364 research outputs found
Relationship of dietary protein level to carcass characteristics and growth performance of swine
Rapid Evolution of BRCA1 and BRCA2 in Humans and Other Primates
The maintenance of chromosomal integrity is an essential task of every living organism and cellular repair mechanisms exist to guard against insults to DNA. Given the importance of this process, it is expected that DNA repair proteins would be evolutionarily conserved, exhibiting very minimal sequence change over time. However, BRCA1, an essential gene involved in DNA repair, has been reported to be evolving rapidly despite the fact that many protein-altering mutations within this gene convey a significantly elevated risk for breast and ovarian cancers. Results: To obtain a deeper understanding of the evolutionary trajectory of BRCA1, we analyzed complete BRCA1 gene sequences from 23 primate species. We show that specific amino acid sites have experienced repeated selection for amino acid replacement over primate evolution. This selection has been focused specifically on humans and our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). After examining BRCA1 polymorphisms in 7 bonobo, 44 chimpanzee, and 44 rhesus macaque (Macaca mulatta) individuals, we find considerable variation within each of these species and evidence for recent selection in chimpanzee populations. Finally, we also sequenced and analyzed BRCA2 from 24 primate species and find that this gene has also evolved under positive selection. Conclusions: While mutations leading to truncated forms of BRCA1 are clearly linked to cancer phenotypes in humans, there is also an underlying selective pressure in favor of amino acid-altering substitutions in this gene. A hypothesis where viruses are the drivers of this natural selection is discussed.National Institutes of Health R01-GM-093086, 8U42OD011197-13National Science Foundation BCS-07115972Burroughs Wellcome FundMolecular Bioscience
Guidance and Control Design for High-Speed Rollout and Turnoff (ROTO)
A ROTO architecture, braking and steering control law and display designs for a research high speed Rollout and Turnoff (ROTO) system applicable to transport class aircraft are described herein. Minimum surface friction and FMS database requirements are also documented. The control law designs were developed with the aid of a non-real time simulation program incorporating airframe and gear dynamics as well as steering and braking guidance algorithms. An attainable objective of this ROTO system, as seen from the results of this study, is to assure that the studied aircraft can land with runway occupancy times less then 53 seconds. Runway occupancy time is measured from the time the aircraft crosses the runway threshold until its wing tip clears the near side of the runway. Turnoff ground speeds of 70 knots onto 30 degree exits are allowed with dry and wet surface conditions. Simulation time history and statistical data are documented herein. Parameters which were treated as variables in the simulation study include aircraft touchdown weight/speed/location, aircraft CG, runway friction, sensor noise and winds. After further design and development of the ROTO control system beyond the system developed earlier, aft CG MD-11 aircraft no longer require auto-asymmetric braking (steering) and fly-by-wire nose gear steering. However, the auto ROTO nose gear hysteresis must be less than 2 degrees. The 2 sigma dispersion certified for MD-11 CATIIIB is acceptable. Using this longitudinal dispersion, three ROTO exits are recommended at 3300, 4950 and 6750 feet past the runway threshold. The 3300 foot exit is required for MD-81 class aircraft. Designs documented in this report are valid for the assumptions/models used in this simulation. It is believed that the results will apply to the general class of transport aircraft; however further effort is required to validate this assumption for the general case
Probing the equation of state in the AGS energy range with 3-d hydrodynamics
The effect of (i) the phase transition between a quark gluon plasma (QGP) and
a hadron gas and (ii) the number of resonance degrees of freedom in the
hadronic phase on the single inclusive distributions of 16 different types of
produced hadrons for Au+Au collisions at AGS energies is studied.
We have used an exact numerical solution of the relativistic hydrodynamical
equations without free parameters which, because of its 3-d character,
constitutes a considerable improvement over the classical Landau solution.
Using two different equations of state (eos) - one containing a phase
transition from QGP to the Hadronic Phase and two versions of a purely hadronic
eos - we find that the first one gives an overall better description of the
Au+Au experimental data at energies.
We reproduce and analyse measured meson and proton spectra and also make
predictions for anti-protons, deltas, anti-deltas and hyperons. The low m_t
enhancement in pi- spectra is explained by baryon number conservation and
strangeness equilibration.
We also find that negative kaon data are more sensitive to the eos, as well
as the K-/pi- ratio. All hyperons and deltas are sensitive to the presence of a
phase transition in the forward rapidity region. Anti-protons, Omegas and heavy
anti-baryons are sensitive in the whole rapidity range.Comment: 25 pages (.tex) and 9 figures (.ps
Examining mindfulness-based stress reduction: Perceptions from minority older adults residing in a low-income housing facility
<p>Abstract</p> <p>Background</p> <p>Mindfulness-based stress reduction (MBSR) programs are becoming increasingly common, but have not been studied in low income minority older populations. We sought to understand which parts of MBSR were most important to practicing MBSR members of this population, and to understand whether they apply their training to daily challenges.</p> <p>Methods</p> <p>We conducted three focus groups with 13 current members of an MBSR program. Participants were African American women over the age of 60 in a low-income housing residence. We tape recorded each session and subsequently used inductive content analysis to identify primary themes.</p> <p>Results and discussion</p> <p>Analysis of the focus group responses revealed three primary themes stress management, applying mindfulness, and the social support of the group meditation. The stressors they cited using MBSR with included growing older with physical pain, medical tests, financial strain, and having grandchildren with significant mental, physical, financial or legal hardships. We found that participants particularly used their MBSR training for coping with medical procedures, and managing both depression and anger.</p> <p>Conclusion</p> <p>A reflective stationary intervention delivered in-residence could be an ideal mechanism to decrease stress in low-income older adult's lives and improve their health.</p
Pancreatic carcinoma
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44375/1/10620_2005_Article_BF02235997.pd
Pharmacological and rAAV Gene Therapy Rescue of Visual Functions in a Blind Mouse Model of Leber Congenital Amaurosis
BACKGROUND: Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for ~15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat (−/−) mouse, recapitulates clinical features of the human disease. Here, we report that two interventions—intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds—each restore retinal function to Lrat (−/−) mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to ~50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat (−/−) mice increased ~2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from ~5% of wild-type levels in Lrat (−/−) mice to ~50% of wild-type levels in treated Lrat (−/−) mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and ~1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness
Synthesis of a square-planar rhodium alkylidene N-heterocyclic carbene complex and its reactivity toward alkenes
The first rhodium alkylidene square-planar complex stabilized by an N-heterocyclic carbene ligand, RhCl(-CHPh)(IPr)PPh3 (2; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-carbene), has been prepared by reaction of RhCl(IPr)(PPh3)2 (1) with phenyldiazomethane and its dynamic behavior in solution studied. Treatment of 2 with alkenes results in the formation of the ¿2-olefin complexes RhCl(¿2-CH2-CHR)(IPr)PPh3 (3, R = H; 4, R = Ph; 5, R = OEt) and new olefins arising from the coupling of the alkylidene with the alkenes, likely via a metallacyclobutane intermediate
Biochemical evidence for the tyrosine involvement in cationic intermediate stabilization in mouse β-carotene 15, 15'-monooxygenase
<p>Abstract</p> <p>Background</p> <p>β-carotene 15,15'-monooxygenase (BCMO1) catalyzes the crucial first step in vitamin A biosynthesis in animals. We wished to explore the possibility that a carbocation intermediate is formed during the cleavage reaction of BCMO1, as is seen for many isoprenoid biosynthesis enzymes, and to determine which residues in the substrate binding cleft are necessary for catalytic and substrate binding activity. To test this hypothesis, we replaced substrate cleft aromatic and acidic residues by site-directed mutagenesis. Enzymatic activity was measured <it>in vitro </it>using His-tag purified proteins and <it>in vivo </it>in a β-carotene-accumulating <it>E. coli </it>system.</p> <p>Results</p> <p>Our assays show that mutation of either Y235 or Y326 to leucine (no cation-π stabilization) significantly impairs the catalytic activity of the enzyme. Moreover, mutation of Y326 to glutamine (predicted to destabilize a putative carbocation) almost eliminates activity (9.3% of wt activity). However, replacement of these same tyrosines with phenylalanine or tryptophan does not significantly impair activity, indicating that aromaticity at these residues is crucial. Mutations of two other aromatic residues in the binding cleft of BCMO1, F51 and W454, to either another aromatic residue or to leucine do not influence the catalytic activity of the enzyme. Our <it>ab initio </it>model of BCMO1 with β-carotene mounted supports a mechanism involving cation-π stabilization by Y235 and Y326.</p> <p>Conclusions</p> <p>Our data are consistent with the formation of a substrate carbocation intermediate and cation-π stabilization of this intermediate by two aromatic residues in the substrate-binding cleft of BCMO1.</p
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