1,037 research outputs found
Hemifacial Spasm and Neurovascular Compression
Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve
Protein structure generation via folding diffusion
The ability to computationally generate novel yet physically foldable protein
structures could lead to new biological discoveries and new treatments
targeting yet incurable diseases. Despite recent advances in protein structure
prediction, directly generating diverse, novel protein structures from neural
networks remains difficult. In this work, we present a new diffusion-based
generative model that designs protein backbone structures via a procedure that
mirrors the native folding process. We describe protein backbone structure as a
series of consecutive angles capturing the relative orientation of the
constituent amino acid residues, and generate new structures by denoising from
a random, unfolded state towards a stable folded structure. Not only does this
mirror how proteins biologically twist into energetically favorable
conformations, the inherent shift and rotational invariance of this
representation crucially alleviates the need for complex equivariant networks.
We train a denoising diffusion probabilistic model with a simple transformer
backbone and demonstrate that our resulting model unconditionally generates
highly realistic protein structures with complexity and structural patterns
akin to those of naturally-occurring proteins. As a useful resource, we release
the first open-source codebase and trained models for protein structure
diffusion
Point-charge electrostatics in disordered alloys
A simple analytic model of point-ion electrostatics has been previously
proposed in which the magnitude of the net charge q_i on each atom in an
ordered or random alloy depends linearly on the number N_i^(1) of unlike
neighbors in its first coordination shell. Point charges extracted from recent
large supercell (256-432 atom) local density approximation (LDA) calculations
of Cu-Zn random alloys now enable an assessment of the physical validity and
accuracy of the simple model. We find that this model accurately describes (i)
the trends in q_i vs. N_i^(1), particularly for fcc alloys, (ii) the magnitudes
of total electrostatic energies in random alloys, (iii) the relationships
between constant-occupation-averaged charges and Coulomb shifts
(i.e., the average over all sites occupied by either or atoms) in the
random alloy, and (iv) the linear relation between the site charge q_i and the
constant- charge-averaged Coulomb shift (i.e., the average over all sites with
the same charge) for fcc alloys. However, for bcc alloys the fluctuations
predicted by the model in the q_i vs. V_i relation exceed those found in the
LDA supercell calculations. We find that (a) the fluctuations present in the
model have a vanishing contribution to the electrostatic energy. (b)
Generalizing the model to include a dependence of the charge on the atoms in
the first three (two) shells in bcc (fcc) - rather than the first shell only -
removes the fluctuations, in complete agreement with the LDA data. We also
demonstrate an efficient way to extract charge transfer parameters of the
generalized model from LDA calculations on small unit cells.Comment: 15 pages, ReVTeX galley format, 7 eps figures embedded using psfig,
to be published in Phys. Rev.
Universality in the Screening Cloud of Dislocations Surrounding a Disclination
A detailed analytical and numerical analysis for the dislocation cloud
surrounding a disclination is presented. The analytical results show that the
combined system behaves as a single disclination with an effective fractional
charge which can be computed from the properties of the grain boundaries
forming the dislocation cloud. Expressions are also given when the crystal is
subjected to an external two-dimensional pressure. The analytical results are
generalized to a scaling form for the energy which up to core energies is given
by the Young modulus of the crystal times a universal function. The accuracy of
the universality hypothesis is numerically checked to high accuracy. The
numerical approach, based on a generalization from previous work by S. Seung
and D.R. Nelson ({\em Phys. Rev A 38:1005 (1988)}), is interesting on its own
and allows to compute the energy for an {\em arbitrary} distribution of
defects, on an {\em arbitrary geometry} with an arbitrary elastic {\em energy}
with very minor additional computational effort. Some implications for recent
experimental, computational and theoretical work are also discussed.Comment: 35 pages, 21 eps file
Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites
Peer reviewedPublisher PD
RT-GENE: Real-time eye gaze estimation in natural environments
In this work, we consider the problem of robust gaze estimation in natural environments. Large camera-to-subject distances and high variations in head pose and eye gaze angles are common in such environments. This leads to two main shortfalls in state-of-the-art methods for gaze estimation: hindered ground truth gaze annotation and diminished gaze estimation accuracy as image resolution decreases with distance. We first record a novel dataset of varied gaze and head pose images in a natural environment, addressing the issue of ground truth annotation by measuring head pose using a motion capture system and eye gaze using mobile eyetracking glasses. We apply semantic image inpainting to the area covered by the glasses to bridge the gap between training and testing images by removing the obtrusiveness of the glasses. We also present a new real-time algorithm involving appearance-based deep convolutional neural networks with increased capacity to cope with the diverse images in the new dataset. Experiments with this network architecture are conducted on a number of diverse eye-gaze datasets including our own, and in cross dataset evaluations. We demonstrate state-of-the-art performance in terms of estimation accuracy in all experiments, and the architecture performs well even on lower resolution images
Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family
Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al
Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure
Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature
Effects of anharmonic strain on phase stability of epitaxial films and superlattices: applications to noble metals
Epitaxial strain energies of epitaxial films and bulk superlattices are
studied via first-principles total energy calculations using the local-density
approximation. Anharmonic effects due to large lattice mismatch, beyond the
reach of the harmonic elasticity theory, are found to be very important in
Cu/Au (lattice mismatch 12%), Cu/Ag (12%) and Ni/Au (15%). We find that
is the elastically soft direction for biaxial expansion of Cu and Ni, but it is
for large biaxial compression of Cu, Ag, and Au. The stability of
superlattices is discussed in terms of the coherency strain and interfacial
energies. We find that in phase-separating systems such as Cu-Ag the
superlattice formation energies decrease with superlattice period, and the
interfacial energy is positive. Superlattices are formed easiest on (001) and
hardest on (111) substrates. For ordering systems, such as Cu-Au and Ag-Au, the
formation energy of superlattices increases with period, and interfacial
energies are negative. These superlattices are formed easiest on (001) or (110)
and hardest on (111) substrates. For Ni-Au we find a hybrid behavior:
superlattices along and like in phase-separating systems, while for
they behave like in ordering systems. Finally, recent experimental
results on epitaxial stabilization of disordered Ni-Au and Cu-Ag alloys,
immiscible in the bulk form, are explained in terms of destabilization of the
phase separated state due to lattice mismatch between the substrate and
constituents.Comment: RevTeX galley format, 16 pages, includes 9 EPS figures, to appear in
Physical Review
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