BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance

Since the initial discovery that a subset of patients with cutaneous melanoma harbor BRAF mutations, substantial research has been focused on determining the pathologic consequences of BRAF mutations, optimizing diagnostic techniques to identify these mutations, and developing therapeutic interventions to inhibit the function of this target in mutation-bearing tumors. Recently, advances have been made which are revolutionizing the standard of care for patients with BRAF mutant melanoma. This paper provides an overview on the pathogenic ramifications of mutant BRAF signaling, the latest molecular testing methods to detect BRAF mutations, and the most recent clinical data of BRAF pathway inhibitors in patients with melanoma and BRAF mutations. Finally, emerging mechanisms of resistance to BRAF inhibitors and ways of overcoming this resistance are discussed

Comparing stakeholder attitudes toward white-tailed deer and rare plant management in Canaan Valley, West Virginia

Canaan Valley, West Virginia, USA provides habitat for many plants considered rare in West Virginia. The local white-tailed deer (Odocoileus virginianus Zimm.) are a popular attraction for visitors as well as resident and nonresident hunters. However, concerns exist over the impact of white-tailed deer herbivory on rare plant communities in the wetlands. We evaluated stakeholder attitudes regarding white-tailed deer management and rare plant conservation by mailing surveys to property owners in Canaan Valley and Tucker County, WV, and providing surveys to visitors at Canaan Valley State Park and National Wildlife Refuge. Individuals that had incurred crop damage were more likely to view the Canaan Valley population as overabundant while nonresident landowners placed higher values on the conservation of rare plants and plant communities in Canaan Valley. We found that hunters were more likely than nonhunters to support white-tailed deer management actions. Results of this survey may help managers to direct management and education goals toward actual rather than perceived stakeholder attitudes

Information Technology Usage In Accounting Firms: The Best Versus The Rest

The purpose of this paper is to analyze information technology expenditures in public accounting firms from a multi-year sample.  This study also focuses on identifying possible IT spending trends in public accounting firms and attempts to determine if additional spending on IT increased the profitability of these firms

An explanation of the Newman-Janis Algorithm

After the original discovery of the Kerr metric, Newman and Janis showed that this solution could be ``derived'' by making an elementary complex transformation to the Schwarzschild solution. The same method was then used to obtain a new stationary axisymmetric solution to Einstein's field equations now known as the Kerr-newman metric, representing a rotating massive charged black hole. However no clear reason has ever been given as to why the Newman-Janis algorithm works, many physicist considering it to be an ad hoc procedure or ``fluke'' and not worthy of further investigation. Contrary to this belief this paper shows why the Newman-Janis algorithm is successful in obtaining the Kerr-Newman metric by removing some of the ambiguities present in the original derivation. Finally we show that the only perfect fluid generated by the Newman-Janis algorithm is the (vacuum) Kerr metric and that the only Petrov typed D solution to the Einstein-Maxwell equations is the Kerr-Newman metric.Comment: 14 pages, no figures, submitted to Class. Quantum Gra

A variational principle for stationary, axisymmetric solutions of Einstein's equations

Stationary, axisymmetric, vacuum, solutions of Einstein's equations are obtained as critical points of the total mass among all axisymmetric and $(t,\phi)$ symmetric initial data with fixed angular momentum. In this variational principle the mass is written as a positive definite integral over a spacelike hypersurface. It is also proved that if absolute minimum exists then it is equal to the absolute minimum of the mass among all maximal, axisymmetric, vacuum, initial data with fixed angular momentum. Arguments are given to support the conjecture that this minimum exists and is the extreme Kerr initial data.Comment: 21 page

Characterization Of Individual Submicron Perfluorocarbon Gas Bubbles By Ultrasonic Backscatter

Measurements were undertaken to determine the unknown microbubble-size distribution of a dodecafluoropentane (DDFP) emulsion consisting of in surfactant-stabilized water. The acoustic backscatter of 2-microsecond-duration tonebursts of 30-MHz focused ultrasound was measured from the emulsion as it moved in a coaxial flow. Calibration for the system was accomplished using 3-μm-radius polystyrene spheres, using a linear scattering model and literature values for polystyrene. Applying viscous linear scattering theory to the backscatter data from individual DDFP bubbles allowed inversion of the radius–backscatter relation. A mean microbubble radius of 130 nm was inferred for the DDFP population. © 2005 Acoustical Society of America

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

The Outburst of V1647 Ori Revealed by Spitzer

We present Spitzer Space Telescope observations of V1647 Ori, the outbursting source lighting McNeil's nebula, taken near the optical peak of the outburst in early March 2004. The source is easily detected in all Spitzer imaging bands from 3.6 - 70 microns. The fluxes at all wavelengths are roughly a factor of 15 brighter than pre-outburst levels; we measure a bolometric luminosity of 44 Lsun. We posit that this event is due to an increase in the accretion luminosity of the source. Simple models of an accretion disk plus tenuous envelope can qualitatively explain the observed pre- and post-outburst spectral energy distributions. The accretion activity implied by our results indicates that the outburst may be intermediate between FUor and EXor-type events. We also report the discovery of a previously unknown mid-infrared counterpart to the nearby Herbig-Haro object HH 22.Comment: 12 pages, 3 figures, accepted by ApJ Letter