Abstract Mechanical anisotropy is an important property of fibrous tissues; for example, the anisotropic mechanical properties of brain white matter may play a key role in the mechanics of traumatic ...brain injury (TBI). The simplest anisotropic material model for small deformations of soft tissue is a nearly incompressible, transversely isotropic (ITI) material characterized by three parameters: minimum shear modulus ( µ ) , shear anisotropy ( ϕ = µ 1 µ − 1 ) and tensile anisotropy ( ζ = E 1 / E 2 − 1 ). These parameters can be determined using magnetic resonance elastography (MRE) to visualize shear waves, if the angle between the shear-wave propagation direction and fiber direction is known. Most MRE studies assume isotropic material models with a single shear ( µ ) or tensile ( E ) modulus. In this study, two types of shear waves, “fast” and “slow”, were analyzed for a given propagation direction to estimate anisotropic parameters µ , ϕ , and ζ in two fibrous soft materials: turkey breast ex vivo and aligned fibrin gels. As expected, the speed of slow shear waves depended on the angle between fiber direction and propagation direction. Fast shear waves were observed when the deformations due to wave motion induced stretch in the fiber direction. Finally, MRE estimates of anisotropic mechanical properties in turkey breast were compared to estimates from direct mechanical tests.
High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the ...generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders.
Successful vaccine development for infectious diseases has largely been achieved in settings where natural immunity to the pathogen results in clearance in at least some individuals. HIV presents an ...additional challenge in that natural clearance of infection does not occur, and the correlates of immune protection are still uncertain. However, partial control of viremia and markedly different outcomes of disease are observed in HIV-infected persons. Here, we examine the antiviral mechanisms implicated by one variable that has been consistently associated with extremes of outcome, namely HLA class I alleles, and in particular HLA-B, and examine the mechanisms by which this modulation is likely to occur and the impact of these interactions on evolution of the virus and the host. Studies to date provide evidence for both HLA-dependent and epitope-dependent influences on viral control and viral evolution and have important implications for the continued quest for an effective HIV vaccine.
We present a survey for transient and variable sources, on time-scales from 28 s to ∼1 yr, using the Murchison Widefield Array (MWA) at 182 MHz. Down to a detection threshold of 0.285 Jy, no ...transient candidates were identified, making this the most constraining low-frequency survey to date and placing a limit on the surface density of transients of <4.1 × 10−7 deg−2 for the shortest time-scale considered. At these frequencies, emission from Fast Radio Bursts (FRBs) is expected to be detectable in the shortest time-scale images without any corrections for interstellar or intergalactic dispersion. At an FRB limiting flux density of 7980 Jy, we find a rate of <82 FRBs per sky per day for dispersion measures <700 pc cm−3. Assuming a cosmological population of standard candles, our rate limits are consistent with the FRB rates obtained by Thornton et al. if they have a flat spectral slope. Finally, we conduct an initial variability survey of sources in the field with flux densities ≳0.5 Jy and identify no sources with significant variability in their light curves. However, we note that substantial further work is required to fully characterize both the short-term and low-level variability within this field.
Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly ...transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.
We present first results from radio observations with the Murchison Widefield Array seeking to constrain the power spectrum of 21 cm brightness temperature fluctuations between the redshifts of 11.6 ...and 17.9 (113 and 75 MHz). 3 h of observations were conducted over two nights with significantly different levels of ionospheric activity. We use these data to assess the impact of systematic errors at low frequency, including the ionosphere and radio-frequency interference, on a power spectrum measurement. We find that after the 1–3 h of integration presented here, our measurements at the Murchison Radio Observatory are not limited by RFI, even within the FM band, and that the ionosphere does not appear to affect the level of power in the modes that we expect to be sensitive to cosmology. Power spectrum detections, inconsistent with noise, due to fine spectral structure imprinted on the foregrounds by reflections in the signal-chain, occupy the spatial Fourier modes where we would otherwise be most sensitive to the cosmological signal. We are able to reduce this contamination using calibration solutions derived from autocorrelations so that we achieve an sensitivity of 104 mK on comoving scales k ≲ 0.5 h Mpc−1. This represents the first upper limits on the 21 cm power spectrum fluctuations at redshifts 12 ≲ z ≲ 18 but is still limited by calibration systematics. While calibration improvements may allow us to further remove this contamination, our results emphasize that future experiments should consider carefully the existence of and their ability to calibrate out any spectral structure within the EoR window.
The Magnetospheric Multiscale spacecraft encountered an electron diffusion region (EDR) in a symmetric reconnection in the Earth's magnetotail. The EDR contained a guide field of about 2 nT, which ...was 13% of the magnetic field in the inflow region, and its thickness was about 2 local electron inertial lengths. Intense energy dissipation, a super-Alfvénic electron jet, electron nongyrotropy, and crescent-shaped electron velocity distributions were observed in association with this EDR. These features are similar to those of the EDRs in asymmetric reconnection at the dayside magnetopause. Electrons gained about 50% of their energy from the immediate upstream to the EDR. Crescent electron distributions were seen at the boundary of the EDR, while highly curved magnetic field lines inside the EDR may have gyrotropized the electrons. The EDR was characterized by a parallel current that was carried by antiparallel drifting electrons that were probably accelerated by a parallel electric field along the guide field. These results reveal the essential electron physics of the EDR and provide a significant example of an EDR in symmetric reconnection with a weak guide field.
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