bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of A1 and A2B adenosine receptor activity: a new strategy to sensitise glioblastoma stem cells to chemotherapy
Authors: Daniele S , Zappelli E , Natali L , Martini C , Trincavelli M L 
Published: November 2014

AbstractTherapies that target the signal transduction and biological characteristics of cancer stem cells (CSCs) are innovative strategies that are used in combination with conventional chemotherapy and radiotherapy to effectively reduce the recurrence and significantly improve the treatment of glioblastoma multiforme (GBM). The two main strategies that are currently being exploited to eradicate CSCs are (a) chemotherapeutic regimens that specifically drive CSCs toward cell death and (b) those that promote the differentiation of CSCs, thereby depleting the tumour reservoir. Extracellular purines, particularly adenosine triphosphate, have been implicated in the regulation of CSC formation, but currently, no data on the role of adenosine and its receptors in the biological processes of CSCs are available. In this study, we investigated the role of adenosine receptor (AR) subtypes in the survival and differentiation of CSCs isolated from human GBM cells. Stimulation of A1AR and A2BAR had a prominent anti-proliferative/pro-apoptotic effect on the CSCs. Notably, an A1AR agonist also promoted the differentiation of CSCs toward a glial phenotype. The differential effects of the two AR agonists on the survival and/or differentiation of CSCs may be ascribed to their distinct regulation of the kinetics of ERK/AKT phosphorylation and the expression of hypoxia-inducible factors. Most importantly, the AR agonists sensitised CSCs to the genotoxic activity of temozolomide (TMZ) and prolonged its effects, most likely through different mechanisms, are as follows: (i) by A2BAR potentiating the pro-apoptotic effects of TMZ and (ii) by A1AR driving cells toward a differentiated phenotype that is more sensitive to TMZ. Taken together, the results of this study suggested that the purinergic system is a novel target for a stem cell-oriented therapy that could reduce the recurrence of GBM and improve the survival rate of GBM patients.
ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells
Authors: Ci Y , Shi K , An J , Yang Y , Hui K , Wu P , Shi L , Xu C 
Published: November 2014

AbstractReactive oxygen species (ROS) have an important role in regulating various cellular processes. Our previous study confirmed that selenite, an anti-tumour agent, triggered apoptosis through the production of ROS in multiple types of cancer cells. In this study, we discovered that ROS also inhibited protective autophagy by decreasing the expression of ULK1, an initiator of autophagy, in selenite-treated NB4 cells. Further experiments demonstrated that p-p53 (S392), a phosphorylation event promoted by p70S6K, bound to the promoter of ULK1 and modulated its expression. Experiments in a mouse tumour model with NB4 cells provided in vivo confirmation of the alterations in the p70S6K/p53/ULK1 axis. Collectively, our results show that ROS inhibited autophagy by downregulating the p70S6K/p53/ULK1 axis in selenite-treated NB4 cells.
Inhibition of phosphodiesterase 5 reduces bone mass by suppression of canonical Wnt signaling
Authors: Gong Y , Xu C Y , Wang J R , Hu X H , Hong D , Ji X , Shi W , Chen H X , Wang H B , Wu X M 
Published: November 2014

AbstractInhibitors of phosphodiesterase 5 (PDE5) are widely used to treat erectile dysfunction and pulmonary hypertension in clinics. PDE5, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) are important components of the non-canonical Wnt signaling. This study aimed to investigate the effect of PDE5 inhibition on canonical Wnt signaling and osteoblastogenesis, using both in vitro cell culture and in vivo animal models. In the in vitro experiments, PDE5 inhibition resulted in activation of cGMP-dependent protein kinase 2 and consequent inhibition of glycogen synthase kinase 3β phosphorylation, destabilization of cytosolic β-catenin and the ultimate suppression of canonical Wnt signaling and reduced osteoblastic differentiation in HEK293T and C3H10T1/2 cells. In animal experiments, systemic inhibition of PDE5 suppressed the activity of canonical Wnt signaling and osteoblastogenesis in bone marrow-derived stromal cells, resulting in the reduction of bone mass in wild-type adult C57B/6 mice, significantly attenuated secreted Frizzled-related protein-1 (SFRP1) deletion-induced activation of canonical Wnt signaling and excessive bone growth in adult SFRP1−/− mice. Together, these results uncover a hitherto uncharacterized role of PDE5/cGMP/PKG signaling in bone homeostasis and provide the evidence that long-term treatment with PDE5 inhibitors at a high dosage may potentially cause bone catabolism.
Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast
Authors: Ard Ryan , Tong Pin , Allshire Robin C. 
Published: November 2014

AbstractMost long non-coding RNAs (lncRNAs) encoded by eukaryotic genomes remain uncharacterized. Here we focus on a set of intergenic lncRNAs in fission yeast. Deleting one of these lncRNAs exhibited a clear phenotype: drug sensitivity. Detailed analyses of the affected locus revealed that transcription of the nc-tgp1 lncRNA regulates drug tolerance by repressing the adjacent phosphate-responsive permease gene transporter for glycerophosphodiester 1 (tgp1+). We demonstrate that the act of transcribing nc-tgp1 over the tgp1+ promoter increases nucleosome density, prevents transcription factor access and thus represses tgp1+ without the need for RNA interference or heterochromatin components. We therefore conclude that tgp1+ is regulated by transcriptional interference. Accordingly, decreased nc-tgp1 transcription permits tgp1+ expression upon phosphate starvation. Furthermore, nc-tgp1 loss induces tgp1+ even in repressive conditions. Notably, drug sensitivity results directly from tgp1+ expression in the absence of the nc-tgp1 RNA. Thus, transcription of an lncRNA governs drug tolerance in fission yeast.
Double-sieving-defective aminoacyl-tRNA synthetase causes protein mistranslation and affects cellular physiology and development
Authors: Lu Jiongming , Bergert Martin , Walther Anita , Suter Beat 
Published: November 2014

AbstractAminoacyl-tRNA synthetases (aaRSs) constitute a family of ubiquitously expressed essential enzymes that ligate amino acids to their cognate tRNAs for protein synthesis. Recently, aaRS mutations have been linked to various human diseases; however, how these mutations lead to diseases has remained unclear. In order to address the importance of aminoacylation fidelity in multicellular organisms, we generated an amino-acid double-sieving model in Drosophila melanogaster using phenylalanyl-tRNA synthetase (PheRS). Double-sieving-defective mutations dramatically misacylate non-cognate Tyr, induce protein mistranslation and cause endoplasmic reticulum stress in flies. Mutant adults exhibit many defects, including loss of neuronal cells, impaired locomotive performance, shortened lifespan and smaller organ size. At the cellular level, the mutations reduce cell proliferation and promote cell death. Our results also reveal the particular importance of the first amino-acid recognition sieve. Overall, these findings provide new mechanistic insights into how malfunctioning of aaRSs can cause diseases.
The role of different social contexts in shaping influenza transmission during the 2009 pandemic
Authors: Ajelli Marco , Poletti Piero , Melegaro Alessia , Merler Stefano 
Published: November 2014

AbstractEvaluating the relative importance of different social contexts in which infection transmission occurs is critical for identifying optimal intervention strategies. Nonetheless, an overall picture of influenza transmission in different social contexts has yet to emerge. Here we provide estimates of the fraction of infections generated in different social contexts during the 2009 H1N1 pandemic in Italy by making use of a highly detailed individual-based model accounting for time use data and parametrized on the basis of observed age-specific seroprevalence. We found that 41.6% (95%CI: 39–43.7%) of infections occurred in households, 26.7% (95%CI: 21–33.2) in schools, 3.3% (95%CI: 1.7–5%) in workplaces and 28.4% (95%CI: 24.6–31.9%) in the general community. The above estimates strongly depend on the lower susceptibility to infection of individuals 19+ years old compared to younger ones, estimated to be 0.2 (95%CI 0.12–0.28). We also found that school closure over the weekends contributed to decrease the effective reproduction number of about 8% and significantly affected the pattern of transmission. These results highlight the pivotal role played by schools in the transmission of the 2009 H1N1 influenza. They may be relevant in the evaluation of intervention options and, hence, for informing policy decisions.
Lung epithelial NOX/DUOX and respiratory virus infections
Authors: Grandvaux Nathalie , Mariani Mélissa , Fink Karin 
Published: November 2014

Determining the role of NADPH oxidases in the context of virus infection is an emerging area of research and our knowledge is still sparse. The expression of various isoforms of NOX/DUOX (NADPH oxidase/dual oxidase) in the epithelial cells (ECs) lining the respiratory tract renders them primary sites from which to orchestrate the host defence against respiratory viruses. Accumulating evidence reveals distinct facets of the involvement of NOX/DUOX in host antiviral and pro-inflammatory responses and in the control of the epithelial barrier integrity, with individual isoforms mediating co-operative, but surprisingly also opposing, functions. Although in vivo studies in mice are in line with some of these observations, a complete understanding of the specific functions of epithelial NOX/DUOX awaits lung epithelial-specific conditional knockout mice. The goal of the present review is to summarize our current knowledge of the role of individual NOX/DUOX isoforms expressed in the lung epithelium in the context of respiratory virus infections so as to highlight potential opportunities for therapeutic intervention.
Measurement and application of vertical inductors in high‐speed broadband circuit
Authors: Belfiore G. , Henker R. , Ellinger F. 
Published: November 2014

The measurement results and a practical application of vertical inductors (VIs) are presented. VIs are on‐chip inductors designed to save chip area. In VI the spiral plane is oriented perpendicularly with respect to the substrate. An inductance of 318 pH with a self‐resonance frequency of 66.5 GHz is implemented in a 130 nm bipolar complementary metal–oxide semiconductor (BiCMOS) technology and results are compared with three‐dimensional (3D) planar EM (ground–signal–ground) simulations. The inductance per unit area is 424 nH/mm2, more than 1.7 times higher than other simulated spiral horizontal inductors. Moreover, VIs have been applied in the design of a broadband amplifier leading to a 25% bandwidth enhancement.
Practical implementation of a silicon carbide‐based 300 kHz, 1.2 kW hard‐switching boost‐converter and comparative thermal performance evaluation
Authors: Kim Taekyun , Jang Minsoo , Agelidis Vassilios G. 
Published: November 2014

Field experience shows that the vast majority of solar photovoltaic (PV) energy system failures are related to the power conditioning system (PCS). Among the principal reliability issues of PV PCSs are thermal management and heat extraction mechanisms. The study considers practical implementation of a DC–DC boost converter as a solar PV pre‐regulator in terms of thermal management, with comparative thermal performance evaluations of silicon carbide (SiC) semiconductors and silicon (Si) metal‐oxide‐semiconductor field‐effect transistors (MOSFETs). Thermal performance evaluation of power semiconductors is based on a 1.2 kW DC–DC converter with: (i) various switching frequencies up to 300 kHz, in steps of 25 kHz; (ii) case temperatures from 25 to 150°C; and (iii) a natural convection heatsink with temperature increase rate of 0.5°C/W. Simulation and experimental results verify that losses from SiC semiconductors are low compared with Si MOSFETs. This provides an opportunity for designing a pre‐regulator DC–DC boost converter with less effort required for thermal management and enhanced reliability.
Waveform diversity for ultra‐wide band surveillance radars
Authors: Davis Mark E. , Pillai S. Unnikrishna 
Published: November 2014

The radio frequency spectrum has become very crowded with the increased use of commercial and personal communications devices. The worldwide spectrum committees require extreme measures to insure frequency avoidance by radar systems, to insure communications are maintained for emergency systems and flight safety. Radars operating in the frequency bands below 2 GHz have limited spectrum allocation, and are asking for more bandwidth for detection and localisation of earth resource and military uses. Hence, the radar community needs to adopt the techniques from cognitive radars to continue to provide the needed detection and characterisation of objects under concealing cover. This survey study attempts to provide an assessment for future research.
Evolution in changing environments: Modifiers of mutation, recombination, and migration
Authors: Carja Oana , Liberman Uri , Feldman Marcus W. 
Published: November 2014

SignificanceEnvironmental variability is known to promote the evolution of mechanisms that increase phenotypic diversity. The evolution of recombination, mutation, and migration, which endow a population with the needed genetic and phenotypic variability, has been a focus of study in population genetics for more than five decades. Theoretical approaches have focused on conditions for the evolution of recombination, mutation, and migration when environments change periodically and with symmetric selection pressures. Here we extend these models to incorporate random and asymmetric selection. We compare and contrast how fluctuating selection affects the stable rates of these three evolutionary forces and highlight surprising similarities in their evolution under fluctuating selection. This study offers insights into the role of environmental duration, shape, and randomness in predicting the long-term evolutionary advantage of recombination, mutation, and migration.
A bio-inspired computing model for ovarian carcinoma classification and oncogene detection
Authors: Tsai Meng-Hsiun , Chen Mu-Yen , Huang Steve G. , Hung Yao-Ching , Wang Hsin-Chieh 
Published: November 2014

Abstract
Motivation: Ovarian cancer is the fifth leading cause of cancer deaths in women in the western world for 2013. In ovarian cancer, benign tumors turn malignant, but the point of transition is difficult to predict and diagnose. The 5-year survival rate of all types of ovarian cancer is 44%, but this can be improved to 92% if the cancer is found and treated before it spreads beyond the ovary. However, only 15% of all ovarian cancers are found at this early stage. Therefore, the ability to automatically identify and diagnose ovarian cancer precisely and efficiently as the tissue changes from benign to invasive is important for clinical treatment and for increasing the cure rate. This study proposes a new ovarian carcinoma classification model using two algorithms: a novel discretization of food sources for an artificial bee colony (DfABC), and a support vector machine (SVM). For the first time in the literature, oncogene detection using this method is also investigated.
Results: A novel bio-inspired computing model and hybrid algorithms combining DfABC and SVM was applied to ovarian carcinoma and oncogene classification. This study used the human ovarian cDNA expression database to collect 41 patient samples and 9600 genes in each pathological stage. Feature selection methods were used to detect and extract 15 notable oncogenes. We then used the DfABC-SVM model to examine these 15 oncogenes, dividing them into eight different classifications according to their gene expressions of various pathological stages. The average accuracyof the eight classification experiments was 94.76%. This research also found some oncogenes that had not been discovered or indicated in previous scientific studies. The main contribution of this research is the proof that these newly discovered oncogenes are highly related to ovarian or other cancers.
Availability and implementation: http://mht.mis.nchu.edu.tw/moodle/course/view.php?id=7
Contact: mychen@nutc.edu.tw
ModuleBlast: identifying activated sub-networks within and across species
Authors: Zinman Guy E. , Naiman Shoshana , O'Dee Dawn M. , Kumar Nishant , Nau Gerard J. , Cohen Haim Y. , Bar-Joseph Ziv 
Published: November 2014

Abstract
Identifying conserved and divergent response patterns in gene networks is becoming increasingly important. A common approach is integrating expression information with gene association networks in order to find groups of connected genes that are activated or repressed. In many cases, researchers are also interested in comparisons across species (or conditions). Finding an active sub-network is a hard problem and applying it across species requires further considerations (e.g. orthology information, expression data and networks from different sources). To address these challenges we devised ModuleBlast, which uses both expression and network topology to search for highly relevant sub-networks. We have applied ModuleBlast to expression and interaction data from mouse, macaque and human to study immune response and aging. The immune response analysis identified several relevant modules, consistent with recent findings on apoptosis and NFκB activation following infection. Temporal analysis of these data revealed cascades of modules that are dynamically activated within and across species. We have experimentally validated some of the novel hypotheses resulting from the analysis of the ModuleBlast results leading to new insights into the mechanisms used by a key mammalian aging protein.
Spectro-polarimetric properties of small-scale plasma eruptions driven by magnetic vortex tubes
Authors: Kitiashvili Irina N. 
Published: November 2014

Abstract
The highly turbulent nature of convection on the Sun causes strong multi-scale interaction of subsurface layers with the photosphere and chromosphere. According to realistic 3D radiative magnetohydrodynamic numerical simulations, ubiquitous small-scale vortex tubes are generated by turbulent flows below the visible surface and concentrated in the intergranular lanes. The vortex tubes can capture and amplify magnetic field, penetrate into chromospheric layers and initiate quasi-periodic flow eruptions that generate Alfvénic waves, and transport mass and energy into the solar atmosphere. The simulations revealed high-speed flow patterns, and complicated thermodynamic and magnetic structures in the erupting vortex tubes. The spontaneous eruptions are initiated and driven by strong pressure gradients in the near-surface layers, and accelerated by the Lorentz force in the low chromosphere. In this paper, the simulation data are used to further investigate the dynamics of the eruptions, their spectro-polarimetric characteristics for the Fe i 6301.5 and 6302.5 Å spectral lines, and demonstrate expected signatures of the eruptions in the Hinode Spectro-Polarimeter (SP) data. We found that the complex dynamical structure of vortex tubes (downflows in the vortex core and upflows on periphery) can be captured by the Stokes I profiles. During an eruption, the ratio of down and upflows can suddenly change, and this effect can be observed in the Stokes V profile. Also, during the eruption the linear polarization signal increases, and this also can be detected with Hinode SP.
Coronal loops above an active region: Observation versus model
Authors: Bourdin Philippe-A. , Bingert Sven , Peter Hardi 
Published: November 2014

Abstract
We conducted a high-resolution numerical simulation of the solar corona above a stable active region. The aim is to test the field line braiding mechanism for a sufficient coronal energy input. We also check the applicability of scaling laws for coronal loop properties like the temperature and density. Our 3D MHD model is driven from below by Hinode observations of the photosphere, in particular a high-cadence time series of line-of-sight magnetograms and horizontal velocities derived from the magnetograms. This driving applies stress to the magnetic field and thereby delivers magnetic energy into the corona, where currents are induced that heat the coronal plasma by Ohmic dissipation. We compute synthetic coronal emission that we directly compare to coronal observations of the same active region taken by Hinode. In the model, coronal loops form at the same places as they are found in coronal observations. Even the shapes of the synthetic loops in 3D space match those found from a stereoscopic reconstruction based on STEREO spacecraft data. Some loops turn out to be slightly over-dense in the model, as expected from observations. This shows that the spatial and temporal distribution of the Ohmic heating produces the structure and dynamics of a coronal loops system close to what is found in observations.
Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma
Authors: Boxerman Jerrold L. , Ellingson Benjamin M. , Jeyapalan Suriya , Elinzano Heinrich , Harris Robert J. , Rogg Jeffrey M. , Pope Whitney B. , Safran Howard 
Published: November 2014

Objective:
For patients with high-grade glioma on clinical trials it is important to accurately assess time of disease progression. However, differentiation between pseudoprogression (PsP) and progressive disease (PD) is unreliable with standard magnetic resonance imaging (MRI) techniques. Dynamic susceptibility contrast perfusion MRI (DSC-MRI) can measure relative cerebral blood volume (rCBV) and may help distinguish PsP from PD.

Methods:
A subset of patients with high-grade glioma on a phase II clinical trial with temozolomide, paclitaxel poliglumex, and concurrent radiation were assessed. Nine patients (3 grade III, 6 grade IV), with a total of 19 enhancing lesions demonstrating progressive enhancement (≥25% increase from nadir) on postchemoradiation conventional contrast-enhanced MRI, had serial DSC-MRI. Mean leakage-corrected rCBV within enhancing lesions was computed for all postchemoradiation time points.

Results:
Of the 19 progressively enhancing lesions, 10 were classified as PsP and 9 as PD by biopsy/surgery or serial enhancement patterns during interval follow-up MRI. Mean rCBV at initial progressive enhancement did not differ significantly between PsP and PD (2.35 vs. 2.17; P=0.67). However, change in rCBV at first subsequent follow-up (−0.84 vs. 0.84; P=0.001) and the overall linear trend in rCBV after initial progressive enhancement (negative vs. positive slope; P=0.04) differed significantly between PsP and PD.

Conclusions:
Longitudinal trends in rCBV may be more useful than absolute rCBV in distinguishing PsP from PD in chemoradiation-treated high-grade gliomas with DSC-MRI. Further studies of DSC-MRI in high-grade glioma as a potential technique for distinguishing PsP from PD are indicated.