McPhee Research (United States)

In situ measurements of flow and stratification in the vicinity of the Erebus Glacier Tongue, a 12 km long floating Antarctic glacier, show the significant influence of the glacier. Three ADCPs (75, 300, and 600 kHz) were deployed close (<50 m) to the sidewall of the glacier in order to capture near-field flow distortion. Scalar (temperature and conductivity) and shear microstructure profiling captured small-scale vertical variability. Flow magnitudes exceeded 0.3 m s−1 through a combination of tidal flow (∼8 cm s−1) and a background/residual flow (∼4–10 cm s−1) flowing to the NW. Turbulence was dominated by deeper mixing during spring tide, likely indicative of the role of bathymetric variation which locally forms an obstacle as great as the glacier. During the neap tide, near-surface mixing was as energetic as that seen in the spring tide, suggesting the presence of buoyancy-driven near-surface flows. Estimates of integrated dissipation rate suggest that these floating extensions of the Antarctic ice sheet alter energy budgets through enhanced dissipation, and thus influence coastal near-surface circulation.

Nonsteroidal agonists have been developed that selectively bind to and activate estrogen receptor beta (ERbeta) rather than estrogen receptor alpha (ERalpha). ERbeta is expressed equally in both male and female mammals in multiple extragonadal tissues. Work reported elsewhere has demonstrated that ERbeta agonists have beneficial effects in multiple (but not all) models of inflammatory diseases and also increase survival in experimentally induced sepsis. In these experiments, ERbeta agonists (ERB-041 or WAY-202196) were compared with vehicle control in the murine cecal ligation and puncture (CLP) model and in the pneumococcal pneumonia model of sepsis. The effect of WAY-202196 on the gene expression profile in the CLP model was further studied by transcriptome analysis of lung and small intestine tissue samples. ERbeta agonists provided a significant survival benefit in both experimental models of bacterial sepsis. This survival advantage was accompanied by reduced histologic evidence of tissue damage, reduced transcription of multiple proinflammatory proteins by transcriptome analysis and was not associated with increased bacterial outgrowth. ERbeta agonist administration provided a survival advantage in septic animals and appears to be a promising therapeutic modality in sepsis.

Sea ice plays a crucial role in the exchange of heat between the ocean and the atmosphere, and areas of intense air‐sea‐ice interaction are important sites for water mass modification. The Weddell Sea is one of these sites where a relatively thin first‐year ice cover is constantly being changed by mixing of heat from below and stress exerted from the rapidly changing and intense winds. This study presents mixed layer turbulence measurements obtained during two wintertime drift stations in August 2005 in the eastern Weddell Sea, close to the Maud Rise seamount. Turbulence in the boundary layer is found to be controlled by the drifting ice. Directly measured heat fluxes compare well with previous studies and are well estimated from the mixed layer temperatures and mixing. Heat fluxes are also found to roughly balance the conductive heat flux in the ice; hence, little freezing/melting was observed. The under‐ice topography is estimated to be hydraulically very smooth; comparison with a steady 1‐D model shows that these estimates are made too close to the ice‐ocean interface to be representative for the entire ice floe. The main source and sink of turbulent kinetic energy are shear production and dissipation. Observations indicate that the dynamics of the under‐ice boundary layer are influenced by a horizontal variability in mixed layer density and an increasing amount of open leads in the area.

Properly describing heat and salt flux at the ice/ocean interface is essential for understanding and modeling the energy and mass balance of drifting sea ice. Basal growth or ablation depends on the ratio, R, of the interface heat exchange coefficient to that of salt, such that as R increases so does the rate‐limiting impact of salt diffusion. Observations of relatively slow melt rates in above freezing seawater (plus migration of summer “false bottoms”) suggest by analogy with laboratory studies that double diffusion of heat and salt from the ocean is important during the melting process, with numeric values for R estimated to range from 35 to 70. If the same double‐diffusive principles apply for ice growth as for melting (i.e., if the process is symmetric), supercooling (possibly relieved by frazil crystal production) would occur under rapidly growing ice, yet neither extensive supercooling nor frazil accumulation is found in Arctic pack ice with limited atmospheric contact. Physical properties and turbulent fluxes of heat and salt were measured in the relatively controlled setting of a tidally driven Svalbard fjord, under growing fast ice in late winter. The data failed to show supercooling, frazil production, or enhanced heat flux, suggesting that the double diffusive process is asymmetric. Modeling results compared with measured turbulent fluxes imply that R = 1 when ice freezes; i.e., that double‐diffusive tendencies are relieved at or above the immediate interface. An algorithm for calculating ice/ocean heat and salt flux accommodating the different processes is presented, along with recommended ranges for the interface exchange coefficients.

An area of unmet medical need in clinical oncology has been optimizing patient selection for a given therapeutic with the goal of getting the right drug to the right patient. Recent studies have developed preclinical approaches to identifying molecular 'signatures of resistance' for cytotoxic therapies and prospective validation of this strategy is ongoing in the clinic. New challenges in this setting include identifying approaches to patient selection for cytostatic compounds such as signaling pathway inhibitors and stem cell targets. Here, we discuss the biomarker methodologies developed using traditional cytotoxic drugs and how these approaches can be adapted to identify biomarkers of patient selection for novel signaling inhibitors and other novel targets. It has become increasingly clear that such biomarker discovery and validation needs to begin early and continue throughout the drug development process.