9,646 research outputs found
Oncometabolites: tailoring our genes
Increased glucose metabolism in cancer cells is a phenomenon that has been known for over 90 years, allowing maximal cell growth through faster ATP production and redistribution of carbons towards nucleotide, protein and fatty acid synthesis. Recently, metabolites that can promote tumorigeneis by altering the epigenome have been identified. These âoncometabolitesâ include the tricarboxylic acid cycle metabolites succinate and fumarate, whose levels are elevated in rare tumours with succinate dehydrogenase and fumarate hydratase mutations, respectively. 2-Hydroxyglutarate is another oncometabolite; it is produced de novo as a result of the mutation of isocitrate dehydrogenase, and is commonly found in gliomas and acute myeloid leukaemia. Interestingly, the structural similarity of these oncometabolites to their precursor metabolite, α-ketoglutarate, explains the tumorigenic potential of these metabolites, by competitive inhibition of a superfamily of enzymes called the α-ketoglutarate-dependent dioxygenases. These enzymes utilize α-ketoglutarate as a cosubstrate, and are involved in fatty acid metabolism, oxygen sensing, collagen biosynthesis, and modulation of the epigenome. They include enzymes that are involved in regulating gene expression via DNA and histone tail demethylation. In this review, we will focus on the link between metabolism and epigenetics, and how we may target oncometabolite-induced tumorigenesis in the future
On the interaction of ultrasound with cracks: Applications to fatigue crack growth
Partial contact of two rough fatigue crack surfaces leads to transmission and diffraction of an acoustic signal at those contacts. Recent experimental and theoretical efforts to understand and quantify such contact in greater detail are discussed. The objective is to develop an understanding of the closure phenomenon and its application to the interpretation of fatigue data, in particular the R-ratio, spike overload/underload and threshold effects on crack propagation
Characterization of Knots and Links Arising From Site-specific Recombination on Twist Knots
We develop a model characterizing all possible knots and links arising from
recombination starting with a twist knot substrate, extending previous work of
Buck and Flapan. We show that all knot or link products fall into three
well-understood families of knots and links, and prove that given a positive
integer , the number of product knots and links with minimal crossing number
equal to grows proportionally to . In the (common) case of twist knot
substrates whose products have minimal crossing number one more than the
substrate, we prove that the types of products are tightly prescribed. Finally,
we give two simple examples to illustrate how this model can help determine
previously uncharacterized experimental data.Comment: 32 pages, 7 tables, 27 figures, revised: figures re-arranged, and
minor corrections. To appear in Journal of Physics
Perceived Barriers to the Pre-Transplant Evaluation: A Patient Perspective
Patients who are afforded the opportunity for a kidney transplant tend to have better short and long-term outcomes, including improved physical health, quality of life, and long-term survival over those who are treated with prolonged dialysis (Landreneau, Lee, & Landreneau, 2010; Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients (OPTN/SRTR), 2014; Wolfe et al., 1999). At the end of 2012, 402,514 people were being treated with hemodialysis while 40,605 were receiving peritoneal dialysis (USRDS, 2014). At this same time, only 92,885 people were listed on the OPTN national waitlist for kidney transplantation. The aim of this project was to identify barriers that might delay or halt progress toward waitlist placement in a midwestern hospital transplant program.
A patient-focused survey was sent to 346 end stage renal disease patients referred to a kidney transplant center for a pre-transplant work-up in 2014. The survey collected demographic and health literacy data as well as data focused on patient concerns and attitudes toward kidney transplantation. Eighty-eight patients (30% response rate) completed and returned the survey (50% male, 78% White, and a mean age of 62). Data were evaluated in aggregate with further evaluation of data based on race and sex. The question âhow confident are you filling out medical formsâ was statistically significant (p = .002) for âsexâ and âhealth literacy.â The greatest concerns were âlength of time to wait for a kidney transplantâ and issues inherent to âfinding a living donor.â The survey prompt that âdialysis is not that badâ generated the most negative rating in the attitudes section of the survey.
Thirty-eight percent of respondents were identified as having limited health literacy (Short Literacy Survey [SLS] score 3-9). It is recommended that the SLS be added to initial patient screenings, with findings used to create an individualized care plan designed to assist patients through the pre-transplant evaluation. All patient educational materials need to be evaluated for ease of reading and grade level. Patient education materials must also be created to address specific patient identified barriers (e.g. long wait time for a kidney transplant, finding a living donor, coping with long-term dialysis)
The development of a cislunar space infrastructure
The primary objective of this Advanced Mission Design Program is to define the general characteristics and phased evolution of a near-Earth space infrastructure. The envisioned foundation includes a permanently manned, self-sustaining base on the lunar surface, a space station at the Libration Point between earth and the moon (L1), and a transportation system that anchors these elements to the Low Earth Orbit (LEO) station. The implementation of this conceptual design was carried out with the idea that the infrastructure is an important step in a larger plan to expand man's capabilities in space science and technology. Such expansion depends on low cost, reliable, and frequent access to space for those who wish to use the multiple benefits of this environment. The presence of a cislunar space infrastructure would greatly facilitate the staging of future planetary missions, as well as the full exploration of the lunar potential for science and industry. The rationale for, and a proposed detailed scenario in support of, the cislunar space infrastructure are discussed
Radii and Binding Energies of Nuclei in the Alpha-Cluster Model
The alpha-cluster model is based on two assumptions that the proton-neutron
pair interactions are responsible for adherence between alpha-clusters and that
the NN-interaction in the alpha-clusters is isospin independent. It allows one
to estimate the Coulomb energy and the short range inter-cluster bond energy in
dependence on the number of clusters. The charge radii are calculated on the
number of alpha-clusters too. Unlike the Weizsacker formula in this model the
binding energies of alpha-clusters and excess neutrons are estimated
separately. The calculated values are in a good agreement with the experimental
data.Comment: Latex2e 2.09, 13 pages, 4 figure
- âŠ