Advanced manufacturing techniques like additive manufacturing (AM) have poised themselves to revolutionize metal manufacturing. A wide range of AM techniques are capable of manufacturing metal ...components with unique, complex geometries and hastening the scientific-engineering-development cycle. Metal AM relies on a layer-by-layer rapid manufacturing process to build components from the substrate up. Rapid solidification is a large departure from traditional metal manufacturing due to its complex physics. Characterization of rapid solidification is difficult, stemming from the small volumes used in AM and the fast dynamics of the process. High energy X-ray diffraction (HEXRD) is a solution to the characterization problems of rapidly solidified alloys and AM. HEXRD can probe small volumes at fast rates and provides a wide range of thermomechanical and kinetic information. This thesis presents the application of HEXRD to rapidly solidified titanium and stainless steel alloys through a series of case studies. In the first two studies, HEXRD is applied torapidly solidified titanium and stainless steel welds. The materials are characterized for their temperature history, phase changes, kinetics, and microstructural evolution. In the next case study, HEXRD is applied to characterize phase changes in elastocaloric NiTi shape memory alloys (SMAs) under thermomechanical load. HEXRD, in conjunction with other tools,is used to explain the superior performance of the additively manufactured SMAs. In the final two case studies, HEXRD is used to measure the mechanical response of AM parts with complex geometries; namely, the octet truss lattice. Diffraction reveals a wide range of materials information about the AM microstructure including unexpected phases, texture,and mechanical response to loading. The mechanical results from HEXRD and then compared with theoretical predictions about the performance of octet truss lattices. Summarily, HEXRD is a diverse tool that is poised to address the complex characterization problems of many aspects of the additive manufacturing process.
Ensembl (http://www.ensembl.org) integrates genomic information for a comprehensive set of chordate genomes with a particular focus on resources for human, mouse, rat, zebrafish and other high-value ...sequenced genomes. We provide complete gene annotations for all supported species in addition to specific resources that target genome variation, function and evolution. Ensembl data is accessible in a variety of formats including via our genome browser, API and BioMart. This year marks the tenth anniversary of Ensembl and in that time the project has grown with advances in genome technology. As of release 56 (September 2009), Ensembl supports 51 species including marmoset, pig, zebra finch, lizard, gorilla and wallaby, which were added in the past year. Major additions and improvements to Ensembl since our previous report include the incorporation of the human GRCh37 assembly, enhanced visualisation and data-mining options for the Ensembl regulatory features and continued development of our software infrastructure.
Aging is a universal phenomenon that cuts across culture, ethnicity, and gender. Neuroimaging studies have demonstrated that the aging process affects multiple brain systems. For example, aging ...results in reduced cerebral macrostructural integrity (e.g., cortical thinning, whole-brain atrophy), and reduced white matter (WM) microstructural integrity (e.g., decreased axonal and myelin integrity). However, there is evidence that some age-related cerebral declines may be attenuated by positive lifestyle variables. For example, socioeconomic status (SES) and cardiorespiratory fitness (CRF) have been shown to attenuate age-related declines in cortical macrostructural volume. However, less work has explored the relationship between these reserve variables and WM microstructure. The current dissertation sought to determine the relationship between these two lifestyle variables and age-related microstructural integrity declines. Diffusion tensor imaging (DTI), a magnetic resonance imaging (MRI) technique sensitized to the diffusion of water in the brain, was used to assess WM microstructural integrity. Experiment 1 included both young adults and seniors in order to explore the effects of SES on age-related WM integrity declines. Results revealed a positive relationship between SES and WM integrity in healthy seniors in tracts showing age-related declines. Furthermore, SES moderated the relationship between age and WM integrity in several frontal tracts, suggesting that long-term exposure to high SES may help to protect against age-related declines of WM integrity in frontal cortex. Experiment 2 explored the relationship between CRF and WM integrity in a separate group of healthy seniors, while controlling for SES. Results revealed a positive correlation between CRF and WM integrity in tracts interconnecting homologous frontal regions associated with high-level motor planning. Collectively, the current dissertation suggests that two lifestyle variables—SES and CRF—may attenuate some age-related WM microstructural integrity declines. KEY WORDS: Exercise, Fitness, Socioeconomic Status, White Matter Integrity, Diffusion Tensor Imaging
To systematically assess the effectiveness of EDTA in unmasking clinically relevant HLA alloantibodies
Serum samples from transplant (txp) patients collected for clinical testing were pre-treated ...with various concentrations of EDTA for 15 min at room temperature and then tested with Luminex-based solid phase assays using HLA mixed beads (HMB) and Single antigen beads (SAB) for the presence and identification, respectively, of HLA alloantibodies.
Utility of pretreating sera with heat inactivation, dithiothreitol and/or EDTA to overcome prozone-like inhibition (PZLI) has been demonstrated. However, lack of details vis-à-vis time and concentration used, prompted us to systematically assess the effectiveness of EDTA in unmasking presence of clinically relevant HLA alloantibodies in serum samples with PZLI. Titration analysis using EDTA concentrations ranging from 0–50 mM indicated that 1.25 mM EDTA was ineffective, while 2.5 mM EDTA was moderately effective, in removing PZLI. EDTA concentration =/>5 mM was effective in removing PZLI in all serum samples. Therefore, we selected 5 mM EDTA for all subsequent studies. We observed that 5 mM EDTA did not give rise to high background and/or false positives, i.e., no unmasking of “new” specificities in serum samples with cPRA = 0% or in serum samples that demonstrated presence of limited HLA alloantibody specificities with MFI <10,000. Most common HLA antibody specificities unmasked were anti-A1, -A2 (and associated CREGs), -DR53, and -DQ. EDTA treatment also removed non-specific reactivity observed in HMB and SAB. In the pre-txp setting, EDTA unmasked presence of DSAs that can cause positive flow cytometric crossmatch. This enabled a better correlation with virtual crossmatch calls. In the post-txp setting, EDTA aided in unmasking de novo DSA associated with episodes of rejection allowing a stronger clinical correlation with histological detection of rejection.
The PZLI phenomenon observed due to presence of activated complement components in sera, challenges the ability of HLA labs to accurately identify HLA alloantibodies. Our study underscores the utility of treating serum with EDTA in identifying pre-formed and de novo DSAs that would be deleterious to the allograft in txp recipients.
The tolerances of alloys to impurities can vary significantly across impurity-alloy combinations and are largely unknown beyond the most common alloys and impurities. Further, a more general ...framework to quantify, compare, and practically utilize the tolerance of elements and alloys to impurities is missing. Here, we propose such a framework based on the parameter CIM, the maximum content of an impurity that can be added to a pure element before it no longer crystallizes and instead vitrifies, as measured under sputtering conditions. Using high throughput combinatorial methods, CIM can be readily determined for practically important impurity-element combinations. We argue that CIM generally indicates impurity tolerance because it ubiquitously measures solid solution stability and provide arguments on how conclusions may be drawn from impurity-element to impurity-alloy tolerance. This practical metric for evaluating impurity tolerances for alloys may help metallurgy by enabling greater recycled feedstock compatibility during manufacturing and, in the future, the design of more impurity tolerant alloys.
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The impact of waiting time and comorbid conditions on the survival benefit of kidney transplantation.
Longer waiting times may limit the survival benefit of kidney transplantation in older patients ...or those with a high burden of comorbid disease.
We performed a longitudinal study of mortality among 63,783 transplant candidates who started dialysis between April 1995 and December 2000. We determined the relative risk (RR) of death and increase in life expectancy among subjects who received a first deceased donor transplant after different waiting times compared to subjects who had equivalent waiting times but remained on dialysis.
Transplant recipients had a lower long-term RR of death and the risk reduction was greatest in recipients with longer waiting times (RR of death 12 months after transplantation for recipients with waiting times of 0, 1, 2, 3 years was 0.49, 0.43, 0.38, 0.34, P = 0.0006).The average increase in life expectancy in transplant recipients was 9.8 years and was lower in older recipients and recipients with comorbid conditions. Increased waiting times from 1 to 3 years only moderately decreased the overall survival benefit of transplantation from 7.1 to 5.6 years, and all subjects derived a survival benefit from transplantation with waiting times up to 3 years.
These findings do not support limiting access to transplantation for otherwise suitable candidates on the basis of longer anticipated waiting times.