Algebraic Monte Carlo precedure reduces statistical analysis time and cost factors

Algebraic Monte Carlo procedure statistically analyzes performance parameters in large, complex systems. The individual effects of input variables can be isolated and individual input statistics can be changed without having to repeat the entire analysis

Sequence-Specific Inhibition of a Nonspecific Protease

A nonspecific exopeptidase, aminopeptidase N (APN), is inhibited sequence-specifically by a synthetic host, cucurbit[7]uril (Q7), which binds with high affinity and specificity to N-terminal phenylalanine (Phe) and 4-(aminomethyl)phenylalanine (AMPhe) and prevents their removal from the peptide. Liquid chromatography experiments demonstrated that in the presence of excess Q7, APN quantitatively converts the pentapeptides Thr-Gly-Ala-X-Met into the dipeptides X-Met (X = Phe, AMPhe). The resulting Q7-bound products are completely stable to proteolytic digestion for at least 24 h. Structure–activity studies revealed a direct correlation between the extent of protection of an N-terminal amino acid and its affinity for Q7. Therefore, Q7 provides predictable sequence-specificity to an otherwise nonspecific protease and enables the production of a single peptide product. Conversely, APN uncovers a high-affinity epitope that is subsequently bound by Q7, and thus this approach should also facilitate the molecular recognition of peptides

Targeting DNA repair pathways for cancer treatment: what's new?

Disruptions in DNA repair pathways predispose cells to accumulating DNA damage. A growing body of evidence indicates that tumors accumulate progressively more mutations in DNA repair proteins as cancers progress. DNA repair mechanisms greatly affect the response to cytotoxic treatments, so understanding those mechanisms and finding ways to turn dysregulated repair processes against themselves to induce tumor death is the goal of all DNA repair inhibition efforts. Inhibition may be direct or indirect. This burgeoning field of research is replete with promise and challenge, as more intricacies of each repair pathway are discovered. In an era of increasing concern about healthcare costs, use of DNA repair inhibitors can prove to be highly effective stewardship of R&D resources and patient expenses

Structure of IL-22 Bound to Its High-Affinity IL-22R1 Chain

SummaryIL-22 is an IL-10 family cytokine that initiates innate immune responses against bacterial pathogens and contributes to immune disease. IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22R1 also pairs with the IL-20R2 chain to induce IL-20 and IL-24 signaling. To define the molecular basis of these diverse interactions, we have determined the structure of the IL-22/sIL-22R1 complex. The structure, combined with homology modeling and surface plasmon resonance studies, defines the molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses

Shear History Extensional Rheology Experiment: A Proposed ISS Experiment

The Shear History Extensional Rheology Experiment (SHERE) is a proposed International Space Station (ISS) glovebox experiment designed to study the effect of preshear on the transient evolution of the microstructure and viscoelastic tensile stresses for monodisperse dilute polymer solutions. Collectively referred to as Boger fluids, these polymer solutions have become a popular choice for rheological studies of non-Newtonian fluids and are the non-Newtonian fluid used in this experiment. The SHERE hardware consists of the Rheometer, Camera Arm, Interface Box, Cabling, Keyboard, Tool Box, Fluid Modules, and Stowage Tray. Each component will be described in detail in this paper. In the area of space exploration, the development of in-situ fabrication and repair technology represents a critical element in evolution of autonomous exploration capability. SHERE has the capability to provide data for engineering design tools needed for polymer parts manufacturing systems to ensure their rheological properties have not been impacted in the variable gravity environment and this will be briefly addressed

The Exemplar T8 Subdwarf Companion of Wolf 1130

We have discovered a wide separation (188.5") T8 subdwarf companion to the sdM1.5+WD binary Wolf 1130. Companionship of WISE J200520.38+542433.9 is verified through common proper motion over a ~3 year baseline. Wolf 1130 is located 15.83 +/- 0.96 parsecs from the Sun, placing the brown dwarf at a projected separation of ~3000 AU. Near-infrared colors and medium resolution (R~2000-4000) spectroscopy establish the uniqueness of this system as a high-gravity, low-metallicity benchmark. Although there are a number of low-metallicity T dwarfs in the literature, WISE J200520.38+542433.9 has the most extreme inferred metallicity to date with [Fe/H] = -0.64 +/- 0.17 based on Wolf 1130. Model comparisons to this exemplar late-type subdwarf support it having an old age, a low metallicity, and a small radius. However, the spectroscopic peculiarities of WISE J200520.38+542433.9 underscore the importance of developing the low-metallicity parameter space of the most current atmospheric models.Comment: Accepted to ApJ on 05 September 2013; 33 pages in preprint format, 8 figures, 3 table

Surface Gravities for 228 M, L, and T Dwarfs in the NIRSPEC Brown Dwarf Spectroscopic Survey

We combine 131 new medium-resolution (R~2000) J-band spectra of M, L, and T dwarfs from the Keck NIRSPEC Brown Dwarf Spectroscopic Survey (BDSS) with 97 previously published BDSS spectra to study surface-gravity-sensitive indices for 228 low-mass stars and brown dwarfs spanning spectral types M5-T9. Specifically, we use an established set of spectral indices to determine surface gravity classifications for all M6-L7 objects in our sample by measuring equivalent widths (EW) of the K I lines at 1.1692, 1.1778, 1.2529 um, and the 1.2 um FeHJ absorption index. Our results are consistent with previous surface gravity measurements, showing a distinct double peak - at ~L5 and T5 - in K I EW as a function of spectral type. We analyze K I EWs of 73 objects of known ages and find a linear trend between log(Age) and EW. From this relationship, we assign age ranges to the very low gravity, intermediate gravity, and field gravity designations for spectral types M6-L0. Interestingly, the ages probed by these designations remain broad, change with spectral type, and depend on the gravity sensitive index used. Gravity designations are useful indicators of the possibility of youth, but current datasets cannot be used to provide a precise age estimate.Comment: 33 pages, 13 figures, ApJ in pres