Insights into p53-Dependent Apoptotic Signaling and Cell Fate vis-a-vis Functional Cooperation among BCL-xL, Cytoplasmic p53, and PUMA

Following DNA damage, nuclear p53 induces the expression of PUMA (p53 upregulated modulator of apoptosis), a BH3‑only protein that binds and inhibits the anti‑apoptotic BCL‑2 repertoire, including BCL‑xL. Structural investigations of PUMA and the BCL‑xL×PUMA BH3 domain complex by X‑ray crystallography and nuclear magnetic resonance (NMR) spectroscopy reveal a novel, PUMA‑induced, domain‑swapped dimerization of BCL‑xL that requires a π‑stacking interaction between PUMA W71 and BCL‑xL H113. PUMA is an intrinsically disordered protein, but upon interaction with BCL‑xL, PUMA W71 and the PUMA BH3 domain residues fold into an alpha helix and subtly remodel BCL‑xL to trigger its dimerization. Wild type PUMA or a PUMA mutant incapable of promoting BCL‑xL dimerization (PUMA W71A) equivalently inhibit the anti‑apoptotic BCL‑2 repertoire to sensitize for death receptor‑activated apoptosis, but only wild type PUMA promotes p53‑dependent DNA damage‑induced apoptosis. Biochemical and cellular data demonstrate that PUMA‑mediated structural remodeling and dimerization of BCL‑xL modulates its affinity for cytosolic p53, providing a detailed mechanism of BCL‑xL, cytosolic p53, and PUMA functional cooperation. Our data suggest that within the BCL‑2 family, ligand binding‑induced, domain‑swapped dimerization is a critical control point to increase signal transduction complexity within the apoptotic pathways

Neutron isotope reactions

The field of low temperature nuclear reactions has made slow but steady progress. Evidence has accumulated for production of energy at the level of a few watts, for production of helium in proportion to energy, for energetic particles, and for transmutations of elements. But there is no generally accepted theory for these phenomena. Progress requires a body of experimental evidence and a candidate theory through which theory and experiment can gain mutual support and acceptance. We explore the possibility that transfer of neutrons from neutron isotopes to ordinary nuclei, followed by beta decay of the neutron-enriched nuclei, facilitates a class of low-temperature transmutations. We have tested this possibility by comparing the implications of neutron isotope theory with the transmutations reported by Iwamura and associates. We find that experiment quantifies and supports the theory, and that theory clarifies and supports the experimental observations

Trends and Regional Variation in Hip, Knee and Shoulder Replacement

Analyzes patterns in underuse or overuse of joint replacements among Medicare beneficiaries by geographic regions and race/ethnicity. Explores underlying factors and highlights the need for physician and patient education and shared decision making

The relation between the frequency distributions of sieve diameters and fall velocities of sediment particles

A relation between the frequency distributions of sieve diameters and fall velocities is developed. The relation shows that if the sieve diameters of a sediment are log-normally distributed, the fall velocities will also have this distribution, but with a different standard deviation which can be calculated. The results of detailed measurements of the fall velocities of two different natural sands are presented, and the distributions of fall velocities are found to be in good agreement with the predicted distributions. The sedimentation diameters determined from the measured fall velocities agree very well with those predicted from the sieve diameters by the Inter-Agency Committee on Water Resources [1957]

Improving Patient Decision-Making in Health Care

Outlines regional variations within Minnesota in rates of patients with similar conditions receiving elective surgery, the concept of shared decision making, treatment choices for eight conditions, and steps for ensuring patients make informed decisions

Investigation of Supercritical Water Phenomena for Space and Extraterrestrial Application

The cost of carrying or resupplying life support resources for long duration manned space exploration missions such as a mission to Mars is prohibitive and requires the development of suitable recycling technologies. Supercritical Water Oxidation (SCWO) has been identified as an attractive candidate for these extended missions because (i) pre-drying of wet waste streams is not required, (ii) product streams are relatively benign, microbially inert, and easily reclaimed, (iii) waste conversion is complete and relatively fast, and (iv) with proper design and operation, reactions can be self-sustaining. Initial work in this area at NASA was carried out at the Ames Research Center in the 1990 s with a focus on understanding the linkages between feed stock preparation (i.e., particle size and distribution) of cellulosic based waste streams and destruction rates under a range of operating temperatures and pressures. More recently, work in SCWO research for space and extra-terrestrial application has been performed at NASA s Glenn Research Center where various investigations, with a particular focus in the gravitational effects on the thermo-physical processes occurring in the bulk medium, have been pursued. In 2010 a collaborative NASA/CNES (the French Space Agency) experiment on the critical transition of pure water was conducted in the long duration microgravity environment on the International Space Station (ISS). A follow-on experiment, to study the precipitation of salt in sub-critical, trans-critical and supercritical water is scheduled to be conducted on the ISS in 2013. This paper provides a brief history of NASA s earlier work in SCWO, discusses the potential for application of SCWO technology in extended space and extraterrestrial missions, describes related research conducted on the ISS, and provides a list of future research activities to advance this technology in both terrestrial and extra-terrestrial applications

Photoacoustic effect for multiply scattered light

We consider the photoacoustic effect for multiply scattered light in a random medium. Within the accuracy of the diffusion approximation to the radiative transport equation, we present a general analysis of the sensitivity of a photoacoustic wave to the presence of one or more small absorbing objects. Applications to tumor detection by photoacoustic imaging are suggested