4,457 research outputs found
Vibration Reduction and Performance Enhancement in Rotorcraft Using Active Flaps at High Advance Ratios
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76329/1/AIAA-2006-1861-222.pd
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N-Alpha-Acetylation of α-Synuclein Increases Its Helical Folding Propensity, GM1 Binding Specificity and Resistance to Aggregation
A switch in the conformational properties of α-synuclein (αS) is hypothesized to be a key step in the pathogenic mechanism of Parkinson’s disease (PD). Whereas the beta-sheet-rich state of αS has long been associated with its pathological aggregation in PD, a partially alpha-helical state was found to be related to physiological lipid binding; this suggests a potential role of the alpha-helical state in controlling synaptic vesicle cycling and resistance to β-sheet rich aggregation. N-terminal acetylation is the predominant post-translational modification of mammalian αS. Using circular dichroism, isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed the effects of N-terminal acetylation on the propensity of recombinant human αS to form the two conformational states in interaction with lipid membranes. Small unilamellar vesicles of negatively charged lipids served as model membranes. Consistent with previous NMR studies using phosphatidylserine, we found that membrane-induced α-helical folding was enhanced by N-terminal acetylation and that greater exothermic heat could be measured upon vesicle binding of the modified protein. Interestingly, the folding and lipid binding enhancements with phosphatidylserine in vitro were weak when compared to that of αS with GM1, a lipid enriched in presynaptic membranes. The resultant increase in helical folding propensity of N-acetylated αS enhanced its resistance to aggregation. Our findings demonstrate the significance of the extreme N-terminus for folding nucleation, for relative GM1 specificity of αS-membrane interaction, and for a protective function of N-terminal-acetylation against αS aggregation mediated by GM1
Bacteria and the Aging and Longevity of Caenorhabditis elegans
The molecular genetic analysis of longevity of Caenorhabditis elegans has yielded fundamental insights into evolutionarily conserved pathways and processes governing the physiology of aging. Recent studies suggest that interactions between C. elegans and its microbial environment may influence the aging and longevity of this simple host organism. Experimental evidence supports a role for bacteria in affecting longevity through distinct mechanisms—as a nutrient source, as a potential pathogen that induces double-edged innate immune and stress responses, and as a coevolved sensory stimulus that modulates neuronal signaling pathways regulating longevity. Motivating this review is the anticipation that the molecular genetic dissection of the integrated host immune, stress, and neuroendocrine responses to microbes in C. elegans will uncover basic insights into the cellular and organismal physiology that governs aging and longevity.National Institute of General Medical Sciences (U.S.)Ellison Medical Foundatio
Discovery of a binary icosahedral quasicrystal in ScZn
We report the discovery of a new binary icosahedral phase in a Sc-Zn alloy
obtained through solution-growth, producing millimeter-sized, facetted, single
grain, quasicrystals that exhibit different growth morphologies, pentagonal
dodecahedra and rhombic triacontahedra, under only marginally different growth
conditions. These two morphologies manifest different degrees of
quasicrystalline order, or phason strain. The discovery of i-ScZn
suggests that a reexamination of binary phase diagrams at compositions close to
crystalline approximant structures may reveal other, new binary
quasicrystalline phases.Comment: Incorrect spelling in author list resolve
Capturing Nucleation at 4D Atomic Resolution
Nucleation plays a critical role in many physical and biological phenomena
ranging from crystallization, melting and evaporation to the formation of
clouds and the initiation of neurodegenerative diseases. However, nucleation is
a challenging process to study in experiments especially in the early stage
when several atoms/molecules start to form a new phase from its parent phase.
Here, we advance atomic electron tomography to study early stage nucleation at
4D atomic resolution. Using FePt nanoparticles as a model system, we reveal
that early stage nuclei are irregularly shaped, each has a core of one to few
atoms with the maximum order parameter, and the order parameter gradient points
from the core to the boundary of the nucleus. We capture the structure and
dynamics of the same nuclei undergoing growth, fluctuation, dissolution,
merging and/or division, which are regulated by the order parameter
distribution and its gradient. These experimental observations differ from
classical nucleation theory (CNT) and to explain them we propose the order
parameter gradient (OPG) model. We show the OPG model generalizes CNT and
energetically favours diffuse interfaces for small nuclei and sharp interfaces
for large nuclei. We further corroborate this model using molecular dynamics
simulations of heterogeneous and homogeneous nucleation in liquid-solid phase
transitions of Pt. We anticipate that the OPG model is applicable to different
nucleation processes and our experimental method opens the door to study the
structure and dynamics of materials with 4D atomic resolution.Comment: 42 pages, 5 figures, 12 supplementary figures and one supplementary
tabl
Myokine expression and tumor-suppressive effect of serum following 12 weeks of exercise in prostate cancer patients on ADT
Purpose:
Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines, even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth.
Methods:
Ten prostate cancer patients undertaking androgen deprivation therapy (age, 73.3 ± 5.6 yr) undertook a 12-wk exercise-based intervention including supervised resistance training, self-directed aerobic exercise, and protein supplementation. Body composition was assessed by dual-energy x-ray absorptiometry and muscle strength by the one-repetition maximum method. Fasting blood was collected at baseline and postintervention, and serum levels of myokines—secreted protein acidic and rich in cysteine, oncostatin M (OSM), decorin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 (IGFBP-3)—were measured. The growth of the prostate cancer cell line DU145 with baseline and postintervention serum was measured.
Results:
Body weight (P = 0.011), fat mass (P = 0.012), and percent body fat (P = 0.033) were reduced, whereas percent lean mass (P = 0.001) increased, as did strength (leg press, P = 0.006; chest press, P = 0.020) across the intervention. Serum OSM levels (P = 0.020) and relative serum OSM levels (P = 0.020) increased compared with baseline. A significant reduction in DU145 Cell Index (P = 0.012) and growth rate (P = 0.012) was observed after applying postintervention serum compared with baseline serum.
Conclusion:
This study provides evidence for enhanced myokine expression and tumor-suppressive effects of serum from chronically exercise-trained prostate cancer patients on androgen deprivation therapy
Shaken and stirred: conduction and turbulence in clusters of galaxies
(abridged) Uninhibited radiative cooling in clusters of galaxies would lead
to excessive mass accretion rates contrary to observations. One of the key
proposals to offset radiative energy losses is thermal conduction from outer,
hotter layers of cool core clusters to their centers. However, conduction is
sensitive to magnetic field topology. In cool-core clusters the heat buoyancy
instability (HBI) leads to B-fields ordered preferentially in the direction
perpendicular to that of gravity, which significantly reduces the level of
conduction below the classical Spitzer-Braginskii value. However, the cluster
cool cores are rarely in perfect hydrostatic equilibrium. Sloshing motions due
to minor mergers, galaxy motions or AGN can significantly perturb the gas and
affect the level of thermal conduction. We perform 3D AMR MHD simulations of
the effect of turbulence on the properties of the anisotropic thermal
conduction in cool core clusters. We show that very weak subsonic motions, well
within observational constraints, can randomize the magnetic field and
significantly boost effective thermal conduction beyond the saturated values
expected in the pure unperturbed HBI case. We find that the turbulent motions
can essentially restore the conductive heat flow to the cool core to level
comparable to the theoretical maximum of 1/3 Spitzer for a highly tangled
field. Runs with radiative cooling show that the cooling catastrophe can be
averted and the cluster core stabilized. Above a critical Froude number, these
same turbulent motions also eliminate the tangential bias in the velocity and
magnetic field that is otherwise induced by the trapped g-modes. Our results
can be tested with future radio polarization measurements, and have
implications for efficient metal dispersal in clusters.Comment: submitted to ApJ, references added, expanded Section
Multicritical Points of Potts Spin Glasses on the Triangular Lattice
We predict the locations of several multicritical points of the Potts spin
glass model on the triangular lattice. In particular, continuous multicritical
lines, which consist of multicritical points, are obtained for two types of
two-state Potts (i.e., Ising) spin glasses with two- and three-body
interactions on the triangular lattice. These results provide us with numerous
examples to further verify the validity of the conjecture, which has succeeded
in deriving highly precise locations of multicritical points for several spin
glass models. The technique, called the direct triangular duality, a variant of
the ordinary duality transformation, directly relates the triangular lattice
with its dual triangular lattice in conjunction with the replica method.Comment: 18 pages, 2, figure
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