Experimental investigation of a mach 5 isentropic spike inlet at and below design speed

Zero angle of attack performance of isentropic spike inlet designed for maximum external compression at hypersonic spee

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

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

Expression of Cadherin-11 during Organogenesis in the Chick Embryo

Cadherin-11 (cad-11) is primarily a mesenchymal cadherin that appears in delaminating neural crest cells. Its expression correlates with morphogenetic events and the pattern has been studied in mouse, rat and Xenopus embryos, but not during avian organogenesis. Our purpose was to investigate this pattern in the chick embryo during organogenesis using immunolocalization and in situ hybridization. Cad-11 was expressed in mesenchyme around the pharynx and aortic arches, eyes, auditory vesicles, lung buds, stomach, and nasal placodes. Neural expression included some cranial ganglia and also new neuroepithelium within the tail bud region undergoing secondary neurulation. We also found expression in epithelia of the developing circulatory and digestive organs. The limb buds, pineal rudiment and mesonephros were also positive. Cad-11 expression became more widespread with development. Our findings support the role of cad-11 as a mesenchymal cadherin, but provide evidence for a wider role that includes epithelial morphogenesis and secondary neurulation

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

Area-charge inequality for black holes

The inequality between area and charge $A\geq 4\pi Q^2$ for dynamical black holes is proved. No symmetry assumption is made and charged matter fields are included. Extensions of this inequality are also proved for regions in the spacetime which are not necessarily black hole boundaries.Comment: 21 pages, 2 figure

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss