Identification of candidate biomarkers in ovarian cancer serum by depletion of highly abundant proteins and differential in‐gel electrophoresis

Ovarian cancer is the fifth leading cause of cancer death for women in the US, yet survival rates are over 90% when it is diagnosed at an early stage, highlighting the need for biomarkers for early detection. To enhance the discovery of tumor‐specific proteins that could represent novel serum biomarkers for ovarian cancer, we depleted serum of highly abundant proteins which can mask the detection of proteins present in serum at low concentrations. Three commercial immunoaffinity columns were used in parallel to deplete the highly abundant proteins in serum from 60 patients with serous ovarian carcinoma and 60 non‐cancer controls. Medium and low abundance serum proteins from each serum pool were then evaluated by the quantitative proteomic technique of differential in‐gel electrophoresis. The number of protein spots that were elevated in ovarian cancer sera by at least twofold ranged from 36 to 248, depending upon the depletion and separation methods. From the 33 spots picked for MS analysis, nine different proteins were identified, including the novel candidate ovarian cancer biomarkers leucine‐rich α2 glycoprotein‐1 and ficolin 3. Western blotting validated the relative increases in serum protein levels for three of the proteins identified, demonstrating the utility of this approach for the identification of novel serum biomarkers for ovarian cancer.     

Continuous-wave mid-infrared frequency conversion in silicon nanowaveguides

We report the first demonstration of cw wavelength conversion from the telecommunications band to the mid-IR (MIR) region via four-wave mixing in silicon nanowaveguides. We measure a parametric bandwidth of 748 nm by converting a 1636 nm signal to produce a 2384 nm idler and show continuously tunable wavelength conversion from 1792 to 2116 nm. This report indicates that the advantages of silicon photonics may be leveraged to create devices for a large range of MIR applications that require cw operation.     

Adjusting for confounding by cluster using generalized linear mixed models

We show how to use generalized linear mixed models to adjust for confounding by cluster of the effect of a within-cluster covariate. We derive estimators for both a cluster-specific causal effect and a population-averaged causal effect.     

Pricing and volume discounting for a dominant retailer with uncertain manufacturing cost information

A product costs the manufacturer c/unit to produce; the retailer sells it at p/unit to the consumers. The retail-market demand volume V varies with p according to a given demand curve D_p. How would or should the “players” (i.e., the manufacturer and the retailer) set their prices? In contrast to many studies that assume a dominant manufacturer implementing the “manufacturer-Stackelberg” (“[mS]”) game, this paper examines how a dominant retailer should operate when his knowledge of c is imperfect. We first derive optimal decisions (some of them counter-intuitive) for the dominant retailer when he is restricted to choosing between [rS] (retailer-Stackelberg) and [mS]. Second, we propose a “reverse quantity discount” scheme that the dominant retailer (i.e., the downstream player) can offer to the manufacturer (note that the standard discount scheme is offered by the upstream player). We show that this discounting scheme is quite effective compared to the considerably more complicated though nevertheless theoretically optimal “menu of contracts.” We also reveal a largely overlooked function of discounting; i.e., discounting enables an “ignorant” but dominant player to usurp the earnings attributable to the knowledge of the dominated player. Finally, we also show that discounting works well when the demand curve is linear, but becomes ineffective when the demand curve is iso-elastic – a result echoing the conclusions of some earlier related works.     

Jet impingement cooling of a discretely heated portion of a protruding pedestal with a single round air jet

The influence of a protruding pedestal on impinging jet heat transfer is investigated. A discretely heated portion of a protruding pedestal is exposed to a single circular impinging air jet with Re=10,000–30,000. Jet exit diameters of 3.5, 9.5 and 21 mm are positioned at jet exit-to-surface distances of 2–5 diameters. The nondimensional heat transfer over the discretely heated portion of the pedestal is compared to a flat plate design to gauge the effects of Reynolds number, jet diameter and jet exit-surface spacing. In all cases, the presence of the protruding pedestal downstream is found to increase heat transfer.     

Characterization of cell lysis events on a microfluidic device for high-throughput single cell analysis

A microfluidic device capable of rapidly analyzing cells in a high-throughput manner using electrical cell lysis is further characterized. In the experiments performed, cell lysis events were studied using an electron multiplying charge coupled device camera with high frame rate (>100 fps) data collection. It was found that, with this microfluidic design, the path that a cell follows through the electric field affects the amount of lysate injected into the analysis channel. Elimination of variable flow paths through the electric field was achieved by coating the analysis channel with a polyamine compound to reverse the electroosmotic flow (EOF). EOF reversal forced the cells to take the same path through the electric field. The improved control of the cell trajectory will reduce device-imposed bias on the analysis and maximizes the amount of lysate injected into the analysis channel for each cell, resulting in improved analyte detection capabilities.