Free energy simulation to investigate the effect of amino acid sequence environment on the severity of osteogenesis imperfecta by glycine mutations in collagen

Molecular dynamics simulations were carried out to calculate the free energy change difference of two collagen-like peptide models for Gly→Ser mutations causing two different osteogenesis imperfecta phenotypes. These simulations were performed to investigate the impact of local amino acid sequence environment adjacent to a mutation site on the stability of the collagen. The average free energy differences for a Gly→Ser mutant relative to a wild type are 3.4 kcal/mol and 8.2 kcal/mol for a nonlethal site and a lethal site, respectively. The free energy change differences of mutant containing two Ser residues relative to the wild type at the nonlethal and lethal mutation sites are 4.6 and 9.8 kcal/mol, respectively. Although electrostatic interactions stabilize mutants containing one or two Ser residues at both mutation sites, van der Waals interactions are of sufficient magnitude to cause a net destabilization. The presence of Gln and Arg near the mutation site, which contain large and polar side chains, provide more destabilization than amino acids containing small and nonpolar side chains. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 401–409, 2011Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83464/1/21593_ftp.pd

Lithium-6 and Gamma Rays: Complementary Constraints on Cosmic-Ray History

The rare isotope 6Li is made only by cosmic rays, dominantly in alpha+alpha fusion reactions with ISM helium. Consequently, this nuclide provides a unique diagnostic of the history of cosmic rays in our Galaxy. The same hadronic cosmic-ray interactions also produce high-energy gamma rays (mostly via neutral pion production). Thus, hadronic gamma-rays and 6Li are intimately linked. Specifically, 6Li directly encodes the local cosmic-ray fluence over cosmic time, while extragalactic hadronic gamma rays encode an average cosmic-ray fluence over lines of sight out to the horizon. We examine this link and show how 6Li and gamma-rays can be used together to place important model-independent limits on the cosmic-ray history of our Galaxy and the universe. We first constrain gamma-ray production from ordinary Galactic cosmic rays, using the local 6Li abundance. We find that the solar 6Li abundance demands an accompanying extragalactic pionic gamma-ray intensity which exceeds that of the entire observed EGRB by a factor of 2-6. Possible explanations for this discrepancy are discussed. We then constrain Li production using recent determinations of extragalactic gamma-ray background (EGRB). We note that cosmic rays created during cosmic structure formation would lead to pre-Galactic Li production, which would act as a "contaminant" to the primordial 7Li content of metal-poor halo stars. We find the uncertainties in the observed EGRB are so large that we cannot exclude a pre-Galactic Li which is comparable to primordial 7Li. Our limits and their more model-dependent extensions will improve significantly with additional observations of 6Li in halo stars, and with improved measurements of the EGRB spectrum by GLAST. (Abriged abstract)Comment: 24 pages, 1 figure, AASTeX. Comments welcom

Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles

Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient therapeutic effect. We assessed the ability of a peptide based, oligonucleotide condensing, endosomolytic nanoparticle (NP) system to deliver siRNA to KRAS-driven cancers. We show that this peptide-based NP is avidly taken up by cancer cell

Portfolio Vol. III N 4

Moll, Willlie. I Was in Kitchener Camp. Prose. 5-6. Barrington, John. The Pledging of Homer McGunk. Prose. 7-9. Stewart, John. In Time of Death. Prose. 10. Lindsey, Arthur Ward. Retrospect. Prose. 11-13. Phillips, Allison. Blue Moon. Poetry. 14. Yoxall, Lindsey E. Pro Patria. Prose. 15-16. Beckham, Adela. Wind--Dreams. Poetry. 18. Fields, Brooks. The Doctor Takes a Trip. Prose. 19-20. Deane, Dorothy. Review of New Books. Prose. 21. Smith, Duke. Review of New Recordings. Prose. 21. Timrud, David. Refugee. Prose. 22-23

Basket Cases and Breadbaskets: Sacred Rice and Agricultural Development in Postcolonial Africa

Author's final manuscript.Based on ethnographic research among rural Diola in Guinea-Bissau, I provide a broad view of the history and interpenetration of rice in social, political, religious, and ecological domains, while chronicling the current difficulties of residents in this region who are no longer able to grown enough of it. These farmers’ experiences are unfolding at a time of revitalized attention to agricultural development in Africa, particularly under the auspices of the New Green Revolution for Africa. I examine the premises that constitute the resuscitated effort to address the plight of African farmers. I argue that the totalizing quality of rice in Diola and other rice-cultivating societies requires a development approach that takes into account dimensions of agrarian life not encapsulated by the high- modernist and anti-political orientation of the New Green Revolution for Africa

External fishing effort regulates positive effects of no-take marine protected areas

Marine protected areas (MPAs) have been established across the globe to mitigate the effects of multiple stressors on marine communities. In many locations, MPAs have generated positive effects on fish communities, but the impacts of fishing pressure—the primary stressor MPAs seek to manage—have not been well investigated. We examined changes in fish biomass inside and outside of no-take MPAs over 14 years in central California, USA. Using data from the community-based science program, the California Collaborative Fisheries Research Program, we tested which environmental and human-induced stressors most influence the strength of MPA responses. While temperature and productivity were included in the best fit model, we found that fine-scale fishing effort data, following reserve implementation, best explained the spatial variation in fish community responses to MPAs. Specifically, differences in fish biomass between MPAs and sites open to fishing were larger for reserves near heavily fished locations and these areas exhibited the highest rate of change in fish biomass, indicating strong positive effects of the MPA on the most heavily exploited fish communities. As MPAs continue to be used as a prominent conservation strategy in coastal systems, managers should consider both the suite of human-induced (socio-ecological interactions) and environmental conditions that may alter MPA success as well as establish long-term monitoring programs to fully assess the functionality of marine reserves into the future

Search for the Proton Decay Mode proton to neutrino K+ in Soudan 2

We have searched for the proton decay mode proton to neutrino K+ using the one-kiloton Soudan 2 high resolution calorimeter. Contained events obtained from a 3.56 kiloton-year fiducial exposure through June 1997 are examined for occurrence of a visible K+ track which decays at rest into mu+ nu or pi+ pi0. We found one candidate event consistent with background, yielding a limit, tau/B > 4.3 10^{31} years at 90% CL with no background subtraction.Comment: 13 pages, Latex, 3 tables and 3 figures, Accepted by Physics Letters

Large CSC chamber for the PHENIX muon detector with ultra thin cathode foils

The muon tracking system for the PHENIX detector at RHIC uses cathode strip chambers (CSC) for the tracking detectors. These detectors must provide 100 μm resolution per measurement plane to give satisfactory mass resolution of the vector mesons. The intermediate station (station 2) must have a very small radiation length, and large acceptance. We have prototyped a full scale CSC chamber to test the use of 25 micron metalized mylar foils for the cathode strips at station 2. The full scale prototype detector is a trapezoid 2.3 meters high and 2.3 meters wide. The foil and wire planes are mounted on thin 3,2 mm thick by 7.5 cm wide laminated frames and the tension of the planes is maintained by the two large 7.5 cm widex3.0 cm thick aluminum support frames. The total radiation length of the active region is 8.5x104

Subjective utility moderates bidirectional effects of conflicting motivations on pain perception

Minimizing pain and maximizing pleasure are conflicting motivations when pain and reward co-occur. Decisions to prioritize reward consumption or pain avoidance are assumed to lead to pain inhibition or facilitation, respectively. Such decisions are a function of the subjective utility of the stimuli involved, i.e. the relative value assigned to the stimuli to compare the potential outcomes of a decision. To test perceptual pain modulation by varying degrees of motivational conflicts and the role of subjective utility, we implemented a task in which healthy volunteers had to decide between accepting a reward at the cost of receiving a nociceptive electrocutaneous stimulus or rejecting both. Subjective utility of the stimuli was assessed by a matching task between the stimuli. Accepting reward coupled to a nociceptive stimulus resulted in decreased perceived intensity, while rejecting the reward to avoid pain resulted in increased perceived intensity, but in both cases only if a high motivational conflict was present. Subjective utility of the stimuli involved moderated these bidirectional perceptual effects: the more a person valued money over pain, the more perceived intensity increased or decreased. These findings demonstrate pain modulation when pain and reward are simultaneously present and highlight the importance of subjective utility for such modulation

The MINERν\nuA Data Acquisition System and Infrastructure

MINER$\nu$A (Main INjector ExpeRiment $\nu$-A) is a new few-GeV neutrino cross section experiment that began taking data in the FNAL NuMI (Fermi National Accelerator Laboratory Neutrinos at the Main Injector) beam-line in March of 2010. MINER$\nu$A employs a fine-grained scintillator detector capable of complete kinematic characterization of neutrino interactions. This paper describes the MINER$\nu$A data acquisition system (DAQ) including the read-out electronics, software, and computing architecture.Comment: 34 pages, 16 figure