110 research outputs found
Ultrafast transport of laser-excited spin polarized carriers in Au/Fe/MgO(001)
A time domain approach to probe hot carrier-induced spin dynamics is
demonstrated. The experiments are performed in epitaxial Au/Fe/MgO(001), where
spin-polarized hot carriers are excited in the Fe layer by 35 fs laser pulses.
They propagate to the Au surface where the transient spin polarization is
detected by magneto-induced second harmonic generation. Different energies of
majority and minority hot carriers excited in the exchange-split Fe band
structure lead to their spindependent lifetimes in Au. Accordingly, two
spin-polarized current contributions which propagate superdiffusively at
different velocities result in a spin current pulse of about 100 fs duration.Comment: 5 pages, 4 figure
N-Octanoyl Dopamine, a Non-Hemodyanic Dopamine Derivative, for Cell Protection during Hypothermic Organ Preservation
BACKGROUND: Although donor dopamine treatment reduces the requirement for post transplantation dialysis in renal transplant recipients, implementation of dopamine in donor management is hampered by its hemodynamic side-effects. Therefore novel dopamine derivatives lacking any hemodynamic actions and yet are more efficacious in protecting tissue from cold preservation injury are warranted. We hypothesized that variation of the molecular structure would yield more efficacious compounds avoid of any hemodynamic effects. METHODOLOGY/PRINCIPAL FINDINGS: To this end, we assessed protection against cold preservation injury in HUVEC by the attenuation of lactate dehydrogenase (LDH) release. Modification of dopamine by an alkanoyl group increased cellular uptake and significantly improved efficacy of protection. Further variation revealed that only compounds bearing two hydroxy groups in ortho or para position at the benzene nucleus, i.e. strong reductants, were protective. However, other reducing agents like N-acetyl cysteine and ascorbate, or NADPH oxidase inhibition did not prevent cellular injury following cold storage. Unlike dopamine, a prototypic novel compound caused no hemodynamic side-effects. CONCLUSIONS/SIGNIFICANCE: In conclusion, we demonstrate that protection against cold preservation injury by catecholamines is exclusively governed by strong reducing capacity and sufficient lipophilicity. The novel dopamine derivatives might be of clinical relevance in donor pre-conditioning as they are completely devoid of hemodynamic action, their increased cellular uptake would reduce time of treatment and therefore also may have a potential use for non-heart beating donors
Functional Deficits in nNOSμ-Deficient Skeletal Muscle: Myopathy in nNOS Knockout Mice
Skeletal muscle nNOSμ (neuronal nitric oxide synthase mu) localizes to the sarcolemma through interaction with the dystrophin-associated glycoprotein (DAG) complex, where it synthesizes nitric oxide (NO). Disruption of the DAG complex occurs in dystrophinopathies and sarcoglycanopathies, two genetically distinct classes of muscular dystrophy characterized by progressive loss of muscle mass, muscle weakness and increased fatigability. DAG complex instability leads to mislocalization and downregulation of nNOSμ; but this is thought to play a minor role in disease pathogenesis. This view persists without knowledge of the role of nNOS in skeletal muscle contractile function in vivo and has influenced gene therapy approaches to dystrophinopathy, the majority of which do not restore sarcolemmal nNOSμ. We address this knowledge gap by evaluating skeletal muscle function in nNOS knockout (KN1) mice using an in situ approach, in which the muscle is maintained in its normal physiological environment. nNOS-deficiency caused reductions in skeletal muscle bulk and maximum tetanic force production in male mice only. Furthermore, nNOS-deficient muscles from both male and female mice exhibited increased susceptibility to contraction-induced fatigue. These data suggest that aberrant nNOSμ signaling can negatively impact three important clinical features of dystrophinopathies and sarcoglycanopathies: maintenance of muscle bulk, force generation and fatigability. Our study suggests that restoration of sarcolemmal nNOSμ expression in dystrophic muscles may be more important than previously appreciated and that it should be a feature of any fully effective gene therapy-based intervention
Electronic properties of bilayer and multilayer graphene
We study the effects of site dilution disorder on the electronic properties
in graphene multilayers, in particular the bilayer and the infinite stack. The
simplicity of the model allows for an easy implementation of the coherent
potential approximation and some analytical results. Within the model we
compute the self-energies, the density of states and the spectral functions.
Moreover, we obtain the frequency and temperature dependence of the
conductivity as well as the DC conductivity. The c-axis response is
unconventional in the sense that impurities increase the response for low
enough doping. We also study the problem of impurities in the biased graphene
bilayer.Comment: 36 pages, 42 figures, references adde
Sarcopenia and cachexia: the adaptations of negative regulators of skeletal muscle mass
Recent advances in our understanding of the biology of muscle, and how anabolic and catabolic stimuli interact to control muscle mass and function, have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle occurs as a consequence of several chronic diseases (cachexia) as well as normal aging (sarcopenia). Although many negative regulators [Atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.] have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of mediators markedly differs among these conditions. Sarcopenic and cachectic muscles have been demonstrated to be abundant in myostatin- and apoptosis-linked molecules. The ubiquitin–proteasome system (UPS) is activated during many different types of cachexia (cancer cachexia, cardiac heart failure, chronic obstructive pulmonary disease), but not many mediators of the UPS change during sarcopenia. NF-κB signaling is activated in cachectic, but not in sarcopenic, muscle. Some studies have indicated a change of autophagic signaling during both sarcopenia and cachexia, but the adaptation remains to be elucidated. This review provides an overview of the adaptive changes in negative regulators of muscle mass in both sarcopenia and cachexia
Nonlinearity and Topology
The interplay of nonlinearity and topology results in many novel and emergent
properties across a number of physical systems such as chiral magnets, nematic
liquid crystals, Bose-Einstein condensates, photonics, high energy physics,
etc. It also results in a wide variety of topological defects such as solitons,
vortices, skyrmions, merons, hopfions, monopoles to name just a few.
Interaction among and collision of these nontrivial defects itself is a topic
of great interest. Curvature and underlying geometry also affect the shape,
interaction and behavior of these defects. Such properties can be studied using
techniques such as, e.g. the Bogomolnyi decomposition. Some applications of
this interplay, e.g. in nonreciprocal photonics as well as topological
materials such as Dirac and Weyl semimetals, are also elucidated
Whole Body Periodic Acceleration Is an Effective Therapy to Ameliorate Muscular Dystrophy in mdx Mice
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by the absence of dystrophin in both skeletal and cardiac muscles. This leads to severe muscle degeneration, and dilated cardiomyopathy that produces patient death, which in most cases occurs before the end of the second decade. Several lines of evidence have shown that modulators of nitric oxide (NO) pathway can improve skeletal muscle and cardiac function in the mdx mouse, a mouse model for DMD. Whole body periodic acceleration (pGz) is produced by applying sinusoidal motion to supine humans and in standing conscious rodents in a headward-footward direction using a motion platform. It adds small pulses as a function of movement frequency to the circulation thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of NO. In this study, we examined the potential therapeutic properties of pGz for the treatment of skeletal muscle pathology observed in the mdx mouse. We found that pGz (480 cpm, 8 days, 1 hr per day) decreased intracellular Ca2+ and Na+ overload, diminished serum levels of creatine kinase (CK) and reduced intracellular accumulation of Evans Blue. Furthermore, pGz increased muscle force generation and expression of both utrophin and the carboxy-terminal PDZ ligand of nNOS (CAPON). Likewise, pGz (120 cpm, 12 h) applied in vitro to skeletal muscle myotubes reduced Ca2+ and Na+ overload, diminished abnormal sarcolemmal Ca2+ entry and increased phosphorylation of endothelial NOS. Overall, this study provides new insights into the potential therapeutic efficacy of pGz as a non-invasive and non-pharmacological approach for the treatment of DMD patients through activation of the NO pathway
Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems
Exploring Authentic Skim and Nonfat Dry Milk Powder Variance for the Development of Nontargeted Adulterant Detection Methods Using NIR Spectroscopy and Chemometrics
This document provided is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Agricultural and Food Chemistry, copyright © American Chemical Society, after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/jf4023433peer-reviewedA multinational collaborative team led by the U.S. Pharmacopeial Convention is currently investigating the potential of near-infrared (NIR) spectroscopy for nontargeted detection of adulterants in skim and nonfat dry milk powder. The development of a compendial method is challenged by the range of authentic or nonadulterated milk powders available worldwide. This paper investigates the sources of variance in 41 authentic bovine skim and nonfat milk powders as detected by NIR diffuse reflectance spectroscopy and chemometrics. Exploratory analysis by principal component analysis and varimax factor rotation revealed significant variance in authentic samples and highlighted outliers from a single manufacturer. Spectral preprocessing and outlier removal methods reduced ambient and measurement sources of variance, most likely linked to changes in moisture together with sampling, preparation, and presentation factors. Results indicate that significant chemical variance exists in different skim and nonfat milk powders that will likely affect the performance of adulterant detection methods by NIR spectroscopy
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