2,073 research outputs found
Coherent phonon scattering effects on thermal transport in thin semiconductor nanowires
The thermal conductance by phonons of a quasi-one-dimensional solid with
isotope or defect scattering is studied using the Landauer formalism for
thermal transport. The conductance shows a crossover from localized to Ohmic
behavior, just as for electrons, but the nature of this crossover is modified
by delocalization of phonons at low frequency. A scalable numerical
transfer-matrix technique is developed and applied to model
quasi-one-dimensional systems in order to confirm simple analytic predictions.
We argue that existing thermal conductivity data on semiconductor nanowires,
showing an unexpected linear dependence, can be understood through a model that
combines incoherent surface scattering for short-wavelength phonons with nearly
ballistic long-wavelength phonons. It is also found that even when strong
phonon localization effects would be observed if defects are distributed
throughout the wire, localization effects are much weaker when defects are
localized at the boundary, as in current experiments.Comment: 13 page
Genome-wide physical activity interactions in adiposity : a meta-analysis of 200 452 adults
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genomewide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip
ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029).
We standardized PA by categorizing it into a dichotomous variable where, on average, 23%
of participants were categorized as inactive and 77% as physically active. While we replicate
the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which
the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide
meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci,
suggesting that accounting for PA or other environmental factors that contribute to variation
in adiposity may facilitate gene discover
A Theoretical Model for the Relation for Supermassive Black Holes in Galaxies
We construct a model for the formation of black holes within galactic bulges.
The initial state is a slowly rotating isothermal sphere, characterized by
effective transport speed \aeff and rotation rate . The black hole
mass is determined when the centrifugal radius of the collapse flow exceeds the
capture radius of the central black hole. This model reproduces the observed
correlation between black hole masses and galactic velocity dispersions, \mbh
\approx 10^8 M_\odot (\sigma/200 \kms)^4, where \sigma = \sqrt{2} \aeff.
This model also predicts the ratio \mrat of black hole mass to host mass:
\mrat 0.004 (\sigma/200 \kms).Comment: 9 pages, 2 figures, submitted to Astrophysical Journal Letter
Cerebrospinal Fluid YKL-40 and Neurogranin in Familial Alzheimer's Disease: A Pilot Study
BACKGROUND: YKL-40 and neurogranin are promising additional cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) which reflect different underlying disease mechanisms. OBJECTIVE: To compare the levels of CSF YKL-40 and neurogranin between asymptomatic carriers of familial AD (FAD) mutations (MC) and non-carriers (NC) from the same families. Another objective was to assess changes in YKL-40 and neurogranin, from the presymptomatic to clinical phase of FAD. METHODS: YKL-40 and neurogranin, as well as Aβ42, total tau-protein, and phospho-tau, were measured in the CSF of 14 individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G), and PSEN1 (p.H163Y), as well as in 17 NC from the same families. Five of the MC developed mild cognitive impairment (MCI) during follow-up. RESULTS: In this pilot study, there was no difference in either CSF YKL-40 or neurogranin when comparing the presymptomatic MC to the NC. YKL-40 correlated positively with expected years to symptom onset and to age in both the MC and the NC, while neurogranin had no correlation to either variable in either of the groups. A subgroup of the participants underwent more than one CSF sampling in which half of the MC developed MCI during follow-up. The longitudinal data showed an increase in YKL-40 levels in the MC as the expected symptom onset approached. Neurogranin remained stable over time in both the MC and the NC. CONCLUSION: These findings support a positive correlation between progression from presymptomatic to symptomatic AD and levels of CSF YKL-40, but not neurogranin
The effects of different familial Alzheimer's disease mutations on APP processing in vivo
BACKGROUND:
Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer’s disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individuals carrying FAD mutations can give valuable insights into the earliest stages of the disease where therapeutic interventions are thought to be the most effective.
METHODS:In the current cross-sectional study, products of APP processing (e.g., sAPPα, sAPPβ, Aβ38, Aβ40 and Aβ42) were measured in the cerebrospinal fluid (CSF) of individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), as well as in non-mutation carriers from the same families.
RESULTS:
We observed pathological APP processing in presymptomatic carriers of FAD mutations, with different profiles of APP and Aβ isoforms in the three mutation carrier groups, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), except for the well-established decrease in CSF Aβ42 that was found with all mutations.
CONCLUSIONS:
These findings add to the current evidence that AD pathophysiology differs between disease-causing mutations and can be monitored in the presymptomatic disease stage by CSF analyses. This may also be important from a therapeutic standpoint, by opening a window to monitor effects of disease-modifying drugs on AD pathophysiology
Roughness of molecular property landscapes and its impact on modellability
In molecular discovery and drug design, structure-property relationships and
activity landscapes are often qualitatively or quantitatively analyzed to guide
the navigation of chemical space. The roughness (or smoothness) of these
molecular property landscapes is one of their most studied geometric
attributes, as it can characterize the presence of activity cliffs, with
rougher landscapes generally expected to pose tougher optimization challenges.
Here, we introduce a general, quantitative measure for describing the roughness
of molecular property landscapes. The proposed roughness index (ROGI) is
loosely inspired by the concept of fractal dimension and strongly correlates
with the out-of-sample error achieved by machine learning models on numerous
regression tasks.Comment: 17 pages, 6 figures, 2 tables (SI with 17 pages, 16 figures
Gaussian random waves in elastic media
Similar to the Berry conjecture of quantum chaos we consider elastic analogue
which incorporates longitudinal and transverse elastic displacements with
corresponding wave vectors. Based on that we derive the correlation functions
for amplitudes and intensities of elastic displacements. Comparison to numerics
in a quarter Bunimovich stadium demonstrates excellent agreement.Comment: 4 pages, 4 figure
Formation of Supermassive Black Holes in Galactic Bulges: A Rotating Collapse Model Consistent with the \mbh-\sigma Relation
Motivated by the observed correlation between black hole masses \mbh and
the velocity dispersion of host galaxies, we develop a theoretical
model of black hole formation in galactic bulges (this paper generalizes an
earlier ApJ Letter). The model assumes an initial state specified by a a
uniform rotation rate and a density distribution of the form \rho =
\aeff^2 / 2 \pi G r^2 (so that \aeff is an effective transport speed). The
black hole mass is determined when the centrifugal radius of the collapse flow
exceeds the capture radius of the central black hole (for Schwarzschild
geometry). This model reproduces the observed correlation between the estimated
black hole masses and the velocity dispersions of galactic bulges, i.e., \mbh
\approx 10^8 M_\odot (\sigma/200 {\rm km s^{-1}})^4, where \sigma = \sqrt{2}
\aeff. To obtain this normalization, the rotation rate rad/s. The model also defines a bulge mass scale . If we
identify the scale with the bulge mass, the model determines the ratio
\mrat of black hole mass to the host mass: \mrat 0.0024
, again in reasonable agreement with observed
values. In this scenario, supermassive black holes form quickly (in
yr) and are born rapidly rotating (with ). This paper also shows
how these results depend on the assumed initial conditions; the most important
quantity is the initial distribution of specific angular momentum in the
pre-collapse state.Comment: 31 pages, 4 figures, accepted to Ap
the effect of ethnicity and immigration on treatment resistance in schizophrenia
Background: Treatment resistance is a common issue among schizophrenia patients undergoing antipsychotic treatment. According to the American Psychiatric Association (APA) guidelines, treatment-resistant status is defined as little or no symptom reduction to at least two antipsychotics at a therapeutic dose for a trial of at least six weeks. The aim of the current study is to determine whether ethnicity and migration are associated with treatment resistance. Methods: In a sample of 251 participants with schizophrenia spectrum disorders, we conducted cross-sectional assessments to collect information regarding self-identified ethnicity, immigration and treatment history. Ancestry was identified using 292 markers overlapping with the HapMap project. Using a regression analysis, we tested whether a history of migration, ethnicity or genetic ancestry were predictive of treatment resistance. Results: Our logistic regression model revealed no significant association between immigration (OR = 0.04; 95%CI = 0.35–3.07; p = 0.93) and treatment resistant schizophrenia. White Europeans did not show significant association with resistance status regardless of whether ethnicity was determined by self-report (OR = 1.89; 95%CI = 0.89–4.20; p = 0.105) or genetic analysis (OR = −0.73; 95%CI = −0.18–2.97; p = 0.667). Conclusion: Neither ethnicity nor migrant status was significantly associated with treatment resistance in this Canadian study. However, these conclusions are limited by the small sample size of our investigation. Keywords: Schizophrenia, Treatment resistance, Antipsychotics, Ethnicity, Migratio
The OGLE View of Microlensing towards the Magellanic Clouds. II. OGLE-II SMC data
The primary goal of this paper is to provide the evidence that can either
prove or falsify the hypothesis that dark matter in the Galactic halo can clump
into stellar-mass compact objects. If such objects existed, they would act as
lenses to external sources in the Magellanic Clouds, giving rise to an
observable effect of microlensing. We present the results of our search for
such events, based on the data from the second phase of the OGLE survey
(1996-2000) towards the SMC. The data set we used is comprised of 2.1 million
monitored sources distributed over an area of 2.4 square degrees. We found only
one microlensing event candidate, however its poor quality light curve limited
our discussion on the exact distance to the lensing object.
Given a single event, taking the blending (crowding of stars) into account
for the detection efficiency simulations, and deriving the HST-corrected number
of monitored stars, the microlensing optical depth is tau=(1.55+-1.55)10e-7.
This result is consistent with the expected SMC self-lensing signal, with no
need of introducing dark matter microlenses. Rejecting the unconvincing event
leads to the upper limit on the fraction of dark matter in the form of MACHOs
to f<20 per cent for deflectors' masses around 0.4 Msun and f<11 per cent for
masses between 0.003 and 0.2 Msun (95 per cent confidence limit). Our result
indicates that the Milky Way's dark matter is unlikely to be clumpy and form
compact objects in the sub-solar-mass range.Comment: Accepted for publication in MNRAS. Data in electronic form are
available on the OGLE's website: http://ogle.astrouw.edu.pl
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