32,899 research outputs found
Novel Two-dimensional Carbon Allotrope with Strong Electronic Anisotropy
Two novel two-dimensional carbon allotropes comprised of octagons and
pentagons are proposed based on the first-principles calculations. The two
carbon allotropes, named OPG-L and OPG-Z, are found to have distinct
properties. OPG-L is metallic, while OPG-Z is a gapless semimetal. Remarkably,
OPG-Z exhibits pronounced electronic anisotropy with highly anisotropic Dirac
points at the Fermi level. A tight-binding model is suggested to describe the
low-energy quasiparticles, which clarifies the origin of the anisotropic Dirac
points. Such an anisotropic electronic characteristic of OPG-Z is expected to
have wide implications in nano-electronics.Comment: 6 pages, 5 figures (accepted by Physical Review B
Estrogen activation of microglia underlies the sexually dimorphic differences in Nf1 optic glioma-induced retinal pathology
Children with neurofibromatosis type 1 (NF1) develop low-grade brain tumors throughout the optic pathway. Nearly 50% of children with optic pathway gliomas (OPGs) experience visual impairment, and few regain their vision after chemotherapy. Recent studies have revealed that girls with optic nerve gliomas are five times more likely to lose vision and require treatment than boys. To determine the mechanism underlying this sexually dimorphic difference in clinical outcome, we leveraged Nf1 optic glioma (Nf1-OPG) mice. We demonstrate that female Nf1-OPG mice exhibit greater retinal ganglion cell (RGC) loss and only females have retinal nerve fiber layer (RNFL) thinning, despite mice of both sexes harboring tumors of identical volumes and proliferation. Female gonadal sex hormones are responsible for this sexual dimorphism, as ovariectomy, but not castration, of Nf1-OPG mice normalizes RGC survival and RNFL thickness. In addition, female Nf1-OPG mice have threefold more microglia than their male counterparts, and minocycline inhibition of microglia corrects the retinal pathology. Moreover, pharmacologic inhibition of microglial estrogen receptor-β (ERβ) function corrects the retinal abnormalities in female Nf1-OPG mice. Collectively, these studies establish that female gonadal sex hormones underlie the sexual dimorphic differences in Nf1 optic glioma–induced retinal dysfunction by operating at the level of tumor-associated microglial activation
Gate-controlled Guiding of Electrons in Graphene
Ballistic semiconductor structures have allowed the realization of
optics-like phenomena in electronics, including magnetic focusing and lensing.
An extension that appears unique to graphene is to use both n and p carrier
types to create electronic analogs of optical devices having both positive and
negative indices of refraction. Here, we use gate-controlled density with both
p and n carrier types to demonstrate the analog of the fiber-optic guiding in
graphene. Two basic effects are investigated: (1) bipolar p-n junction guiding,
based on the principle of angle-selective transmission though the graphene p-n
interface, and (2) unipolar fiber-optic guiding, using total internal
reflection controlled by carrier density. Modulation of guiding efficiency
through gating is demonstrated and compared to numerical simulations, which
indicates that interface roughness limits guiding performance, with
few-nanometer effective roughness extracted. The development of p-n and
fiber-optic guiding in graphene may lead to electrically reconfigurable wiring
in high-mobility devices.Comment: supplementary materal at
http://marcuslab.harvard.edu/papers/OG_SI.pd
Laser Based Mid-Infrared Spectroscopic Imaging – Exploring a Novel Method for Application in Cancer Diagnosis
A number of biomedical studies have shown that mid-infrared spectroscopic images can provide
both morphological and biochemical information that can be used for the diagnosis of cancer. Whilst
this technique has shown great potential it has yet to be employed by the medical profession. By
replacing the conventional broadband thermal source employed in modern FTIR spectrometers with
high-brightness, broadly tuneable laser based sources (QCLs and OPGs) we aim to solve one of the
main obstacles to the transfer of this technology to the medical arena; namely poor signal to noise
ratios at high spatial resolutions and short image acquisition times. In this thesis we take the first
steps towards developing the optimum experimental configuration, the data processing algorithms
and the spectroscopic image contrast and enhancement methods needed to utilise these high
intensity laser based sources. We show that a QCL system is better suited to providing numerical
absorbance values (biochemical information) than an OPG system primarily due to the QCL pulse
stability. We also discuss practical protocols for the application of spectroscopic imaging to cancer
diagnosis and present our spectroscopic imaging results from our laser based spectroscopic imaging
experiments of oesophageal cancer tissue
SGTA regulates the cytosolic quality control of hydrophobic substrates
Hydrophobic amino acids are normally shielded from the cytosol and their exposure is often used as an indicator of protein misfolding to enable the chaperone-mediated recognition and quality control of aberrant polypeptides. Mislocalised membrane proteins (MLPs) represent a particular challenge to cellular quality control, and, in this study, membrane protein fragments have been exploited to study a specialised pathway that underlies the efficient detection and proteasomal degradation of MLPs. Our data show that the BAG6 complex and SGTA compete for cytosolic MLPs by recognition of their exposed hydrophobicity, and the data suggest that SGTA acts to maintain these substrates in a non-ubiquitylated state. Hence, SGTA might counter the actions of BAG6 to delay the ubiquitylation of specific precursors and thereby increase their opportunity for successful post-translational delivery to the endoplasmic reticulum. However, when SGTA is overexpressed, the normally efficient removal of aberrant MLPs is delayed, increasing their steady-state level and promoting aggregation. Our data suggest that SGTA regulates the cellular fate of a range of hydrophobic polypeptides should they become exposed to the cytosol
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Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds.
The instructive capabilities of extracellular matrix-inspired materials for osteoprogenitor differentiation have sparked interest in understanding modulation of other cell types within the bone regenerative microenvironment. We previously demonstrated that nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffolds efficiently induced osteoprogenitor differentiation and bone healing. In this work, we combined adenovirus-mediated delivery of osteoprotegerin (AdOPG), an endogenous anti-osteoclastogenic decoy receptor, in primary human mesenchymal stem cells (hMSCs) with MC-GAG to understand the role of osteoclast inactivation in augmentation of bone regeneration. Simultaneous differentiation of osteoprogenitors on MC-GAG and osteoclast progenitors resulted in bidirectional positive regulation. AdOPG expression did not affect osteogenic differentiation alone. In the presence of both cell types, AdOPG-transduced hMSCs on MC-GAG diminished osteoclast-mediated resorption in direct contact; however, osteoclast-mediated augmentation of osteogenic differentiation was unaffected. Thus, the combination of OPG with MC-GAG may represent a method for uncoupling osteogenic and osteoclastogenic differentiation to augment bone regeneration
Trajectory-Based Off-Policy Deep Reinforcement Learning
Policy gradient methods are powerful reinforcement learning algorithms and
have been demonstrated to solve many complex tasks. However, these methods are
also data-inefficient, afflicted with high variance gradient estimates, and
frequently get stuck in local optima. This work addresses these weaknesses by
combining recent improvements in the reuse of off-policy data and exploration
in parameter space with deterministic behavioral policies. The resulting
objective is amenable to standard neural network optimization strategies like
stochastic gradient descent or stochastic gradient Hamiltonian Monte Carlo.
Incorporation of previous rollouts via importance sampling greatly improves
data-efficiency, whilst stochastic optimization schemes facilitate the escape
from local optima. We evaluate the proposed approach on a series of continuous
control benchmark tasks. The results show that the proposed algorithm is able
to successfully and reliably learn solutions using fewer system interactions
than standard policy gradient methods.Comment: Includes appendix. Accepted for ICML 201
RANK/RANKL/OPG pathway: genetic associations with stress fracture period prevalence in elite athletes
Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations.
Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes.
Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group, and were sub-stratified into male and cases of multiple stress fracture group. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays.
Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (p<0.05). 8.1% of stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (p<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes to have suffered a stress fracture while 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188, and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (p<0.05).
Conclusions: The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health, and offers potential targets for therapeutic interventions
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