Using Market-Based Spectrum Policy to Promote the Public Interest

With the increasing demand for spectrum to accommodate emerging technologies, and the discovery that higher frequencies are usable, the FCC has replaced its reliance on administrative mechanisms for allocating spectrum with a more flexible, market-based approach. The FCC can best accomplish its mission of promoting the public interest by continuing to rely on competitive market forces and by establishing a clear and consistent paradigm for approaching allocation, assignment, usage, and other policies. Such a paradigm envisions an FCC that would actively monitor spectrum to remedy situations in which it is not used to its full value; establish mechanisms to reduce new services\u27 need for immediate secondary market transactions; set and enforce minimally restrictive baseline rules governing interference and health effects; maximize the amount of spectrum available to users; and, in some cases, intervene in markets to correct significant market failures

Reduced glycogen availability is associated with increased AMPKα2 activity, nuclear AMPKα2 protein abundance, and GLUT4 mRNA expression in contracting human skeletal muscle

Glycogen availability can influence glucose transporter 4 (GLUT4) expression in skeletal muscle through unknown mechanisms. The multisubstrate enzyme AMP-activated protein kinase (AMPK) has also been shown to play an important role in the regulation of GLUT4 expression in skeletal muscle. During contraction, AMPK [alpha]2 translocates to the nucleus and the activity of this AMPK isoform is enhanced when skeletal muscle glycogen is low. In this study, we investigated if decreased pre-exercise muscle glycogen levels and increased AMPK [alpha]2 activity reduced the association of AMPK with glycogen and increased AMPK [alpha]2 translocation to the nucleus and GLUT4 mRNA expression following exercise. Seven males performed 60 min of exercise at ~70% [VO.sub.2] peak on 2 occasions: either with normal (control) or low (LG) carbohydrate pre-exercise muscle glycogen content. Muscle samples were obtained by needle biopsy before and after exercise. Low muscle glycogen was associated with elevated AMPK [alpha]2 activity and acetyl-CoA carboxylase [beta] phosphorylation, increased translocation of AMPK [alpha]2 to the nucleus, and increased GLUT4 mRNA. Transfection of primary human myotubes with a constitutively active AMPK adenovirus also stimulated GLUT4 mRNA, providing direct evidence of a role of AMPK in regulating GLUT4 expression. We suggest that increased activation of AMPK [alpha]2 under conditions of low muscle glycogen enhances AMPK [alpha]2 nuclear translocation and increases GLUT4 mRNA expression in response to exercise in human skeletal muscle. <br /

Precise measurements of torque in von Karman swirling flow driven by a bladed disk

© 2018 Informa UK Limited, trading as Taylor & Francis Group Scrupulous measurements and detailed data analysis of the torque in a swirling turbulent flow driven by counter-rotating bladed disks reveal an apparent breaking of the law of similarity. Potentially, such breakdown could arise from several possible factors, including dependence on dimensionless numbers other than Re or velocity coupling to other fields such as temperature. However, careful redesign and calibration of the experiment showed that this unexpected result was due to background errors caused by minute misalignments which lead to a noisy and irreproducible torque signal at low rotation speeds and prevented correct background subtraction normally ascribed to frictional losses. An important lesson to be learnt is that multiple minute misalignments can nonlinearly couple to the torque signal and provide a dc offset that cannot be removed by averaging. That offset can cause the observed divergence of the friction coefficient (Formula presented.) from its constant value observed in the turbulent regime. By significant modifications of the setup and conducting the experiment with one bladed disk and precisely aligned the disk, torque meter and motor shaft, we are able to conduct precise measurements close to the expected resolution at small torques at low rotation speeds and to confirm the similarity law in a wide range of Re, in particular, in low viscosity fluids

Motif affinity and mass spectrometry proteomic approach for the discovery of cellular AMPK targets: identification of mitochondrial fission factor as a new AMPK substrate

AMP-activated protein kinase (AMPK) is a key cellular energy sensor and regulator of metabolic homeostasis. Although it is best known for its effects on carbohydrate and lipid metabolism, AMPK is implicated in diverse cellular processes, including mitochondrial biogenesis, autophagy, and cell growth and proliferation. To further our understanding of energy homeostasis through AMPK-dependent processes, the design and application of approaches to identify and characterise novel AMPK substrates are invaluable. Here, we report an affinity proteomicstrategy for the discovery and validation of AMPK targets using an antibody to isolate proteins containing the phospho-AMPK substrate recognition motif from hepatocytes that had been treated with pharmacological AMPK activators. We identified 57 proteins that were uniquely enriched in the activator-treated hepatocytes, but were absent in hepatocytes lacking AMPK. We focused on two candidates, cingulin and mitochondrial fission factor (MFF), and further characterised/validated them as AMPK-dependent targets by immunoblotting with phosphorylation site-specific antibodies. A small-molecule AMPK activator caused transient phosphorylation of endogenous cingulin at S137 in intestinal Caco2 cells. Multiple splice-variants of MFF appear to express in hepatocytes and we identified a common AMPK-dependent phospho-site (S129) in all the 3 predominant variants spanning the mass range and a short variant-specific site (S146). Collectively, our proteomic-based approach using a phospho-AMPK substrate antibody in combination with genetic models and selective AMPK activators will provide a powerful and reliable platform for identifying novel AMPK-dependent cellular targets

High intensity interval training improves liver and adipose tissue insulin sensitivity

Objective: Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods: In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results: HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC

Skeletal muscle AMPK is essential for the maintenance of FNDC5 expression

Fibronectin type III domain‐containing protein 5 (FNDC5) expression is controlled by the transcriptional co‐activator, peroxisome proliferator‐activated receptor gamma, coactivator 1 alpha (PGC1α). FNDC5 expression has been shown to be increased in muscle in response to endurance exercise in some but not all studies, therefore a greater understanding of the mechanisms controlling this process are needed. The AMP‐activated protein kinase (AMPK) is activated by exercise in an intensity dependent manner and is an important regulator of PGC1α activity; therefore, we explored the role of AMPK in the regulation of FNDC5 using AMPK β1β2 double muscle‐null mice (AMPK DMKO), which lack skeletal muscle AMPK activity. We found that FNDC5 expression is dramatically reduced in resting muscles of AMPK DMKO mice compared to wild‐type littermates. In wild‐type mice, activating phosphorylation of AMPK was elevated immediately post contraction and was abolished in muscle from AMPK DMKO mice. In contrast, PGC1α was increased in both wild‐type and AMPK DMKO mice 3 h post contraction but FNDC5 protein expression was not altered. Lastly, acute or chronic activation of AMPK with the pharmacological AMPK activator AICAR did not increase PGC1α or FNDC5 expression in muscle. These data indicate that skeletal muscle AMPK is required for the maintenance of basal FNDC5 expression

Lichenoid Reaction Pattern with Pseudoepitheliomatous Hyperplasia – A Rare Tattoo Reaction: A Case Report and Review of the Literature

Pseudoepitheliomatous hyperplasia is a benign histologic reaction pattern that in rare cases can occur shortly after a tattooing procedure. We describe a case of pseudoepitheliomatous hyperplasia in two tattoos on the same patient 1 year after filling with the same batch of red ink