bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the lifetime of intense-laser generated relativistic electrons in solids via gating their Cherenkov emission
Authors: Shaikh Moniruzzaman , Lad Amit D. , Sarkar Deep , Jana Kamalesh , Kumar G. Ravindra , Rajeev P. P.
Published: January 2019

Optical Kerr gating technique has been employed to investigate the life history of relativistic electrons in solids by temporally gating their Cherenkov emission. Mega-ampere currents of relativistic electrons are created during ultra-intense (2 × 1019 W/cm2) laser-solid interactions. In order to measure the lifetime of these relativistic electrons in solids, we temporally gate their Cherenkov emission using an optical Kerr gate (OKG). The OKG is induced in a nonlinear medium, namely, carbon-di-sulphide (CS2), with a measured gate-width (FWHM) of 2 ps. The gate femtosecond laser pulse is synchronized with the intense interaction pulse generating relativistic electrons. The arrival time of the gate laser pulse on the CS2 cell is varied with the help of a delay stage. We find that Cherenkov emission from relativistic electrons created with a ultra-short laser pulse (25 fs) lives as long as 120 ps, a few thousand times that of the incident light pulse.
Ionic polymer pressure sensor with gradient shape based on ion migration
Authors: Zhu Zicai , He Ximing , He Qingsong , Fang Xiaoyong , Hu Qiao , Chen Hualing
Published: January 2019

Inspired by the sensing mechanism of an ionic polymer-metal composite (IPMC) strip, in which an electrical response is induced by an elastic stress gradient across the strip's thickness, we propose a new ionic polymer pressure sensor with a gradient shape that is based on ion migration. Under an applied pressure, an elastic stress gradient is generated across the top and bottom surfaces of the gradient, which then causes cations to migrate toward the lower pressure side. This cation redistribution then generates an electrical response. To verify this concept, a millimeter-scale ionic pressure sensor based on Nafion was fabricated by a casting method. The voltage responses of this sensor were measured using a self-made test setup. The maximum response approached tens of millivolts, which was much greater than that of an IPMC bending sensor. The sensing voltage was also investigated with respect to the various area ratios between the top and bottom surfaces and the various sensor heights. The sensitivity initially increases with increasing area ratio and then tends to reach a saturation state, whereas it rarely changed with variations in the height. Finally, the mechanical analysis showed that the size effects on the sensitivity could be explained qualitatively by the stress difference that occurs between the top and bottom surfaces.
Non-monotonic effect of additive particle size on the glass transition in polymers
Authors: M. Zirdehi Elias , Varnik Fathollah
Published: January 2019

Effect of small additive molecules on the structural relaxation of polymer melts is investigated via molecular dynamics simulations. At a constant external pressure and a fixed number concentration of added molecules, the variation of the particle diameter leads to a non-monotonic change of the relaxation dynamics of the polymer melt. For non-entangled chains, this effect is rationalized in terms of an enhanced added-particle-dynamics which competes with a weaker coupling strength upon decreasing the particle size. Interestingly, cooling simulations reveal a non-monotonic effect on the glass transition temperature also for entangled chains, where the effect of additives on polymer dynamics is more intricate. This observation underlines the importance of monomer-scale packing effects on the glass transition in polymers. In view of this fact, size-adaptive thermosensitive core-shell colloids would be a promising candidate route to explore this phenomenon experimentally.
Photoconductive laser spectroscopy as a method to enhance defect spectral signatures in amorphous oxide semiconductor thin-film transistors
Authors: Dhara Soumen , Niang Kham M. , Flewitt Andrew J. , Nathan Arokia , Lynch Stephen A.
Published: January 2019

Defects in semiconductor thin-films often leave optical spectral signatures that can be used for their identification. In this letter, we report on spectrally resolved photoconductivity measurements of amorphous oxide semiconductor thin-film transistors. In contrast to previously reported photoconductive spectroscopy measurements recorded using spectrally filtered broadband light sources, we used a wavelength tunable picosecond laser to illuminate the thin-film. We extracted the absorption coefficient as a function of wavelength from the photocurrent measurement and showed that it followed the typical characteristic behaviour previously reported for amorphous oxide semiconductor thin-films. However, in addition, we observed several sharp spectral peaks in the photoconductivity spectrum which can be associated with sub-bandgap defects. These enhanced peaks are not normally visible in previously reported photoconductivity spectra. Furthermore, we show that we can control the sensitivity of our measurement by changing the applied gate bias voltage when the thin-films were fabricated into transistors. The enhancement achieved by using the wavelength tunable laser makes this a particularly sensitive characterisation tool and can additionally be used to discriminate between defects which have been incorporated after device fabrication.
Dual-manipulation on wave-front based on reconfigurable water-based metasurface integrated with PIN diodes
Authors: Chen Lei , Ma He Liang , Ruan Ying , Cui Hao Yang
Published: January 2019

In this paper, we propose a dual manipulation on wave-front in the X band based on a reconfigurable water-based metasurface. We design and test a metasurface integrated with a saline-water substrate and PIN diodes. We showed that the wave-front reflected by the metasurface can be modulated by both the degree of salinity and the diode pattern. With these two manipulating methods, the metasurface can not only control the amplitude of the scattered beams but also the beam deflection angles, which promises a more flexible and economical way to manipulate the wave-front. We provide two diode patterns to illustrate the performance. The experimental results agree well with our simulations, further verifying our designs. Superior than the conventional reconfigurable metasurfaces, the proposed metasurface combines both water salinity and diodes, which offers more possibilities in electromagnetic (EM) wave tailoring, as well as potential applications in sensing and detection.
Identification of an internal cavity in the PhoQ sensor domain for PhoQ activity and SafA-mediated control
Authors: Yoshitani Kohei , Ishii Eiji , Taniguchi Katsuhide , Sugimoto Hiroshi , Shiro Yoshitsugu , Akiyama Yoshinori , Kato Akinori , Utsumi Ryutaro , Eguchi Yoko
Published: January 2019

The PhoQ/PhoP two-component signal transduction system is conserved in various Gram-negative bacteria and is often involved in the expression of virulence in pathogens. The small inner membrane protein SafA activates PhoQ in Escherichia coli independently from other known signals that control PhoQ activity. We have previously shown that SafA directly interacts with the sensor domain of the periplasmic region of PhoQ (PhoQ-SD) for activation, and that a D179R mutation in PhoQ-SD attenuates PhoQ activation by SafA. In this study, structural comparison of wild-type PhoQ-SD and D179R revealed a difference in the cavity (SD (sensory domain) pocket) found in the central core of this domain. This was the only structural difference between the two proteins. Site-directed mutagenesis of the residues surrounding the SD pocket has supported the SD pocket as a site involved in PhoQ activity. Furthermore, the SD pocket has also been shown to be involved in SafA-mediated PhoQ control.
Focal adhesions are essential to drive zebrafish heart valve morphogenesis
Authors: Gunawan Felix , Gentile Alessandra , Fukuda Ryuichi , Tsedeke Ayele Taddese , Jiménez-Amilburu Vanesa , Ramadass Radhan , Iida Atsuo , Sehara-Fujisawa Atsuko , Stainier Didier Y.R.
Published: January 2019

Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell–ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.
Novel Miscanthus genotypes selected for different drought tolerance phenotypes show enhanced tolerance across combinations of salinity and drought treatments
Authors: Stavridou Evangelia , Webster Richard J , Robson Paul R H
Published: January 2019

Background and Aims

Water deficit and salinity stresses are often experienced by plants concurrently; however, knowledge is limited about the effects of combined salinity and water deficit stress in plants, and especially in C4 bioenergy crops. Here we aim to understand how diverse drought tolerance traits may deliver tolerance to combinations of drought and salinity in C4 crops, and identify key traits that influence the productivity and biomass composition of novel Miscanthus genotypes under such conditions.

Methods

Novel genotypes used included M. sinensis and M. floridulus species, pre-screened for different drought responses, plus the commercial accession Miscanthus × giganteus (M×g.). Plants were grown under control treatments, single stress or combinations of water deficit and moderate salinity stress. Morphophysiological responses, including growth, yield, gas exchange and leaf water relations and contents of proline, soluble sugars, ash and lignin were tested for significant genotypic and treatment effects.

Key Results

The results indicated that plants subjected to combined stresses showed more severe responses compared with single stresses. All novel drought-tolerant genotypes and M×g. were tolerant to moderate salinity stress. Biomass production in M. sinensis genotypes was more resilient to co-occurring stresses than that in M×g. and M. floridulus, which, despite the yield penalty produced more biomass overall. A stay-green M. sinensis genotype adopted a conservative growth strategy with few significant treatment effects. Proline biosynthesis was species-specific and was triggered by salinity and co-occurring stress treatments, mainly in M. floridulus. The ash content was compartmentalized differently in leaves and stems in the novel genotypes, indicating different mechanisms of ion accumulation.

Conclusions

This study highlights the potential to select novel drought-tolerant Miscanthus genotypes that are resilient to combinations of stress and is expected to contribute to a deeper fundamental knowledge of different mechanistic responses identified for further exploitation in developing resilient Miscanthus crops.
Comparison of early patency rate and long-term outcomes of various techniques for reconstruction of segmental arteries during thoracoabdominal aortic aneurysm repair†
Authors: Henmi Soichiro , Ikeno Yuki , Yokawa Koki , Gotake Yasuko , Nakai Hidekazu , Yamanaka Katsuhiro , Inoue Takeshi , Tanaka Hiroshi , Okita Yutaka
Published: January 2019

OBJECTIVES

This study aimed to analyse the early patency rate and long-term outcomes of reattached segmental intercostal arteries using graft interposition, single-cuff anastomosis or island reconstruction.

METHODS

We selected 172 consecutive patients who underwent open surgery for the thoracoabdominal aorta with reattachment of segmental arteries between October 1999 and March 2018. The early patency of segmental arteries was analysed using enhanced computed tomography. Segmental arteries were reconstructed using graft interposition (n = 111), single-cuff anastomosis (n = 38) or island reconstruction (n = 23).

RESULTS

The hospital mortality was 6.4%. Twenty patients developed spinal cord ischaemic injury (permanent, n = 12 or transient, n = 8). Spinal cord injury was found in 16, 3 and 1 patients in the graft interposition, single-cuff anastomosis and island reconstruction groups, respectively. Overall, 475 segmental arteries were reattached (mean number per patient 2.8 ± 1.3). The overall early patency rate was 63.4%. The patency rates in island reconstruction (91.2%) and single-cuff anastomosis (77.1%) were significantly better than that in graft interposition (54.0%; P < 0.01). However, 6 patients with island reconstruction of segmental arteries had an aneurysm formation at the intercostal artery reconstruction site, of whom 4 patients underwent reoperation during follow-up. None of the patients with graft interposition or single-cuff reattachment had a patch aneurysm in segmental arteries.

CONCLUSIONS

Island reconstruction and single-cuff anastomosis might offer better patency rates and prevent spinal cord ischaemic injury than graft interposition. Because some patients with island reconstruction required reoperation for patch aneurysms in segmental arteries, single-cuff anastomosis is preferable in terms of early- and long-term outcomes.
High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial
Authors: Pérez Astrid , Gato Eva , Pérez-Llarena José , Fernández-Cuenca Felipe , Gude María José , Oviaño Marina , Pachón María Eugenia , Garnacho José , González Verónica , Pascual Álvaro , Cisneros José Miguel , Bou Germán
Published: January 2019

Objectives

To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial.

Methods

Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST.

Results

Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235.

Conclusions

MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains.
A systematic literature review of machine learning in online personal health data
Authors: Yin Zhijun , Sulieman Lina M , Malin Bradley A
Published: January 2019

Objective

User-generated content (UGC) in online environments provides opportunities to learn an individual’s health status outside of clinical settings. However, the nature of UGC brings challenges in both data collecting and processing. The purpose of this study is to systematically review the effectiveness of applying machine learning (ML) methodologies to UGC for personal health investigations.

Materials and Methods

We searched PubMed, Web of Science, IEEE Library, ACM library, AAAI library, and the ACL anthology. We focused on research articles that were published in English and in peer-reviewed journals or conference proceedings between 2010 and 2018. Publications that applied ML to UGC with a focus on personal health were identified for further systematic review.

Results

We identified 103 eligible studies which we summarized with respect to 5 research categories, 3 data collection strategies, 3 gold standard dataset creation methods, and 4 types of features applied in ML models. Popular off-the-shelf ML models were logistic regression (n = 22), support vector machines (n = 18), naive Bayes (n = 17), ensemble learning (n = 12), and deep learning (n = 11). The most investigated problems were mental health (n = 39) and cancer (n = 15). Common health-related aspects extracted from UGC were treatment experience, sentiments and emotions, coping strategies, and social support.

Conclusions

The systematic review indicated that ML can be effectively applied to UGC in facilitating the description and inference of personal health. Future research needs to focus on mitigating bias introduced when building study cohorts, creating features from free text, improving clinical creditability of UGC, and model interpretability.
Serum S100A8/A9 as a Potentially Sensitive Biomarker for Inflammatory Bowel Disease
Authors: Okada Kohki , Okabe Makoto , Kimura Yuto , Itoh Hiroshi , Ikemoto Masaki
Published: January 2019

Background

The clinical significance of human S100A8/A9 (h-S100A8/A9) in patients with inflammatory bowel disease (IBD) is poorly understood.

Objective

To clarify whether serum S100A8/A9 is a sensitive biomarker for IBD.

Methods

Serum specimens from outpatients with IBD (n = 101) and healthy volunteers (HVs) (n = 101) were used in this study. Enzyme-linked immunosorbent assays for h-S100A8/A9 and inflammatory cytokines were performed using these specimens. Further, correlation analysis was performed to investigate the significance of h-S100A8/A9 fluctuation in patients with IBD.

Results

The average of serum h-S100A8/A9 concentration in outpatients with IBD was significantly higher than that in HVs. The concentration of h-S100A8/A9 in patients with IBD was barely correlated with that of CRP and inflammatory cytokines. Despite that finding, the serum level of h-S100A8/A9 in patients with ulcerative colitis (UC) was correlated with the severity of IBD, compared with other inflammatory proteins.

Conclusion

Serum h-S100A8/A9 is superior to CRP as a sensitive biomarker for IBD.
In memoriam Helene Weyl: A sketch, not so much of Hella as of our life together, written at the end of June 1948
Authors: Weyl Hermann
Published: January 2019

This text was composed as a eulogy for Helene Weyl (née Josef) by her husband, the prominent mathematician Hermann Weyl. It is, in his words, a ‘sketch, not so much of Hella as of our life together, written at the end of June 1948’, and covers her early life and their years together as young academics in Göttingen and Zürich, as well as their experiences under the National Socialist dictatorship, leading to their emigration in 1933. It concludes with an account of their last years together in Princeton, where Hermann was a member of the Institute of Advanced Study.
CO Multi-line Imaging of Nearby Galaxies (COMING). VII. Fourier decomposition of molecular gas velocity fields and bar pattern speed
Authors: Salak Dragan , Noma Yuto , Sorai Kazuo , Miyamoto Yusuke , Kuno Nario , Pettitt Alex R , Kaneko Hiroyuki , Tanaka Takahiro , Yasuda Atsushi , Kita Shoichiro , Yajima Yoshiyuki , Shibata Shugo , Nakai Naomasa , Seta Masumichi , Muraoka Kazuyuki , Kuroda Mayu , Nakanishi Hiroyuki , Takeuchi Tsutomu T , Yoda Moe , Morokuma-Matsui Kana , Watanabe Yoshimasa , Matsumoto Naoko , Oi Nagisa , Pan Hsi-An , Kajikawa Ayumi , Yashima Yu , Komatsuzaki Ryusei
Published: January 2019

The 12CO (J = 1→0) velocity fields of a sample of 20 nearby spiral galaxies, selected from the CO Multi-line Imaging of Nearby Galaxies (COMING) legacy project of Nobeyama Radio Observatory, have been analyzed by Fourier decomposition to determine their basic kinematic properties, such as circular and noncircular velocities. On average, the investigated barred (SAB and SB) galaxies exhibit a ratio of noncircular to circular velocities of molecular gas larger by a factor of 1.5–2 than non-barred (SA) spiral galaxies at radii within the bar semimajor axis ab at 1 kpc resolution, with a maximum at a radius of R/ab ≈ 0.3. Residual velocity field images, created by subtracting model velocity fields from the data, reveal that this trend is caused by kpc-scale streaming motions of molecular gas in the bar region. Applying a new method based on radial velocity reversal, we estimated the corotation radius RCR and bar pattern speed Ωb in seven SAB and SB systems. The ratio of the corotation to bar radius is found to be in a range of $\mathcal {R}\equiv R_\mathrm{CR}/a_\mathrm{b} \approx 0.8$–1.6, suggesting that intermediate (SBb–SBc), luminous barred spiral galaxies host fast and slow rotator bars. Tentative negative correlations are found for Ωb vs. ab and Ωb vs. total stellar mass M*, indicating that bars in massive disks are larger and rotate slower, possibly a consequence of angular momentum transfer. The kinematic properties of SAB and SB galaxies, derived from Fourier decomposition, are compared with recent numerical simulations that incorporate various rotation curve models and galaxy interactions.
Family functioning among adolescents with narcolepsy
Authors: Parmar Arpita , Yeh Eluen Ann , Korczak Daphne J , Weiss Shelly K , Lu Zihang , Zweerink Allison , Toulany Alene , Murray Brian J , Narang Indra
Published: January 2019

Background

Narcolepsy is a sleep disorder with no cure with onset typically during adolescence. Caring for an adolescent with a lifelong medical condition can negatively impact family structure, cohesion, relationships, and overall functioning. The primary objective of this study was to evaluate family functioning in a cohort of adolescents with narcolepsy using the PedsQL Family Impact Module. The secondary objective was to compare family functioning in adolescents with narcolepsy to adolescents with chronic pain based on published data.

Methods

This was a cross-sectional study of adolescents (aged 10 to 18 years) with narcolepsy. The narcolepsy group was recruited from The Hospital for Sick Children in Toronto, Canada. Family functioning was assessed by the PedsQL family impact module total scores, which was completed by the patient’s caregiver. The PedsQL family impact module yields a total scale which encompasses parent health-related quality of life, daily activities, family relationships, communication, and worry subscales. Lower scores suggest poorer family functioning. Secondary data analyses were used to compare participants’ family functioning to a cohort of adolescents with chronic pain.

Results

Thirty adolescents with narcolepsy participated (mean age=13.8 ± 2.2 years, 76.7% male). Family functioning was impaired in this cohort of adolescents with narcolepsy and similar to adolescents with chronic pain (64.0 ± 19.8 versus 64.7 ± 19.5; P=0.849).

Conclusion

Family functioning is impaired in adolescents with narcolepsy. Clinical teams should assess family functioning at routine clinic visits by asking about concerns and challenges related to caring for an adolescent with narcolepsy and providing resources and support as needed.
T cells in primary Sjögren’s syndrome: targets for early intervention
Authors: Verstappen Gwenny M , Kroese Frans G. M , Bootsma Hendrika
Published: January 2019

A histologic hallmark of primary SS (pSS) is lymphocytic infiltration of the salivary and lacrimal glands, in particular by CD4+ T and B cells. In the early stages of the disease, infiltrates are dominated by CD4+ T cells, while B cell accumulation occurs at later stages. Activated T cells contribute to pathogenesis by producing pro-inflammatory cytokines and by inducing B cell activation, which results in the establishment of a positive feedback loop. In the inflamed glandular tissues, many different CD4+ effector subsets are present, including IFN-γ-producing Th1 cells, IL-17-producing Th17 cells and IL-21-producing T follicular helper cells. In blood from pSS patients, frequently observed abnormalities of the T cell compartment are CD4+ T cell lymphopenia and enrichment of circulating follicular helper T (Tfh) cells. Tfh cells are critical mediators of T cell–dependent B cell hyperactivity and these cells can be targeted by immunotherapy. Inhibition of T cell activation, preferably early in the disease process, can mitigate B cell activity and may be a promising treatment approach in this disease.
Social Support in America: Stratification and Trends in Access over Two Decades
Authors: Verdery Ashton , Campbell Colin
Published: January 2019

Social networks of family and friends are key resources that individuals turn to in times of need. When family and friends can provide assistance, they constitute a form of social capital that individuals may draw on for social support. Although a large body of research has examined the use of social support in its own right and as a predictor or moderator of other outcomes, few studies have explored differentials in access to social support for the general population or how these access levels have changed over time. There are many open questions. Is access to social support broadly distributed in the population or does it differ by demographic subgroups? Have levels of access remained constant? We compare levels of access to social support through both family and friends across population subgroups and describe the changing contours of access to it in the general population. Using repeated cross-sectional measurements that we compile from nearly two decades of surveys conducted as part of the Survey of Income and Program Participation, we expand on a literature that has, to date, focused almost exclusively on the use of social support as a predictor of other outcomes using non-representative data. This article presents, to our knowledge, the first nationally representative study of stratification and trends in access to social support for individuals in the United States.
Genome-wide Prediction of Potential Polycomb Response Elements and their Functions
Authors: Khabiri Morteza , Freddolino Peter L.
Published: January 2019

The Polycomb-group proteins (PcG) and Trithorax-group proteins (TrxG) are two major epigenetic regulators important for proper differentiation during development (1, 2). InDrosophila melanogaster(D. melanogaster), Polycomb response elements (PREs) are short segments of DNA with a high density of binding sites for transcription factors (TFs) that recruit PcG and TrxG proteins to chromatin. Each PRE has a different number of binding sites for PcG and TrxG, and these binding sites have different topological organizations. It is thus difficult to find general rules to discover the locations of PREs over the entire genome. We have developed a framework to predict the locations and roles of potential PRE regions over the entireD. melanogastergenome using machine learning algorithms. Using a combination of motif-based and simple sequence-based features, we were able to train a random forest (RF) model with very high performance in predicting active PRE regions. This model could distinguish potential PRE regions from non-PRE regions (precision and recall ~0.92 upon cross-validation). In the process, the model suggests that previously unrecognized TFs might contribute to PcG/TrxG recruitment at the PRE locations, as the presence of binding sites for those factors is strongly informative of active PREs. A secondary regression model provides information on features that further differentiate PREs into functional subclasses. Our findings provide both new predictions of 7887 potential PREs in theD. melanogastergenome, and new mechanistic insight into the set of DNA-associated proteins that may contribute to PcG recruitment and/or activity.
RBM10 variants and RBM5 involve in alternative splicing of RBM10v1 pre-mRNA: RBM10v1 includes its own exon 4, but RBM10v2 and RBM5 skip it
Authors: Nishio Koji
Published: January 2019

RNA binding motif (RBM) proteins, RBM10v1, RBM10v2 and RBM5 have quite similar molecular structures with a high degree of the conserved domains. Alternative splicing of RBM10 pre-mRNA produces the two mRNA variants, RBM10v1 (exon 4-included) and RBM10v2 (exon 4-skipped). RBM10v1 has a 77 amino acids-domain coded by its exon 4, but RBM10v2 lacks it. I explored the alternative splicing of the RBM10 pre-mRNA by the above three RBMs in COS-7, lung adenocarcinoma A549 and differentiated mouse cardiomyocytes H9c2 cells. Firstly, COS-7 and A549 cells express both RBM10v1 and RBM10v2 mRNA variants in contrast to H9c2 cells which express RBM10v2 variant alone. Transfection experiments of RBM10v1, RBM10v2 or RBM5 were performed to examine the alternative splicing of RBM10v1 pre-mRNA in COS-7, A549 and H9c2 cells. The result showed that RBM10v1 includes, by itself, its own exon 4 of the pre-mRNA in contrast to RBM10v2 and RBM5 which exclude the exon 4. The inclusion of the exon 4 seems to be repressed in differentiated H9c2 cells.
Most of transcriptional alterations in glioma result from DNA-methylation independent mechanisms
Authors: Court Franck , Boiteux Elisa Le , Fogli Anne , Müller-Barthélémy Mélanie , Vaurs-Barrière Catherine , Chautard Emmanuel , Pereira Bruno , Biau Julian , Kemeny Jean-Louis , Khalil Toufic , Karayan-Tapon Lucie , Verrelle Pierre , Arnaud Philippe
Published: January 2019

Background

Aberrant DNA methylation is a cancer cell feature that is commonly associated with transcriptional alterations. However, the primary role of this defect in the genome-wide cancer-associated gene deregulation is not clear. Here, we evaluated the relative contribution of DNA methylation-dependent and -independent mechanisms to transcriptional alterations at CpG-island/promoter-associated genes in samples of adult glioma, a widespread type of brain tumor.

Results

Extensive molecular analyses of glioma samples with wild type IDH (IDHwt) and mutated IDH (IDHmut) found DNA hypermethylation only in a minority of genes showing loss or gain of expression. Specifically, in IDHwt samples, more than 75% of aberrantly repressed genes did not display DNA methylation defects at their CpG-island promoter. Conversely, altered H3K27me3 was the predominant molecular defect at deregulated genes. Moreover, the presence of a bivalent chromatin signature at CpG-island promoters in stem cells might not only predispose to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Our findings support a model whereby the altered control of H3K27me3 dynamics, more specifically defects in the interplay between polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells.

Conclusions

Our study provides a comprehensive and updated description of the epigenetic deregulations in glioma that could be useful for the design of drugs to target cancer-related epigenetic defects.
Oxidized products ofα-linolenic acid negatively regulate cellular survival and motility of breast cancer cells
Authors: Gutierrez-Pajares Jorge L. , Hassen Celine Ben , Oger Camille , Galano Jean-Marie , Durand Thierry , Frank Philippe G.
Published: January 2019

Background

Cancer is a major cause of death in the world, and more than six million new cases are reported every year. Despite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of α-linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively.

Methods

In this work, seven PhytoPs (PP1-PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines.

Results

Among the compounds tested, only three PhytoPs had a significant effect on cell viability compared to the control group:Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability in MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs significantly enhanced the cytotoxic effect on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays,Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells in a wound-healing and a transwell assays. In addition,Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells.

Conclusions

This study shows for the first time that the plant-derived compounds PhytoPs and PhytoFs could be further exploited alone or in combination with chemotherapy to improve the arsenal of therapies available against breast cancer.
A novel role for the tumor suppressor geneITF2in lung tumorigenesis and chemotherapy response
Authors: Pernía Olga , Sastre-Perona Ana , Rodriguez-Antolín Carlos , García-Guede Alvaro , Palomares-Bralo María , Rosas Rocío , Sanchez-Cabrero Darío , Cruz Patricia , Rodriguez Carmen , Diestro MDolores , Martín-Arenas Rubén , Pulido Verónica , Santisteban Pilar , de Castro Javier , Vera Olga , Ibáñez de Cáceres Inmaculada
Published: January 2019

Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyze the cytogenetic alterations that arise after cisplatin treatment providing novel insights into the molecular biology and the cellular mechanisms involved in the acquired resistance in these tumor types.

Methods

In this study, we used 1 million array-CGH and qRT-PCR methodologies to identify and validate cytogenetic alterations that arise after cisplatin treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines. We used whole transcriptome sequencing (RNA-seq), functional transfection assays and gene-pathway activity analysis in our experimental cellular models and in fresh frozen primary NSCLC tumors to identify genes with a potential role in the development of this malignancy. Results were further explored in 55 lung and ovarian primary tumors and control samples and in two extensive in silico databases (TCGA and KMplotter) with 1,926 NSCLC and 1,425 additional epithelial tumors.

Results

Long-term cell exposure to platinum induces the frequent deletion ofITF2gene. Restoration ofITF2expression re-sensitizes tumor cells to platinum and recovers the levels of Wnt/β-catenin transcriptional activity.ITF2expression was also frequently downregulated in NSCLC, ovarian and other epithelial tumors, predicting a worse overall survival. We also identified an inverse correlation in expression betweenITF2andHOXD9, revealing that NSCLC patients with lower expression ofHOXD9have a better overall survival rate that was independent of the tumor histology.

Conclusion

We have defined the implication ofITF2as a molecular mechanism behind the development of cisplatin resistance probably through the activation of the Wnt-signaling pathway. Our translational data suggest thatITF2could be used as a general epithelial tumor platinum-predictive marker and have identifiedHOXD9as a potential prognostic biomarker in NSCLC, a gene which expression is induced byWntsignaling. Furthermore, this data highlights the possible role ofITF2andHOXD9as a novel therapeutic target for platinum resistant tumors.
Stem-cell-ubiquitous genes spatiotemporally coordinate division through regulation of stem-cell-specific gene networks
Authors: Clark Natalie M , Buckner Eli , Fisher Adam P , Nelson Emily C , Nguyen Thomas T , Simmons Abigail R , de Luis Balaguer Maria A , Butler-Smith Tiara , Sheldon Parnell J , Bergmann Dominique C , Williams Cranos M , Sozzani Rosangela
Published: January 2019

Stem cells are responsible for generating all of the differentiated cells, tissues, and organs in a multicellular organism and, thus, play a crucial role in cell renewal, regeneration, and organization. A number of stem cell type-specific genes have a known role in stem cell maintenance, identity, and/or division. Yet, how genes expressed across different stem cell types, referred here as stem-cell-ubiquitous genes, contribute to stem cell regulation is less understood. Here, we find that, in the Arabidopsis root, a stem-cell-ubiquitous gene, TESMIN-LIKE CXC2 (TCX2), controls stem cell division by regulating stem cell-type specific networks. Development of a mathematical model of TCX2 expression allowed us to show that TCX2 orchestrates the coordinated division of different stem cell types. Our results highlight that genes expressed across different stem cell types ensure cross-communication among cells, allowing them to divide and develop harmonically together.
The Relationship between Parasitic Fleas and Small Mammals in Household of Western Yunnan Province, China
Authors: Yin Jia-Xiang , Cheng Xiao-Ou , Zhao Qiu-Fang , Wei Zhao-Fei , Xu Dan-Dan , Wang Meng-Di , Zhou Yun , Wang Xiu-Fang , Liu Zheng-Xiang
Published: January 2019

The Yunnan Province has one of the most serious outbreaks of the plague epidemic in China. Small mammals and fleas are risk factors for the occurrence of plague in commensal plague foci. Understanding the relationship between parasitic fleas and small mammals will help control fleas and prevent the onset of the plague. Four hundred and twenty-one small mammals, belonging to 9 species, were captured. Of these, 170 small mammals (40.4%) were infested with fleas. A total of 992 parasitic fleas (including 5 species) was collected. The number of Leptopsylla Segnis and Xenopsylla Cheopis was 91.0%. The final multiple hurdle negative binomial regression model showed that when compared with Rattus Tanezumi, the probability of flea infestation on Mus musculus and other host species decreased from 58% to 99%, while the infestation with fleas from other host species increased 4.7 fold. The probability of flea prevalence in adult hosts increased by 74%, while the number of fleas decreased by 76%. The number of flea infestations in small male mammals increased by 62%. The number of fleas in small mammals weighing more than 59 grams has been multiplied by about 4. Rattus Tanezumi is the predominant species in households in West Yunnan Province, while Leptopsylla Segnis and Xenopsylla Cheopis are dominant parasitic fleas. There is a strong relationship between the abundance of parasitic fleas and the characteristics of small mammals (e.g. Species, age, sex, and body weight).
E6 proteins from high-risk HPV, low-risk HPV, and animal papillomaviruses activate the Wnt/β-catenin pathway through E6AP-dependent degradation of NHERF1
Authors: Drews Camille M. , Case Samuel , Vande Pol Scott B.
Published: January 2019

High-risk human papillomavirus (HPV) E6 proteins associate with the cellular ubiquitin ligase E6-Associated Protein (E6AP), and then recruit both p53 and certain cellular PDZ proteins for ubiquitination and degradation by the proteasome. Low-risk HPV E6 proteins also associate with E6AP, yet fail to recruit p53 or PDZ proteins; their E6AP-dependent targets have so far been uncharacterized. We found a cellular PDZ protein called Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) is targeted for degradation by both high and low-risk HPV E6 proteins as well as E6 proteins from diverse non-primate mammalian species. NHERF1 was degraded by E6 in a manner dependent upon E6AP ubiquitin ligase activity but independent of PDZ interactions. A novel structural domain of E6, independent of the p53 recognition domain, was necessary to associate with and degrade NHERF1, and the NHERF1 EB domain was required for E6-mediated degradation. Degradation of NHERF1 by E6 activated canonical Wnt/β-catenin signaling, a key pathway that regulates cell growth and proliferation. Expression levels of NHERF1 increased with increasing cell confluency. This is the first study in which a cellular protein has been identified that is targeted for degradation by both high and low-risk HPV E6 as well as E6 proteins from diverse animal papillomaviruses. This suggests that NHERF1 plays a role in regulating squamous epithelial growth and further suggests that the interaction of E6 proteins with NHERF1 could be a common therapeutic target for multiple papillomavirus types.

Author summary

Papillomaviruses cause benign squamous epithelial tumors through the action of virally encoded oncoproteins termed E6 and E7, which are classified as either high or low-risk based upon the propensity of the tumor to evolve into cancer. E6 proteins from both high and low-risk HPVs interact with a cellular ubiquitin ligase called E6AP. High-risk E6 proteins hijack E6AP ubiquitin ligase activity to target p53 for degradation. Degradation targets of the low-risk E6 proteins in complex with E6AP have not been described. Here, we describe a protein called NHERF1 that is targeted for degradation by both high and low-risk E6 proteins, as well as E6 proteins from diverse animal species. Degradation of NHERF1 resulted in activation of an oncogenic cellular signaling pathway called Wnt. Identification of NHERF1 as a highly conserved E6 degradation target could inform therapies directed against both low-risk HPVs and cancer-inducing high-risk HPVs.
On the hot-rolled recycled carbon steels: their oxide formation, pickling ability and scale adhesion
Authors: Chandra-ambhorn Somrerk , Tungtrongpairoj Jennarong , Jutilarptavorn Anuwat , Nilsonthi Thanasak , Somphakdee Tanongsak
Published: January 2019

Purpose

The purpose of this study is to investigate the formation, pickling ability and adhesion of thermal oxide scales on the hot-rolled recycled steels produced from the medium and thin slabs. Because the scale on the steel produced from the medium slab was relatively thick of about 11 µm, it contained cracks after hot-rolling. Thus during pickling, the scale was uniformly attacked with the simultaneous dissolution of the inner scale because of the penetration of acid through cracks. However, the scale on the steel produced from the thin slab was thinner of about 6 µm and thus, nearly crack-free. The pickling solution thus attacked the scale surface uniformly. At longer pickling periods, pits were also nucleated and propagated. Concurrently, the tensile testing machine with a CCD camera has been applied to observe scale adhesion.

Design/methodology/approach

The formation, pickling ability and adhesion of thermal oxide scales on the hot-rolled recycled steels produced from the recycled slab, e.g. medium slab and thin slab, were investigated. The morphology and phase identification were examined by using scanning electron microscopy, X-ray diffraction and Raman spectroscopy. Furthermore, the adhesion behaviour of oxide scale was investigated by immersion test and tensile test with a CCD camera.

Findings

For the scale formation, it was found that the hematite and magnetite were formed on the hot-rolled recycled steels produced from the medium and thin slabs. For the immersion test, it was found that the scale on hot-rolled recycled steels produced from the medium slab was more difficult to be pickled as represented by the longer time for the complete pickling. This was consistent with the result of tensile test; the steel produced from the medium slab had better scale adhesion as represented by the higher strain initiating the first spallation of scale.

Originality/value

The effects of slab types and its alloying element were investigated to understand the scale adhesion behaviour. The empirical pickling mechanisms and the mechanical adhesion energy were proposed. It led to the understanding in the control of alloying element in the hot-rolled steel.
The role of central government and local government and the moderating effect of good governance on forest fire policy in Indonesia
Authors: Brotestes Panjaitan Raffles , Sumartono Sumartono , Sarwono Sarwono , Saleh Choirul
Published: January 2019

Purpose

The purpose of this paper is to investigate forest fires and their relationship to prevention and mitigation strategies based on the empirical problems raised by this study. Public policy implementation (in this case, the policy of forest fire management) is influenced by the role played by government and by the participation of the public and stakeholders (in this case, companies), as well as the effects of good governance. Thus, from the empirical problems associated with theoretical problems and normative problems, this study raises the influence of the role of central and local government on the implementation of forest fire prevention policy in Indonesia, which is moderated by the good governance variable.

Design/methodology/approach

This study used a quantitative approach by adopting survey methodology. The study has aimed to assess both large and small population groups, by selecting and reviewing carefully chosen samples of the population to find the incidence, distribution and relative interrelation of the variables considered (Kerlinger and Lee, 2000). The survey was undertaken in areas of Indonesia that have a high level of vulnerability to forest fires. There are currently six provinces – Riau, Jambi, South Sumatra, West Kalimantan, East Kalimantan and South Kalimantan – that have the highest intensity of forest fires. The study population was taken from 105 villages in those six major provinces experiencing forest fires. Sample size precision was determined by using Slovin’s formula with a precision of 10 percent and, thus, a sample size of 52 was obtained.

Findings

The central government’s activities have no significant effect on regional forest fire prevention. However, the results found that there is a significant effect caused by the interaction between the central and local governments and their governance of forest fire prevention. Even though the direct effect is not significant, the interaction effect significantly influences the forest fire prevention governance variable, which is a pure moderator. This study found that the role of central government has no effect on forest fire prevention. If the role of the central government is high, it will not impact the effectiveness of forest fire prevention, which is reflected in the aspects of prevention and early warning, reward and punishment, the improvement and management of ecosystems by reviewing courts, law enforcement and national and regional synergy.

Originality/value

This is one of the few public administration science studies to have investigated the relationship between good governance and forest fire policy in Indonesia, particularly the combined roles played by central and local governments.