bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma
Authors: Lopes Alessandra , Vanvarenberg Kevin , Kos Špela , Lucas Sophie , Colau Didier , Van den Eynde Benoît , Préat Véronique , Vandermeulen Gaëlle 
Published: October 2018

AbstractDNA vaccination against cancer has become a promising strategy for inducing a specific and long-lasting antitumor immunity. However, DNA vaccines fail to generate potent immune responses when used as a single therapy. To enhance their activity into the tumor, a DNA vaccine against murine P815 mastocytoma was combined with antibodies directed against the immune checkpoints CTLA4 and PD1. The combination of these two strategies delayed tumor growth and enhanced specific antitumor immune cell infiltration in comparison to the corresponding single therapies. The combination also promoted IFNg, IL12 and granzyme B production in the tumor microenvironment and decreased the formation of liver metastasis in a very early phase of tumor development, enabling 90% survival. These results underline the complementarity of DNA vaccination and immune checkpoint blockers in inducing a potent immune response, by exploiting the generation of antigen-specific T cells by the vaccine and the ability of immune checkpoint blockers to enhance T cell activity and infiltration in the tumor. These findings suggest how and why a rational combination therapy can overcome the limits of DNA vaccination but could also allow responses to immune checkpoint blockers in a larger proportion of subjects.
Frequencies of poor metabolizer alleles of 12 pharmacogenomic actionable genes in Punjabi Sikhs of Indian Origin
Authors: Sanghera Dharambir K. , Bejar Cynthia , Sapkota Bishwa , Wander Gurpreet S. , Ralhan Sarju 
Published: October 2018

AbstractDiversity in drug response is attributed to both genetic and non-genetic factors. However, there is paucity of pharmacogenetics information across ethnically and genetically diverse populations of India. Here, we have analyzed 21 SNPs from 12 pharmacogenomics genes in Punjabi Sikhs of Indian origin (N = 1,616), as part of the Sikh Diabetes Study (SDS). We compared the allele frequency of poor metabolism (PM) phenotype among Sikhs across other major global populations from the Exome Aggregation Consortium and 1000 Genomes. The PM phenotype of CYP1A2*1 F for slow metabolism of caffeine and carcinogens was significantly higher in Indians (SDS 42%, GIH [Gujarati] 51%, SAS [Pakistani] 45%) compared to Europeans 29% (pgenotype = 5.3E-05). Similarly, South Asians had a significantly higher frequency of CYP2C9*3 (12% SDS, 13% GIH, 11% SAS) vs. 7% in Europeans (pgenotype = <1.0E-05) and ‘T’ allele of CYP4F2 (36%) SDS, (43%) GIH, 40% (SAS) vs. (29%) in Europeans (pgenotype = <1.0E-05); both associated with a higher risk of bleeding with warfarin. All South Asians –the Sikhs (0.36), GIH (0.34), and SAS (0.36) had a higher frequency of the NAT2*6 allele (linked with slow acetylation of isoniazid) compared to Europeans (0.29). Additionally, the prevalence of the low activity ‘C’ allele of MTHFR (rs1801131) was highest in Sikhs compared to all other ethnic groups [SDS (44%), GIH (39%), SAS (42%) and European (32%) (pgenotype = <1.0E-05)]. SNPs in MTHFR affect metabolism of statins, 5-fluorouracil and methotrexate-based cancer drugs. These findings underscore the need for evaluation of other endogamous ethnic groups of India and beyond for establishing a global benchmark for pre-emptive genotyping in drug metabolizing genes before beginning therapeutic intervention.
Collective behavior of oscillating electric dipoles
Authors: Olmi Simona , Gori Matteo , Donato Irene , Pettini Marco 
Published: October 2018

AbstractWe investigate the dynamics of a population of identical biomolecules mimicked as electric dipoles with random orientations and positions in space and oscillating with their intrinsic frequencies. The biomolecules, beyond being coupled among themselves via the dipolar interaction, are also driven by a common external energy supply. A collective mode emerges by decreasing the average distance among the molecules as testified by the emergence of a clear peak in the power spectrum of the total dipole moment. This is due to a coherent vibration of the most part of the molecules at a frequency definitely larger than their own frequencies corresponding to a partial cluster synchronization of the biomolecules. These results can be verified experimentally via spectroscopic investigations of the strength of the intermolecular electrodynamic interactions, thus being able to test the possible biological relevance of the observed macroscopic mode.
Impact of pulmonary emphysema on exercise capacity and its physiological determinants in chronic obstructive pulmonary disease
Authors: Smith Benjamin M. , Jensen Dennis , Brosseau Marc , Benedetti Andrea , Coxson Harvey O. , Bourbeau Jean 
Published: October 2018

AbstractExercise limitation is common in chronic obstructive pulmonary disease (COPD). We determined the impact of pulmonary emphysema on the physiological response to exercise independent of contemporary measures of COPD severity. Smokers 40–79 years old with COPD underwent computed tomography, pulmonary function tesing, and symptom-limited incremental exercise testing. COPD severity was quantified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) by spirometry (GOLD 1–4); and symptom burden and exacerbation risk (GOLD A-D). Emphysema severity was quantified as the percent lung volume <−950 Hounsfield units. Regression models adjusted for age, gender, body size, smoking status, airflow limitation, symptom burden and exacerbation risk. Among 67 COPD subjects (age 67 ± 8 years; 75% male; GOLD 1–4: 11%, 43%, 30%, 16%), median percent emphysema was 11%, and peak power output (PPO) was 61 ± 32 W. Higher percent emphysema independently predicted lower PPO (−24 W per 10% increment in emphysema; 95%CI −41 to −7 W). Throughout exercise, higher percent emphysema predicted 1) higher minute ventilation, ventilatory equivalent for CO2, and heart rate; and 2) lower oxy-hemoglobin saturation, and end-tidal PCO2. Independent of contemporary measures of COPD severity, the extent of pulmonary emphysema predicts lower exercise capacity, ventilatory inefficiency, impaired gas-exchange and increased heart rate response to exercise.
Withaferin A inhibits Epithelial to Mesenchymal Transition in Non-Small Cell Lung Cancer Cells
Authors: Kyakulaga Al Hassan , Aqil Farrukh , Munagala Radha , Gupta Ramesh C. 
Published: October 2018

AbstractLung cancer is the leading cause of cancer-related deaths worldwide and in the United States. Despite recent advancements in treatment approaches, metastasis remains a major therapeutic challenge in lung cancer and explains the extremely poor prognosis. Epithelial to mesenchymal transition (EMT), a complex process of cellular reprogramming has become an attractive drug target because it plays a crucial role in the metastasis of non-small cell lung cancer (NSCLC). In the present study, we examined the effects of withaferin A (WFA), a plant-derived steroidal lactone on EMT in human NSCLC cell lines. First, we demonstrated that WFA displayed time- and concentration-dependent cytotoxicity on A549 and H1299 NSCLC cells. Then, cells were exposed to ≤ 0.5 µM WFA for ≤ 4 h to minimize cytotoxicity and determined its effects on EMT, cell adhesion, motility, migration, and invasion. EMT induction was performed by culturing cells in serum-free media containing TGFβ1 (5 ng/mL) and TNFα (25 ng/mL) for 48 h. We observed that pretreatment of cells with WFA inhibited cell adhesion, migration, and invasion of A549 and H1299 cells. Using western blot, immunofluorescence, and qRT-PCR analysis, we demonstrated that WFA suppressed TGFβ1 and TNFα-induced EMT in both cell lines. Mechanistically, WFA suppressed the phosphorylation and nuclear translocation of Smad2/3 and NF-κB in A549 and H1299 cells. Together, our study provides additional evidence demonstrating the inhibitory effects of WFA on EMT induction in NSCLC cells and further demonstrates the therapeutic potential of WFA against the metastasis in NSCLC.
OsARD4 encoding an acireductone dioxygenase improves root architecture in rice by promoting development of secondary roots
Authors: Ramanathan Valarmathi , Rahman Hifzur , Subramanian Saravanan , Nallathambi Jagadeeshselvam , Kaliyaperumal Ashokkumar , Manickam Sudha , Ranganathan Chandrababu , Muthurajan Raveendran 
Published: October 2018

AbstractThis study was aimed at unravelling the molecular basis of root growth behavior in a drought-tolerant upland rice genotype, Nootripathu. Root tips of Nootripathu were found to possess shorter root caps and a greater number of dividing cells, favoring faster elongation compared to shallow-rooted IR20. Width and length of cortical cells in the roots of rapidly growing Nootripathu were found to be two to three times higher than IR20. Evaluation of shallow-rooted IR20, deep-rooted Nootripathu and their Recombinant Inbred Lines (RILs) for root characteristics revealed the presence of genetic variation for root traits among RILs. 2D-PAGE analysis of proteins in roots of IR20, Nootripathu and bulks of extreme RILs differing in root traits resulted in the identification of proteins co-segregating with root growth behavior and co-localized with QTLs for root traits. A putative candidate gene, OsARD4, encoding an “acireductone dioxygenase” was validated for its role in modulating the root growth pattern through genetic transformation. Transgenic ASD16 rice plants engineered for the overexpression of OsARD4 exhibited root growth characteristics similar to those of Nootripathu, including faster radical emergence, more rapid elongation of primary roots, early initiation of crown/lateral roots, and higher root biomass than the non-transgenic plants.
Negative Magnetoresistance in Nanotwinned NiMnGa Epitaxial Films
Authors: Golub V. O. , Chernenko V. A. , Apolinario A. , Aseguinolaza I. R. , Araujo J. P. , Salyuk O. , Barandiaran J. M. , Kakazei G. N. 
Published: October 2018

AbstractMagnetic shape memory alloys are under intensive investigation due to their unusual physical properties, such as magnetic shape memory effect, magnetic field induced superelasticity, direct and inverse magnetocaloric effect etc., promising for novel applications. One of the intriguing properties of these materials in a single phase state is a giant magnetoresistance. Here we report the remarkable results about the magnetoresistive properties of epitaxial films of Ni52.3Mn26.8Ga20.9 magnetic shape memory alloy in the temperature range of 100–370 K, well below the martensitic transformation temperature. It was found that the formation of non-collinear magnetic structure due to a nanotwinning of the film results in electron scattering on such a structure and noticeable negative magnetoresistance in the entire investigated temperature range.
The transcriptomic response of Streptococcus pneumoniae following exposure to cigarette smoke extract
Authors: Manna Sam , Waring Alicia , Papanicolaou Angelica , Hall Nathan E. , Bozinovski Steven , Dunne Eileen M. , Satzke Catherine 
Published: October 2018

AbstractExposure to cigarette smoke is a risk factor for respiratory diseases. Although most research has focused on its effects on the host, cigarette smoke can also directly affect respiratory pathogens, in some cases enhancing virulence. Streptococcus pneumoniae (the pneumococcus) is a leading cause of community-acquired pneumonia worldwide, however data on the effects of cigarette smoke on the pneumococcus are sparse. Using RNA-seq, we show that pneumococci exposed to cigarette smoke extract in a concentrated acute exposure in vitro model initiate a ‘survival’ transcriptional response including the upregulation of detoxification enzymes, efflux pumps and osmoregulator transporters, as well as the downregulation of fatty acid and D-alanyl lipoteichoic acid biosynthesis genes. Except for the downregulation of the pneumolysin gene, there were no changes in the expression of major virulence factors following exposure to cigarette smoke. Compared to unexposed pneumococci, smoke-exposed pneumococci did not exhibit any changes in viability, adherence, hydrophobicity or cell lysis susceptibility. In this study, we demonstrate that pneumococci adapt to acute noxious cigarette smoke exposure by inducing a gene expression signature that allows the bacteria to resist its harmful effects.
Quantification of ash sedimentation dynamics through depolarisation imaging with AshCam
Authors: Esse Ben , Burton Michael , Varnam Matthew , Kazahaya Ryunosuke , Wallace Paul A. , Von-Aulock Felix , Lavallée Yan , Salerno Giuseppe , Scollo Simona , Coe Hugh 
Published: October 2018

AbstractEven modest ash-rich volcanic eruptions can severely impact a range of human activities, especially air travel. The dispersal of ash in these eruptions depends critically on aggregation and sedimentation processes – however these are difficult to quantify in volcanic plumes. Here, we image ash dynamics from mild explosive activity at Santiaguito Volcano, Guatemala, by measuring the depolarisation of scattered sunlight by non-spherical ash particles, allowing the dynamics of diffuse ash plumes to be investigated with high temporal resolution (>1 Hz). We measure the ash settling velocity downwind from the main plume, and compare it directly with ground sampled ash particles, finding good agreement with a sedimentation model based on particle size. Our new, cost-effective technique leverages existing technology, opening a new frontier of integrated ash visualisation and ground collection studies which could test models of ash coagulation and sedimentation, leading to improved ash dispersion forecasts. This will provide risk managers with improved data quality on ash location, reducing the economic and societal impacts of future ash-rich eruptions.
Production of value-added chemicals from glycerol using in vitro enzymatic cascades
Authors: Li Zhong , Yan Jinxin , Sun Jinkai , Xu Ping , Ma Cuiqing , Gao Chao 
Published: October 2018

AbstractThe large surplus of glycerol derived from the expanding biofuel industry raises economic and environmental concerns regarding disposal. In vitro synthetic biology is emerging as a useful biomanufacturing platform while the conversion of glycerol is rarely investigated. Here we develop a thermostable in vitro synthetic biosystem consisting of three enzymatic cascades for the biotransformation of glycerol into valuable chemicals with different degrees of reduction. Condensation of glycerol, phenol, and ammonium into l-tyrosine is achieved using four enzymes without the assistance of NAD+/NADH-related redox reactions. Production of chemicals with high degrees of reduction (e.g., optically pure l-lactate and d-lactate) is also verified through coupling with an NADH-regeneration system. The biotransformation of glycerol and ammonium into l-serine is achieved using four enzymes with self-sufficient NADH recycling.
Power‐efficient error‐resilient network‐on‐chip router using selective error correction code scheme
Authors: Li C.‐L. , Kim Y.‐W. , Lee Y.S. , Han T.H. 
Published: October 2018

In this Letter, a new error‐resilient router design for network‐on‐chips (NoCs) is proposed to effectively address various transient errors considering power efficiency and implementation complexity. To cope with the most probable error conditions, a selective error correction code (ECC) is embraced in router design, which combines an optimised double‐bit error‐correcting Bose–Chaudhuri–Hocquenghem (BCH) code and a single‐bit error‐correcting Hamming code. To reduce the inherent delay overhead of the BCH code, the parallel BCH coding scheme is designed and implemented into the proposed router. Furthermore, the associated ECC controller is designed for switching into an appropriate ECC mode without an additional delay at runtime. The proposed router is synthesised using 28 nm CMOS technology. Experimental results with a variety of common error conditions show that the proposed method improves the average latency by up to 13.8% and achieves up to 11.5% power reduction with the area increase of 5.7%, when compared to the conventional error correction scheme.
Survey of connected automated vehicle perception mode: from autonomy to interaction
Authors: Wei ShangGuan , Yu Du , Lin Guo Chai , Dan Liu , Wei Shu Wang 
Published: October 2018

For enhancing the intelligence of urban traffic, connected automated vehicle (CAV) is recognised as the leading technology in the near future. With on‐board sensors and communication devices, status of the vehicles can be obtained to better coordinate the traffic. However, the limited environmental perception range cannot lead to the best efficiency of the global urban traffic. In this study, a three‐step evolution strategy of the CAV perception mode is proposed, from autonomous perception to interactive perception to networked perception. Key technologies in these three steps are studied. In autonomous perception, vehicle positioning and dynamic target tracking approaches are proposed. In interactive perception, a reliable multi‐mode information exchange mechanism is studied. Finally, a new traffic big data storage and advanced analytics solution in networked perception is introduced. Related experiments about the above key issues are designed, implemented, and verified based on the hardware platform, open source dataset, and cloud platform, respectively. The results show that the positioning distance root mean square achieves 3.9 m, object tracking speed reaches 30fps, and communication average packet loss rate is 2%. As can be seen from testing and simulation results, our proposed approaches can meet technical requirements and support environment perception mode evolution of CAV.
Magnetic properties of a long-lived sunspot
Authors: Schmassmann M. , Schlichenmaier R. , Bello González N. 
Published: October 2018

Context. In a recent statistical study of sunspots in 79 active regions, the vertical magnetic field component Bver averaged along the umbral boundary is found to be independent of sunspot size. The authors of that study conclude that the absolute value of Bver at the umbral boundary is the same for all spots.
Aims. We investigate the temporal evolution of Bver averaged along the umbral boundary of one long-lived sunspot during its stable phase.
Methods. We analysed data from the HMI instrument on-board SDO. Contours of continuum intensity at Ic = 0.5Iqs, whereby Iqs refers to the average over the quiet sun areas, are used to extract the magnetic field along the umbral boundary. Projection effects due to different formation heights of the Fe I 617.3 nm line and continuum are taken into account. To avoid limb artefacts, the spot is only analysed for heliocentric angles smaller than 60°.
Results. During the first disc passage, NOAA AR 11591, Bver remains constant at 1693 G with a root-mean-square deviation of 15 G, whereas the magnetic field strength varies substantially (mean 2171 G, rms of 48 G) and shows a long term variation. Compensating for formation height has little influence on the mean value along each contour, but reduces the variations along the contour when away from disc centre, yielding a better match between the contours of Bver = 1693 G and Ic = 0.5Iqs.
Conclusions. During the disc passage of a stable sunspot, its umbral boundary can equivalently be defined by using the continuum intensity Ic or the vertical magnetic field component Bver. Contours of fixed magnetic field strength fail to outline the umbral boundary.
Principal component analysis of sunspot cycle shape
Authors: Takalo Jouni , Mursula Kalevi 
Published: October 2018

Aims. We study the shape of sunspot cycles using the Wolf sunspot numbers and group sunspot numbers of solar cycles 1–23. We determine the most typical “model” cycles and the most asymmetric cycles, and test the validity of the two Waldmeier rules: the anti-correlation between cycle height and the length of its ascending phase (rule 1), and between cycle height and the length of the preceding cycle (rule 2).
Methods. We applied the principal component analysis to sunspot cycles and studied the first two components, which describe the average cycle shape and cycle asymmetry, respectively. We also calculated their autocorrelation in order to study their recurrence properties.
Results. The best model cycles for Wolf numbers are SC12, SC14, and SC16, the successive even cycles from a long period of rather low overall solar activity. We find that the model cycles in eight different analyses using both sunspot series are almost exclusively even cycles. Correspondingly, the most asymmetric cycles are odd cycles. We find that both Waldmeier rules are valid for the whole Wolf number series of 23 cycles. Waldmeier rule 2 is also valid for group number series although its significance is weaker. Waldmeier rule 1 is not significant for the original group number series, but becomes significant for the proxy series. For separate centuries, Waldmeier rules are not always valid for Wolf numbers and very rarely for group numbers.
Conclusions. The preference of even cycles as model cycles supports the Gnevyshev-Ohl rule and the related 22-year alternation of cycle amplitudes and intensities, with even cycles on average being 10–15% lower than odd cycles. Our results also offer a new interpretation for the Gnevyshev gap. In addition to being a local depression of solar activity, the Gnevyshev gap is a separatrix that divides cycles into two parts whose relative intensities determine the cycle asymmetry. The Gnevyshev gap is the zero value time of PC2, located approximately 33–42% into the cycle after its start.
Rückenschmerz: gezielte Anamnese und klinische Untersuchung
Authors: Chenot Jean-François 
Published: October 2018

AbstractLow back pain is common, but serious underlying disorders are infrequent in ambulatory care. Extensive diagnostic testing is neither feasable nor reasonable due to epidemiological and economical considerations. A structured step wise approach allows to differentiate between specific and unspecific low back pain.
Agentes hepatoespecíficos, usos actuales: más allá de la caracterización de lesiones focales
Authors: Castrillón G. A. , Espinosa J. P. , P. M. Noriega , Royero M. , Gómez D. V. 
Published: October 2018

ResumenCon el ácido gadoxético, el realce dinámico de las lesiones focales es igual a los demás medios de contraste extracelulares, por lo que su utilidad principal está en la obtención de una fase hepatobiliar que permita diferenciar y caracterizar lesiones que contienen hepatocitos como en el caso de la hiperplasia nodular focal (HNF) y los nódulos regenerativos. Las lesiones que no tienen hepatocitos o que son carentes de conductos biliares, demuestran baja señal con respecto al parénquima hepático en esa fase, lo que ocurre con los adenomas hepatocelulares (AHC), nódulos displásicos de alto grado, carcinoma hepatocelular (CHC) y metástasis entre otras. Hacer esta diferenciación cambia el manejo de la lesión focal, permitiendo en la mayoría de los casos caracterizar las lesiones que contienen hepatocitos que no requieren biopsia, como las benignas, de aquellas que si pudieran requerir la confirmación histológica. Otros usos de estos medios de contraste órgano específicos es la evaluación de la integridad de la vía biliar especialmente en pacientes posquirúrgicos y la diferenciación de quistes que tienen comunicación con la vía biliar de aquellos que son quistes hepáticos simples.El objetivo de este artículo es realizar una revisión sobre la evidencia actual del papel emergente de los contrastes órgano específicos, incluyendo no solo la evaluación de las lesiones focales hepáticas, sino también otras utilidades como el análisis de la patología biliar.