2,963 research outputs found
Size does matter: overcoming the adeno-associated virus packaging limit
Recombinant adeno-associated virus (rAAV) vectors mediate long-term gene transfer without any known toxicity. The primary limitation of rAAV has been the small size of the virion (20 nm), which only permits the packaging of 4.7 kilobases (kb) of exogenous DNA, including the promoter, the polyadenylation signal and any other enhancer elements that might be desired. Two recent reports (D Duan et al: Nat Med 2000, 6:595-598; Z Yan et al: Proc Natl Acad Sci USA 2000, 97:6716-6721) have exploited a unique feature of rAAV genomes, their ability to link together in doublets or strings, to bypass this size limitation. This technology could improve the chances for successful gene therapy of diseases like cystic fibrosis or Duchenne muscular dystrophy that lead to significant pulmonary morbidity
Non-syndromic Hearing Impairment in a Hungarian Family with the m.7510T>C Mutation of Mitochondrial tRNA^^Ser(UCN)^^^ and Review of Published Cases
The m.7510T>C mitochondrial DNA (mtDNA) mutation is a tRNA(Ser(UCN)) alteration leading to matrilineal isolated hearing impairment. The current paper reviews the available reports on the m.7510T>C mtDNA mutation, with special attention to phenotypic variations and haplogroup background. A Hungarian family, the fourth family reported in the literature, is presented, in which analysis of three generations with bilateral isolated hearing loss revealed the m.7510T>C tRNA(Ser(UCN)) mutation in homoplasmic form in the affected members. Haplogroup analysis verified an unnamed subgroup of mitochondrial haplogroup H. Previously reported Spanish and North American Caucasian families belong to different subgroups of haplogroup H. Analyzing our biobank of Hungarian patients with sensorineural hearing loss, we did not detect this mutation in any other patient, nor was it found in Caucasian haplogroup H control samples. Comparing the cases reported so far, there is interfamilial variablity in the age of onset, accompanying symptoms, and haplogroup background. Our case adds further genetic evidence for the pathogenicity of the m.7510T>C mutation and underlines the need to include full mtDNA sequencing in the screening for unexplained hearing loss
Tailoring the atomic structure of graphene nanoribbons by STM lithography
The practical realization of nano-scale electronics faces two major
challenges: the precise engineering of the building blocks and their assembly
into functional circuits. In spite of the exceptional electronic properties of
carbon nanotubes only basic demonstration-devices have been realized by
time-consuming processes. This is mainly due to the lack of selective growth
and reliable assembly processes for nanotubes. However, graphene offers an
attractive alternative. Here we report the patterning of graphene nanoribbons
(GNRs) and bent junctions with nanometer precision, well-defined widths and
predetermined crystallographic orientations allowing us to fully engineer their
electronic structure using scanning tunneling microscope (STM) lithography. The
atomic structure and electronic properties of the ribbons have been
investigated by STM and tunneling spectroscopy measurements. Opening of
confinement gaps up to 0.5 eV, allowing room temperature operation of GNR-based
devices, is reported. This method avoids the difficulties of assembling
nano-scale components and allows the realization of complete integrated
circuits, operating as room temperature ballistic electronic devices.Comment: 8 pages text, 5 figures, Nature Nanotechnology, in pres
Combined mirror visual and auditory feedback therapy for upper limb phantom pain: a case report
<p>Abstract</p> <p>Introduction</p> <p>Phantom limb sensation and phantom limb pain is a very common issue after amputations. In recent years there has been accumulating data implicating 'mirror visual feedback' or 'mirror therapy' as helpful in the treatment of phantom limb sensation and phantom limb pain.</p> <p>Case presentation</p> <p>We present the case of a 24-year-old Caucasian man, a left upper limb amputee, treated with mirror visual feedback combined with auditory feedback with improved pain relief.</p> <p>Conclusion</p> <p>This case may suggest that auditory feedback might enhance the effectiveness of mirror visual feedback and serve as a valuable addition to the complex multi-sensory processing of body perception in patients who are amputees.</p
Emergent dynamic chirality in a thermally driven artificial spin ratchet
Modern nanofabrication techniques have opened the possibility to create novel functional materials, whose properties transcend those of their constituent elements. In particular, tuning the magnetostatic interactions in geometrically frustrated arrangements of nanoelements called artificial spin ice1, 2 can lead to specific collective behaviour3, including emergent magnetic monopoles4, 5, charge screening6, 7 and transport8, 9, as well as magnonic response10, 11, 12. Here, we demonstrate a spin-ice-based active material in which energy is converted into unidirectional dynamics. Using X-ray photoemission electron microscopy we show that the collective rotation of the average magnetization proceeds in a unique sense during thermal relaxation. Our simulations demonstrate that this emergent chiral behaviour is driven by the topology of the magnetostatic field at the edges of the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a bias field can be used to modify the sense of rotation of the average magnetization. This opens the possibility of implementing a magnetic Brownian ratchet13, 14, which may find applications in novel nanoscale devices, such as magnetic nanomotors, actuators, sensors or memory cells
Early star-forming galaxies and the reionization of the Universe
Star forming galaxies represent a valuable tracer of cosmic history. Recent
observational progress with Hubble Space Telescope has led to the discovery and
study of the earliest-known galaxies corresponding to a period when the
Universe was only ~800 million years old. Intense ultraviolet radiation from
these early galaxies probably induced a major event in cosmic history: the
reionization of intergalactic hydrogen. New techniques are being developed to
understand the properties of these most distant galaxies and determine their
influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted
version of the review formatted by the authors, in accordance with Nature
publication policies. For the official, published version of the review,
please see http://www.nature.com/nature/archive/index.htm
Numerical instability of the Akhmediev breather and a finite-gap model of it
In this paper we study the numerical instabilities of the NLS Akhmediev
breather, the simplest space periodic, one-mode perturbation of the unstable
background, limiting our considerations to the simplest case of one unstable
mode. In agreement with recent theoretical findings of the authors, in the
situation in which the round-off errors are negligible with respect to the
perturbations due to the discrete scheme used in the numerical experiments, the
split-step Fourier method (SSFM), the numerical output is well-described by a
suitable genus 2 finite-gap solution of NLS. This solution can be written in
terms of different elementary functions in different time regions and,
ultimately, it shows an exact recurrence of rogue waves described, at each
appearance, by the Akhmediev breather. We discover a remarkable empirical
formula connecting the recurrence time with the number of time steps used in
the SSFM and, via our recent theoretical findings, we establish that the SSFM
opens up a vertical unstable gap whose length can be computed with high
accuracy, and is proportional to the inverse of the square of the number of
time steps used in the SSFM. This neat picture essentially changes when the
round-off error is sufficiently large. Indeed experiments in standard double
precision show serious instabilities in both the periods and phases of the
recurrence. In contrast with it, as predicted by the theory, replacing the
exact Akhmediev Cauchy datum by its first harmonic approximation, we only
slightly modify the numerical output. Let us also remark, that the first rogue
wave appearance is completely stable in all experiments and is in perfect
agreement with the Akhmediev formula and with the theoretical prediction in
terms of the Cauchy data.Comment: 27 pages, 8 figures, Formula (30) at page 11 was corrected, arXiv
admin note: text overlap with arXiv:1707.0565
Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain
Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. We hypothesized that dysregulated translation regulation pathways may underlie neuropathic pain. Peripheral nerve injury induced reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity, increased phosphorylation of mTOR and ERK downstream targets, augmented eIF4F complex formation and enhanced nascent protein synthesis. The AMP activated protein kinase (AMPK) activators, metformin and A769662, inhibited translation regulation signaling pathways, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia. Therefore, injury-induced dysregulation of translation control underlies pathology leading to neuropathic pain and reveals AMPK as a novel therapeutic target for the potential treatment of neuropathic pain
Segmentation of Fluorescence Microscopy Cell Images Using Unsupervised Mining
The accurate measurement of cell and nuclei contours are critical for the sensitive and specific detection of changes in normal cells in several medical informatics disciplines. Within microscopy, this task is facilitated using fluorescence cell stains, and segmentation is often the first step in such approaches. Due to the complex nature of cell issues and problems inherent to microscopy, unsupervised mining approaches of clustering can be incorporated in the segmentation of cells. In this study, we have developed and evaluated the performance of multiple unsupervised data mining techniques in cell image segmentation. We adapt four distinctive, yet complementary, methods for unsupervised learning, including those based on k-means clustering, EM, Otsu’s threshold, and GMAC. Validation measures are defined, and the performance of the techniques is evaluated both quantitatively and qualitatively using synthetic and recently published real data. Experimental results demonstrate that k-means, Otsu’s threshold, and GMAC perform similarly, and have more precise segmentation results than EM. We report that EM has higher recall values and lower precision results from under-segmentation due to its Gaussian model assumption. We also demonstrate that these methods need spatial information to segment complex real cell images with a high degree of efficacy, as expected in many medical informatics applications
Metabolic rate limits the effect of sperm competition on mammalian spermatogenesis.
Sperm competition leads to increased sperm production in many taxa. This response may result from increases in testes size, changes in testicular architecture or changes in the kinetics of spermatogenesis, but the impact of each one of these processes on sperm production has not been studied in an integrated manner. Furthermore, such response may be limited in species with low mass-specific metabolic rate (MSMR), i.e., large-bodied species, because they cannot process energy and resources efficiently enough both at the organismic and cellular levels. Here we compare 99 mammalian species and show that higher levels of sperm competition correlated with a) higher proportions of seminiferous tubules, b) shorter seminiferous epithelium cycle lengths (SECL) which reduce the time required to produce sperm, and c) higher efficiencies of Sertoli cells (involved in sperm maturation). These responses to sperm competition, in turn, result in higher daily sperm production, more sperm stored in the epididymides, and more sperm in the ejaculate. However, the two processes that require processing resources at faster rates (SECL and efficiency of Sertoli cells) only respond to sperm competition in species with high MSMR. Thus, increases in sperm production with intense sperm competition occur via a complex network of mechanisms, but some are constrained by MSMR
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