4,686 research outputs found
Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease
Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response, heat shock factor 1 (HSF1), would play an important role in prion disease. Uninoculated HSF1 knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions HSF1 KO mice had a dramatically shortened lifespan, succumbing to disease ≈20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in HSF1 KO and control mice. The accumulation of proteinase K (PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease
Theoretical investigation of the evolution of the topological phase of BiSe under mechanical strain
The topological insulating phase results from inversion of the band gap due
to spin-orbit coupling at an odd number of time-reversal symmetric points. In
BiSe, this inversion occurs at the point. For bulk
BiSe, we have analyzed the effect of arbitrary strain on the
point band gap using Density Functional Theory. By computing the band structure
both with and without spin-orbit interactions, we consider the effects of
strain on the gap via Coulombic interaction and spin-orbit interaction
separately. While compressive strain acts to decrease the Coulombic gap, it
also increases the strength of the spin-orbit interaction, increasing the
inverted gap. Comparison with BiTe supports the conclusion that effects
on both Coulombic and spin-orbit interactions are critical to understanding the
behavior of topological insulators under strain, and we propose that the
topological insulating phase can be effectively manipulated by inducing strain
through chemical substitution
Solid friction between soft filaments
Any macroscopic deformation of a filamentous bundle is necessarily
accompanied by local sliding and/or stretching of the constituent filaments.
Yet the nature of the sliding friction between two aligned filaments
interacting through multiple contacts remains largely unexplored. Here, by
directly measuring the sliding forces between two bundled F-actin filaments, we
show that these frictional forces are unexpectedly large, scale logarithmically
with sliding velocity as in solid-like friction, and exhibit complex dependence
on the filaments' overlap length. We also show that a reduction of the
frictional force by orders of magnitude, associated with a transition from
solid-like friction to Stokes' drag, can be induced by coating F-actin with
polymeric brushes. Furthermore, we observe similar transitions in filamentous
microtubules and bacterial flagella. Our findings demonstrate how altering a
filament's elasticity, structure and interactions can be used to engineer
interfilament friction and thus tune the properties of fibrous composite
materials
Effects of Gypsy Moth Outbreaks on North American Woodpeckers
We examined the effects of the introduced gypsy moth (Lymantria dispar) on seven species of North American woodpeckers by matching spatially explicit data on gypsy moth outbreaks with data on breeding and wintering populations. In general, we detected modest effects during outbreaks: during the breeding season one species, the Red-headed Woodpecker (Melanerpes erythrocephalus), increased over pre-outbreak levels, while during the winter one species, the Yellow-bellied Sapsucker (Sphyrapicus varius), increased and one, the Downy Woodpecker (Picoides pubescens), decreased from pre-outbreak levels. Responses following outbreaks were similarly variable, and in general we were unsuccessful at predicting population responses to outbreaks from a priori knowledge of woodpecker ecology and behavior. We did, however, find evidence that the response of at least half of the species changed over the 34-year period covered by the study: except for the Northern Flicker (Colaptes auratus), whose response to outbreaks during the winter decreased, populations generally responded more positively to outbreaks with time. This temporal response suggests that North American woodpeckers may be taking greater advantage of the resource pulse and/or habitat changes caused by outbreaks of this exotic pest now than previously, so in the future the effects of gypsy moth outbreaks on these species may increase
A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia.
Inguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment
The Brown Dwarf Kinematics Project (BDKP). II. Details on Nine Wide Common Proper Motion Very Low-Mass Companions to Nearby Stars
We report on nine wide common proper motion systems containing late-type M,
L, or T companions. We confirm six previously reported companions, and identify
three new systems. The ages of these systems are determined using diagnostics
for both stellar primaries and low--mass secondaries and masses for the
secondaries are inferred using evolutionary models. Of our three new
discoveries, the M3+T6.5 pair G 204-39 and SDSS J1758+4633 has an age
constrained to 0.5-1.5 Gyr making the secondary a potentially useful brown
dwarf benchmark. The G5+L4 pair G 200-28 and SDSS J1416+5006 has a projected
separation of ~25,000 AU making it one of the widest and lowest binding energy
systems known to date. The system containing NLTT 2274 and SDSS J0041+1341 is
an older M4+L0 (>4.5 Gyr) pair which shows Halpha activity in the secondary but
not the primary making it a useful tracer of age/mass/activity trends. We find
a resolved binary frequency for widely-separated (> 100 AU) low--mass
companions (i.e. at least a triple system) which is at least twice the
frequency found for the field ultracool dwarf population. The ratio of triples
to binaries and quadruples to binaries is also high for this sample: 3:5 and
1:4, respectively, compared to 8-parsec sample values of 1:4 and 1:26. The
additional components in these wide companion systems indicates a formation
mechanism that requires a third or fourth component to maintain gravitational
stability or facilitate the exchange of angular momentum. The binding energies
for the nine multiples discussed in this text are among the lowest known for
wide low-mass systems, suggesting that weakly bound, low--to--intermediate mass
(0.2M_sun < M_tot <1.0M_sun) multiples can form and survive to exist in the
field (1-8 Gyr).Comment: 62 pages, 12 figures, 11 Tables, AJ accepted for publicatio
Small scale rotational disorder observed in epitaxial graphene on SiC(0001)
Interest in the use of graphene in electronic devices has motivated an
explosion in the study of this remarkable material. The simple, linear Dirac
cone band structure offers a unique possibility to investigate its finer
details by angle-resolved photoelectron spectroscopy (ARPES). Indeed, ARPES has
been performed on graphene grown on metal substrates but electronic
applications require an insulating substrate. Epitaxial graphene grown by the
thermal decomposition of silicon carbide (SiC) is an ideal candidate for this
due to the large scale, uniform graphene layers produced. The experimental
spectral function of epitaxial graphene on SiC has been extensively studied.
However, until now the cause of an anisotropy in the spectral width of the
Fermi surface has not been determined. In the current work we show, by
comparison of the spectral function to a semi-empirical model, that the
anisotropy is due to small scale rotational disorder ( 0.15)
of graphene domains in graphene grown on SiC(0001) samples. In addition to the
direct benefit in the understanding of graphene's electronic structure this
work suggests a mechanism to explain similar variations in related ARPES data.Comment: 5 pages, 4 figure
Association of early versus delayed normalisation of left ventricular ejection fraction with mortality in ischemic cardiomyopathy
OBJECTIVE: In patients with non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (LVEF), normalisation of LVEF is associated with improved outcomes. However, data on patients with ischaemic cardiomyopathy and recovered LVEF are lacking. The goal of this study was to assess the prognostic significance of normalisation of the LVEF in patients with ischaemic cardiomyopathy.
METHODS/RESULTS: We performed a non-prespecified post hoc analysis of the Surgical Treatment for Ischaemic Heart Failure (STICH) trial to determine the association between normalisation of LVEF (\u3e50%) and mortality during follow-up. Of the 1212 patients with LVEF \u3c35% enroled in the STICH trial, 932 underwent assessment of LVEF at 4 months and/or 2 years after enrolment. Among them, 18 patients experienced normalisation in LVEF at 4-month follow-up and 35 patients experienced recovery in LVEF at 2 years. Recovery of LVEF at 4 months and recovery of LVEF at 2 years were not correlated. Recovery of LVEF at 4 months was not associated with reduced all-cause mortality in unadjusted analysis (log-rank test p=0.54) or in Cox proportional hazards analysis (HR: 0.93; 95% CI: 0.48 to 1.80; p=0.82). Ejection fraction recovery at 2 years was associated with a reduction in all-cause mortality, both in unadjusted analysis (log-rank test p=0.004) and in the Cox proportional hazard model (HR: 0.41; 95% CI: 0.21 to 0.80; p=0.009).
CONCLUSIONS: In patients with ischaemic cardiomyopathy, delayed normalisation of LVEF is associated with reduced mortality, whereas early recovery of LVEF is not. Further studies are needed to confirm these findings
Highly p-doped graphene obtained by fluorine intercalation
We present a method for decoupling epitaxial graphene grown on SiC(0001) by
intercalation of a layer of fluorine at the interface. The fluorine atoms do
not enter into a covalent bond with graphene, but rather saturate the substrate
Si bonds. This configuration of the fluorine atoms induces a remarkably large
hole density of p \approx 4.5 \times 1013 cm-2, equivalent to the location of
the Fermi level at 0.79 eV above the Dirac point ED .Comment: 4 pages, 2 figures, in print AP
- …