876 research outputs found
Method for reinforcing tubing joints
Joint repair technique uses a longitudinally split aluminum shield over the joint ferrule and immediately adjacent tubing to reseal or reinforce leaking or weak joints in small tubing. Epoxy resin coating on inside surfaces of the two shield halves provides a tightly sealed bond between shield and tubing
Surface finishing
A surface of an article adapted for relative motion with a fluid environment is finished by coating the surface with a fluid adhesive. The adhesive is covered with a sheet of flexible film material under tension, and the adhesive is set while maintaining tension on the film material
Surface finishing
A surface of an article adapted for relative motion with a fluid environment is finished by coating the surface with a fluid adhesive, covering the adhesive with a sheet of flexible film material under tension on the film material whereby the tensioned film material is bonded to the surface by the adhesive
Plastic covering on airfoil structure provides smooth uninterrupted surface
Primed surface is covered with adhesive. Sheet of plastic film is stretched over adhesive and mechanical holder is used to apply tension to ends of sheet to make it conform to surface of airfoil. After adhesive cures, plastic can be trimmed with sharp cutting tool
Patient-oriented gene set analysis for cancer mutation data
Recent research has revealed complex heterogeneous genomic landscapes in human cancers. However, mutations tend to occur within a core group of pathways and biological processes that can be grouped into gene sets. To better understand the significance of these pathways, we have developed an approach that initially scores each gene set at the patient rather than the gene level. In mutation analysis, these patient-oriented methods are more transparent, interpretable, and statistically powerful than traditional gene-oriented methods
Accumulation of driver and passenger mutations during tumor progression
Major efforts to sequence cancer genomes are now occurring throughout the
world. Though the emerging data from these studies are illuminating, their
reconciliation with epidemiologic and clinical observations poses a major
challenge. In the current study, we provide a novel mathematical model that
begins to address this challenge. We model tumors as a discrete time branching
process that starts with a single driver mutation and proceeds as each new
driver mutation leads to a slightly increased rate of clonal expansion. Using
the model, we observe tremendous variation in the rate of tumor development -
providing an understanding of the heterogeneity in tumor sizes and development
times that have been observed by epidemiologists and clinicians. Furthermore,
the model provides a simple formula for the number of driver mutations as a
function of the total number of mutations in the tumor. Finally, when applied
to recent experimental data, the model allows us to calculate, for the first
time, the actual selective advantage provided by typical somatic mutations in
human tumors in situ. This selective advantage is surprisingly small, 0.005 +-
0.0005, and has major implications for experimental cancer research
IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patients
New biomarkers with improved accuracy could be helpful for monitoring disease in patients with Non-Hodgkin's lymphomas (NHL). Towards this end, we have explored the feasibility of identifying the sequence of rearranged IgH genes using next-generation sequencing, then using PCR to detect specific rearranged DNA fragments in patients' plasma. By capturing and sequencing the IgH genomic regions (IgCap), we were able to detect and precisely determine the sequence of rearranged IgH loci in the tumors of three NHL patients. Moreover, circulating rearranged DNA fragments could be identified in the plasma of all three patients. Even in cases wherein tumor biopsies were unavailable, we were able to use the IgH capture approach to identify rearranged DNA loci in the plasma of 8 of 14 patients. IgCap may enable a more informed management of selected patients with NHL and other B-cell malignancies in the future
Genetic progression and the waiting time to cancer
Cancer results from genetic alterations that disturb the normal cooperative
behavior of cells. Recent high-throughput genomic studies of cancer cells have
shown that the mutational landscape of cancer is complex and that individual
cancers may evolve through mutations in as many as 20 different
cancer-associated genes. We use data published by Sjoblom et al. (2006) to
develop a new mathematical model for the somatic evolution of colorectal
cancers. We employ the Wright-Fisher process for exploring the basic parameters
of this evolutionary process and derive an analytical approximation for the
expected waiting time to the cancer phenotype. Our results highlight the
relative importance of selection over both the size of the cell population at
risk and the mutation rate. The model predicts that the observed genetic
diversity of cancer genomes can arise under a normal mutation rate if the
average selective advantage per mutation is on the order of 1%. Increased
mutation rates due to genetic instability would allow even smaller selective
advantages during tumorigenesis. The complexity of cancer progression thus can
be understood as the result of multiple sequential mutations, each of which has
a relatively small but positive effect on net cell growth.Comment: Details available as supplementary material at
http://www.people.fas.harvard.edu/~antal/publications.htm
Mutant PIK3CA promotes cell growth and invasion of human cancer cells
SummaryPIK3CA is mutated in diverse human cancers, but the functional effects of these mutations have not been defined. To evaluate the consequences of PIK3CA alterations, the two most common mutations were inactivated by gene targeting in colorectal cancer (CRC) cells. Biochemical analyses of these cells showed that mutant PIK3CA selectively regulated the phosphorylation of AKT and the forkhead transcription factors FKHR and FKHRL1. PIK3CA mutations had little effect on growth under standard conditions, but reduced cellular dependence on growth factors. PIK3CA mutations resulted in attenuation of apoptosis and facilitated tumor invasion. Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells. These data have important implications for therapy of cancers harboring PIK3CA alterations
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