In an effort to identify tumor-associated proteins from plasma of tumor-bearing mice that may be used as diagnostic biomarkers, we developed a strategy that combines a tumor xenotransplantation model in nude mice with comparative proteomic technology. Five human cancer cell lines (SC-M1, HONE-1, CC-M1, OECM1, GBM 8401) derived from stomach, nasopharyngeal, colon, oral and brain cancers were subcutaneously inoculated into nude mice and compared to control nude mice injected with phosphate-buffered saline. One month later, plasma from mice inoculated with cancer cells was collected for proteomic analysis using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Comparison of plasma 2-DE maps from tumor-bearing mice with those produced from control mice revealed the overexpression of several mouse acute phase proteins (APPs) such as haptoglobin. Another APP, serum amyloid A (SAA), was found only in mice bearing tumors induced by the stomach cancer cell line SC-M1, which has not previously been demonstrated in xenotransplatation experiment. Furthermore, by using immunohistochemistry, SAA and haptoglobin were found to originate from the mouse hosts and not from the human cancer cell line donors. The protein alterations were further confirmed on patients with stomach cancers where up-regulated levels of SAA were also observed. These results indicate that APPs may be used as nonspecific tumor-associated serum markers. SAA in particular may serve as a potential marker for detecting stomach cancer. Taken together, the combination of the xenotransplatation model in nude mice and proteomics analysis provided a valuable impact for clinical applications in cancer diagnostics. In addition, our findings demonstrate that a panel of APPs might serve as screening biomarkers for early cancer detection.

The proposed CADe system provides an automatic and quantitative procedure for tumor detection in ABUS images. Further studies are needed to reduce the FP rate of the CADe algorithm.

BackgroundThe timely and accurate diagnosis of specific influenza virus strains is crucial to effective prophylaxis, vaccine preparation and early antiviral therapy. The detection of influenza A viruses is mainly accomplished using polymerase chain reaction (PCR) techniques or antibody-based assays. In conjugation with the immunoassay utilizing monoclonal antibody, mass spectrometry is an alternative to identify proteins derived from a target influenza virus. Taking advantage of the large surface area-to-volume ratio, antibody-conjugated magnetic nanoparticles can act as an effective probe to extract influenza virus for sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and on-bead mass spectrometric analysis.ResultsIron oxide magnetic nanoparticles (MNP) were functionalized with H5N2 viral antibodies targeting the hemagglutinin protein and capped with methoxy-terminated ethylene glycol to suppress nonspecific binding. The antibody-conjugated MNPs possessed a high specificity to H5N2 virus without cross-reactivity with recombinant H5N1 viruses. The unambiguous identification of the captured hemagglutinin on magnetic nanoparticles was realized by SDS-PAGE visualization and peptide sequence identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS).ConclusionsThe assay combining efficient magnetic separation and MALDI-MS readout offers a rapid and sensitive method for virus screening. Direct on-MNP detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provided high sensitivity (~103 EID50 per mL) and a timely diagnosis within one hour. The magnetic nanoparticles encapsulated with monoclonal antibodies could be used as a specific probe to distinguish different subtypes of influenza.

Shear stress stimuli differentially regulate cellular functions based on the pattern, magnitude as well as duration of the flow. Shear stress can modify intracellular kinase activities and cytoskeleton reorganization to result in changes of cell behavior. Mesenchymal stem cells (MSCs) are mechano-sensitive cells, but little is known about the effects of oscillatory shear stress (OS). In this study, we demonstrate that OS of 0.5 6 4 dyn/cm 2 induces directional reorganization of Factin to mediate the fate choice of MSCs through the regulation of b-catenin. We also found that intercellular junction molecules are the predominant mechanosensors of OS in MSCs to deliver the signals that result in directional rearrangement of F-actin, as well as the increase of phosphorylated b-catenin (pb-catenin) after 30 minutes of OS stimulation. Depolymerization of F-actin and increase in pb-catenin also lead to the upregulation of Wnt inhibitory factors sclerostin and dickkopf-1. Inhibition of b-catenin/Wnt signaling pathway is accompanied by the upregulation of sex determining region Y-box2 and NANOG to control self-renewal. In conclusion, the reorganization of actin cytoskeleton and increase in b-catenin phosphorylation triggered by OS regulate the expression of pluripotency genes via the b-catenin/Wnt signaling pathway to differentially direct fate choices of MSCs at different time points. Results from this study have provided new information regarding how MSCs respond to mechanical cues from their microenvironment in a time-dependent fashion, and such biophysical stimuli could be administered to guide the fate and differentiation of stem cells in addition to conventional biochemical approaches. STEM CELLS 2015;33:429-442

The non-toxic and wide bandgap material TiO2 is explored as an n-type buffer layer on p-type Cu(In,Ga)Se2 (CIGS) absorber layer for thin film solar cells. The amorphous TiO2 thin film deposited by atomic layer deposition process at low temperatures shows conformal coverage on the CIGS absorber layer. Solar cells from non-vacuum deposited CIGS absorbers with TiO2 buffer layer result in a high short-circuit current density of 38.9 mA/cm2 as compared to 36.9 mA/cm2 measured in the reference cell with CdS buffer layer, without compromising open-circuit voltage. The significant photocurrent gain, mainly in the UV part of the spectrum, can be attributed to the low parasitic absorption loss in the ultrathin TiO2 layer (~10 nm) with a larger bandgap of 3.4 eV compared to 2.4 eV of the traditionally used CdS. Overall the solar cell conversion efficiency was improved from 9.5% to 9.9% by substituting the CdS by TiO2 on an active cell area of 10.5 mm2. Optimized TiO2/CIGS solar cells show excellent long-term stability. The results imply that TiO2 is a promising buffer layer material for CIGS solar cells, avoiding the toxic CdS buffer layer with added performance advantage.

have the highest reported effi ciencies, [ 1 ] the manufacturing is still complex and costly. [ 2,3 ] There is a need for new materials growth, processing and fabrication techniques to address this major shortcoming of III-V-based photovoltaics. Signifi cant progress on this front has been made by the epitaxial lift-off and transfer technique developed for gallium arsenide (GaAs), [ 1,4,5 ] which allows for limited reuse of costly epitaxial substrates.Here we present an alternative approach using indium phosphide (InP) thin fi lms grown directly on metal substrates. InP has a direct band gap of 1.344 eV, which is optimal for maximum effi ciency in single junction solar cells. [ 6 ] Recently we developed the thin-fi lm vapor-liquid-solid (TF-VLS) growth technique to produce high optoelectronic quality InP absorber layers directly on molybdenum (Mo) substrates. In this implementation of the technique, a layer of indium (In) confi ned between a Mo substrate and a silica (SiO x ) cap is heated to a temperature at which In is a liquid. The SiO x cap serves to prevent In evaporation and dewetting of the liquid In. Then, phosphorus vapor is introduced which diffuses through the SiO x cap into the In liquid, causing precipitation of solid InP. The InP grows into a polycrystalline fi lm with ultra-large (>100 µm) lateral grain sizes. [ 7,8 ] This templated process extends the use of VLS for growth of structures beyond nanowires. [9][10][11] The The design and performance of solar cells based on InP grown by the nonepitaxial thin-fi lm vapor-liquid-solid (TF-VLS) growth technique is investigated. The cell structure consists of a Mo back contact, p -InP absorber layer, n -TiO 2 electron selective contact, and indium tin oxide transparent top electrode. An ex situ p -doping process for TF-VLS grown InP is introduced. Properties of the cells such as optoelectronic uniformity and electrical behavior of grainboundaries are examined. The power conversion effi ciency of fi rst generation cells reaches 12.1% under simulated 1 sun illumination with open-circuit voltage ( V OC ) of 692 mV, short-circuit current ( J SC ) of 26.9 mA cm −2 , and fi ll factor (FF) of 65%. The FF of the cell is limited by the series resistances in the device, including the top contact, which can be mitigated in the future through device optimization. The highest measured V OC under 1 sun is 692 mV, which approaches the optically implied V OC of ≈795 mV extracted from the luminescence yield of p -InP.Figure 4. a) Calculated equilibrium band diagram of the top surface region of the device. b) J -V measurements for a cell under simulated 1 sun illumination (solid line) and in the dark (dotted line). Device parameters were V OC of 692 mV, J SC of 26.9 mA cm −2 , FF of 65%, and power conversion effi ciency of 12.1%. Cell area was 0.5 × 0.5 mm 2 . c) Corresponding EQE and 1-R curves.

DNA damage responses contribute to cisplatin resistance; however, therapeutic strategies to overcome cisplatin resistance have not yet been established. Here, we demonstrate that inhibition of ATR-Chk1 pathway with the potent inhibitor WYC0209 sensitizes bladder cancer cells to cisplatin. In the clinical microarray profile, high ATR expression is associated with poor prognosis in bladder cancer patients who receive chemotherapy. We show that pharmacological and genetic suppressing of ATR sensitized cells to cisplatin. Treatment with WYC0209 or siATR increased levels of cisplatin-DNA adducts, concomitant with decreased levels of p-glycoprotein expression. Additionally, Combinations of cisplatin and WYC0209 show synergistic activity against bladder cancer. Ultimately, WYC0209 enhanced the anti-tumor effects of cisplatin and suppressed p-glycoprotein expression in bladder cancer xenografts. These results indicate that inhibiting ATR-Chk1 activation with WYC0209 suppresses p-glycoprotein expression and increases cisplatin activity in bladder cancer. Our findings collectively suggest that ATR-Chk1 is a target for improving the efficacy of cisplatin in bladder cancer.

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