bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice
Authors: Bortolussi G , Codarin E , Antoniali G , Vascotto C , Vodret S , Arena S , Cesaratto L , Scaloni A , Tell G , Muro A F 
Published: May 2015

AbstractSevere hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration.
Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and anticancer stem cell agent using public gene expression data
Authors: Cheng H-W , Liang Y-H , Kuo Y-L , Chuu C-P , Lin C-Y , Lee M-H , Wu A T H , Yeh C-T , Chen E I-T , Whang-Peng J , Su C-L , Huang C-YF 
Published: May 2015

AbstractGlioblastoma (GBM) is a common and malignant tumor with a poor prognosis. Glioblastoma stem cells (GSCs) have been reported to be involved in tumorigenesis, tumor maintenance and therapeutic resistance. Thus, to discover novel candidate therapeutic drugs for anti-GBM and anti-GSCs is an urgent need. We hypothesized that if treatment with a drug could reverse, at least in part, the gene expression signature of GBM and GSCs, this drug may have the potential to inhibit pathways essential in the formation of GBM and thereby treat GBM. Here, we collected 356 GBM gene signatures from public databases and queried the Connectivity Map. We systematically evaluated the in vitro antitumor effects of 79 drugs in GBM cell lines. Of the drugs screened, thioridazine was selected for further characterization because it has potent anti-GBM and anti-GSCs properties. When investigating the mechanisms underlying the cytocidal effects of thioridazine, we found that thioridazine induces autophagy in GBM cell lines, and upregulates AMPK activity. Moreover, LC3-II was upregulated in U87MG sphere cells treated with thioridazine. In addition, thioridazine suppressed GBM tumorigenesis and induced autophagy in vivo. We not only repurposed the antipsychotic drug thioridazine as a potent anti-GBM and anti-GSCs agent, but also provided a new strategy to search for drugs with anticancer and anticancer stem cell properties.
Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization
Authors: Mahale S , Bharate S B , Manda S , Joshi P , Jenkins P R , Vishwakarma R A , Chaudhuri B 
Published: May 2015

AbstractThe marine natural product fascaplysin (1) is a potent Cdk4 (cyclin-dependent kinase 4)-specific inhibitor, but is toxic to all cell types possibly because of its DNA-intercalating properties. Through the design and synthesis of numerous fascaplysin analogues, we intended to identify inhibitors of cancer cell growth with good therapeutic window with respect to normal cells. Among various non-planar tryptoline analogues prepared, N-(biphenyl-2-yl) tryptoline (BPT, 6) was identified as a potent inhibitor of cancer cell growth and free from DNA-binding properties owing to its non-planar structure. This compound was tested in over 60 protein kinase assays. It displayed inhibition of Cdk4-cyclin D1 enzyme in vitro far more potently than many other kinases including Cdk family members. Although it blocks growth of cancer cells deficient in the mitotic-spindle checkpoint at the G0/G1 phase of the cell cycle, the block occurs primarily at the G2/M phase. BPT inhibits tubulin polymerization in vitro and acts as an enhancer of tubulin depolymerization of paclitaxel-stabilized tubulin in live cells. Western blot analyses indicated that, in p53-positive cells, BPT upregulates the expression of p53, p21 and p27 proteins, whereas it downregulates the expression of cyclin B1 and Cdk1. BPT selectively kills SV40-transformed mouse embryonic hepatic cells and human fibroblasts rather than untransformed cells. BPT inhibited the growth of several human cancer cells with an IC50 <1 μM. The pharmacokinetic study in BALB/c mice indicated good plasma exposure after intravenous administration. It was found to be efficacious at 1/10th the maximum-tolerated dose (1000 mg/kg) against human tumours derived from HCT-116 (colon) and NCI-H460 (lung) cells in SCID (severe-combined immunodeficient) mice models. BPT is a relatively better anticancer agent than fascaplysin with an unusual ability to block two overlapping yet crucial phases of the cell cycle, mitosis and G0/G1. Its ability to effectively halt tumour growth in human tumour-bearing mice would suggest that BPT has the potential to be a candidate for further clinical development.
Decoupling the Lattice Distortion and Charge Doping Effects on the Phase Transition Behavior of VO2 by Titanium (Ti4+) Doping
Authors: Wu Yanfei , Fan Lele , Liu Qinghua , Chen Shi , Huang Weifeng , Chen Feihu , Liao Guangming , Zou Chongwen , Wu Ziyu 
Published: May 2015

AbstractThe mechanism for regulating the critical temperature (TC) of metal-insulator transition (MIT) in ions-doped VO2 systems is still a matter of debate, in particular, the unclear roles of lattice distortion and charge doping effects. To rule out the charge doping effect on the regulation of TC, we investigated Ti4+-doped VO2 (TixV1-xO2) system. It was observed that the TC of TixV1-xO2 samples first slightly decreased and then increased with increasing Ti concentration. X-ray absorption fine structure (XAFS) spectroscopy was used to explore the electronic states and local lattice structures around both Ti and V atoms in TixV1-xO2 samples. Our results revealed the local structure evolution from the initial anatase to the rutile-like structure around the Ti dopants. Furthermore, the host monoclinic VO2 lattice, specifically, the VO6 octahedra would be subtly distorted by Ti doping. The distortion of VO6 octahedra and the variation of TC showed almost the similar trend, confirming the direct effect of local structural perturbations on the phase transition behavior. By comparing other ion-doping systems, we point out that the charge doping is more effective than the lattice distortion in modulating the MIT behavior of VO2 materials.
Seawater Incursion Events in a Cretaceous Paleo-lake Revealed by Specific Marine Biological Markers
Authors: Hu J. F. , Peng P. A. , Liu M. Y. , Xi D. P. , Song J. Z. , Wan X. Q. , Wang C. S. 
Published: May 2015

AbstractMany large paleo-lakes in North China were formed after the Triassic Era. Seawater incursion events (SWIEs) in these lakes have been extensively discussed in the literature, yet lack reliable methodology and solid evidence, which are essential for reconstructing and confirming SWIEs. The present study employs specific marine biological markers (24-n-propyl and 24-isopropyl cholestanes) to trace SWIEs in a dated core taken from the Songliao Basin (SLB). Two SWIEs were identified. The first SWIE from 91.37 to 89.00 Ma, was continuous and variable but not strong, while the second SWIE from 84.72 to 83.72 Ma was episodic and strong. SWIEs caused high total organic carbon (TOC) and negative δ13Corgvalues in the sediments, which were interpreted as an indication of high productivity in the lake, due to the enhancement of nutrient supplies as well as high levels of aqueous CO2, due to the mixing of alkaline seawater and acidic lake water. The SWIEs in SLB were controlled by regional tectonic activity and eustatic variation. Movement direction changes of the Izanagi/Kula Plate in 90 Ma and 84 Ma created faults and triggered SWIEs. A high sea level, from 90 to 84 Ma, also facilitated the occurrence of SWIEs in SLB.
Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms
Authors: Li Shaoxin , Li Linfang , Zeng Qiuyao , Zhang Yanjiao , Guo Zhouyi , Liu Zhiming , Jin Mei , Su Chengkang , Lin Lin , Xu Junfa , Liu Songhao 
Published: May 2015

AbstractThis study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481–486, 682–687, 1018–1034, 1313–1323, 1450–1459 and 1582–1587 cm−1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.
Multi-Service Highly Sensitive Rectifier for Enhanced RF Energy Scavenging
Authors: Shariati Negin , Rowe Wayne S. T. , Scott James R. , Ghorbani Kamran 
Published: May 2015

AbstractDue to the growing implications of energy costs and carbon footprints, the need to adopt inexpensive, green energy harvesting strategies are of paramount importance for the long-term conservation of the environment and the global economy. To address this, the feasibility of harvesting low power density ambient RF energy simultaneously from multiple sources is examined. A high efficiency multi-resonant rectifier is proposed, which operates at two frequency bands (478–496 and 852–869 MHz) and exhibits favorable impedance matching over a broad input power range (−40 to −10 dBm). Simulation and experimental results of input reflection coefficient and rectified output power are in excellent agreement, demonstrating the usefulness of this innovative low-power rectification technique. Measurement results indicate an effective efficiency of 54.3% and an output DC voltage of 772.8 mV is achieved for a multi-tone input power of −10 dBm. Furthermore, the measured output DC power from harvesting RF energy from multiple services concurrently exhibits a 3.14 and 7.24 fold increase over single frequency rectification at 490 and 860 MHz respectively. Therefore, the proposed multi-service highly sensitive rectifier is a promising technique for providing a sustainable energy source for low power applications in urban environments.
Design of On-Chip N-Fold Orbital Angular Momentum Multicasting Using V-Shaped Antenna Array
Authors: Du Jing , Wang Jian 
Published: May 2015

AbstractWe design a V-shaped antenna array to realize on-chip multicasting from a single Gaussian beam to four orbital angular momentum (OAM) beams. A pattern search assisted iterative (PSI) algorithm is used to design an optimized continuous phase pattern which is further discretized to generate collinearly superimposed multiple OAM beams. Replacing the designed discrete phase pattern with corresponding V-shaped antennas, on-chip N-fold OAM multicasting is achieved. The designed on-chip 4-fold OAM multicasting exploiting V-shaped antenna array shows favorable operation performance with low crosstalk less than -15 dB.
Optimal search strategies on complex multi-linked networks
Authors: Di Patti Francesca , Fanelli Duccio , Piazza Francesco 
Published: May 2015

AbstractIn this paper we consider the problem of optimal search strategies on multi-linked networks, i.e. graphs whose nodes are endowed with several independent sets of links. We focus preliminarily on agents randomly hopping along the links of a graph, with the additional possibility of performing non-local hops to randomly chosen nodes with a given probability. We show that an optimal combination of the two jump rules exists that maximises the efficiency of target search, the optimum reflecting the topology of the network. We then generalize our results to multi-linked networks with an arbitrary number of mutually interfering link sets.
Prediction of novel alloy phases of Al with Sc or Ta
Authors: Bilić Ante , Gale Julian D. , Gibson Mark A. , Wilson Nick , McGregor Kathie 
Published: May 2015

AbstractUsing the evolutionary optimization algorithm, as implemented in the USPEX crystal predictor program and first principles total energy calculations, the compositional phase diagrams for Al-Sc and Al-Ta alloy systems at zero temperature and pressure have been calculated. In addition to the known binary intermetallic phases, new potentially stable alloys, AlSc3 and AlTa7, have been identified in the Al-poor region of the phase diagram. The dynamic and thermal stability of their lattices has been confirmed from the calculated vibrational normal mode spectra in the harmonic approximation.
Role of RNase H1 in DNA repair: removal of single ribonucleotide misincorporated into DNA in collaboration with RNase H2
Authors: Tannous Elias , Kanaya Eiko , Kanaya Shigenori 
Published: May 2015

AbstractSeveral RNases H1 cleave the RNA-DNA junction of Okazaki fragment-like RNA-DNA/DNA substrate. This activity, termed 3’-junction ribonuclease (3’-JRNase) activity, is different from the 5’-JRNase activity of RNase H2 that cleaves the 5’-side of the ribonucleotide of the RNA-DNA junction and is required to initiate the ribonucleotide excision repair pathway. To examine whether RNase H1 exhibits 3’-JRNase activity for dsDNA containing a single ribonucleotide and can remove this ribonucleotide in collaboration with RNase H2, cleavage of a DNA8-RNA1-DNA9/DNA18 substrate with E. coli RNase H1 and H2 was analyzed. This substrate was cleaved by E. coli RNase H1 at the (5’)RNA-DNA(3’) junction, regardless of whether it was cleaved by E. coli RNase H2 at the (5’)DNA-RNA(3’) junction in advance or not. Likewise, this substrate was cleaved by E. coli RNase H2 at the (5’)DNA-RNA(3’) junction, regardless of whether it was cleaved by E. coli RNase H1 at the (5’)RNA-DNA(3’) junction in advance or not. When this substrate was cleaved by a mixture of E. coli RNases H1 and H2, the ribonucleotide was removed from the substrate. We propose that RNase H1 is involved in the excision of single ribonucleotides misincorporated into DNA in collaboration with RNase H2.
Different strategies, but indifferent strategy adaptation during action cascading
Authors: Mückschel Moritz , Stock Ann-Kathrin , Beste Christian 
Published: May 2015

AbstractEvery day, we need to apply different action control strategies to successfully interact with ever-changing environments. In situations requiring several responses, we often have to cascade different actions. The strategies used to accomplish this have been subject to extensive research in cognitive psychology and neuroscience but it has remained rather unclear if and to what degree such strategies are adapted while performing a task. Furthermore, we do not know if such adaptations are subject to differential effects depending on an individual’s preferred initial strategy to cope with multiple-demand situations. Using Bayesian analyses, we were able to show that even though the applied strategy is subject to slight modulations over the course of an action cascading task, this shift is equally strong for subjects who differ their general action cascading strategy. The action cascading strategy subjects apply to cope with multiple-demand situations is adapted independent of the preferred, inter-individually varying strategy that is initially used. Future research needs to test if the task goal activation strategy applied during action cascading reflects a ‘cognitive trait’ and is stable across different situations.
Dual-color dual-focus line-scanning FCS for quantitative analysis of receptor-ligand interactions in living specimens
Authors: Dörlich René M. , Chen Qing , Niklas Hedde Per , Schuster Vittoria , Hippler Marc , Wesslowski Janine , Davidson Gary , Nienhaus G. Ulrich 
Published: May 2015

AbstractCellular communication in multi-cellular organisms is mediated to a large extent by a multitude of cell-surface receptors that bind specific ligands. An in-depth understanding of cell signaling networks requires quantitative information on ligand-receptor interactions within living systems. In principle, fluorescence correlation spectroscopy (FCS) based methods can provide such data, but live-cell applications have proven extremely challenging. Here, we have developed an integrated dual-color dual-focus line-scanning fluorescence correlation spectroscopy (2c2f lsFCS) technique that greatly facilitates live-cell and tissue experiments. Absolute ligand and receptor concentrations and their diffusion coefficients within the cell membrane can be quantified without the need to perform additional calibration experiments. We also determine the concentration of ligands diffusing in the medium outside the cell within the same experiment by using a raster image correlation spectroscopy (RICS) based analysis. We have applied this robust technique to study the interactions of two Wnt antagonists, Dickkopf1 and Dickkopf2 (Dkk1/2), to their cognate receptor, low-density-lipoprotein-receptor related protein 6 (LRP6), in the plasma membrane of living HEK293T cells. We obtained significantly lower affinities than previously reported using in vitro studies, underscoring the need to measure such data on living cells or tissues.
Variation in Vowel Duration Among Southern African American English Speakers
Authors: Holt Yolanda Feimster , Jacewicz Ewa , Fox Robert Allen 
Published: May 2015

Purpose
Atypical duration of speech segments can signal a speech disorder. In this study, we examined variation in vowel duration in African American English (AAE) relative to White American English (WAE) speakers living in the same dialect region in the South to characterize the nature of systematic variation between the 2 groups. The goal was to establish whether segmental durations in minority populations differ from the well-established patterns in mainstream populations.

Method

Participants were 32 AAE and 32 WAE speakers differing in age who, in their childhood, attended either segregated (older speakers) or integrated (younger speakers) public schools. Speech materials consisted of 14 vowels produced in
hVd
-frame.

Results
AAE vowels were significantly longer than WAE vowels. Vowel duration did not differ as a function of age. The temporal tense–lax contrast was minimized for AAE relative to WAE. Vowels produced by females were significantly longer than vowels produced by males for both AAE and WAE.

Conclusions
African American speakers should be expected to produce longer vowels relative to White speakers in a common geographic area. These longer durations are not deviant but represent a typical feature of AAE. This finding has clinical importance in guiding assessments of speech disorders in AAE speakers.
Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex
Authors: Neubert Franz-Xaver , Mars Rogier B. , Sallet Jérôme , Rushworth Matthew F. S. 
Published: May 2015

Significance
Because of the interest in reward-guided learning and decision making, these neural mechanisms have been studied in both humans and monkeys. But whether and how key brain areas correspond between the two species has been uncertain. Areas in the two species can be compared as a function of the brain circuits in which they participate, which can be estimated from patterns of correlation in brain activity measured with functional MRI. Taking such measurements in 38 humans and 25 macaques, we identified fundamental similarities between the species and one human frontal area with no monkey counterpart. Altogether these findings suggest that everyday human decision-making capitalizes on a neural apparatus similar to the one that supports monkeys when foraging in the wild.
Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc
Authors: Anderson Charles T. , Radford Robert J. , Zastrow Melissa L. , Zhang Daniel Y. , Apfel Ulf-Peter , Lippard Stephen J. , Tzounopoulos Thanos 
Published: May 2015

Significance
As an essential element for living organisms, zinc is a cofactor in many enzymes and regulatory proteins. After the surprising discovery of mobile zinc in synaptic vesicles throughout many areas of the brain, numerous investigators have studied its possible roles during neurotransmission. Nonetheless, knowledge of the physiology of zinc at the synapse is still in its infancy. Here, we show that synaptic and tonic zinc inhibit extrasynaptic NMDA receptors (NMDARs), which are widely distributed in the CNS and are important for normal and pathological excitatory signaling. Our work indicates that this newly discovered interaction between zinc and extrasynaptic NMDARs can provide a general mechanism for controlling neuronal excitability in the CNS.