bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis
Authors: Grabner Beatrice , Schramek Daniel , Mueller Kristina M. , Moll Herwig P. , Svinka Jasmin , Hoffmann Thomas , Bauer Eva , Blaas Leander , Hruschka Natascha , Zboray Katalin , Stiedl Patricia , Nivarthi Harini , Bogner Edith , Gruber Wolfgang , Mohr Thomas , Zwick Ralf Harun , Kenner Lukas , Poli Valeria , Aberger Fritz , Stoiber Dagmar , Egger Gerda , Esterbauer Harald , Zuber Johannes , Moriggl Richard , Eferl Robert , Győrffy Balázs , Penninger Josef M. , Popper Helmut , Casanova Emilio 
Published: March 2015

AbstractSTAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice results in increased KrasG12D-driven AC initiation and malignant progression leading to markedly reduced survival. Knockdown of STAT3 in xenografted human AC cells increases tumour growth. Clinically, low STAT3 expression levels correlate with poor survival and advanced malignancy in human lung AC patients with smoking history, which are prone to KRAS mutations. Consistently, KRAS mutant lung tumours exhibit reduced STAT3 levels. Mechanistically, we demonstrate that STAT3 controls NF-κB-induced IL-8 expression by sequestering NF-κB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression. These results elucidate a novel STAT3–NF-κB–IL-8 axis in KRAS mutant AC with therapeutic and prognostic relevance.
Snake trajectories in ultraclean graphene p–n junctions
Authors: Rickhaus Peter , Makk Péter , Liu Ming-Hao , Tóvári Endre , Weiss Markus , Maurand Romain , Richter Klaus , Schönenberger Christian 
Published: March 2015

AbstractSnake states are trajectories of charge carriers curving back and forth along an interface. There are two types of snake states, formed by either inverting the magnetic field direction or the charge carrier type at an interface. The former has been demonstrated in GaAs–AlGaAs heterostructures, whereas the latter has become conceivable only with the advance of ballistic graphene where a gap-less p–n interface governed by Klein tunnelling can be formed. Such snake states were hidden in previous experiments due to limited sample quality. Here we report on magneto-conductance oscillations due to snake states in a ballistic suspended graphene p–n junction, which occur already at a very small magnetic field of 20 mT. The visibility of 30% is enabled by Klein collimation. Our finding is firmly supported by quantum transport simulations. We demonstrate the high tunability of the device and operate it in different magnetic field regimes.
Evaluation of 68Ga-Labeled MG7 Antibody: A Targeted Probe for PET/CT Imaging of Gastric Cancer
Authors: Xu Bing , Li Xiaowei , Yin Jipeng , Liang Cong , Liu Lijuan , Qiu Zhaoyan , Yao Liping , Nie Yongzhan , Wang Jing , Wu Kaichun 
Published: March 2015

AbstractMG7-Ag, a specific gastric cancer-associated antigen, can be used to non-invasively monitor gastric cancer by molecular imaging with positron emission tomography/computed tomography (PET/CT). In this study, we prepared and evaluated a68Ga-labeled MG7 antibody as a molecular probe for nanoPET/CT imaging of gastric cancer in a BGC-823 tumor xenografted mouse model. Macrocyclic chelator 1,4,7-triazacyclononane-N,N0,N00-triacetic acid (NOTA)-conjugated MG7 antibody was synthesized and radiolabeled with68Ga (t1/2= 67.71 min). Then,68Ga-NOTA-MG7 was tested using in vitro cytological studies, in vivo nanoPET/CT and Cerenkov imaging studies as well as ex vivo biodistribution and histology studies. The in vitro experiments demonstrated that68Ga-NOTA-MG7 has an excellent radiolabeling efficiency of approximately 99% without purification and it is stable in serum after 120 min of incubation. Cell uptake and retention studies confirmed that68Ga-NOTA-MG7 has good binding affinity and tumor cell retention. For the nanoPET imaging study, the predominant uptake of68Ga-NOTA-MG7 was visualized in tumor, liver and kidneys. The tumor uptake reached at its peak (2.53 ± 0.28%ID/g) at 60 min pi. Cherenkov imaging also confirmed the specificity of tumor uptake. Moreover, the biodistribution results were consistent with the quantification data of nanoPET/CT imaging. Histologic analysis also demonstrated specific staining of BGC-823 tumor cell lines.
Goos-Hänchen effect in epsilon-near-zero metamaterials
Authors: Xu Yadong , Chan C. T. , Chen Huanyang 
Published: March 2015

AbstractLight reflection and refraction at an interface between two homogeneous media is analytically described by Snell's law. For a beam with a finite waist, it turns out that the reflected wave experiences a lateral displacement from its position predicted by geometric optics. Such Goos-Hänchen (G-H) effect has been extensively investigated among all kinds of optical media, such as dielectrics, metals, photonic crystals and metamaterials. As a fundamental physics phenomenon, the G-H effect has been extended to acoustics and quantum mechanics. Here we report the unusual G-H effect in zero index metamaterials. We show that when linearly polarized light is obliquely incident from air to epsilon-near-zero metamaterials, no G-H effect could be observed for p polarized light. While for s polarization, the G-H shift is a constant value for any incident angle.
Cumulus cells accelerate oocyte aging by releasing soluble Fas Ligand in mice
Authors: Zhu Jiang , Zhang Jie , Li Hong , Wang Tian-Yang , Zhang Chuan-Xin , Luo Ming-Jiu , Tan Jing-He 
Published: March 2015

AbstractAlthough previous studies have suggested that cumulus cells (CCs) accelerate oocyte aging by secreting soluble and heat-sensitive paracrine factors, the factors involved are not well characterized. Because Fas-mediated apoptosis represents a major pathway in induction of apoptosis in various cells, we proposed that CCs facilitate oocyte aging by releasing soluble Fas ligand (sFasL). In this study, we reported that when the aging of freshly ovulated mouse oocytes were studied in vitro, both the apoptotic rates of CCs and the amount of CCs produced sFasL increased significantly with the culture time. We found that oocytes expressed stable levels of Fas receptors up to 24 h of in vitro aging. Moreover, culture of cumulus-denuded oocytes in CCs-conditioned CZB medium (CM), in CZB supplemented with recombinant sFasL, or in CM containing sFasL neutralizing antibodies all showed that sFasL impaired the developmental potential of the oocytes whereas facilitating activation and fragmentation of aging oocytes. Furthermore, CCs from the FasL-defective gld mice did not accelerate oocyte aging due to the lack of functional FasL. In conclusion, we propose that CCs surrounding aging oocytes released sFasL in an apoptosis-related manner and the released sFasL accelerated oocyte aging by binding to Fas receptors.
Massive expansion and functional divergence of innate immune genes in a protostome
Authors: Zhang Linlin , Li Li , Guo Ximing , Litman Gary W. , Dishaw Larry J. , Zhang Guofan 
Published: March 2015

AbstractThe molecules that mediate innate immunity are encoded by relatively few genes and exhibit broad specificity. Detailed annotation of the Pacific oyster (Crassostrea gigas) genome, a protostome invertebrate, reveals large-scale duplication and divergence of multigene families encoding molecules that effect innate immunity. Transcriptome analyses indicate dynamic and orchestrated specific expression of numerous innate immune genes in response to experimental challenge with pathogens, including bacteria and a pathogenic virus. Variable expression of individual members of the multigene families encoding these genes also occurs during different types of abiotic stress (environmentally-equivalent conditions of temperature, salinity and desiccation). Multiple families of immune genes are responsive in concert to certain biotic and abiotic challenges. Individual members of expanded families of immune genes are differentially expressed under both biotic challenge and abiotic stress conditions. Members of the same families of innate immune molecules also are transcribed in developmental stage- and tissue-specific manners. An integrated, highly complex innate immune system that exhibits remarkable discriminatory properties and responses to different pathogens as well as environmental stress has arisen through the adaptive recruitment of tandem duplicated genes. The co-adaptive evolution of stress and innate immune responses appears to have an ancient origin in phylogeny.
Borna disease virus possesses an NF-ĸB inhibitory sequence in the nucleoprotein gene
Authors: Makino Akiko , Fujino Kan , Parrish Nicholas F. , Honda Tomoyuki , Tomonaga Keizo 
Published: March 2015

AbstractBorna disease virus (BDV) has a non-segmented, negative-stranded RNA genome and causes persistent infection in many animal species. Previous study has shown that the activation of the IκB kinase (IKK)/NF-κB pathway is reduced by BDV infection even in cells expressing constitutively active mutant IKK. This result suggests that BDV directly interferes with the IKK/NF-κB pathway. To elucidate the mechanism for the inhibition of NF-κB activation by BDV infection, we evaluated the cross-talk between BDV infection and the NF-κB pathway. Using Multiple EM for Motif Elicitation analysis, we found that the nucleoproteins of BDV (BDV-N) and NF-κB1 share a common ankyrin-like motif. When THP1-CD14 cells were pre-treated with the identified peptide, NF-κB activation by Toll-like receptor ligands was suppressed. The 20S proteasome assay showed that BDV-N and BDV-N-derived peptide inhibited the processing of NF-κB1 p105 into p50. Furthermore, immunoprecipitation assays showed that BDV-N interacted with NF-κB1 but not with NF-κB2, which shares no common motif with BDV-N. These results suggest BDV-N inhibits NF-κB1 processing by the 20S proteasome through its ankyrin-like peptide sequence, resulting in the suppression of IKK/NF-κB pathway activation. This inhibitory effect of BDV on the induction of the host innate immunity might provide benefits against persistent BDV infection.
Mechanically durable, superoleophobic coatings prepared by layer-by-layer technique for anti-smudge and oil-water separation
Authors: Brown Philip S. , Bhushan Bharat 
Published: March 2015

AbstractSuperoleophobic surfaces are of interest for anti-fouling, self-cleaning, anti-smudge, low-drag, anti-fog and oil-water separation applications. Current bioinspired surfaces are of limited use due to a lack of mechanical durability. A so-called layer-by-layer approach, involving charged species with electrostatic interactions between layers, can provide the flexibility needed to improve adhesion to the substrate while providing a low surface tension coating at the air interface. In this work, a polyelectrolyte binder, SiO2 nanoparticles and a fluorosurfactant are spray deposited separately to create a durable, superoleophobic coating. Polydiallyldimethylammonium chloride (PDDA) polyelectrolyte was complexed with a fluorosurfactant layer (FL), which provides oil repellency while being hydrophilic. This oleophobic/superhydrophilic behavior was enhanced through the use of roughening with SiO2 particles resulting in a superoleophobic coating with hexadecane contact angles exceeding 155° and tilt angles of less than 4°. The coating is also superhydrophilic, which is desirable for oil-water separation applications. The durability of these coatings was examined through the use of micro- and macrowear experiments. These coatings currently display characteristics of transparency. Fabrication of these coatings via the layer-by-layer technique results in superoleophobic surfaces displaying improved durability compared to existing work where either the durability or the oil-repellency is compromised.
Trans-splicing repair of mutant p53 suppresses the growth of hepatocellular carcinoma cells in vitro and in vivo
Authors: He Xingxing , Liu Fang , Yan Jingjun , Zhang Yunan , Yan Junwei , Shang Haitao , Dou Qian , Zhao Qiu , Song Yuhu 
Published: March 2015

AbstractReactivation of wild-type p53 (wt-p53) function is an attractive therapeutic approach to p53-defective cancers. An ideal p53-based gene therapy should restore wt-p53 production and reduces mutant p53 transcripts simultaneously. In this study, we described an alternative strategy named as trans-splicing that repaired mutant p53 transcripts in hepatocellular carcinoma (HCC) cells. The plasmids which encoded a pre-trans-splicing molecule (PTM) targeting intron 6 of p53 were constructed and then transfected into HCC cells carrying p53 mutation. Phenotypic changes of HCC cells induced by p53-PTM were analyzed through cell cycle, cell apoptosis and the expression of p53 downstream target genes. Spliceosome mediated RNA trans-splicing (SMaRT) reduced mutant p53 transcripts and produced functional wt-p53 protein after the delivery of p53-PTM plasmids, which resulted in phenotype correction of HCC cells. In tumor xenografts established by p53-mutated HCC cells, adenovirus encoding p53-PTM induced cell cycle arrest and apoptosis and then blocked the growth of tumors in mice. Collectively, our results demonstrated for the first time that mutant p53 transcripts were functionally corrected in p53-defective HCC cells and xenografts using trans-splicing, which indicated the feasibility of using trans-splicing to repair p53 mutation in p53-defective cancers.
Enzymatic production of defined chitosan oligomers with a specific pattern of acetylation using a combination of chitin oligosaccharide deacetylases
Authors: Hamer Stefanie Nicole , Cord-Landwehr Stefan , Biarnés Xevi , Planas Antoni , Waegeman Hendrik , Moerschbacher Bruno Maria , Kolkenbrock Stephan 
Published: March 2015

AbstractChitin and chitosan oligomers have diverse biological activities with potentially valuable applications in fields like medicine, cosmetics, or agriculture. These properties may depend not only on the degrees of polymerization and acetylation, but also on a specific pattern of acetylation (PA) that cannot be controlled when the oligomers are produced by chemical hydrolysis. To determine the influence of the PA on the biological activities, defined chitosan oligomers in sufficient amounts are needed. Chitosan oligomers with specific PA can be produced by enzymatic deacetylation of chitin oligomers, but the diversity is limited by the low number of chitin deacetylases available. We have produced specific chitosan oligomers which are deacetylated at the first two units starting from the non-reducing end by the combined use of two different chitin deacetylases, namely NodB fromRhizobiumsp. GRH2 that deacetylates the first unit and COD fromVibrio choleraethat deacetylates the second unit starting from the non-reducing end. Both chitin deacetylases accept the product of each other resulting in production of chitosan oligomers with a novel and defined PA. When extended to further chitin deacetylases, this approach has the potential to yield a large range of novel chitosan oligomers with a fully defined architecture.
Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes
Authors: Malki K , Pain O , Tosto M G , Du Rietz E , Carboni L , Schalkwyk L C 
Published: March 2015

AbstractDespite moderate heritability estimates, progress in uncovering the molecular substrate underpinning major depressive disorder (MDD) has been slow. In this study, we used prefrontal cortex (PFC) gene expression from a genetic rat model of MDD to inform probe set prioritization in PFC in a human post-mortem study to uncover genes and gene pathways associated with MDD. Gene expression differences between Flinders sensitive (FSL) and Flinders resistant (FRL) rat lines were statistically evaluated using the RankProd, non-parametric algorithm. Top ranking probe sets in the rat study were subsequently used to prioritize orthologous selection in a human PFC in a case–control post-mortem study on MDD from the Stanley Brain Consortium. Candidate genes in the human post-mortem study were then tested against a matched control sample using the RankProd method. A total of 1767 probe sets were differentially expressed in the PFC between FSL and FRL rat lines at (q⩽0.001). A total of 898 orthologous probe sets was found on Affymetrix’s HG-U95A chip used in the human study. Correcting for the number of multiple, non-independent tests, 20 probe sets were found to be significantly dysregulated between human cases and controls at q⩽0.05. These probe sets tagged the expression profile of 18 human genes (11 upregulated and seven downregulated). Using an integrative rat–human study, a number of convergent genes that may have a role in pathogenesis of MDD were uncovered. Eighty percent of these genes were functionally associated with a key stress response signalling cascade, involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), AP-1 (activator protein 1) and ERK/MAPK, which has been systematically associated with MDD, neuroplasticity and neurogenesis.
In-use product stocks link manufactured capital to natural capital
Authors: Chen Wei-Qiang , Graedel T. E. 
Published: March 2015

Significance
The determination of long-term in-use stocks of manufactured products can complement existing monetary approaches to measuring manufactured capital and helps to explore the linkage between manufactured capital and natural capital in terms of materials transfer. The development of new products, substitution among products, and the historical evolution of in-use product stocks in the United States reveal the increase in variety, improvement in quality, and growth in quantity of US manufactured capital. Because products are produced from materials, and products developed more recently tend to use a greater diversity of materials, this study also reveals that US modern manufactured capital relies on the use of more diverse materials and on the increasing use of materials that originate from natural capital.
Dynamical evidence for causality between galactic cosmic rays and interannual variation in global temperature
Authors: Tsonis Anastasios A. , Deyle Ethan R. , May Robert M. , Sugihara George , Swanson Kyle , Verbeten Joshua D. , Wang Geli 
Published: March 2015

Significance
Here we use newly available methods to examine the dynamical association between cosmic rays (CR) and global temperature (GT) in the 20th-century observational record. We find no measurable evidence of a causal effect linking CR to the overall 20th-century warming trend; however, on short interannual timescales, we find a significant, although modest, causal effect of CR on short-term, year-to-year variability in GT. Thus, although CR clearly do not contribute measurably to the 20th-century global warming trend, they do appear as a nontraditional forcing in the climate system on short interannual timescales, providing another interesting piece of the puzzle in our understanding of factors influencing climate variability.
Cryoprecipitate administration after trauma
Authors: Olaussen Alexander , Fitzgerald Mark C. , Tan Gim A. , Mitra Biswadev 
Published: March 2015

Objectives
Haemorrhage remains among the most preventable causes of trauma death. Massive transfusion protocols, as part of ‘haemostatic resuscitation’, have been implemented in most trauma centres. Relative to the attention to the ideal ratio of red blood cells to fresh frozen plasma and platelets, cryoprecipitate treatment has been infrequently discussed. We aimed to outline the use of cryoprecipitate during trauma resuscitation and analyse outcomes in patients who received cryoprecipitate after hypofibrinogenaemia detection.

Methods
A retrospective review of registry data on all major trauma patients (Injury Severity Score>15) presenting to a level I trauma centre over a 4-year period (2008–2011) was conducted. We selected all patients who had received cryoprecipitate and then analysed patients who had received cryoprecipitate following the detection of hypofibrinogenaemia (<1.0 g/l). Mortality at hospital discharge among hypofibrinogenaemic patients who had received cryoprecipitate was compared with that among patients who had not received cryoprecipitate.

Results
Of 3996 trauma patients, 3571 had fibrinogen levels recorded. Most patients (n=3517, 98.5%) had initial fibrinogen counts of 1.0 g/l or higher, and cryoprecipitate was administered to a small proportion of these patients (n=126, 3.6%). Of the 54 patients with hypofibrinogenaemia on arrival, one patient died immediately and was excluded from further analysis. Of the 53 patients, 30 received cryoprecipitate and 28/53 died (53%). There was no difference in mortality between those who had received and those who had not received cryoprecipitate (14/30 vs. 14/23, P=0.31).

Conclusion
Administration of cryoprecipitate was uncommon during trauma resuscitation, even among patients with hypofibrinogenaemia on presentation. This study provides no evidence towards improved outcomes from administration of cryoprecipitate.
Numerical simulation of gas-solid two-phase reaction flow with multiple moving boundaries
Authors: Luo Qiao , Zhang Xiaobing 
Published: March 2015

Purpose
– In engineering applications, gas-solid two-phase reaction flow with multi-moving boundaries is a common phenomenon. The launch process of multiple projectiles is a typical example. The flow of adjacent powder chambers is coupled by projectile’s motion. The purpose of this paper is to study this flow by numerical simulation.

Design/methodology/approach
– A one-dimensional two-phase reaction flow model and MacCormack difference scheme are implemented in a computational code, and the code is used to simulate the launch process of a system of multiple projectiles. For different launching rates and loading conditions, the simulated results of the launch process of three projectiles are obtained and discussed.

Findings
– At low launching rates, projectiles fired earlier in the series have little effect on the launch processes of projectiles fired later. However, at higher launching rates, the projectiles fired first have a great influence on the launch processes of projectiles fired later. As the launching rate increases, the maximum breech pressure for the later projectiles increases. Although the muzzle velocities increase initially, they reach a maximum at some launching rate, and then decrease rapidly. The muzzle velocities and maximum breech pressures of the three projectiles have an approximate linear relationship with the charge weight, propellant web size and chamber volume.

Originality/value
– This paper presents a prediction tool to understand the physical phenomenon of the gas-solid two-phase reaction flow with multi-moving boundaries, and can be used as a research tool for future interior ballistics studies of launch system of multiple projectiles.