bluuebunny/crossref_metadata_2025 huggingface dataset:
Unprecedented Atmospheric Ammonia Concentrations Detected in the High Arctic From the 2017 Canadian Wildfires
Authors: Lutsch Erik , Strong Kimberly , Jones Dylan B. A. , Ortega Ivan , Hannigan James W. , Dammers Enrico , Shephard Mark W. , Morris Eleanor , Murphy Killian , Evans Mathew J. , Parrington Mark , Whitburn Simon , Van Damme Martin , Clarisse Lieven , Coheur Pierre‐Francois , Clerbaux Cathy , Croft Betty , Martin Randall V. , Pierce Jeffrey R. , Fisher Jenny A.
Published: July 2019

From 17–22 August 2017 simultaneous enhancements of ammonia (NH3), carbon monoxide (CO), hydrogen cyanide (HCN), and ethane (C2H6) were detected from ground‐based solar absorption Fourier transform infrared (FTIR) spectroscopic measurements at two high‐Arctic sites: Eureka (80.05°N, 86.42°W) Nunavut, Canada, and Thule (76.53°N, 68.74°W), Greenland. These enhancements were attributed to wildfires in British Columbia and the Northwest Territories of Canada using FLEXPART back‐trajectories and fire locations from Moderate Resolution Imaging Spectroradiometer (MODIS) and found to be the greatest observed enhancements in more than a decade of measurements at Eureka (2006–2017) and Thule (1999–2017). Observations of gas‐phase NH3 from these wildfires illustrate that boreal wildfires may be a considerable episodic source of NH3 in the summertime high Arctic. Comparisons of GEOS‐Chem model simulations using the Global Fire Assimilation System (GFASv1.2) biomass burning emissions to FTIR measurements and Infrared Atmospheric Sounding Interferometer (IASI) measurements showed that the transport of wildfire emissions to the Arctic was underestimated in GEOS‐Chem. However, GEOS‐Chem simulations showed that these wildfires contributed to surface layer NH3 and NH
enhancements of 0.01–0.11 ppbv and 0.05–1.07 ppbv, respectively, over the Canadian Archipelago from 15–23 August 2017.
Dissimilatory Nitrate/Nitrite Reduction Processes in River Sediments Across Climatic Gradient: Influences of Biogeochemical Controls and Climatic Temperature Regime
Authors: Li Xiaofei , Sardans Jordi , Hou Lijun , Gao Dengzhou , Liu Min , Peñuelas Josep
Published: July 2019

Dissimilatory nitrate/nitrite reduction processes play an important role in controlling nitrogen loading in river environments. However, the relative importance of climatic temperature regime and biogeochemical controls to dissimilatory nitrate/nitrite reduction processes remains unclear. We used nitrogen isotope tracer approach to investigate geographical variabilities of denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) in river sediments from temperate to tropical climates of China. Denitrification, anammox, and DNRA varied greatly across the climatic gradient, with potential rates of 1.47–25.7, 0.54–3.4, and 0.15–7.17 nmol N g−1 h−1, respectively. Mean measured rates throughout the sampling sites were 9.73 nmol N g−1 h−1 for denitrification, 1.29 nmol N g−1 h−1 for anammox, and 1.61 nmol N g−1 h−1 for DNRA. Denitrification and DNRA rates increased significantly from temperate to tropical climates, while no significantly spatial difference was observed for anammox rates along the climatic gradient. Mean annual temperature, total organic carbon, dissolved organic carbon, pH, NH4+, NO3–, C/N, Fe2+, and functional genes were the crucial factors affecting denitrification, anammox, and DNRA. High dissolved organic carbon and NO3– availability determined nitrogen removal capacity in river sediments. Mean annual temperature was the most important factor explaining the geographical variances of denitrification and DNRA, while the critical predictor of anammox variance was sediment pH along the climatic gradient. Our results highlight that biogeochemical controls and climatic temperature regime are important coregulators affecting the geographical variabilities of dissimilatory nitrate/nitrite reduction processes in river sediments at the continental‐scale variation.
Statistical Analysis of the Correlation Between Anomalies in the Czech Electric Power Grid and Geomagnetic Activity
Authors: Výbošt’oková Tatiana , Švanda Michal
Published: July 2019

Eruptive events on the Sun have an impact on the immediate surroundings of the Earth. Through induction of electric currents, they also affect Earth‐bound structures such as the electric power transmission networks. Inspired by recent studies we investigate the correlation between the disturbances recorded in 12 years in the maintenance logs of the Czech electric power distributors with the geomagnetic activity represented by the K index. We find that in case of the data sets recording the disturbances on power lines at the high and very high voltage levels and disturbances on electrical substations, there is a statistically significant increase of anomaly rates in the periods of tens of days around maxima of geomagnetic activity compared to the adjacent minima of activity. There are hints that the disturbances are more pronounced shortly after the maxima than shortly before the maxima of activity. Our results provide indirect evidence that the geomagnetically induced currents may affect the occurrence rate of anomalies registered on power‐grid equipment even in the midlatitude country in the middle of Europe. A follow‐up study that includes the modeling of geomagnetically induced currents is needed to confirm our findings.
A Joint Soil‐Vegetation‐Atmospheric Water Tagging Procedure With WRF‐Hydro: Implementation and Application to the Case of Precipitation Partitioning in the Upper Danube River Basin
Authors: Arnault Joël , Wei Jianhui , Rummler Thomas , Fersch Benjamin , Zhang Zhenyu , Jung Gerlinde , Wagner Sven , Kunstmann Harald
Published: July 2019

Atmospheric models such as the Weather Research and Forecasting (WRF) model provide a tool to evaluate the behavior of regional hydrological cycle components, including precipitation, evapotranspiration, soil water storage, and runoff. Recent model developments have focused on coupled atmospheric‐hydrological modeling systems, such as WRF‐Hydro, in order to account for subsurface, overland, and river flow and potentially improve the representation of land‐atmosphere interactions. The aim of this study is to investigate the contribution of lateral terrestrial water flow to the regional hydrological cycle, with the help of a joint soil‐vegetation‐atmospheric water tagging procedure newly developed in the so‐called WRF‐tag and WRF‐Hydro‐tag models. An application of both models for the high precipitation event on 15 August 2008 in the German and Austrian parts of the upper Danube river basin (94,100 km2) is presented. The precipitation that fell in the basin during this event is considered as a water source, is tagged, and subsequently tracked for a 40‐month period until December 2011. At the end of the study period, in both simulations, approximately 57% of the tagged water has run off, while 41% has evaporated back to the atmosphere, including 2% that has recycled in the upper Danube river basin as precipitation. In WRF‐Hydro‐tag, the surface evaporation of tagged water is slightly enhanced by surface flow infiltration and slightly reduced by subsurface lateral water flow in areas with low topography gradients. This affects the source precipitation recycling only in a negligible amount.
Molecular basis for hierarchical histone de-β-hydroxybutyrylation by SIRT3
Authors: Zhang Xingrun , Cao Ruili , Niu Jinrong , Yang Shumin , Ma Huida , Zhao Shuai , Li Haitao
Published: July 2019

Chemical modifications on histones constitute a key mechanism for gene regulation in chromatin context. Recently, histone lysine β-hydroxybutyrylation (Kbhb) was identified as a new form of histone acylation that connects starvation-responsive metabolism to epigenetic regulation. Sirtuins are a family of NAD+-dependent deacetylases. Through systematic profiling studies, we show that human SIRT3 displays class-selective histone de-β-hydroxybutyrylase activities with preference for H3 K4, K9, K18, K23, K27, and H4K16, but not for H4 K5, K8, K12, which distinguishes it from the Zn-dependent HDACs. Structural studies revealed a hydrogen bond-lined hydrophobic pocket favored for the S-form Kbhb recognition and catalysis. β-backbone but not side chain-mediated interactions around Kbhb dominate sequence motif recognition, explaining the broad site-specificity of SIRT3. The observed class-selectivity of SIRT3 is due to an entropically unfavorable barrier associated with the glycine-flanking motif that the histone Kbhb resides in. Collectively, we reveal the molecular basis for class-selective histone de-β-hydroxybutyrylation by SIRT3, shedding lights on the function of sirtuins in Kbhb biology through hierarchical deacylation.
Quantifying individual differences in brain morphometry underlying symptom severity in Autism Spectrum Disorders
Authors: Pua Emmanuel Peng Kiat , Ball Gareth , Adamson Chris , Bowden Stephen , Seal Marc L.
Published: July 2019

The neurobiology of heterogeneous neurodevelopmental disorders such as autism spectrum disorders (ASD) are still unclear. Despite extensive efforts, most findings are difficult to reproduce due to high levels of individual variance in phenotypic expression. To quantify individual differences in brain morphometry in ASD, we implemented a novel subject-level, distance-based method on subject-specific attributes. In a large multi-cohort sample, each subject with ASD (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.58) was strictly matched to a control participant (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.70). Intrapair Euclidean distance of MRI brain morphometry and symptom severity measures (Social Responsiveness Scale) were entered into a regularised machine learning pipeline for feature selection, with rigorous out-of-sample validation and permutation testing. Subject-specific structural morphometry features significantly predicted individual variation in ASD symptom severity (19 cortical thickness features,p = 0.01, n = 5000 permutations; 10 surface area features,p = 0.006, n = 5000 permutations). Findings remained robust across subjects and were replicated in validation samples. Identified cortical regions implicate key hubs of the salience and default mode networks as neuroanatomical features of social impairment in ASD. Present results highlight the importance of subject-level markers in ASD, and offer an important step forward in understanding the neurobiology of heterogeneous disorders.
The Pol β variant containing exon α is deficient in DNA polymerase but has full dRP lyase activity
Authors: Dai Da-Peng , Prasad Rajendra , Strauss Phyllis R. , Wilson Samuel H.
Published: July 2019

DNA polymerase (Pol) β is a key enzyme in base excision repair (BER), an important repair system for maintaining genomic integrity. We previously reported the presence of a Pol β transcript containing exon α (105-nucleotide) in normal and colon cancer cell lines. The transcript carried an insertion between exons VI and VII and was predicted to encode a ~42 kDa variant of the wild-type 39 kDa enzyme. However, little is known about the biochemical properties of the exon α-containing Pol β (exon α Pol β) variant. Here, we first obtained evidence indicating expression of the 42 kDa exon α Pol β variant in mouse embryonic fibroblasts. The exon α Pol β variant was then overexpressed in E. coli, purified, and characterized for its biochemical properties. Kinetic studies of exon α Pol β revealed that it is deficient in DNA binding to gapped DNA, has strongly reduced polymerase activity and higher Km for dNTP during gap-filling. On the other hand, the 5′-dRP lyase activity of the exon α Pol β variant is similar to that of wild-type Pol β. These results indicate the exon α Pol β variant is base excision repair deficient, but does conduct 5′-trimming of a dRP group at the gap margin. Understanding the biological implications of this Pol β variant warrants further investigation.
Environment shapes sleep patterns in a wild nocturnal primate
Authors: Reinhardt Kathleen D. , Vyazovskiy Vladyslav V. , Hernandez-Aguilar R. Adriana , Imron Muhammad Ali , Nekaris K. Anne-Isola
Published: July 2019

Among primates, the suborder Haplorhini is considered to have evolved a consolidated monophasic sleep pattern, with diurnal species requiring a shorter sleep duration than nocturnal species. Only a few primate species have been systematically studied in their natural habitat where environmental variables, including temperature and light, have a major influence on sleep and activity patterns. Here we report the first sleep study on a nocturnal primate performed in the wild. We fitted seven wild Javan slow lorises (Nycticebus javanicus) in West Java, Indonesia with accelerometers that collected activity data, and installed climate loggers in each individual’s home range to collect ambient temperature readings (over 321 days in total). All individuals showed a strictly nocturnal pattern of activity and displayed a striking synchronisation of onset and cessation of activity in relation to sunset and sunrise. The longest consolidated rest episodes were typically clustered near the beginning and towards the end of the light period, and this pattern was inversely related to daily fluctuations of the ambient temperature. The striking relationship between daily activity patterns, light levels and temperature suggests a major role of the environment in shaping the daily architecture of waking and sleep. We concluded that well-known phenotypic variability in daily sleep amount and architecture across species may represent an adaptation to changes in the environment. Our data suggest that the consolidated monophasic sleep patterns shaped by environmental pressures observed in slow lorises represent phylogenetic inertia in the evolution of sleep patterns in humans.
Structural changes within the bifunctional cryptochrome/photolyase CraCRY upon blue light excitation
Authors: Franz-Badur Sophie , Penner Alexander , Straß Simon , von Horsten Silke , Linne Uwe , Essen Lars-Oliver
Published: July 2019

Cryptochromes (CRYs) are an ubiquitously occurring class of photoreceptors, which are important for regulating the circadian rhythm of animals via a time-delayed transcription-translation feedback loop (TTFL). Due to their protein architecture and common FAD chromophore, they belong to the same superfamily as photolyases (PHLs), an enzyme class that repairs UV-induced DNA lesions upon blue light absorption. Apart from their different functions the only prominent structural difference between CRY and PHL is the highly variable C-terminal extension (CTE) of the former. The nature of the CTE is still unclear and highly speculated. In this study, we show by hydrogen/deuterium exchange and subsequent mass-spectrometric analysis that the CTE of the animal-like cryptochrome from the green algae Chlamydomonas reinhardtii (CraCRY) binds to the surface of the photolyase homology region, which flanks the DNA binding site. We also compared the fully oxidized and fully reduced states of the flavoprotein and designed a tool, so called light chamber, for automated HDX-MS measurements of photoreceptors in defined photostates. We could observe some striking differences between the two photostates and propose a model for light-dependent switching of this bifunctional cryptochrome.
Tunable magnetoplasmonics in lattices of Ni/SiO2/Au dimers
Authors: Pourjamal Sara , Kataja Mikko , Maccaferri Nicolò , Vavassori Paolo , van Dijken Sebastiaan
Published: July 2019

We present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By considering the excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically demonstrate that the magnetoplasmonic response of dimer lattices is governed by a complex interplay of near- and far-field interactions. Near-field coupling between dipoles in Ni and low-loss Au enhances the polarizabilty of single dimers compared to that of isolated Ni nanodisks. Far-field diffractive coupling in periodic lattices of these two particle types enlarges the difference in effective polarizability further. This effect is explained by an inverse relationship between the damping of collective surface lattice resonances and the imaginary polarizability of individual scatterers. Optical reflectance measurements, magneto-optical Kerr effect spectra, and finite-difference time-domain simulations confirm the analytical results. Hybrid dimer arrays supporting intense plasmon excitations are a promising candidate for active magnetoplasmonic devices.
Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms
Authors: Slater Ross T. , Frost Lucy R. , Jossi Sian E. , Millard Andrew D. , Unnikrishnan Meera
Published: July 2019

The anaerobic gut pathogen, Clostridioides difficile, forms adherent biofilms that may play an important role in recurrent C. difficile infections. The mechanisms underlying C. difficile community formation and inter-bacterial interactions are nevertheless poorly understood. C. difficile produces AI-2, a quorum sensing molecule that modulates biofilm formation across many bacterial species. We found that a strain defective in LuxS, the enzyme that mediates AI-2 production, is defective in biofilm development in vitro. Transcriptomic analyses of biofilms formed by wild type (WT) and luxS mutant (luxS) strains revealed a downregulation of prophage loci in the luxS mutant biofilms compared to the WT. Detection of phages and eDNA within biofilms may suggest that DNA release by phage-mediated cell lysis contributes to C. difficile biofilm formation. In order to understand if LuxS mediates C. difficile crosstalk with other gut species, C. difficile interactions with a common gut bacterium, Bacteroides fragilis, were studied. We demonstrate that C. difficile growth is significantly reduced when co-cultured with B. fragilis in mixed biofilms. Interestingly, the absence of C. difficile LuxS alleviates the B. fragilis-mediated growth inhibition. Dual species RNA-sequencing analyses from single and mixed biofilms revealed differential modulation of distinct metabolic pathways for C. difficile WT, luxS and B. fragilis upon co-culture, indicating that AI-2 may be involved in induction of selective metabolic responses in B. fragilis. Overall, our data suggest that C. difficile LuxS/AI-2 utilises different mechanisms to mediate formation of single and mixed species communities.
A general non-rectangular hyperbola equation for photosynthetic light response curve of rice at various leaf ages
Authors: Xu Junzeng , Lv Yuping , Liu Xiaoyin , Wei Qi , Qi Zhiming , Yang Shihong , Liao Linxian
Published: July 2019

Photosynthetic light response (PLR) curves of leaves are usually fitted by non-rectangular hyperbola (NRH) equation, and those fitted NRH parameters may change with leaf aging. The objectives of this study were 1) to reveal the response of NRH parameters of rice leaves, light-saturated net photosynthetic rate (Pnmax), quantum yield of assimilation (φ), dark respiration rate (Rd) and convexity of the curve (k), to leaf age; and 2) to improve the performance of NRH equation in simulating the PLR curves for leaves at various ages. The PLR for rice leaves at ages of 3–53 days were measured, and the general NRH equation was developed by incorporating the relationship between NRH parameters and leaf age into the NRH equation. The results showed that the NRH parameters of Pnmax, φ and Rd increased rapidly to maximum at approximately 10 days and then declined linearly toward the age of 53 days. However, the value of k was not sensitive to leaf age. The general NRH equation can be used to simulate leaf PLR continuously along with leaf aging.
Discovery of novel oestrogen receptor α agonists and antagonists by screening a revisited privileged structure moiety for nuclear receptors
Authors: Masuya Takahiro , Iwamoto Masaki , Liu Xiaohui , Matsushima Ayami
Published: July 2019

Bisphenol A (BPA) is used as an industrial raw material for polycarbonate plastics and epoxy resins; however, various concerns have been reported regarding its status as an endocrine-disrupting chemical. BPA interacts not only with oestrogen receptors (ERs) but constitutive androstane receptor, pregnane X receptor, and oestrogen-related receptor γ (ERRγ); therefore, the bisphenol structure represents a privileged structure for the nuclear-receptor superfamily. Here, we screen 127 BPA-related compounds by competitive-binding assay using [3H]oestradiol and find that 20 compounds bind to ERα with high affinity. We confirm most of these as ERα agonists; however, four compounds, including bisphenol M and bisphenol P act as novel antagonists. These structures harbour three benzene rings in tandem with terminal hydroxy groups at para-positions, with this tandem tri-ring bisphenol structure representing a novel privileged structure for an ERα antagonist. Additionally, we perform an ab initio calculation and develop a new clipping method for halogen bonding or non-covalent interaction using DV-Xα evaluation for biomolecules.
Dual Kit/Aur Inhibitors as Chemosensitizing Agents for the Treatment of Melanoma: Design, Synthesis, Docking Studies and Functional Investigation
Authors: Quattrini Luca , Coviello Vito , Sartini Stefania , Di Desidero Teresa , Orlandi Paola , Ke Yi-Yu , Liu Kai-Lun , Hsieh Hsing-Pang , Bocci Guido , La Motta Concettina
Published: July 2019

Melanoma is the most serious form of skin cancer but its medication is still far from being safe and thoroughly effective. The search of novel therapeutic approaches represents therefore a health emergency to push through eagerly. In this study, we describe a novel class of dual c-Kit/Aur inhibitors, characterized by a 1,2,4-triazole core and developed by a structure-based optimization of a previously developed hit, and report the evidence of their significance as drug candidates for the treatment of melanoma. Compound6a, merging the best inhibitory profile against the target kinases, showed anti-proliferative efficacy against the human melanoma cell lines A2058, expressing the BRAF V600D mutation, and WM266-4, expressing BRAF V600E. Significantly, it displayed also a highly synergistic profile when tested in combination with vemurafenib, thus proving its efficacy not onlyper sebut even in a combination therapy, which is nowadays acknowledged as the cornerstone approach of the forthcoming tumour management.
Bio-enzymes for inhibition and elimination of Escherichia coli O157:H7 biofilm and their synergistic effect with sodium hypochlorite
Authors: Lim Eun Seob , Koo Ok Kyung , Kim Min-Jeong , Kim Joo-Sung
Published: July 2019

Escherichia coli O157:H7 is one of the most important pathogens worldwide. In this study, three different kinds of enzymes, DNase I, proteinase K and cellulase were evaluated for inhibitory or degrading activity against E. coli O157:H7 biofilm by targeting extracellular DNA, proteins, and cellulose, respectively. The cell number of biofilms formed under proteinase K resulted in a 2.43 log CFU/cm2 reduction with an additional synergistic 3.72 log CFU/cm2 reduction after NaClO post-treatment, while no significant reduction occurred with NaClO treatment alone. It suggests that protein degradation could be a good way to control the biofilm effectively. In preformed biofilms, all enzymes showed a significant reduction of 16.4–36.7% in biofilm matrix in 10-fold diluted media (p < 0.05). The sequential treatment with proteinase K, cellulase, and NaClO showed a significantly higher synergistic inactivation of 2.83 log CFU/cm2 compared to 1.58 log CFU/cm2 in the sequence of cellulase, proteinase K, and NaClO (p < 0.05). It suggests that the sequence of multiple enzymes can make a significant difference in the susceptibility of biofilms to NaClO. This study indicates that the combination of extracellular polymeric substance-degrading enzymes with NaClO could be useful for the efficient control of E. coli O157:H7 biofilms.
Human Schwann cells are susceptible to infection with Zika and yellow fever viruses, but not dengue virus
Authors: Dhiman Gaurav , Abraham Rachy , Griffin Diane E.
Published: July 2019

Zika virus (ZIKV) is a re-emerged flavivirus transmitted by Aedes spp mosquitoes that has caused outbreaks of fever and rash on islands in the Pacific and in the Americas. These outbreaks have been associated with neurologic complications that include congenital abnormalities and Guillain-Barré syndrome (GBS). The pathogenesis of ZIKV-associated GBS, a potentially life-threatening peripheral nerve disease, remains unclear. Because Schwann cells (SCs) play a central role in peripheral nerve function and can be the target for damage in GBS, we characterized the interactions of ZIKV isolates from Africa, Asia and Brazil with human SCs in comparison with the related mosquito-transmitted flaviviruses yellow fever virus 17D (YFV) and dengue virus type 2 (DENV2). SCs supported sustained replication of ZIKV and YFV, but not DENV. ZIKV infection induced increased SC expression of IL-6, interferon (IFN)β1, IFN-λ, IFIT-1, TNFα and IL-23A mRNAs as well as IFN-λ receptors and negative regulators of IFN signaling. SCs expressed baseline mRNAs for multiple potential flavivirus receptors and levels did not change after ZIKV infection. SCs did not express detectable levels of cell surface Fcγ receptors. This study demonstrates the susceptibility and biological responses of SCs to ZIKV infection of potential importance for the pathogenesis of ZIKV-associated GBS.
Human intestinal spheroids cultured using Sacrificial Micromolding as a model system for studying drug transport
Authors: Samy Karen E. , Levy Elizabeth S. , Phong Kiet , Demaree Benjamin , Abate Adam R. , Desai Tejal A.
Published: July 2019

In vitro models of the small intestine are crucial tools for the prediction of drug absorption. The Caco-2 monolayer transwell model has been widely employed to assess drug absorption across the intestine. However, it is now well-established that 3D in vitro models capture tissue-specific architecture and interactions with the extracellular matrix and therefore better recapitulate the complex in vivo environment. However, these models need to be characterized for barrier properties and changes in gene expression and transporter function. Here, we report that geometrically controlled self-assembling multicellular intestinal Caco-2 spheroids cultured using Sacrificial Micromolding display reproducible intestinal features and functions that are more representative of the in vivo small intestine than the widely used 2D transwell model. We show that Caco-2 cell maturation and differentiation into the intestinal epithelial phenotype occur faster in spheroids and that they are viable for a longer period of time. Finally, we were able to invert the polarity of the spheroids by culturing them around Matrigel beads allowing superficial access to the apical membrane and making the model more physiological. This robust and reproducible in vitro intestinal model could serve as a valuable system to expedite drug screening as well as to study intestinal transporter function.
Development of orthotopic tumour models using ultrasound-guided intrahepatic injection
Authors: McVeigh L. E. , Wijetunga I. , Ingram N. , Marston G. , Prasad R. , Markham A. F. , Coletta P. L.
Published: July 2019

Mouse models of human diseases are an essential part of the translational pipeline. Orthotopic tumour mouse models are increasingly being used in cancer research due to their increased clinical relevance over subcutaneous xenograft models, particularly in relation to metastatic disease. In this study, we have developed orthotopic colorectal cancer liver metastases (CRCLM) and primary cholangiocarcinoma (CCA) models in BALB/c nude mice using minimally invasive ultrasound-guided intrahepatic injection. Due to its minimally invasive nature, the method reduced risk from surgical complications whilst being fast and easy to perform and resulted in measurable tumour volumes 1 to 3 weeks post-injection. Tumour volumes were monitored in vivo by weekly high-frequency ultrasound (HF-US) and/or twice weekly bioluminescence imaging (BLI) and confirmed with end-point histology. Take rates were high for human CRC cells (>73%) and for CCA cells (90%). We have demonstrated that this method reliably induces CRCLM and CCAs, in which tumour volume can be monitored throughout using HF-US and/or BLI. This provides a promising experimental tool for future testing of cancer therapeutics in an orthotopic model.
A spliceosomal twin intron (stwintron) participates in both exon skipping and evolutionary exon loss
Authors: Kavalecz Napsugár , Ág Norbert , Karaffa Levente , Scazzocchio Claudio , Flipphi Michel , Fekete Erzsébet
Published: July 2019

Spliceosomal twin introns (stwintrons) are introns where any of the three consensus sequences involved in splicing is interrupted by another intron (internal intron). In Aspergillus nidulans, a donor-disrupted stwintron (intron-1) is extant in the transcript encoding a reticulon-like protein. The orthologous transcript of Aspergillus niger can be alternatively spliced; the exon downstream the stwintron could be skipped by excising a sequence that comprises this stwintron, the neighbouring intron-2, and the exon bounded by these. This process involves the use of alternative 3′ splice sites for the internal intron, the resulting alternative intervening sequence being a longer 3′-extended stwintron. In 29 species of Onygenales, a multi-step splicing process occurs in the orthologous transcript, in which a complex intervening sequence including the stwintron and neigbouring intron-2, generates by three splicing reactions a “second order intron” which must then be excised with a fourth splicing event. The gene model in two species can be envisaged as one canonical intron (intron-1) evolved from this complex intervening sequence of nested canonical introns found elsewhere in Onygenales. Postulated splicing intermediates were experimentally verified in one or more species. This work illustrates a role of stwintrons in both alternative splicing and the evolution of intron structure.
Formic acid as a hydrogen source for the iridium-catalyzed reductive amination of levulinic acid and 2-formylbenzoic acid
Authors: Wang Shengdong , Huang Haiyun , Bruneau Christian , Fischmeister Cédric
Published: July 2019

A robust iridium catalyst performs the reductive amination of the renewable levulinic acid and of 2-formylbenzoic acid in water under mild conditions. This catalyst tolerates very bulky reagents.
Elucidating the special role of strong metal–support interactions in Pt/MnO2 catalysts for total toluene oxidation
Authors: Mo Shengpeng , Zhang Qi , Zhang Mingyuan , Zhang Qian , Li Jiaqi , Fu Mingli , Wu Junliang , Chen Peirong , Ye Daiqi
Published: July 2019

A series of Pt/MnO2 catalysts with different MnO2 crystal structures (α-, β-, γ- and hollow-MnO2) were prepared to elucidate the special role of strong metal–support interactions (SMSIs) in the total toluene deep oxidation on supported Pt catalysts.
Regular tuning of the ESIPT reaction of 3-hydroxychromone-based derivatives by substitution of functional groups
Authors: Sun Chaofan , Su Xing , Zhou Qiao , Shi Ying
Published: July 2019

The electron-withdrawing ability of an atom and length of substitution groups would affect the ESIPT reaction and photophysical properties of 3-hydroxychromone-based derivatives.
Co-Catalyzed decarbonylative alkylative esterification of styrenes with aliphatic aldehydes and hypervalent iodine(iii) reagents
Authors: Peng Yong , Jiang Yuan-Yuan , Du Xue-Jiao , Ma Da-You , Yang Luo
Published: July 2019

Decarbonylation of aliphatic aldehydes into 1°, 2° and 3° alkyl radicals to construct C(sp3)–C(sp3) bond via radical addition and C(sp3)–O bond via the interconversion of CoII–CoIII–CoI.
Solidly mounted resonator sensor for biomolecule detections
Authors: Han Chengzhang , Wang Xia , Zhao Qiuling , Teng Lihua , Zhang Shuaiyi , Lv Hao , Liu Jing , Ma Haoran , Wang Yanping
Published: July 2019

We report the fabrication of a solidly mounted resonator (SMR) that can also function as a sensor for biological molecules.
Analysis of the autothermal operability of the Sabatier reaction in a heat-recirculating microreactor using CFD
Authors: Raghu Aswathy K. , Kaisare Niket S.
Published: July 2019

The Sabatier reaction in a U-bend micro-reactor benefits from a favourable temperature profile owing to heat recirculation, which improves methane yield and enables stable operation even with feed at ambient temperature.
Locust bean gum/gellan gum double-network hydrogels with superior self-healing and pH-driven shape-memory properties
Authors: Lv Yukai , Pan Zheng , Song Cunzheng , Chen Yulong , Qian Xin
Published: July 2019

Double-network hydrogels based on two natural polysaccharide polymers, locust bean gum and gellan gum, have been fabricated and exhibited excellent self-healing, thermo-processability, and pH-driven shape memory properties.
In situ generated chromophore as the indicator for background-free sensing strategy of hydrazine with high sensitivity with in vitro and in vivo applications
Authors: Zhang Peng , Gong Yan , Zhang Qian , Guo Xinjie , Ding Caifeng
Published: July 2019

A background-free sensing assay for hydrazine was developed by using a fluorescent chromophore generated in situ as the signal indicator.
Design of mobile band subsurface antenna for drainage infrastructure monitoring
Authors: See Chan H. , Kosha Jamal , Mshwat Widad A. , Abd‐Alhameed Raed A. , Ong Felicia L.C. , McEwan Neil J. , Excell Peter S.
Published: July 2019

This study presents an underground subsurface wireless sensor for drainage infrastructure water level monitoring. It operates from 800 to 2170 MHz to cover the required GSM850/900, GSM1800/1900 and Universal Mobile Telecommunications System (UMTS) bands. The system consists of a wideband antenna, transceiver, data acquisition unit and an ultrasonic sensor. The proposed antenna is a three‐dimensional inverted double F antenna and has an envelope size of 90 × 63.5 × 32 mm3, which is acceptably small for a cramped subsurface passageway environment. The antenna design was developed using software simulation to optimise its key parameters of return loss and radiation pattern, these were evaluated both in free space and in the partially underground environment. The design developed was then realised in hardware and tested in a representative subsurface location: a utility manhole chamber. It was found that the location of the antenna in the chamber had a significant effect on its performance, but a location that was acceptable for operational purposes was found by experiment. The overall system, including a transceiver, was demonstrated to operate satisfactorily for utility monitoring purposes, including acceptable levels of path loss for communication with mobile communication base stations.
Estimation and use materials of the airily-depressed surveys on the coal mines of Ukraine
Authors: Bunko Tetiana , Shyshov Maksym , Myroshnychenko Vadym , Kokoulin Ivan , Dudnyk Mykhailo
Published: July 2019

Need to improve the methodological and technical means of obtaining, adjusting and updating the results of the airly-depressed surveys (ADS). With this purpose, identified issues that do not respond modern tasks of the ADS concerning the control of the aerological condition of coal mines. Methods of structural and parametric identification of the mine ventilation network are developed. It is proposed to replace obsolete control devices of aerodynamic parameters more modern, developed by Institute of Geotechnical Mechanics named by N. Poljakov of National Academy of Sciences of Ukraine, devices: anemometer portable mine APR-2, micromanometer differential mine MDR-6, the converter difference of pressure PRD-1. It is proposed a new approach to actualization of information, consisting in the joint of measurements by stationary and portable control devices. Methods of structural-parametric identification and measuring instruments of the aerodynamic parameters of a new technical level offered for the first time. Use of the proposed methods and technical means processing the results of the ADS will improve the quality of aerodynamic information received.
Determination of the kinetic constants of the process of plasma gasification of coal-water fuel
Authors: Kholiavchenko Leonid , Pihida Yevhen , Demchenko Serhii , Davydov Serhii
Published: July 2019

The chemical kinetics of processes of thermal transformations of carbon-containing media was studied at high-temperature processing (2000 K ≤ T ≤ 5000 K) in the chamber of a plasma-jet reactor using water vapor as an oxidizer. The chemical reactions rate was calculated according to the method of determining the kinetic constants of the process of gasification of coal-water fuel. The influence of the temperature of the gaseous environment in the chamber on the time of complete carbon conversion of the fuel particles is established. An example of calculating the parameters of the gasification process of coke residue particles with a size of (5 - 20)·10-5 m with an oxidizer excess coefficient α = 0.45 and fuel consumption mf = 100 kg/hr is given. The expediency of the process of vapor-plasma gasification at the temperature of gases in the reactor chamber up to 3000 K is shown.
Laws of gas draining in the massif disturbed by mining operations
Authors: Kurnosov Serhii , Zerkal Volodymyr
Published: July 2019

A method for calculating gas permeability of the rock massif depending on its stress-strain state is presented. By using methods of the mine experimental studies, influence of mining operations in the adjacent long walls on intensity of gas release from the previously worked-out long-pillar was determined, as well as impact of the massif stress-strain state on efficiency of the drainage boreholes. Formulas were obtained for calculating coefficients of the impact of zones with static and dynamic abutment pressure on intensity of gas draining in the previously worked-out long-pillar.
The results of experimental research of the parameters of methane capturing by local degassing wells in the undermining area
Authors: Sofiiskyi Kostiantyn , Petukh Oleksandr
Published: July 2019

The article is devoted to the analysis of the results of the mine instrumental measurements of the local degassing system of the m3 seam on the horizon of 1100 m of the mine named. V.M. Bazhanov to establish the basic rational parameters with the subsequent application of the biotechnological method of reducing the concentration of methane. As a result of mine instrumental measurements (vacuum-gas surveys at the borehole heads), the parameters of the degassing process (methane flow rate at the borehole heads and the average vacuum on them), technological parameters (angle of turn and tilt of wells, their length), well flow rate efficiency from the distance to the bottom of the longwall and the displacement of the undermined rocks. Establishing the basic parameters of degassing will allow you to quickly manage the flow rate of wells and underpressure at their mouths, taking into account the specific mining and geological and mining conditions. The use of biofilters allows controlling the concentration of methane in the atmosphere of mine roadway by methanotrophic bacteria.
Control of the mud pulse method the loosening of coal layers by amplitude-frequency recommendation of acoustic signal by the APSS-1 system
Authors: Zberovskyi Vasyl
Published: July 2019

The article presents the research results of parameters of the mud pulse method the loosening of outburst-hazardous coal seams in the faces of development workings system APSS-1. The results of the monitoring and evaluation of the effectiveness of pulse loosening a coal seam in static and pulsed mode of injection fluid, the main provisions of the developed techniques and additions to methods of acoustic control with a view to their use in hydroimpulsive impact. It is established that application of pulsed injection of fluid leads to a decrease in the active phase of the process pulse loosening a coal seam, to increase its efficiency and increase the speed of the output.
Real-world biologic treatment and associated cost in patients with inflammatory bowel disease
Authors: Brandes Alina , Groth Antje , Gottschalk Fraence , Wilke Thomas , Ratsch Boris A. , Orzechowski Hans-Dieter , Fuchs Andreas , Deiters Barthold , Bokemeyer Bernd
Published: July 2019

Objectives This study aimed to describe biologic treatment of German inflammatory bowel disease (IBD) patients, including biologics’ dosage, health care resource use, and treatment-associated cost.

Methods In this retrospective claims data analysis, all continuously insured adult IBD patients (Crohnʼs disease [CD] or ulcerative colitis [UC]) who started a new therapy with an anti-tumor necrosis factor alpha (anti-TNF-α) or vedolizumab (VDZ) were included. Observation started with the date of the first prescription of index biologic therapy and lasted 12 months.

Results In the database, 1248 out of 57 296 IBD patients started a biologic treatment of interest (1020 anti-TNF-α, 228 VDZ), and 837 patients were bio-naïve (773 anti-TNF-α, 64 VDZ). The mean age of bio-naïve/bio-experienced anti-TNF-α patients was 39.2/38.1 years (54.9 %/56.7 % female) and 42.6/37.8 years for VDZ patients (56.3 %/54.9 % female). The proportion of patients receiving a maintenance dosage > 150 % compared to SmPC was 15.1 % for Adalimumab, 5.2–39.0 % for Golimumab, 14.7–34.5 % for Infliximab, and 19.7 % for VDZ patients. During the maintenance phase, up to 58.8 % of patients received at least 1 prescription of any CS, and 41.7 %/47.1 % (anti-TNF-α/VDZ) were treated in a hospital due to IBD. The mean IBD-related direct health care cost per patient year was € 30 246 (anti-TNF-α)/ € 28 227 (VDZ) for bio-naïve patients (p = 0.288) and € 34 136 (anti-TNF-α)/ € 32 112 (VDZ) for bio-experienced patients (p = 0.011).

Conclusions A substantial percentage of patients receive a high biologic dosage in the maintenance phase. Despite biologic therapy, 30–40 % receive a CS therapy and/or experience at least 1 IBD-associated hospitalization within a year, possibly indicating a remaining disease activity.
Simple Febrile Seizures: A Benign Phenomena?
Authors: Andrade Edgard
Published: July 2019

Febrile seizures are one of the most common neurological causes of visits to the emergency room. This article is a review of the current literature concerning the evaluation and treatment of children with febrile seizures. Longitudinal prospective studies such as the FEBSTAT study (consequences of prolonged febrile seizures in childhood) have contributed to elucidate the long-term outcome of patients with prolonged febrile seizures. Neurogenetic research also demonstrated the role of genetic mutations (mainly voltage-gated ion channels) in the etiology of febrile seizures. Most febrile seizures are self-limited events with low risk of injury or evolution into status epilepticus or sudden death. However, the use of rectal diazepam as acute abortive treatment for febrile seizures lasting 5 minutes or longer has gained acceptance as a first-line home intervention. Most patients with febrile seizures do not require extensive investigations, but the treatment involves a customized plan. Efforts should be directed to educate caregivers about prognosis and management of potential recurrences. In selected cases, appropriate use of preventive antiseizure medication may be a consideration.
Novel Missense Variants in ADAT3 as a Cause of Syndromic Intellectual Disability
Authors: Thomas Elizabeth , Lewis Andrea M. , Yang Yaping , Chanprasert Sirisak , Potocki Lorraine , Scott Daryl A.
Published: July 2019

Autosomal recessive variants in the adenosine deaminase, tRNA specific 3 (ADAT3) gene cause a syndromic form of intellectual disability due to a loss of ADAT3 function. This disorder is characterized by developmental delay, intellectual disability, speech delay, abnormal brain structure, strabismus, microcephaly, and failure to thrive. A small subset of individuals with ADAT3 deficiency have other structural birth defects including atrial septal defect, patent ductus arteriosus, hypospadias, cryptorchidism, and micropenis. Here, we report a sibling pair with novel compound heterozygous missense variants that affect a conserved amino acid in the deaminase domain of ADAT3. These siblings have many of the features characteristic of this syndrome, including, intellectual disability, hypotonia, esotropia, failure to thrive, and microcephaly. Both had gastroesophageal reflux disease (GERD), feeding problems, and aspiration requiring thickening of feeds. Although they have no words, their communication abilities progressed rapidly when they began to use augmentative and alternative communication (AAC) devices. One of these siblings was born with an anterior congenital diaphragmatic hernia, which has not been reported previously in association with ADAT3 deficiency. We conclude that individuals with ADAT3 deficiency should be monitored for GERD, feeding problems, and aspiration in infancy. They may also benefit from the use of AAC devices and individualized educational programs that take into account their capacity for nonverbal language development. Additional studies in humans or animal models will be needed to determine if ADAT3 deficiency predisposes to the development of structural birth defects.
How character limit affects language usage in tweets
Authors: Boot Arnout B. , Tjong Kim Sang Erik , Dijkstra Katinka , Zwaan Rolf A.
Published: July 2019

In November 2017 Twitter doubled the available character space from 140 to 280 characters. This provided an opportunity for researchers to investigate the linguistic effects of length constraints in online communication. We asked whether the character limit change (CLC) affected language usage in Dutch tweets and hypothesized that there would be a reduction in the need for character-conserving writing styles. Pre-CLC tweets were compared with post-CLC tweets. Three separate analyses were performed: (I) general analysis: the number of characters, words, and sentences per tweet, as well as the average word and sentence length. (II) Token analysis: the relative frequency of tokens and bigrams; (III) part-of-speech analysis: the grammatical structure of the sentences in tweets (i.e., adjectives, adverbs, articles, conjunctives, interjections, nouns, prepositions, pronouns, and verbs); pre-CLC tweets showed relatively more textisms, which are used to abbreviate and conserve character space. Consequently, they represent more informal language usage (e.g., internet slang); in turn, post-CLC tweets contained relatively more articles, conjunctions, and prepositions. The results show that online language producers adapt their texts to overcome limit constraints.
Hysteresis and critical transitions in a coffee agroecosystem
Authors: Vandermeer John , Perfecto Ivette
Published: July 2019

Seeking to employ ecological principles in agricultural management, a classical ecological debate provides a useful framing. Whether ecosystems are controlled from above (predators are the limiting force over herbivores) or from below (overutilization of plant resources is the limiting force over herbivores) is a debate that has motivated much research. The dichotomous nature of the debate (above or below) has been criticized as too limiting, especially in light of contemporary appreciation of ecological complexity—control is more likely from a panoply of direct and indirect interactions. In the context of the agroecosystem, regulation is assumed to be from above and pests are controlled, a way of using ecological insights in service of an essential ecosystem service—pest control. However, this obvious resolution of the old debate does not negate the deeper appreciation of complexity—the natural enemies themselves constitute a complex system. Here we use some key concepts from complexity science to interrogate the natural functioning of pest regulation through spatially explicit dynamics of a predator and a disease operating simultaneously but distributed in space. Using the green coffee scale insect as a focal species, we argue that certain key ideas of complexity science shed light on how that system operates. In particular, a hysteretic pattern associated with distance to a keystone ant is evident.