bluuebunny/crossref_metadata_2025 huggingface dataset:
Equatorial Ionospheric Scintillation During Daytime
Authors: Underwood Emily
Published: September 2018

Scintillation—flickers and distortions in radio waves passing through the ionosphere—can happen during daytime and at much lower dip latitudes than previously thought.
The Intermittency Regions of Powder Snow Avalanches
Authors: Sovilla B. , McElwaine J. N. , Köhler A.
Published: September 2018

Powder snow avalanches are typically composed of several regions characterized by different flow regimes. These include a turbulent suspension cloud of fine particles, a dense basal flow, and an intermittency frontal region, which is characterized by large fluctuations in impact pressure, air pressure, velocity, and density, but whose origin remains unknown. In order to describe the physical processes governing the intermittency region, we present data from four large powder snow avalanches measured at the Vallée de la Sionne test site in Switzerland, which show that the intermittency is caused by mesoscale coherent structures. These structures have a length of 3–14 m and a height of 10 m or more. The structures can have velocities as much as 60% larger than the avalanche front speed and are characterized by an air/particle mixture whose average density can be as high as 20 kg/m3. This average density increases the drag on large granules by a factor of up to 20 compared to pure air, so that each structure can maintain denser snow clusters and single snow granules in suspension for several seconds. The intermittency region has importance for the dynamics of an avalanche, as it provides an efficient mechanism for moving snow from the dense layer to the powder cloud, but also for risk assessment, as it can cause large forces at large heights above the basal dense layer.
Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers
Authors: Zhang Yan , Zheng Dayong , Zhou Ting , Song Haiping , Hulsurkar Mohit , Su Ning , Liu Ying , Wang Zheng , Shao Long , Ittmann Michael , Gleave Martin , Han Huanxing , Xu Feng , Liao Wangjun , Wang Hongbo , Li Wenliang
Published: September 2018

The incidence of aggressive neuroendocrine prostate cancers (NEPC) related to androgen-deprivation therapy (ADT) is rising. NEPC is still poorly understood, such as its neuroendocrine differentiation (NED) and angiogenic phenotypes. Here we reveal that NED and angiogenesis are molecularly connected through EZH2 (enhancer of zeste homolog 2). NED and angiogenesis are both regulated by ADT-activated CREB (cAMP response element-binding protein) that in turn enhances EZH2 activity. We also uncover anti-angiogenic factor TSP1 (thrombospondin-1, THBS1) as a direct target of EZH2 epigenetic repression. TSP1 is downregulated in advanced prostate cancer patient samples and negatively correlates with NE markers and EZH2. Furthermore, castration activates the CREB/EZH2 axis, concordantly affecting TSP1, angiogenesis and NE phenotypes in tumor xenografts. Notably, repressing CREB inhibits the CREB/EZH2 axis, tumor growth, NED, and angiogenesis in vivo. Taken together, we elucidate a new critical pathway, consisting of CREB/EZH2/TSP1, underlying ADT-enhanced NED and angiogenesis during prostate cancer progression.
Stepwise oxygenation of the Paleozoic atmosphere
Authors: Krause Alexander J. , Mills Benjamin J. W. , Zhang Shuang , Planavsky Noah J. , Lenton Timothy M. , Poulton Simon W.
Published: September 2018

Oxygen is essential for animal life, and while geochemical proxies have been instrumental in determining the broad evolutionary history of oxygen on Earth, much of our insight into Phanerozoic oxygen comes from biogeochemical modelling. The GEOCARBSULF model utilizes carbon and sulphur isotope records to produce the most detailed history of Phanerozoic atmospheric O2 currently available. However, its predictions for the Paleozoic disagree with geochemical proxies, and with non-isotope modelling. Here we show that GEOCARBSULF oversimplifies the geochemistry of sulphur isotope fractionation, returning unrealistic values for the O2 sourced from pyrite burial when oxygen is low. We rebuild the model from first principles, utilizing an improved numerical scheme, the latest carbon isotope data, and we replace the sulphur cycle equations in line with forwards modelling approaches. Our new model, GEOCARBSULFOR, produces a revised, highly-detailed prediction for Phanerozoic O2 that is consistent with available proxy data, and independently supports a Paleozoic Oxygenation Event, which likely contributed to the observed radiation of complex, diverse fauna at this time.
Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells
Authors: Stone Oliver A. , El-Brolosy Mohamed , Wilhelm Kerstin , Liu Xiaojing , Romão Ana M. , Grillo Elisabetta , Lai Jason K. H. , Günther Stefan , Jeratsch Sylvia , Kuenne Carsten , Lee I-Ching , Braun Thomas , Santoro Massimo M. , Locasale Jason W. , Potente Michael , Stainier Didier Y. R.
Published: September 2018

Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB transcription factor RELB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs.
Prolonged bacterial lag time results in small colony variants that represent a sub-population of persisters
Authors: Vulin Clément , Leimer Nadja , Huemer Markus , Ackermann Martin , Zinkernagel Annelies S.
Published: September 2018

Persisters are a subpopulation of bacteria that are not killed by antibiotics even though they lack genetic resistance. Here we provide evidence that persisters can manifest as small colony variants (SCVs) in clinical infections. We analyze growth kinetics of Staphylococcus aureus sampled from in vivo conditions and in vitro stress conditions that mimic growth in host compartments. We report that SCVs arise as a result of a long lag time, and that this phenotype emerges de novo during the growth phase in various stress conditions including abscesses and acidic media. We further observe that long lag time correlates with antibiotic usage. These observations suggest that treatment strategies should be carefully tailored to address bacterial persisters in clinics.
Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese
Authors: Zheng Ruijuan , Li Zhiqiang , He Fusheng , Liu Haipeng , Chen Jianhua , Chen Jiayu , Xie Xuefeng , Zhou Juan , Chen Hao , Wu Xiangyang , Wu Juehui , Chen Boyu , Liu Yahui , Cui Haiyan , Fan Lin , Sha Wei , Liu Yin , Wang Jiqiang , Huang Xiaochen , Zhang Linfeng , Xu Feifan , Wang Jie , Feng Yonghong , Qin Lianhua , Yang Hua , Liu Zhonghua , Cui Zhenglin , Liu Feng , Chen Xinchun , Gao Shaorong , Sun Silong , Shi Yongyong , Ge Baoxue
Published: September 2018

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist. We perform a multistage genome-wide association study on 2949 pulmonary TB patients and 5090 healthy controls (833 cases and 1220 controls were genome-wide genotyped) from Han Chinese population. We discover two risk loci: 14q24.3 (rs12437118, Pcombined = 1.72 × 10−11, OR = 1.277, ESRRB) and 20p13 (rs6114027, Pcombined = 2.37 × 10−11, OR = 1.339, TGM6). Moreover, we determine that the rs6114027 risk allele is related to decreased TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB disease. Furthermore, we find that tgm6-deficient mice are more susceptible to Mtb infection. Our results provide new insights into the genetic etiology of TB.
Repurposing of promoters and enhancers during mammalian evolution
Authors: Carelli Francesco N. , Liechti Angélica , Halbert Jean , Warnefors Maria , Kaessmann Henrik
Published: September 2018

Promoters and enhancers—key controllers of gene expression—have long been distinguished from each other based on their function. However, recent work suggested that common architectural and functional features might have facilitated the conversion of one type of element into the other during evolution. Here, based on cross-mammalian analyses of epigenome and transcriptome data, we provide support for this hypothesis by detecting 445 regulatory elements with signatures of activity turnover (termed P/E elements). Most events represent transformations of putative ancestral enhancers into promoters, leading to the emergence of species-specific transcribed loci or 5′ exons. Distinct GC sequence compositions and stabilizing 5′ splicing (U1) regulatory motif patterns may have predisposed P/E elements to regulatory repurposing, and changes in the U1 and polyadenylation signal densities and distributions likely drove the evolutionary activity switches. Our work suggests that regulatory repurposing facilitated regulatory innovation and the origination of new genes and exons during evolution.
Twist angle-dependent conductivities across MoS2/graphene heterojunctions
Authors: Liao Mengzhou , Wu Ze-Wen , Du Luojun , Zhang Tingting , Wei Zheng , Zhu Jianqi , Yu Hua , Tang Jian , Gu Lin , Xing Yanxia , Yang Rong , Shi Dongxia , Yao Yugui , Zhang Guangyu
Published: September 2018

Van der Waals heterostructures stacked from different two-dimensional materials offer a unique platform for addressing many fundamental physics and construction of advanced devices. Twist angle between the two individual layers plays a crucial role in tuning the heterostructure properties. Here we report the experimental investigation of the twist angle-dependent conductivities in MoS2/graphene van der Waals heterojunctions. We found that the vertical conductivity of the heterojunction can be tuned by ∼5 times under different twist configurations, and the highest/lowest conductivity occurs at a twist angle of 0°/30°. Density functional theory simulations suggest that this conductivity change originates from the transmission coefficient difference in the heterojunctions with different twist angles. Our work provides a guidance in using the MoS2/graphene heterojunction for electronics, especially on reducing the contact resistance in MoS2 devices as well as other TMDCs devices contacted by graphene.
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls
Authors: Momozawa Yukihide , Iwasaki Yusuke , Parsons Michael T. , Kamatani Yoichiro , Takahashi Atsushi , Tamura Chieko , Katagiri Toyomasa , Yoshida Teruhiko , Nakamura Seigo , Sugano Kokichi , Miki Yoshio , Hirata Makoto , Matsuda Koichi , Spurdle Amanda B. , Kubo Michiaki
Published: September 2018

Pathogenic variants in highly penetrant genes are useful for the diagnosis, therapy, and surveillance for hereditary breast cancer. Large-scale studies are needed to inform future testing and variant classification processes in Japanese. We performed a case-control association study for variants in coding regions of 11 hereditary breast cancer genes in 7051 unselected breast cancer patients and 11,241 female controls of Japanese ancestry. Here, we identify 244 germline pathogenic variants. Pathogenic variants are found in 5.7% of patients, ranging from 15% in women diagnosed <40 years to 3.2% in patients ≥80 years, with BRCA1/2, explaining two-thirds of pathogenic variants identified at all ages. BRCA1/2, PALB2, and TP53 are significant causative genes. Patients with pathogenic variants in BRCA1/2 or PTEN have significantly younger age at diagnosis. In conclusion, BRCA1/2, PALB2, and TP53 are the major hereditary breast cancer genes, irrespective of age at diagnosis, in Japanese women.
A ballistic graphene superconducting microwave circuit
Authors: Schmidt Felix E. , Jenkins Mark D. , Watanabe Kenji , Taniguchi Takashi , Steele Gary A.
Published: September 2018

Josephson junctions (JJ) are a fundamental component of microwave quantum circuits, such as tunable cavities, qubits, and parametric amplifiers. Recently developed encapsulated graphene JJs, with supercurrents extending over micron distance scales, have exciting potential applications as a new building block for quantum circuits. Despite this, the microwave performance of this technology has not been explored. Here, we demonstrate a microwave circuit based on a ballistic graphene JJ embedded in a superconducting cavity. We directly observe a gate-tunable Josephson inductance through the resonance frequency of the device and, using a detailed RF model, we extract this inductance quantitatively. We also observe the microwave losses of the device, and translate this into sub-gap resistances of the junction at μeV energy scales, not accessible in DC measurements. The microwave performance we observe here suggests that graphene Josephson junctions are a feasible platform for implementing coherent quantum circuits.
Improvement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies
Authors: Roncato Francesco , Rruga Fatlum , Porcù Elena , Casarin Elisabetta , Ronca Roberto , Maccarinelli Federica , Realdon Nicola , Basso Giuseppe , Alon Ronen , Viola Giampietro , Morpurgo Margherita
Published: September 2018

Nowadays, personalized cancer therapy relies on small molecules, monoclonal antibodies, or antibody–drug conjugates (ADC). Many nanoparticle (NP)-based drug delivery systems are also actively investigated, but their advantage over ADCs has not been demonstrated yet. Here, using the Avidin-Nucleic-Acid-Nano-Assemblies (ANANAS), a class of polyavidins multifuctionalizable with stoichiometric control, we compare quantitatively anti-EGFR antibody(cetuximab)-targeted NPs to the corresponding ADC. We show that ANANAS tethering of cetuximab promotes a more efficient EGFR-dependent vesicle-mediated internalization. Cetuximab-guided ANANAS carrying doxorubicin are more cytotoxic in vitro and much more potent in vivo than the corresponding ADC, leading to 43% tumor reduction at low drug dosage (0.56 mg/kg). Advantage of cetuximab-guided ANANAS with respect to the ADC goes beyond the increase in drug-to-antibody ratio. Even if further studies are needed, we propose that NP tethering could expand application of the anti-EGFR antibody to a wider number of cancer patients including the KRAS-mutated ones, currently suffering from poor prognosis.
Resolving the mechanisms of hygroscopic growth and cloud condensation nuclei activity for organic particulate matter
Authors: Liu Pengfei , Song Mijung , Zhao Tianning , Gunthe Sachin S. , Ham Suhan , He Yipeng , Qin Yi Ming , Gong Zhaoheng , Amorim Juliana C. , Bertram Allan K. , Martin Scot T.
Published: September 2018

Hygroscopic growth and cloud condensation nuclei activation are key processes for accurately modeling the climate impacts of organic particulate matter. Nevertheless, the microphysical mechanisms of these processes remain unresolved. Here we report complex thermodynamic behaviors, including humidity-dependent hygroscopicity, diameter-dependent cloud condensation nuclei activity, and liquid–liquid phase separation in the laboratory for biogenically derived secondary organic material representative of similar atmospheric organic particulate matter. These behaviors can be explained by the non-ideal mixing of water with hydrophobic and hydrophilic organic components. The non-ideality-driven liquid–liquid phase separation further enhances water uptake and induces lowered surface tension at high relative humidity, which result in a lower barrier to cloud condensation nuclei activation. By comparison, secondary organic material representing anthropogenic sources does not exhibit complex thermodynamic behavior. The combined results highlight the importance of detailed thermodynamic representations of the hygroscopicity and cloud condensation nuclei activity in models of the Earth’s climate system.
Ultra-low-field magneto-elastocaloric cooling in a multiferroic composite device
Authors: Hou Huilong , Finkel Peter , Staruch Margo , Cui Jun , Takeuchi Ichiro
Published: September 2018

The advent of caloric materials for magnetocaloric, electrocaloric, and elastocaloric cooling is changing the landscape of solid state cooling technologies with potentials for high-efficiency and environmentally friendly residential and commercial cooling and heat-pumping applications. Given that caloric materials are ferroic materials that undergo first (or second) order phase transitions near room temperature, they open up intriguing possibilities for multiferroic devices with hitherto unexplored functionalities coupling their thermal properties with different fields (magnetic, electric, and stress) through composite configurations. Here we demonstrate a magneto-elastocaloric effect with ultra-low magnetic field (0.16 T) in a compact geometry to generate a cooling temperature change as large as 4 K using a magnetostriction/superelastic alloy composite. Such composite systems can be used to circumvent shortcomings of existing technologies such as the need for high-stress actuation mechanism for elastocaloric materials and the high magnetic field requirement of magnetocaloric materials, while enabling new applications such as compact remote cooling devices.
Drivers of within-field spatial and temporal variability of crop yield across the US Midwest
Authors: Maestrini Bernardo , Basso Bruno
Published: September 2018

Not all areas of a farmer’s field are equal; some always produce more relative to the rest of the field, others always less, while still other areas fluctuate in their production capacity from one year to the next, depending on the interaction between climate, soil, topography and management. Understanding why the yield in certain portions of a field has a high variability over time—we call these areas unstable—is of paramount importance both from an economic and an environmental point of view, as it is through the better management of these areas that we can improve yields or reduce input costs and environmental impact. In this research, we analyzed data from 338 fields cultivated with maize, soybean, wheat and cotton in the US Midwest to understand how topographic attributes and rain affect yield stability over time. In addition to this high resolution yield monitor dataset, we used publicly available data on topography, rain and soil information to test the hypothesis that within-field areas characterized by a low topographic wetness index (proxy for areas with probability of lower water content) always perform poorly (low and stable yield) compared to the rest of the field because they are drier, and that areas of a field characterized by a mid-high wetness index (high and stable yield) always perform well relative to rest of the field because they have greater water availability to plants. The relative performance of areas of a field with a very high wetness index (e.g. depressions) strongly depends on rain patterns because they may be waterlogged in wet years, yielding less than the rest of the field, or wetter during dry years, yielding more than the rest of the field. We present three different observations from this dataset to support our hypothesis. First, we show that the average topographic wetness index in the different stability zones is lower in low and stable yield areas, high in high and stable yield areas and even higher in unstable yield areas (p < 0.05). Second, we show that in dry years (low precipitation at plant emergence or in July), unstable zones perform relatively better compared to the rest of the field. Third, we show that temporal yield variability is positively correlated (p < 0.05) with the probability of observing gleying processes associated with waterlogging for part of the year. These findings shed light on mechanisms underlying temporal variability of yield and can help guide management solutions to increase profit and improve environmental quality.
Risk of Incident Cardiovascular Disease and Cardiovascular Risk Factors in First and Second-Generation Indians: The Singapore Indian Eye Study
Authors: Gupta Preeti , Gan Alfred Tau Liang , Man Ryan Eyn Kidd , Fenwick Eva K. , Tham Yih-Chung , Sabanayagam Charumathi , Wong Tien Yin , Cheng Ching-Yu , Lamoureux Ecosse L.
Published: September 2018

Population-based data investigating generational differences in the risk of incident cardiovascular disease (CVD) and its risk determinants are rare. We examined the 6-year incidence of CVD and its risk factors in first- and second-generation ethnic Indians living in Singapore. 1749 participants (mean age [SD]: 55.5 [8.8] years; 47.5% male) from a population-based, longitudinal study of Indian adults were included for incident CVD outcome. Incident CVD was defined as self-reported myocardial infarction, angina pectoris or stroke which developed between baseline and follow-up. CVD-related risk factors included incident diabetes, hypertension, hyperlipidemia, obesity and chronic kidney disease (CKD). For incident CVD outcome, of the 1749 participants, 406 (23.2%) and 1343 (76.8%) were first and second-generation Indians, respectively. Of these, 73 (4.1%) reported incident CVD. In multivariable models, second-generation individuals had increased risk of developing CVD (RR = 2.04; 95% CI 1.04, 3.99; p = 0.038), hyperlipidemia (RR = 1.27; 95% CI 1.06, 1.53; p = 0.011), and CKD (RR = 1.92; 95% CI 1.22, 3.04; p = 0.005), compared to first-generation Indians. Second-generation Indians have increased risk of developing CVD and its associated risk factors such as hyperlipidemia and CKD compared to first-generation immigrants, independent of traditional CVD risk factors. More stratified and tailored CVD prevention strategies on second and subsequent generations of Indian immigrants in Singapore are warranted.
Analysis of the mechanisms regulating the expression of isoprenoid biosynthesis genes in hydroponically-grown Nicotiana benthamiana plants using virus-induced gene silencing
Authors: Atsumi Go , Kagaya Uiko , Tabayashi Noriko , Matsumura Takeshi
Published: September 2018

Secondary metabolites in plants play important roles in defence against biotic and abiotic stresses. Although the biosynthesis pathways of secondary metabolites have been extensively studied, the regulatory mechanism of gene expression involved in these pathways remains poorly understood. In this study, we develop a virus-induced gene silencing (VIGS) system that enables a rapid analysis of the regulatory mechanism of genes involved in the biosynthesis of isoprenoids, one of the largest groups in secondary metabolites, using hydroponically-grown Nicotiana benthamiana. Using VIGS, we successfully reduced the transcript levels of 3-hydroxy-3-methylglutaryl-CoA reductase 1 (HMGR1), cycloartenol synthase 1 (CAS1), sterol side chain reductase 2 (SSR2) and S-adenosyl-L-Met-dependent C-24 sterol methyltransferase 1 (SMT1) in leaf, stem and root tissues in approximately 2 weeks. We identified novel feedback and feed-forward regulation of isoprenoid biosynthesis genes when CAS1, which encodes a key enzyme involved in the biosynthesis of sterols and steroidal glycoalkaloids, was down-regulated. Furthermore, the regulation of these genes differed among different tissues. These results demonstrate that our system can rapidly analyse the regulatory mechanisms involved in the biosynthesis of secondary metabolites.
Author Correction: Tropical protected areas reduced deforestation carbon emissions by one third from 2000–2012
Authors: Bebber Daniel P. , Butt Nathalie
Published: September 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Experimental Observation of the High Pressure Induced Substitutional Solid Solution and Phase Transformation in Sb2S3
Authors: Wang Yingying , Ma Yanmei , Liu Guangtao , Wang Jianyun , Li Yue , Li Quan , Zhang Jian , Ma Yanming , Zou Guangtian
Published: September 2018

The substitutional solid solutions composed of group VA-VIA nonmetallic elements has attracted considerable scientific interest since they provide a pressure-induced route to search for novel types of solid solutions with potential applications. Yet, the pressure-induced solid solution phase is unprecedented in the sulfide family. In this paper, the structural behavior of antimony trisulfide, Sb2S3, has been investigated in order to testify whether or not it can also be driven into the substitutional solid solution phase by high pressures. The experiments were carried out by using a diamond anvil cell and angle dispersive synchrotron X-ray diffraction up to 50.2 GPa at room temperature. The experimental results indicate that Sb2S3 undergoes a series of phase transitions at 5.0, 12.6, 16.9, 21.3, and 28.2 GPa, and develops ultimately into an Sb-S substitutional solid solution, which adopts a body-centered cubic disordered structure. In this structure, the Sb and S atoms are distributed randomly on the bcc lattice sites with space group Im-3m. The structural behavior of Sb2S3 is tentatively assigned by comparison within the A2B3 (A = Sb, Bi; B = Se, Te, S) series under high pressures.
Structural Analysis of Inhibitor Binding to CAMKK1 Identifies Features Necessary for Design of Specific Inhibitors
Authors: Santiago André da Silva , Couñago Rafael M. , Ramos Priscila Zonzini , Godoi Paulo H. C. , Massirer Katlin B. , Gileadi Opher , Elkins Jonathan M.
Published: September 2018

The calcium/calmodulin-dependent protein kinases (CAMKKs) are upstream activators of CAMK1 and CAMK4 signalling and have important functions in neural development, maintenance and signalling, as well as in other aspects of biology such as Ca2+ signalling in the cardiovascular system. To support the development of specific inhibitors of CAMKKs we have determined the crystal structure of CAMKK1 with two ATP-competitive inhibitors. The structures reveal small but exploitable differences between CAMKK1 and CAMKK2, despite the high sequence identity, which could be used in the generation of specific inhibitors. Screening of a kinase inhibitor library revealed molecules that bind potently to CAMKK1. Isothermal titration calorimetry revealed that the most potent inhibitors had binding energies largely dependent on favourable enthalpy. Together, the data provide a foundation for future inhibitor development activities.
Molecular characterization, antimicrobial resistance and clinico-bioinformatics approaches to address the problem of extended-spectrum β-lactamase-producing Escherichia coli in western Saudi Arabia
Authors: Yasir Muhammad , Ajlan Abeer M. , Shakil Shazi , Jiman-Fatani Asif A. , Almasaudi Saad B. , Farman Muhammad , Baazeem Zainah M. , Baabdullah Rnda , Alawi Maha , Al-Abdullah Nabeela , Ismaeel Nashat A. , Shukri Hani A. , Azhar Esam I.
Published: September 2018

The goal of this study was to genotypically characterize extended-spectrum β-lactamase-producing Escherichia coli isolates from the western region of Saudi Arabia and to identify active antibiotics against these isolates using phenotypic and molecular modeling. In total, 211 ESBL-producing E. coli isolates recovered from heterogeneous clinical specimens were identified by MALDI-TOF. Thirty-two sequence types (STs) were identified from a multilocus sequence typing (MLST) analysis of ESBL-producing E. coli, including a novel ST (ST8162). The most common ST in the Saudi and expatriate population was ST131, followed by ST38. All the isolates were multidrug resistant (MDR), and >95% of the isolates were resistant to third-generation (ceftriaxone and ceftazidime) and fourth-generation (cefepime) cephalosporins. The ESBL-positive E. coli isolates primarily harbored the blaCTX-M and blaTEM genes. No resistance was observed against the carbapenem antibiotic group. All the ESBL-producing E. coli isolates were observed to be susceptible to a ceftazidime/avibactam combination. Molecular interaction analyses of the docked complexes revealed the amino acid residues crucial for the binding of antibiotics and inhibitors to the modeled CTX-M-15 enzyme. Importantly, avibactam displayed the most robust interaction with CTX-M-15 among the tested inhibitors in the docked state (∆G = −6.6 kcal/mol). The binding free energy values for clavulanate, tazobactam and sulbactam were determined to be −5.7, −5.9 and −5.2 kcal/mol, respectively. Overall, the study concludes that ‘ceftazidime along with avibactam’ should be carefully used as a treatment option against only carbapenem-resistant MDR ESBL-producing E. coli in this region.
Determination of the Main Phase Transition Temperature of Phospholipids by Nanoplasmonic Sensing
Authors: Chen Wen , Duša Filip , Witos Joanna , Ruokonen Suvi-Katriina , Wiedmer Susanne K.
Published: September 2018

Our study demonstrates that nanoplasmonic sensing (NPS) can be utilized for the determination of the phase transition temperature (Tm) of phospholipids. During the phase transition, the lipid bilayer undergoes a conformational change. Therefore, it is presumed that the Tm of phospholipids can be determined by detecting conformational changes in liposomes. The studied lipids included 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Liposomes in gel phase are immobilized onto silicon dioxide sensors and the sensor cell temperature is increased until passing the Tm of the lipid. The results show that, when the system temperature approaches the Tm, a drop of the NPS signal is observed. The breakpoints in the temperatures are 22.5 °C, 41.0 °C, and 55.5 °C for DMPC, DPPC, and DSPC, respectively. These values are very close to the theoretical Tm values, i.e., 24 °C, 41.4 °C, and 55 °C for DMPC, DPPC, and DSPC, respectively. Our studies prove that the NPS methodology is a simple and valuable tool for the determination of the Tm of phospholipids.
Potential identification of vitamin B6 responsiveness in autism spectrum disorder utilizing phenotype variables and machine learning methods
Authors: Obara Taku , Ishikuro Mami , Tamiya Gen , Ueki Masao , Yamanaka Chizuru , Mizuno Satoshi , Kikuya Masahiro , Metoki Hirohito , Matsubara Hiroko , Nagai Masato , Kobayashi Tomoko , Kamiyama Machiko , Watanabe Mikako , Kakuta Kazuhiko , Ouchi Minami , Kurihara Aki , Fukuchi Naru , Yasuhara Akihiro , Inagaki Masumi , Kaga Makiko , Kure Shigeo , Kuriyama Shinichi
Published: September 2018

We investigated whether machine learning methods could potentially identify a subgroup of persons with autism spectrum disorder (ASD) who show vitamin B6 responsiveness by selected phenotype variables. We analyzed the existing data from our intervention study with 17 persons. First, we focused on signs and biomarkers that have been identified as candidates for vitamin B6 responsiveness indicators. Second, we conducted hypothesis testing among these selected variables and their combinations. Finally, we further investigated the results by conducting cluster analyses with two different algorithms, affinity propagation and k-medoids. Statistically significant variables for vitamin B6 responsiveness, including combination of hypersensitivity to sound and clumsiness, and plasma glutamine level, were included. As an a priori variable, the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS) scores was also included. The affinity propagation analysis showed good classification of three potential vitamin B6-responsive persons with ASD. The k-medoids analysis also showed good classification. To our knowledge, this is the first study to attempt to identify subgroup of persons with ASD who show specific treatment responsiveness using selected phenotype variables. We applied machine learning methods to further investigate these variables’ ability to identify this subgroup of ASD, even when only a small sample size was available.
Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells
Authors: Fujiwara Chiaki , Muramatsu Yukiko , Nishii Megumi , Tokunaka Kazuhiro , Tahara Hidetoshi , Ueno Masaru , Yamori Takao , Sugimoto Yoshikazu , Seimiya Hiroyuki
Published: September 2018

Telomere maintenance by telomerase activity supports the infinite growth of cancer cells. MST-312, a synthetic telomerase inhibitor, gradually shortens telomeres at non-acute lethal doses and eventually induces senescence and apoptosis of telomerase-positive cancer cells. Here we report that MST-312 at higher doses works as a dual inhibitor of telomerase and DNA topoisomerase II and exhibits acute anti-proliferative effects on cancer cells and xenografted tumours in vivo. Our cell-based chemical fingerprinting approach revealed that cancer cells with shorter telomeres and lower expression of lamin A, a nuclear architectural protein, exhibited higher sensitivity to the acute deleterious effects of MST-312, accompanied by formation of telomere dysfunction-induced foci and DNA double-strand breaks. Telomere elongation and lamin A overexpression attenuated telomeric and non-telomeric DNA damage, respectively, and both conferred resistance to apoptosis induced by MST-312 and other DNA damaging anticancer agents. These observations suggest that sufficient pools of telomeres and a nuclear lamina component contribute to the cellular robustness against DNA damage induced by therapeutic treatment in human cancer cells.
Self-triggered Asynchronous Optical Sampling Terahertz Spectroscopy using a Bidirectional Mode-locked Fiber Laser
Authors: Baker R. Dawson , Yardimci N. Tolga , Ou Yi-Hsin , Kieu Khanh , Jarrahi Mona
Published: September 2018

We report a self-triggered asynchronous optical sampling terahertz spectroscopy system based on a single bidirectional mode-locked fiber laser and plasmonics-enhanced photoconductive nanoantennas. The fiber laser generates two optical mutually coherent pulse trains with a stable repetition rate difference, enabling time-domain terahertz spectroscopy without using any mechanical delay line, stabilization electronics, or external trigger. The resolved terahertz spectra over a 0.1–2 THz frequency range and a 30-second measurement time show more than a 70-dB dynamic range, revealing water absorption lines matching the HITRAN database, through a light-weight and compact spectroscopy setup.
Continuous theta-burst stimulation over the dorsolateral prefrontal cortex inhibits improvement on a working memory task
Authors: Vékony Teodóra , Németh Viola Luca , Holczer Adrienn , Kocsis Krisztián , Kincses Zsigmond Tamás , Vécsei László , Must Anita
Published: September 2018

Theta-burst stimulation (TBS) over the dorsolateral prefrontal cortex (DLPFC) may be more effective for modulating cortical excitability compared to standard repetitive transcranial magnetic stimulation. However, the impact of intermittent (iTBS) and continuous TBS (cTBS) on working memory (WM) is poorly studied. The aim of our study was to compare the effects of iTBS and cTBS on WM over the left and right DLPFC. iTBS, cTBS or sham stimulation was administered over the right and left hemisphere of fifty-one healthy human subjects. WM was assessed before and after TBS using the 1-back, 2-back, and 3-back tasks. We found classical practice effects in the iTBS and the sham group: WM performance improved following stimulation as measured by the discriminability index. However, this effect could not be observed in the cTBS group. We did not find any hemisphere-dependent effects, suggesting that the practice effect is not lateralized, and TBS affects WM performance in a comparable manner if administered either over the left or the right hemisphere. We propose that our findings represent a useful addition to the literature of TBS-induced effects on WM. Moreover, these results indicate the possibility of clarifying processes underlying WM performance changes by using non-invasive brain stimulation.
Genome-wide analysis of horizontally acquired genes in the genus Mycobacterium
Authors: Panda Arup , Drancourt Michel , Tuller Tamir , Pontarotti Pierre
Published: September 2018

Horizontal gene transfer (HGT) was attributed as a major driving force for the innovation and evolution of prokaryotic genomes. Previously, multiple research endeavors were undertaken to decipher HGT in different bacterial lineages. The genus Mycobacterium houses some of the most deadly human pathogens; however, the impact of HGT in Mycobacterium has never been addressed in a systematic way. Previous initiatives to explore the genomic imprints of HGTs in Mycobacterium were focused on few selected species, specifically among the members of Mycobacterium tuberculosis complex. Considering the recent availability of a large number of genomes, the current study was initiated to decipher the probable events of HGTs among 109 completely sequenced Mycobacterium species. Our comprehensive phylogenetic analysis with more than 9,000 families of Mycobacterium proteins allowed us to list several instances of gene transfers spread across the Mycobacterium phylogeny. Moreover, by examining the topology of gene phylogenies here, we identified the species most likely to donate and receive these genes and provided a detailed overview of the putative functions these genes may be involved in. Our study suggested that horizontally acquired foreign genes had played an enduring role in the evolution of Mycobacterium genomes and have contributed to their metabolic versatility and pathogenicity.
Exonuclease III-assisted multiple cycle amplification for the sensitive detection of DNA with zero background signal
Authors: Liu Wen-Jing , Xu Qinfeng , Ma Fei , Li Chen-Chen , Zhang Chun-Yang
Published: September 2018

We demonstrate the development of Exo III-assisted multiple cycle amplification for the sensitive detection of DNA with zero background signal.
Nickel-catalysed alkylation of C(sp3)–H bonds with alcohols: direct access to functionalised N-heteroaromatics
Authors: Vellakkaran Mari , Das Jagadish , Bera Sourajit , Banerjee Debasis
Published: September 2018

Base-metal catalysed C(sp3)–H bond functionalisation of methyl-N-heteroaromatics with alcohols is reported for the first time.
Salt-mediated synthesis of bimetallic networks with structural defects and their enhanced catalytic performances
Authors: Zhang Pei , Zhang Xiudong , Kang Xinchen , Liu Huizhen , Chen Chunjun , Xie Chao , Han Buxing
Published: September 2018

Bimetallic alloys with abundant of structural defects and enhanced catalytic performances were prepared tailoring by salts.
X-ray Raman scattering: a newin situprobe of molecular structure during nucleation and crystallization from liquid solutions
Authors: Al-Madhagi Laila H. , Chang Sin-Yuen , Balasubramanian Mahalingam , Kroner Anna B. , Shotton Elizabeth J. , Willneff Elizabeth A. , Mishra Bhoopesh , Schroeder Sven L. M.
Published: September 2018

X-ray Raman scattering (XRS) has been used forin situprobing of solute molecule speciation in solution during cooling crystallization.
Assignment of photoelectron spectra of intramolecular silicon complexes: 1-vinyl- and 1-phenylsilatranes
Authors: Belogolova Elena F. , Doronina Evgeniya P. , Sidorkin Valery F.
Published: September 2018

The problematic photoelectron spectra of 1-vinyl- and 1-phenylsilatranes were theoretically studied and the correlation between the VIE and thedSiNwas proposed to be used for the identification of orbitals in the Si←N coordination bond in XSi[OCH2CH2]3N.
Local elasticity in nonlinear rheology of interacting colloidal glasses revealed by neutron scattering and rheometry
Authors: Wang Zhe , Iwashita Takuya , Porcar Lionel , Wang Yangyang , Liu Yun , Sánchez-Díaz Luis E. , Wu Bin , Huang Guan-Rong , Egami Takeshi , Chen Wei-Ren
Published: September 2018

The transient elasticity zone determines the nonlinear rheology of interacting colloids.
Particularities of photocatalysis and formation of reactive oxygen species on insulators and semiconductors: cases of SiO2, TiO2and their composite SiO2–TiO2
Authors: Anastasescu Crina , Negrila Catalin , Angelescu Daniel G. , Atkinson Irina , Anastasescu Mihai , Spataru Nicolae , Zaharescu Maria , Balint Ioan
Published: September 2018

Highly defected tubular SiO2outperforms the photocatalytic activity of TiO2-P25 and the SiO2–TiO2composite.
Differences in bulk and microscale yttrium speciation in coal combustion fly ash
Authors: Taggart Ross K. , Rivera Nelson A. , Levard Clément , Ambrosi Jean-Paul , Borschneck Daniel , Hower James C. , Hsu-Kim Heileen
Published: September 2018

Yttrium speciation in coal fly ash differs depending on the scale of the analysis.
Extending the dynamic range of biochemical oxygen demand sensing with multi-stage microbial fuel cells
Authors: Spurr Martin W. A. , Yu Eileen H. , Scott Keith , Head Ian M.
Published: September 2018

With multi-stage MFCs the dynamic sensing range for BOD can be significantly increased allowing for monitoring of higher strength wastewaters.
Saponins fromBoussingaultia gracilisprevent obesity and related metabolic impairments in diet-induced obese mice
Authors: Liu Lei , Wang Ningning , Ma Yanan , Liu Yang , Wen Deliang
Published: September 2018

Saponins fromBoussingaultia gracilisattenuate obesity and its related metabolic disorders in diet-induced obese mice.
Preparation of asphalt-based microporous organic polymers catalyzed by heteropoly acids
Authors: Yu Qi , Tan Donggui , Huang Ting , Zhao Tiansheng , Li Lei
Published: September 2018

A green and sustainable strategy catalyzed by heteropoly acids for the preparation of asphalt-based MOPs.
Screening of nutritional and genetic anemias using elastic light scattering
Authors: Tong Lieshu , Kauer Josef , Chen Xi , Chu Kaiqin , Dou Hu , Smith Zachary J.
Published: September 2018

Elastic light scattering and machine learning accurately discriminates between healthy children, those with iron deficiency, and those with thalassemia minor.
3D Hierarchical heterostructures of Bi2W1−xMoxO6 with enhanced oxygen evolution reaction from water under natural sunlight
Authors: Kulkarni Aniruddha K. , Panmand Rajendra P. , Sethi Yogesh A. , Kadam Sunil R. , Patil Deepak R. , Ghule Anil V. , Kale Bharat B.
Published: September 2018

Self-assembled 3D hierarchical Bi2W1−xMoxO6 heterostructures with varying x (x = 0, 0.2, 0.4, 0.6, 0.8 or 1.0) with different morphologies were synthesised via a facile one-pot solvothermal method and their photocatalytic activity towards the oxygen evolution reaction (OER) from water under natural sunlight was tested.
Design of phosphorene/graphene heterojunctions for high and tunable interfacial thermal conductance
Authors: Liu Xiangjun , Gao Junfeng , Zhang Gang , Zhang Yong-Wei
Published: September 2018

Using density functional theory calculations and molecular dynamics simulations, we systematically explore various possible atomic structures of phosphorene/graphene in-plane heterojunctions and their effects on interfacial thermal conductance (ITC).
Poly(ethylene glycol) (PEG)-crosslinked poly(vinyl pyridine)–PEG–poly(vinyl pyridine)-based triblock copolymers prepared by RAFT polymerization as novel gel polymer electrolytes
Authors: Shin Inseop , Nam Jaebin , Lee Kukjoo , Kim Eunsoo , Kim Tae-Hyun
Published: September 2018

A series of triblock copolymers based on poly(vinyl pyridine)–PEG–poly(vinyl pyridine) (PVP–PEG–PVP) with different PEG-to-PVP ratios (1 : 200, 1 : 250, and 1 : 500) were prepared using the RAFT polymerization.
Mechanistic studies: enantioselective palladium(ii)-catalyzed intramolecular aminoarylation of alkenes by dual N–H and aryl C–H bond cleavage
Authors: Zhou Yu , Shang Zhenfeng , Li Ruifang , Xu Xiufang
Published: September 2018

The role of PGA and the origin of the enantioselectivity in the palladium(ii)-catalyzed intramolecular aminoarylation of alkenes.
Strain-engineering the electronic properties and anisotropy of GeSe2 monolayers
Authors: Li Zongbao , Wang Xia , Shi Wei , Xing Xiaobo , Xue Ding-Jiang , Hu Jin-Song
Published: September 2018

GeSe2 has attracted significant attention recently due to its distinctive in-plane anisotropic properties originated from the in-plane anisotropic crystal structure and excellent performance in polarization-sensitive photodetection.
Asymmetric vinylogous aldol addition of alkylidene oxindoles on trifluoromethyl-α,β-unsaturated ketones
Authors: Crotti Simone , Belletti Giada , Di Iorio Nicola , Marotta Emanuela , Mazzanti Andrea , Righi Paolo , Bencivenni Giorgio
Published: September 2018

The vinylogous aldol addition of alkylidene oxindole with 1-trifluoromethyl-3-alkylidene-propan-2-ones was developed. The reaction, provides straightforward access to enantioenriched trifluoromethylated allylic alcohols.
Multiple adaptation of constitutional dynamic networks and information storage in constitutional distributions of acylhydrazones
Authors: Men Guangwen , Lehn Jean-Marie
Published: September 2018

Acylhydrazone-based constitutional dynamic networks respond to three agents by interesting multi-adaptive behavior for processing molecular information through constituent distributions.
A novel theranostic agent based on porous bismuth nanosphere for CT imaging-guided combined chemo-photothermal therapy and radiotherapy
Authors: Ma Guochang , Liu Xijian , Deng Guoying , Yuan Haikuan , Wang Qiugen , Lu Jie
Published: September 2018

A novel theranostic agent based on porous bismuth (pBi) nanospheres was developed for tumor imaging and combined chemotherapy, photothermal therapy and radiotherapy.
Design and analysis of a three‐phase brushless flux switching generator for aircraft ground power units
Authors: Selema Ahmed , Osheba Dina S.M. , Tahoon S.M.R. , El‐Shanawany Mohamed M.
Published: September 2018

This study proposes a new three‐phase dual‐rotor middle‐stator brushless flux switching generator for 400Hz diesel‐driven aircraft ground power units. For the proposed machine, both field and armature windings are hosted in the stator in such a way that not only fulfils brushless structure, but also realises the flux switching function. Moreover, both windings have non‐overlapping concentrated windings to shorten the end‐windings and reduce the copper losses. In the meantime, the rotor has only slots without any active parts. First, the machine detailed design is provided, and its performance is analysed using finite element method. Also, a selection topology of both stator and rotor pole arcs is carried out, targeting maximum generated electromotive force, minimum harmonic content, and minimum cogging torque. Then, a prototype is implemented and experimented to confirm the feasibility of the proposed machine.