806 research outputs found
Recommended from our members
The effects of severe myopia on the properties of sampling units in peripheral retina
Significance: Poor peripheral visual acuity in myopia may reflect, in part, photoreceptor misalignment with the exit pupil of the eye. We speculate that if such misalignment causes sufficient visual deprivation and/or disrupts retinal feedback processes, it may influence eye growth itself. Purpose: It is known that myopic eyes have a reduced peripheral resolution acuity relative to emmetropic eyes, though it remains unclear how mechanical stretching of the retina in myopia impacts on peripheral visual performance. Our aim was to determine how retinal stretching affects the properties of sampling units in peripheral vision. Methods: Three-dimensional magnetic resonance imaging provided a depiction in vivo of ocular shape, allowing the inter-eye ratio of retinal image surface areas and the relative alignment of surfaces to be determined in our observer, who was unique in having severe myopia in the right eye (~21D) but only modest myopia in the left (~3D). Visual performance was assessed for the detection and direction discrimination of drifting sinusoids positioned 40Âș in the temporal retina. Applying the sampling theorem to our measures, we estimated the density and cut-off frequency of the underlying sampling units. Results: The retinal image surface area of the right eye was 40% larger than that of the left, and was rotated 8.9Âș anticlockwise relative to the left eyeâs image surface. In agreement with a linear stretch model of myopia, the sampling density of the right eye was reduced by approximately the same ratio as that predicted from the inter-eye MRI data, namely 1.18. However, the cut-off frequency (cycles/mm) of the right eye was approximately half that of the left, a reduction that cannot be explained solely by a linear areal expansion of retinal sampling units. Conclusions: Poor peripheral acuity in severe myopia may be caused, at least in part, by receptoral misalignment with the exit pupil
Chirped pulse Raman amplification in warm plasma: towards controlling saturation
Stimulated Raman backscattering in plasma is potentially an efficient method of amplifying laser pulses to reach exawatt powers because plasma is fully broken down and withstands extremely high electric fields. Plasma also has unique nonlinear optical properties that allow simultaneous compression of optical pulses to ultra-short durations. However, current measured efficiencies are limited to several percent. Here we investigate Raman amplification of short duration seed pulses with different chirp rates using a chirped pump pulse in a preformed plasma waveguide. We identify electron trapping and wavebreaking as the main saturation mechanisms, which lead to spectral broadening and gain saturation when the seed reaches several millijoules for durations of 10's - 100's fs for 250 ps, 800 nm chirped pump pulses. We show that this prevents access to the nonlinear regime and limits the efficiency, and interpret the experimental results using slowly-varying-amplitude, current-averaged particle-in-cell simulations. We also propose methods for achieving higher efficiencies.close0
Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis
In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing
Nonlinear analysis of biomagnetic signals recorded from uterine myomas
OBJECTIVE: To determine if there is any non-linearity in the biomagnetic recordings of uterine myomas and to find any differences that may be present in the mechanisms underlying their signal dynamics. METHODS: Twenty-four women were included in the study. Sixteen of them were characterised with large myomas and 8 with small ones. Uterine artery waveform measurements were evaluated by use of Pulsatility Index (PI) (normal value PI<1.45). RESULTS: Applying nonlinear analysis to the biomagnetic signals of the uterine myomas, we observed a clear saturation value for the group of large ones (mean = 11.35 ± 1.49) and no saturation for the small ones. CONCLUSION: The comparison of the saturation values in the biomagnetic recordings of large and small myomas may be a valuable tool in the evaluation of functional changes in their dynamic behavior
Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin
Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature America for personal use, not for redistribution. The definitive version was published in Nature Neuroscience 12 (2009): 864-871, doi:10.1038/nn.2346.Selected vulnerability of neurons in Huntingtonâs disease (HD) suggests alterations in a cellular
process particularly critical for neuronal function. Supporting this idea, pathogenic Htt (polyQ-Htt)
inhibits fast axonal transport (FAT) in various cellular and animal HD models (mouse and squid),
but the molecular basis of this effect remains unknown. Here we show that polyQ-Htt inhibits FAT
through a mechanism involving activation of axonal JNK. Accordingly, increased activation of JNK
was observed in vivo in cellular and animal HD models. Additional experiments indicate that
polyQ-Htt effects on FAT are mediated by the neuron-specific JNK3, and not ubiquitously
expressed JNK1, providing a molecular basis for neuron-specific pathology in HD. Mass
spectrometry identified a residue in the kinesin-1 motor domain phosphorylated by JNK3, and this
modification reduces kinesin-1 binding to microtubules. These data identify JNK3 as a critical
mediator of polyQ-Htt toxicity and provides a molecular basis for polyQ-Htt-induced inhibition of
FAT.This work was supported by 2007/2008 MBL summer fellowship to GM; an HDSA
grant to GM; NIH grants MH066179 to GB; and ALSA, Muscular Dystrophy Association, and NIH
(NS23868, NS23320, NS41170) grants to STB
Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma
Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, nonrandomised dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10â150âmgâmlâ1 in 60âml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150âmgâmlâ1. Urinary VEGF was affected by Suramin at doses above 50âmgâmlâ1, corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100âmgâmlâ1 intravesically
Nanofriction in Cold Ion Traps
Sliding friction between crystal lattices and the physics of cold ion traps
are so far non-overlapping fields. Two sliding lattices may either stick and
show static friction or slip with dynamic friction; cold ions are known to form
static chains, helices, or clusters, depending on trapping conditions. Here we
show, based on simulations, that much could be learnt about friction by
sliding, via e.g. an electric field, the trapped ion chains over a periodic
corrugated potential. Unlike infinite chains where, according to theory, the
classic Aubry transition to free sliding may take place, trapped chains are
always pinned. Nonetheless we find that a properly defined static friction
still vanishes Aubry-like at a symmetric-asymmetric structural transition,
ubiquitous for decreasing corrugation in both straight and zig-zag trapped
chains. Dynamic friction can also be addressed by ringdown oscillations of the
ion trap. Long theorized static and dynamic one dimensional friction phenomena
could thus become exquisitely accessible in future cold ion tribology
Continuum Molecular Simulation of Large Conformational Changes during IonâChannel Gating
A modeling framework was developed to simulate large and gradual conformational changes within a macromolecule (protein) when its low amplitude high frequency vibrations are not concerned. Governing equations were derived as alternative to Langevin and Smoluchowski equations and used to simulate gating conformational changes of the Kv7.1 ion-channel over the time scale of its gating process (tens of milliseconds). The alternative equations predict the statistical properties of the motion trajectories with good accuracy and do not require the force field to be constant over the diffusion length, as assumed in Langevin equation. The open probability of the ionâchannel was determined considering cooperativity of four subunits and solving their concerted transition to the open state analytically. The simulated open probabilities for a series of voltage clamp tests produced current traces that were similar to experimentally recorded currents
Observation of associated near-side and away-side long-range correlations in âsNN=5.02ââTeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (ÎÏ) and pseudorapidity (Îη) are measured in âsNN=5.02ââTeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1ââÎŒb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Îη|<5) ânear-sideâ (ÎÏâŒ0) correlation that grows rapidly with increasing ÎŁETPb. A long-range âaway-sideâ (ÎÏâŒÏ) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Îη and ÎÏ) and ÎŁETPb dependence. The resultant ÎÏ correlation is approximately symmetric about Ï/2, and is consistent with a dominant cosâĄ2ÎÏ modulation for all ÎŁETPb ranges and particle pT
Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at âs = 7 TeV with the ATLAS detector
This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of âs = 7 TeV;{\rm Te}{\rm V}4.6\;{\rm f}{{{\rm b}}^{-1}}{{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}|\eta |\lt 1.9{{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
- âŠ