Fibroblast growth factor receptor 4 single nucleotide polymorphism Gly388Arg in head and neck carcinomas

BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases (RTKs) and members of the fibroblast growth factor receptors (FGFR)-family. Single-nucleotide polymorphism (SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC. AIM To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted. METHODS Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany. Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP. Patients' clinical data with a minimum follow-up of 5 syears were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis. RESULTS Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high" (+++) in 74 (26%), "intermediate" (++) in 103 (36.3%), and "low" (+) in 107 (36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors (33.8%), 84 of them (29.6%) having a heterozygous and 12 (4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage (P < 0.004), local metastasis (P < 0.0001) and reduced disease-free survival (P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival (P < 0.003). CONCLUSION In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention

Low-energy magnetic radiation: deviations from GOE

A pronounced spike at low energy in the strength function for magnetic radiation (LEMAR) is found by means of Shell Model calculations, which explains the experimentally observed enhancement of the dipole strength. LEMAR originates from statistical low-energy M1-transitions between many excited complex states. Re-coupling of the proton and neutron high-j orbitals generates the strong magnetic radiation. LEMAR is closely related to Magnetic Rotation. LEMAR is predicted for nuclides participating in the r-process of element synthesis and is expected to change the reaction rates. An exponential decrease of the strength function and a power law for the size distribution of the $B(M1)$ values are found, which strongly deviate from the ones of the GOE of random matrices, which is commonly used to represent complex compound states.Comment: Proceedings of the conference on Nuclei and Mesoscopic Physics 2014, MSU, to be published AIP Conference Proceeding

The Impact of "Deregulation" on Regulator Behavior: An Empirical Analysis of the Telecommunications Act of 1996

This paper examines how regulators set local prices in response to the changes brought on by the Telecommunications Act of 1996 (“Telecom Act”). We are particularly interested in the extent to which state regulators set prices that promoted efficiency or were influenced by private-interest groups who had secured rents under a regime of regulated monopoly. Using regional Bell operating company (RBOC) data, our empirical results indicate that private interests continue to influence the structure of retail and wholesale prices, although their influence appears to be waning. We find that changes to the regulatory structure, as measured by federal approval of RBOC Section 271 applications that open up markets to competition and universal service subsidies, resulted in a re-balancing of retail prices and lower overall price levels.competition, political contributions, private interest, public interest, regulation, telecommunications, universal service

One-loop surface tensions of (supersymmetric) kink domain walls from dimensional regularization

We consider domain walls obtained by embedding the 1+1-dimensional $\phi^4$-kink in higher dimensions. We show that a suitably adapted dimensional regularization method avoids the intricacies found in other regularization schemes in both supersymmetric and non-supersymmetric theories. This method allows us to calculate the one-loop quantum mass of kinks and surface tensions of kink domain walls in a very simple manner, yielding a compact d-dimensional formula which reproduces many of the previous results in the literature. Among the new results is the nontrivial one-loop correction to the surface tension of a 2+1 dimensional N=1 supersymmetric kink domain wall with chiral domain-wall fermions.Comment: 23 pages, LATeX; v2: 25 pages, 2 references added, extended discussion of renormalization schemes which dispels apparent contradiction with previous result

Observation of the spin Nernst effect

The observation of the spin Hall effect triggered intense research on pure spin current transport. With the spin Hall effect, the spin Seebeck effect, and the spin Peltier effect already observed, our picture of pure spin current transport is almost complete. The only missing piece is the spin Nernst (-Ettingshausen) effect, that so far has only been discussed on theoretical grounds. Here, we report the observation of the spin Nernst effect. By applying a longitudinal temperature gradient, we generate a pure transverse spin current in a Pt thin film. For readout, we exploit the magnetization-orientation-dependent spin transfer to an adjacent Yttrium Iron Garnet layer, converting the spin Nernst current in Pt into a controlled change of the longitudinal thermopower voltage. Our experiments show that the spin Nernst and the spin Hall effect in Pt are of comparable magnitude, but differ in sign, as corroborated by first-principles calculations

Spin-orbit induced longitudinal spin-polarized currents in non-magnetic solids

For certain non-magnetic solids with low symmetry the occurrence of spin-polarized longitudinal currents is predicted. These arise due to an interplay of spin-orbit interaction and the particular crystal symmetry. This result is derived using a group-theoretical scheme that allows investigating the symmetry properties of any linear response tensor relevant to the field of spintronics. For the spin conductivity tensor it is shown that only the magnetic Laue group has to be considered in this context. Within the introduced general scheme also the spin Hall- and additional related transverse effects emerge without making reference to the two-current model. Numerical studies confirm these findings and demonstrate for (Au$_{1-x}$Pt$_{\rm x}$)$_4$Sc that the longitudinal spin conductivity may be in the same order of magnitude as the conventional transverse one. The presented formalism only relies on the magnetic space group and therefore is universally applicable to any type of magnetic order.Comment: 5 pages, 1 table, 2 figures (3 & 2 subfigures

Manipulating sleep spindles - expanding views on sleep, memory, and disease.

Sleep spindles are distinctive electroencephalographic (EEG) oscillations emerging during non-rapid-eye-movement sleep (NREMS) that have been implicated in multiple brain functions, including sleep quality, sensory gating, learning, and memory. Despite considerable knowledge about the mechanisms underlying these neuronal rhythms, their function remains poorly understood and current views are largely based on correlational evidence. Here, we review recent studies in humans and rodents that have begun to broaden our understanding of the role of spindles in the normal and disordered brain. We show that newly identified molecular substrates of spindle oscillations, in combination with evolving technological progress, offer novel targets and tools to selectively manipulate spindles and dissect their role in sleep-dependent processes

Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver.

Objective: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKCa agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKCa-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. Methods: In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. Results: In livers treated with TLCA (10 mmol/l)+TUDCA (25 mmol/l), combined inhibition of cPKC by the cPKCselective inhibitor Go¨6976 (100 nmol/l) or the nonselective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p,0.05) and 48% (p,0.01), and secretion of the Mrp2/ Abcc2 substrate, 2,4-dinitrophenyl-S-glutathione, by 31% (p,0.05) and 41% (p,0.01), respectively; bile flow was unaffected in control livers or livers treated with TUDCA only or TLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKCa, nPKCe, and PKA, respectively, in a staurosporine-sensitive manner. Conclusion: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKCa-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation