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Controlled Delivery of Sdf-1 Alpha and Igf-1: Cxcr4(+) Cell Recruitment and Functional Skeletal Muscle Recovery
Therapeutic delivery of regeneration-promoting biological factors directly to the site of injury has demonstrated its efficacy in various injury models. Several reports describe improved tissue regeneration following local injection of tissue specific growth factors, cytokines and chemokines. Evidence exists that combined cytokine/growth factor treatment is superior for optimizing tissue repair by targeting different aspects of the regeneration response. The purpose of this study was to evaluate the therapeutic potential of the controlled delivery of stromal cell-derived factor-1alpha (SDF-1 alpha) alone or in combination with insulin-like growth factor-I (SDF-1 alpha/IGF-I) for the treatment of tourniquet-induced ischemia/reperfusion injury (TK-I/R) of skeletal muscle. We hypothesized that SDF-1 alpha will promote sustained stem cell recruitment to the site of muscle injury, while IGF-I will induce progenitor cell differentiation to effectively restore muscle contractile function after TK-I/R injury while concurrently reducing apoptosis. Utilizing a novel poly-ethylene glycol PEGylated fibrin gel matrix (PEG-Fib), we incorporated SDF-1 alpha alone (PEG-Fib/SDF-1 alpha) or in combination with IGF-I (PEG-Fib/SDF-1 alpha/IGF-I) for controlled release at the site of acute muscle injury. Despite enhanced cell recruitment and revascularization of the regenerating muscle after SDF-1 alpha treatment, functional analysis showed no benefit from PEG-Fib/SDF-1 alpha therapy, while dual delivery of PEG-Fib/SDF-1 alpha/IGF-I resulted in IGF-I-mediated improvement of maximal force recovery and SDF-1 alpha-driven in vivo neovasculogenesis. Histological data supported functional data, as well as highlighted the important differences in the regeneration process among treatment groups. This study provides evidence that while revascularization may be necessary for maximizing muscle force recovery, without modulation of other effects of inflammation it is insufficient.Kinesiology and Health Educatio
High resolution scanning tunneling spectroscopy of ultrathin Pb on Si(111)-(6x6) substrate
The electronic structure of Si(111)-(6x6)Au surface covered with submonolayer
amount of Pb is investigated using scanning tunneling spectroscopy. Already in
small islands of Pb with thickness of 1 ML Pb and with the diameter
of only about 2 nm we detected the quantized electronic state with energy 0.55
eV below the Fermi level. Similarly, the I(V) characteristics made for the
Si(111)-(6x6)Au surface reveal a localized energy state 0.3 eV below the Fermi
level. These energies result from fitting of the theoretical curves to the
experimental data. The calculations are based on tight binding Hubbard model.
The theoretical calculations clearly show prominent modification of the I(V)
curve due to variation of electronic and topographic properties of the STM tip
apex.Comment: 7 pages, 7 figures, accepted for publication in Surface Scienc
The cost of prospecting for dispersal opportunities in a social bird
Understanding why individuals delay dispersal and become subordinates within a group is central to studying the evolution of sociality. Hypotheses predict that dispersal decisions are influenced by costs of extra-territorial prospecting that are often required to find a breeding vacancy. Little is known about such costs, partly because it is complicated to demonstrate them empirically. For example, prospecting individuals may be of inferior quality already before prospecting and/or have been evicted. Moreover, costs of prospecting are mainly studied in species where prospectors suffer from predation risk, so how costly prospecting is when predators are absent remains unclear. Here, we determine a cost of prospecting for subordinate Seychelles warblers, Acrocephalus sechellensis, in a population where predators are absent and individuals return to their resident territory after prospecting. Prospecting individuals had 5.2% lower body mass than non-prospecting individuals. Our evidence suggests this may be owing to frequent attacks by resident conspecifics, likely leading to reduced food intake by prospectors. These results support the hypothesis that energetic costs associated with dispersal opportunities are one factor influencing dispersal decisions and shaping the evolution of delayed dispersal in social animals
Delayed dispersal and the cost and benefits of different routes to independent breeding in a cooperative breeding bird
Why sexually mature individuals stay in groups as non-reproductive subordinates is central to the evolution of sociality and cooperative breeding. To understand such delayed dispersal, its costs and benefits need to be compared with those of permanently leaving to float through the population. However, comprehensive comparisons, especially regarding differences in future breeding opportunities, are rare. Moreover, extra-territorial prospecting by philopatric individuals has generally been ignored, even though the factors underlying this route to independent breeding may differ from those of strict philopatry or floating. We use a comprehensive predictive framework to explore how various costs, benefits and intrinsic, environmental and social factors explain philopatry, prospecting and floating in Seychelles warblers (Acrocephalus sechellensis). Floaters more likely obtained an independent breeding position before the next season than strictly philopatric individuals, but also suffered higher mortality. Prospecting yielded similar benefits to floating but lower mortality costs, suggesting that it is overall more beneficial than floating and strict philopatry. Whereas prospecting is probably individual-driven, though limited by resource availability, floating likely results from eviction by unrelated breeders. Such differences in proximate and ultimate factors underlying each route to independent breeding highlight the need for simultaneous consideration when studying the evolution of delayed dispersal
GAN Augmentation: Augmenting Training Data using Generative Adversarial Networks
One of the biggest issues facing the use of machine learning in medical
imaging is the lack of availability of large, labelled datasets. The annotation
of medical images is not only expensive and time consuming but also highly
dependent on the availability of expert observers. The limited amount of
training data can inhibit the performance of supervised machine learning
algorithms which often need very large quantities of data on which to train to
avoid overfitting. So far, much effort has been directed at extracting as much
information as possible from what data is available. Generative Adversarial
Networks (GANs) offer a novel way to unlock additional information from a
dataset by generating synthetic samples with the appearance of real images.
This paper demonstrates the feasibility of introducing GAN derived synthetic
data to the training datasets in two brain segmentation tasks, leading to
improvements in Dice Similarity Coefficient (DSC) of between 1 and 5 percentage
points under different conditions, with the strongest effects seen fewer than
ten training image stacks are available
Functional muscle hypertrophy by increased insulin-like growth factor 1 does not require dysferlin.
IntroductionDysferlin loss-of-function mutations cause muscular dystrophy, accompanied by impaired membrane repair and muscle weakness. Growth promoting strategies including insulin-like growth factor 1 (IGF-1) could provide benefit but may cause strength loss or be ineffective. The objective of this study was to determine whether locally increased IGF-1 promotes functional muscle hypertrophy in dysferlin-null (Dysf-/- ) mice.MethodsMuscle-specific transgenic expression and postnatal viral delivery of Igf1 were used in Dysf-/- and control mice. Increased IGF-1 levels were confirmed by enzyme-linked immunosorbent assay. Testing for skeletal muscle mass and function was performed in male and female mice.ResultsMuscle hypertrophy occurred in response to increased IGF-1 in mice with and without dysferlin. Male mice showed a more robust response compared with females. Increased IGF-1 did not cause loss of force per cross-sectional area in Dysf-/- muscles.DiscussionWe conclude that increased local IGF-1 promotes functional hypertrophy when dysferlin is absent and reestablishes IGF-1 as a potential therapeutic for dysferlinopathies
Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR
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