MicroRNAs in Renal Cell Carcinoma: Diagnostic Implications of Serum miR-1233 Levels

BACKGROUND: MicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC). METHODOLOGY/PRINCIPAL FINDINGS: We first explored microrna expression profiles in tissue and serum using taqman low density arrays in each six malignant and benign samples: Although 109 microRNAs were circulating at higher levels in cancer patients' serum, we identified only 36 microRNAs with up-regulation in RCC tissue and serum of RCC patients. Seven candidate microRNAs were selected for verification based on the finding of up-regulation in serum and tissue of RCC patients: miR-7-1*, miR-93, miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum of healthy controls (n = 30) and RCC (n = 33) patients were determined using quantitative real-time PCR (TaqMan MicroRNA Assays). miR-1233 was increased in RCC patients, and thus validated in a multicentre cohort of 84 RCC patients and 93 healthy controls using quantitative real-time PCR (sensitivity 77.4%, specificity 37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma or oncocytoma, whose serum miR-1233 levels were similar to RCC patients. Circulating microRNAs were not correlated with clinical-pathological parameters. CONCLUSIONS/SIGNIFICANCE: MicroRNA levels are distinctly increased in cancer patients, although only a small subset of circulating microRNAs has a tumor-specific origin. We identify circulating miR-1233 as a potential biomarker for RCC patients. Larger-scaled studies are warranted to fully explore the role of circulating microRNAs in RCC

Flexible In-Ga-Zn-O based circuits with two and three metal layers: simulation and fabrication study

The quest for high-performance flexible circuits call for scaling of the minimum feature size in Thin-Film Transistors (TFTs). Although reduced channel lengths can guarantee an improvement in the electrical properties of the devices, proper design rules also play a crucial role to minimize parasitics when designing fast circuits. In this letter, systematic Computer-Aided Design (CAD) simulations have guided the fabrication of highperformance flexible operational amplifiers (opamps) and logic circuits based on Indium-Gallium-Zinc-Oxide (IGZO) TFTs. In particular, the performance improvements due to the use of an additional third metal layer for the interconnections has been estimated for the first time. Encouraged by the simulated enhancements resulting by the decreased parasitic resistances and capacitances, both TFTs and circuits have been realized on a free-standing 50μm thick polymide foil using three metal layers. Despite the thicker layer stack, the TFTs have shown mechanical stability down to 5mm bending radii. Moreover, the opamps and the logic circuits have yielded improved electrical performance with respect to the architecture with two metal layers: gainbandwidth- product (GBWP) increased by 16:9%, for the first one, and propagation delay (tpd) decreased by 43%, for the latter one

Formality and informality in the summative assessment of motor vehicle apprentices: a case study

This article explores the interaction of formal and informal attributes of competence‐based assessment. Specifically, it presents evidence from a small qualitative case study of summative assessment practices for competence‐based qualifications within apprenticeships in the motor industry in England. The data are analysed through applying an adaptation of a framework for exploring the interplay of formality and informality in learning. This analysis reveals informal mentoring as a significant element which influences not only the process of assessment, but also its outcomes. We offer different possible interpretations of the data and their analysis, and conclude that, whichever interpretation is adopted, there appears to be a need for greater capacity‐building for assessors at a local level. This could acknowledge a more holistic role for assessors; recognise the importance of assessors’ informal practices in the formal retention and achievement of apprentices; and enhance awareness of inequalities that may be reinforced by both informal and formal attributes of assessment practices

Reverse dark current in organic photodetectors and the major role of traps as source of noise

Organic photodetectors have promising applications in low-cost imaging, health monitoring and near-infrared sensing. Recent research on organic photodetectors based on donor–acceptor systems has resulted in narrow-band, flexible and biocompatible devices, of which the best reach external photovoltaic quantum efficiencies approaching 100%. However, the high noise spectral density of these devices limits their specific detectivity to around 1013 Jones in the visible and several orders of magnitude lower in the near-infrared, severely reducing performance. Here, we show that the shot noise, proportional to the dark current, dominates the noise spectral density, demanding a comprehensive understanding of the dark current. We demonstrate that, in addition to the intrinsic saturation current generated via charge-transfer states, dark current contains a major contribution from trap-assisted generated charges and decreases systematically with decreasing concentration of traps. By modeling the dark current of several donor–acceptor systems, we reveal the interplay between traps and charge-transfer states as source of dark current and show that traps dominate the generation processes, thus being the main limiting factor of organic photodetectors detectivity

Radio frequency electronics on plastic

In this paper the recent progress of active high frequency electronics on plastic is discussed. This technology is mechanically flexible, bendable, stretchable and does not need any rigid chips. Indium Gallium Zinc Oxide (IGZO) technology is applied. At 2 V supply and gate length of 0.5 μm, the thin-film transistors (TFTs) yield a measured transit frequency of 138 MHz. Our scalable TFT compact simulation model shows good agreement with measurements. To achieve a sufficiently high yield, TFTs with gate lengths of around 5 μm are used for the circuit design. A Cherry Hopper amplifier with 3.5 MHz bandwidth, 10 dB gain and 5 mW dc power is presented. The fully integrated receiver covering a plastic foil area of 3 × 9 mm2 includes a four stage cascode amplifier, an amplitude detector, a baseband amplifier and a filter. At a dc current of 7.2 mA and a supply of 5 V, a bandwidth of 2 - 20 MHz and a gain beyond 15 dB were measured. Finally, an outlook regarding future advancements of high frequency electronics on plastic is given

Studies of Vibrational Properties in Ga Stabilized d-Pu by Extended X-ray Absorption Fine Structure

Temperature dependent extended x-ray absorption fine structure (EXAFS) spectra were measured for a 3.3 at% Ga stabilized Pu alloy over the range T= 20 - 300 K at both the Ga K-edge and the Pu L_III-edge. The temperature dependence of the pair-distance distribution widths, \sigma(T) was accurately modeled using a correlated-Debye model for the lattice vibrational properties, suggesting Debye-like behavior in this material. We obtain pair- specific correlated-Debye temperatures, \Theta_cD, of 110.7 +/- 1.7 K and 202.6 +/- 3.7 K, for the Pu-Pu and Ga-Pu pairs, respectively. These results represent the first unambiguous determination of Ga-specific vibrational properties in PuGa alloys, and indicate the Ga-Pu bonds are significantly stronger than the Pu-Pu bonds. This effect has important implications for lattice stabilization mechanisms in these alloys.Comment: 7 pages, 4 figures, Phys. Rev. B in pres

The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds