naturally derived cardiac extracellular matrix. Cyclic mechanical strain induced the strongest CPC alignment when cultured on fibronectin or collagen I. This study demonstrates that culturing CPCs on fibronectin with 5% strain magnitude is optimal for their vascular endothelial growth factor A secretion, proliferation, connexin43 expression, and alignment

Yield of Downstream Tests After Exercise Treadmill Testing A Prospective Cohort Study

ObjectivesThe purpose of this study was to estimate the frequency and results of downstream testing after exercise treadmill tests (ETTs).BackgroundThe utility of additional diagnostic testing after ETT is not well characterized.MethodsWe followed consecutive individuals without known coronary artery disease referred for clinical ETT at a large medical center. We measured the frequency and results of downstream imaging tests and invasive angiography within 6 months of ETT and the combined endpoint of survival free from cardiovascular death, myocardial infarction, and coronary revascularization.ResultsAmong 3,656 consecutive subjects who were followed for a mean of 2.5 ± 1.1 years, 332 (9.0%) underwent noninvasive imaging and 84 (2.3%) were referred directly to invasive angiography after ETT. The combined endpoint occurred in 76 (2.2%) patients. The annual incidence of the combined endpoint after negative, inconclusive, and positive ETT was 0.2%, 1.3%, and 12.4%, respectively (p < 0.001). Rapid recovery of electrocardiography (ECG) changes during ETT was associated with negative downstream test results and excellent prognosis, whereas typical angina despite negative ECG was associated with positive downstream tests and adverse prognosis (p < 0.001). Younger age, female sex, higher metabolic equivalents of task achieved, and rapid recovery of ECG changes were predictors of negative downstream tests.ConclusionsAmong patients referred for additional testing after ETT, the lowest yield was observed among individuals with rapid recovery of ECG changes or negative ETT, whereas the highest yield was observed among those with typical angina despite negative ECG or a positive ETT. These findings may be used to identify patients who are most and least likely to benefit from additional testing

Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI

Injectable Materials for the Treatment of Myocardial Infarction and Heart Failure: The Promise of Decellularized Matrices

Cardiovascular disease continues to be the leading cause of death, suggesting that new therapies are needed to treat the progression of heart failure post-myocardial infarction. As cardiac tissue has a limited ability to regenerate itself, experimental biomaterial therapies have focused on the replacement of necrotic cardiomyocytes and repair of the damaged extracellular matrix. While acellular and cellular cardiac patches are applied surgically to the epicardial surface of the heart, injectable materials offer the prospective advantage of minimally invasive delivery directly into the myocardium to either replace the damaged extracellular matrix or to act as a scaffold for cell delivery. Cardiac-specific decellularized matrices offer the further advantage of being biomimetic of the native biochemical and structural matrix composition, as well as the potential to be autologous therapies. This review will focus on the requirements of an ideal scaffold for catheter-based delivery as well as highlight the promise of decellularized matrices as injectable materials for cardiac repair

Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

Background: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings: (99m)Tc-labeled ASCs (1 x 10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[01/0009-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[05/54695-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/06784-4]Ministerio da Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Ministerio da Saude/Departamento Ciencia e Tecnologia (MCT/CNPq/MS/DECIT)[552324/20005-1]Ministerio da Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Ministerio da Saude/Departamento Ciencia e Tecnologia (MCT/CNPq/MS/DECIT)[10120104096700]CNPq[141276/2004-5