Multi-platform data integration in microarray analysis

An increasing number of studies have profiled gene expressions in tumor specimens using distinct microarray platforms and analysis techniques. One challenging task is to develop robust statistical models in order to integrate multi-platform findings. We compare some methodologies on the field with respect to estrogen receptor (ER) status, and focus on a unified-among-platforms scale implemented by Shen et al. in 2004, which is based on a Bayesian mixture model. Under this scale, we study the ER intensity similarities between four breast cancer datasets derived from various platforms. We evaluate our results with an independent dataset in terms of ER sample classification, given the derived gene ER signatures of the integrated data. We found that integrated multi-platform gene signatures and fold-change variability similarities between different platform measurements can assist the statistical analysis of independent microarray datasets in terms of ER classification.     

Peptides for the Biofunctionalization of Silicon for Use in Optical Sensing with Porous Silicon Microcavities

Addressing the surface chemistry of silicon is of fundamental scientific and technical significance due to the wide use of this material in electronics and optics. A novel method of functionalizing silicon (Si) via short peptides with binding specificity for Si is presented. The peptide presenting the highest affinity for Si is identified via phage display technology, and the 12‐mer LLADTTHHRPWT and SPGLSLVSHMQT peptides were found to be specific for the n⁺‐Si and p⁺‐Si surfaces, respectively. In our sensing application, the obtained peptides are used as functionalizing linkers to allow porous silicon microcavities to bind biotin and then capture streptavidin. Molecular detection is monitored via reflectometric interference spectra as shifts in the resonance peaks of the cavity structure. An improved streptavidin sensing (21 times lower detection limit) with peptide‐functionalized porous silicon microcavities is demonstrated, compared to sensing performed with devices functionalized with the commonly used silanization method, suggesting that the modification of Si via Si‐specific peptides provides better interface layers for molecular detection. High‐resolution atomic force microscopy images corroborate this result and reveal the formation of ordered nanometer‐sized molecular layers when peptide‐route functionalization is performed.     

Influence of proceedings papers on citation impact in seven sub-fields of sustainable energy research 2005–2011

This paper analyses the following seven sub-fields of Sustainable Energy Research with respect to the influence of proceedings papers on citation patterns across citing and cited document types, overall sub-field and document type impacts and citedness: the Wind Power, Renewable Energy, Solar and Wave Energy, Geo-thermal, Bio-fuel and Bio-mass energy sub-fields. The analyses cover peer reviewed research and review articles as well as two kinds of proceeding papers from conferences published 2005–2009 in (a) book series or volumes and (b) special journal issues excluding meeting abstracts cited 2005–2011 through Web of Science. Central findings are: The distribution across document types of cited versus citing documents is highly asymmetric. Predominantly proceedings papers from both proceeding volumes as well as published in journals cite research articles (60–76 %). Largely, journal-based proceedings papers are cited rather than papers published in book series or volumes and have field impacts corresponding to research articles. With decreasing proceedings paper dominance in research fields the ratio of proceeding paper volumes over journal-based proceedings papers decreases significantly and the percentage of proceedings papers in journals citing journal-based proceedings papers over all publications citing journal-based proceedings papers decreases significantly (from 26.3 % in Wind Power to 4 % in Bio Fuel). Further, the segment of all kinds of proceedings papers (the combined proceedings paper types) citing all proceedings papers over all publications citing all kinds of proceedings papers decreases significantly (from 36.1 % in Wind Power to 11.3 % in Bio Fuel). Simultaneously the field citedness increases across the seven research fields. The distribution of citations from review articles shows that novel knowledge essentially derives directly from research articles (53–72 %)—to a much less extent from proceedings publications published in journals (9–13 %).     

Particulate matter mass measurements for low emitting diesel powered vehicles: what''s next?

Legislation word-wide imposes stringent emission standards for particulate matter emitted by diesel engines, as an outcome of evidence associating emitted particulate with a series of adverse health effects. Such emission standards call for significant reductions in the particulate matter emission levels for small and large on-road diesel vehicles. In fact, emission levels adopted for the near future are so low that the existing, regulated procedures might not be sensitive enough to accurately determine the absolute level of emissions. In this regard, extensive research is conducted in the direction of both improving existing procedures and developing alternative methods for more sensitive particulate matter measurements. This review paper summarizes the developments in the area and provides an outlook to the future. At first, the character of diesel particulate matter (DPM) is shortly discussed, mainly to show that the complex nature of emitted particulate is responsible for a series of implications when its quantitative determination is considered. Secondly, the regulated procedure for sampling and measurement of DPM is reviewed and its main qualities and shortcomings are presented. The recent technical advances aimed at improving the characteristics of the reference procedure in the measurement of ultra-low emission levels are then presented. Next the presentation of alternative methods follows which are gradually incorporated in regulations for particulate matter sampling. The strength of these techniques is that only a small fraction of exhaust is sampled and conditioned before measurement, hence significantly reducing the cost compared to the reference procedure. In addition to sampling, the determination of the actual particulate mass emitted is an area which has attracted significant developments. The most relevant instrumentation for DPM determination is also described and their potential for application in emissions certification is examined based on published evidence. Finally, the cost of the different sampling and instrumentation techniques is compared to demonstrate the cost-effectiveness of each option.     

Genetic Variants and Tumor Immune Microenvironment: Clues for Targeted Therapies in Inflammatory Breast Cancer (IBC)

To better understand the etiology of inflammatory breast cancer (IBC) and identify potential therapies, we studied genomic alterations in IBC patients. Targeted, next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) (n = 33) and paired DNA from tumor tissues (n = 29) from 32 IBC patients. We confirmed complementarity between cfDNA and tumor tissue genetic profiles. We found a high incidence of germline variants in IBC patients that could be associated with an increased risk of developing the disease. Furthermore, 31% of IBC patients showed deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We also characterized the tumor-infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1, and PD-L1) through immunohistochemistry (IHC) staining. In 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs, making them sensitive to PD-1/PD-L1 blocking therapies. Our results provide a rationale for considering PARP inhibitors and PD-1/PDL1 blocking immunotherapy in qualifying IBC patients.     

Autophagy,Innate Immunity and Tissue Repair in Acute Kidney Injury

Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed.     

Robust blind PIC with adaptive despreader and improved interference estimator

An effective design of multistage parallel interference cancellation (PIC) receiver using blind adaptive (BA) despreader and pre‐respreader interference estimator for uplink CDMA is proposed and analysed. A novel algorithm is designed, which exploits constant modulus (CM) property of the users' transmitted signals and inherent channel condition to perform adaptive despreading based on minimum error variance criteria. This is carried out by BA weighting of each chip signal for accurate tracking of the desired user's signal power and hence for more improved data detection at the output of each stage of PIC. Furthermore, the despreader weights are used within the adaptive pre‐respreader interference estimation and cancellation to obtain online scaling factors during every symbol period, without any knowledge of users' channels or the use of training sequences. It is found that this way of estimation is optimal in minimum mean squared error sense, and hence, significant reduction in interference and noise variance is observed in detection and estimation of the desired users' signals compared with conventional PIC. Bit error probability of the proposed PIC is obtained using Gaussian Approximation method. Extensive simulation results are shown, which demonstrate impressive performance advantage in fading environments, high system loading, and severe near far conditions. Copyright © 2008 John Wiley & Sons, Ltd.     

Mechanical Strength and Surface Roughness of Magnesium-Based Metallic Glasses

This work evaluated the mechanical strength and surface roughness of MgZn₃₀Ca₅ ribbon manufactured via a melt spinning technique for applications in the biomedical field. Annealing was performed at 280°C. The inner side (in contact with the wheel) and the outer side (not in contact with the wheel) of the ribbons were mechanically evaluated using nanoindentation, and its surfaces were analyzed by an optical profilometer. Differential scanning calorimeter (DSC) and X-ray diffraction (XRD) analyses were also performed to identify the structure and devitrification of the magnesium metallic glass (MgMG). The nanohardness and elastic modulus increased after annealing (p < 0.0001). No differences were seen in the strength between the two sides of the ribbons (p > 0.05). Although both sides of the ribbons showed different surface profiles (p < 0.0001), no statistical difference was detected in roughness parameters on either ribbon side before (p = 0.3094) and after (p = 0.8742) annealing. DSC curves showed disturbances in enthalpy attributed to a relaxation in the MgMG structure and free volume annihilation. The DRX diffractogram showed sharp peaks after annealing, with MgZn and Ca₂Mg₅Zn₁₃ phases being identified. Although the use of MgMG in biomedical applications is promising, the ribbons displayed limited ductility, toughness, and a relevant embrittlement after the annealing procedure. There were significant changes in the surface profile of both sides of the ribbons. Nevertheless, neither annealing nor the ribbon side had influenced surface roughness parameters.     

Direct measurement of individual deep traps in single silicon nanowires

The potential of the metal nanocatalyst to contaminate vapor-liquid-solid (VLS) grown semiconductor nanowires has been a long-standing concern, since the most common catalyst material, Au, is known to induce deep gap states in several semiconductors. Here we use Kelvin probe force microscopy to image individual deep acceptor type trapping centers in single undoped Si nanowires grown with an Au catalyst. The switching between occupied and empty trap states is reversibly controlled by the back-gate potential in a nanowire transistor. The trap energy level, i.e., E(C) - E(T) = 0.65 ± 0.1 eV was extracted and the concentration was estimated to be ～2 × 10(16) cm(-3). The energy and concentration are consistent with traps resulting from the unintentional incorporation of Au atoms during the VLS growth.     

ICAN (TRPM4) Contributes to the Intrinsic Excitability of Prefrontal Cortex Layer 2/3 Pyramidal Neurons

Pyramidal neurons in the medial prefrontal cortical layer 2/3 are an essential contributor to the cellular basis of working memory; thus, changes in their intrinsic excitability critically affect medial prefrontal cortex (mPFC) functional properties. Transient Receptor Potential Melastatin 4 (TRPM4), a calcium-activated nonselective cation channel (CAN), regulates the membrane potential in a calcium-dependent manner. In this study, we uncovered the role of TRPM4 in regulating the intrinsic excitability plasticity of pyramidal neurons in the mouse mPFC layer of 2/3 using a combination of conventional and nystatin perforated whole-cell recordings. Interestingly, we found that TRPM4 is open at resting membrane potential, and its inhibition increases input resistance and hyperpolarizes membrane potential. After high-frequency stimulation, pyramidal neurons increase a calcium-activated non-selective cation current, increase the action potential firing, and the amplitude of the afterdepolarization, these effects depend on intracellular calcium. Furthermore, pharmacological inhibition or genetic silencing of TRPM4 reduces the firing rate and the afterdepolarization after high frequency stimulation. Together, these results show that TRPM4 plays a significant role in the excitability of mPFC layer 2/3 pyramidal neurons by modulating neuronal excitability in a calcium-dependent manner.