bluuebunny/crossref_metadata_2025 huggingface dataset:
A MiSeq-HyDRA platform for enhanced HIV drug resistance genotyping and surveillance
Authors: Taylor Tracy , Lee Emma R. , Nykoluk Mikaela , Enns Eric , Liang Binhua , Capina Rupert , Gauthier Marie-Krystel , Domselaar Gary Van , Sandstrom Paul , Brooks James , Ji Hezhao
Published: June 2019

Conventional HIV drug resistance (HIVDR) genotyping utilizes Sanger sequencing (SS) methods, which are limited by low data throughput and the inability of detecting low abundant drug resistant variants (LADRVs). Here we present a next generation sequencing (NGS)-based HIVDR typing platform that leverages the advantages of Illumina MiSeq and HyDRA Web. The platform consists of a fully validated sample processing protocol and HyDRA web, an open web portal that allows automated customizable NGS-based HIVDR data processing. This platform was characterized and validated using a panel of HIV-spiked plasma representing all major HIV-1 subtypes, pedigreed plasmids, HIVDR proficiency specimens and clinical specimens. All examined major HIV-1 subtypes were consistently amplified at viral loads of ≥1,000 copies/ml. The gross error rate of this platform was determined at 0.21%, and minor variations were reliably detected down to 0.50% in plasmid mixtures. All HIVDR mutations identifiable by SS were detected by the MiSeq-HyDRA protocol, while LADRVs at frequencies of 1~15% were detected by MiSeq-HyDRA only. As compared to SS approaches, the MiSeq-HyDRA platform has several notable advantages including reduced cost and labour, and increased sensitivity for LADRVs, making it suitable for routine HIVDR monitoring for both patient care and surveillance purposes.
Inducible knockout of CHUK/IKKα in adult chondrocytes reduces progression of cartilage degradation in a surgical model of osteoarthritis
Authors: Culley Kirsty L. , Lessard Samantha G. , Green Jordan D. , Quinn Justin , Chang Jun , Khilnani Tyler , Wondimu Elisabeth B. , Dragomir Cecilia L. , Marcu Kenneth B. , Goldring Mary B. , Otero Miguel
Published: June 2019

CHUK/IKKα contributes to collagenase-driven extracellular matrix remodeling and chondrocyte hypertrophic differentiation in vitro, in a kinase-independent manner. These processes contribute to osteoarthritis (OA), where chondrocytes experience a phenotypic shift towards hypertrophy concomitant with abnormal matrix remodeling. Here we investigated the contribution of IKKα to OA in vivo. To this end, we induced specific IKKα knockout in adult chondrocytes in AcanCreERT2/+; IKKαf/f mice treated with tamoxifen (cKO). Vehicle-treated littermates were used as wild type controls (WT). At 12 weeks of age, WT and cKO mice were subjected to the destabilization of medial meniscus (DMM) model of post-traumatic OA. The cKO mice showed reduced cartilage degradation and collagenase activity and fewer hypertrophy-like features at 12 weeks after DMM. Interestingly, in spite of the protection from structural articular cartilage damage, the postnatal growth plates of IKKα cKO mice after DMM displayed abnormal architecture and composition associated with increased chondrocyte apoptosis, which were not as evident in the articular chondrocytes of the same animals. Together, our results provide evidence of a novel in vivo functional role for IKKα in cartilage degradation in post-traumatic OA, and also suggest intrinsic, cell-autonomous effects of IKKα in chondrocytes that control chondrocyte phenotype and impact on cell survival, matrix homeostasis, and remodeling.
Direct visualization of charge transport in suspended (or free-standing) DNA strands by low-energy electron microscopy
Authors: Latychevskaia Tatiana , Escher Conrad , Andregg William , Andregg Michael , Fink Hans-Werner
Published: June 2019

Low-energy electrons offer a unique possibility for long exposure imaging of individual biomolecules without significant radiation damage. In addition, low-energy electrons exhibit high sensitivity to local potentials and thus can be employed for imaging charges as small as a fraction of one elementary charge. The combination of these properties makes low-energy electrons an exciting tool for imaging charge transport in individual biomolecules. Here we demonstrate the imaging of individual deoxyribonucleic acid (DNA) molecules at the resolution of about 1 nm with simultaneous imaging of the charging of the DNA molecules that is of the order of less than one elementary charge per nanometer. The cross-correlation analysis performed on different sections of the DNA network reveals that the charge redistribution between the two regions is correlated. Thus, low-energy electron microscopy is capable to provide simultaneous imaging of macromolecular structure and its charge distribution which can be beneficial for imaging and constructing nano-bio-sensors.
Adaptive adipose tissue stromal plasticity in response to cold stress and antibody-based metabolic therapy
Authors: Chang Joshua C. , Durinck Steffen , Chen Mark Z. , Martinez-Martin Nadia , Zhang Jingli A. , Lehoux Isabelle , Li Hong , Lin May , Wu Jiansheng , Bainbridge Travis W. , Ernst James A. , Ramani Sree R. , Paduchuri Sairupa , Kates Lance , Solon Margaret , Buechler Matthew B. , Castiglioni Alessandra , Thai Minh , Breart Beatrice , Modrusan Zora , Peterson Andrew S. , Turley Shannon J. , Sonoda Junichiro
Published: June 2019

In response to environmental and nutrient stress, adipose tissues must establish a new homeostatic state. Here we show that cold exposure of obese mice triggers an adaptive tissue remodeling in visceral adipose tissue (VAT) that involves extracellular matrix deposition, angiogenesis, sympathetic innervation, and adipose tissue browning. Obese VAT is predominated by pro-inflammatory M1 macrophages; cold exposure induces an M1-to-M2 shift in macrophage composition and dramatic changes in macrophage gene expression in both M1 and M2 macrophages. Antibody-mediated CSF1R blocking prevented the cold-induced recruitment of adipose tissue M2 macrophages, suggesting the role of CSF1R signaling in the process. These cold-induced effects in obese VAT are phenocopied by an administration of the FGF21-mimetic antibody, consistent with its action to stimulate sympathetic nerves. Collectively, these studies illuminate adaptive visceral adipose tissue plasticity in obese mice in response to cold stress and antibody-based metabolic therapy.
Verification of mathematical models of response threshold through statistical characterisation of the foraging activity in ant societies
Authors: Yamanaka Osamu , Shiraishi Masashi , Awazu Akinori , Nishimori Hiraku
Published: June 2019

The concept of response threshold (RT) has been developed to explain task allocation in social insect colonies, wherein individual workers engage in tasks depending on their responsiveness to the task-related stimulus. Moreover, a mathematical model of RT has been proposed to explain data obtained from task allocation experiments; however, its applicability range warrants clarification through adequate quantitative analysis. Hence, we used an automatic measuring system to count passage events between a nest chamber and a foraging arena in five colonies of ants, Camponotus japonicus. The events were measured using radio-frequency identification tags attached to all workers of each colony. Here, we examined the detailed forms of i) labour distribution during foraging among workers in each colony and ii) the persistence of rank-order of foraging among workers. We found that labour distribution was characterized by a generalized gamma-distribution, indicating that only few workers carried out a large part of the workload. The rank-order of foraging activity among workers in each colony was maintained for a month and collapsed within a few months. We compared the obtained data with testable predictions of the RT model. The comparison indicated that proper evaluation of the mathematical model is required based on the obtained data.
Gene knockout analysis reveals essentiality of estrogen receptor β1 (Esr2a) for female reproduction in medaka
Authors: Kayo Daichi , Zempo Buntaro , Tomihara Soma , Oka Yoshitaka , Kanda Shinji
Published: June 2019

In vertebrates, sex steroids play crucial roles in multiple systems related to reproduction. In females, estrogens and their receptor estrogen receptor (ER or Esr) play indispensable roles in the negative sex steroid feedback regulation of pituitary gonadotropin secretion, which prevents excessive development of ovarian follicles. However, the mechanism of this feedback regulation of a gonadotropin, follicle stimulating hormone (FSH), which is essential for folliculogenesis throughout vertebrates, is poorly understood. In the present study, we generated knockouts of all subtypes of nuclear estrogen receptors in a model teleost medaka, which is suitable for the study of endocrine control and behavioral assays, and analyzed fertility, behavior and functionality of estrogen feedback in each knockout line. Among the estrogen receptors, we revealed that an estrogen receptor Esr2a plays an essential role in this feedback regulation. In addition to this, we also found that esr2a−/− females showed oviduct atresia, which causes complete infertility. Interestingly, esr2a−/− females showed apparently normal sexual behavior but without oviposition in response to male courtship. This phenotype indicates that physical readiness and motivation of sexual behavior is independently controlled.
On the Relationship between MRI and Local Field Potential Measurements of Spatial and Temporal Variations in Functional Connectivity
Authors: Shi Zhaoyue , Wilkes Don M. , Yang Pai-Feng , Wang Feng , Wu Ruiqi , Wu Tung-Lin , Chen Li Min , Gore John C.
Published: June 2019

Correlations between fluctuations in resting state BOLD fMRI signals are interpreted as measures of functional connectivity (FC), but the neural basis of their origins and their relationships to specific features of underlying electrophysiologic activity, have not been fully established. In particular, the dependence of FC metrics on different frequency bands of local field potentials (LFPs), and the relationship of dynamic changes in BOLD FC to underlying temporal variations of LFP correlations, are not known. We compared the spatial profiles of resting state coherences of different frequency bands of LFP signals, with high resolution resting state BOLD FC measurements. We also compared the probability distributions of temporal variations of connectivity in both modalities using a Markov chain model-based approach. We analyzed data obtained from the primary somatosensory (S1) cortex of monkeys. We found that in areas 3b and 1 of S1 cortex, low frequency LFP signal fluctuations were the main contributions to resting state LFP coherence. Additionally, the dynamic changes of BOLD FC behaved most similarly to the LFP low frequency signal coherence. These results indicate that, within the S1 cortex meso-scale circuit studied, resting state FC measures from BOLD fMRI mainly reflect contributions from low frequency LFP signals and their dynamic changes.
The Notch system during pubertal development of the bovine mammary gland
Authors: Bonadeo Nadia , Becu-Villalobos Damasia , Cristina Carolina , Lacau-Mengido Isabel M.
Published: June 2019

The development of the mammary gland of cows during pre-weaning and puberty will condition its future productive capacity and warrants special study. In this respect, Notch signaling regulates tissue development and fate by modifying cell proliferation and differentiation and has been involved in stem cell maintenance, but has not been extensively studied in the developing mammary glands in cows. We therefore investigated Notch receptor expression and localization, as well as the expression of Notch ligands and target genes in the mammary gland of Holstein heifers in pre- and post-pubertal stages. Notch receptors 1 to 4 were detected by immunohistochemistry in the parenchyma and stroma of the developing gland. The subcellular localization of the four receptors was predominantly cytoplasmic except for NOTCH4, which was mostly nuclear. The membrane and the active intracellular domains of NOTCH paralogues were identified by western blot. NOTCH1 and NOTCH2 active domains increased during pubertal stages while NOTCH3 and NOTCH4 active domains decreased, suggesting strikingly different involvement of NOTCH paralogues in bovine mammary gland development and differentiation. The mRNA expression levels of the target genes HEY1 and HEY2 increased during peri-puberty whereas no variation of HES1 mRNA levels was observed. The mRNA levels of the Notch ligands JAGGED1 and DELTA1 also increased gradually during development. In conclusion, Notch signaling system dynamically varies throughout the development of the mammary gland during puberty pointing to specific time involvement of each component.
Altered intrinsic brain activity associated with outcome in frontal lobe epilepsy
Authors: Wu Xintong , Liu Wenyu , Wang Weina , Gao Hui , Hao Nanya , Yue Qiang , Gong Qiyong , Zhou Dong
Published: June 2019

Frontal lobe epilepsy (FLE) is the second most common type of the focal epilepsies. Our understanding of this disease has been revolutionized over the past decade, but variable treatment outcomes persist and the underlying functional mechanisms responsible for this have yet to be deciphered. This study was designed to determine how intrinsic brain connectivity related to treatment response in patients with FLE. 50 patients with FLE and 28 healthy controls were enrolled in this study and underwent functional MRI at baseline. At the end of 12-month follow up period, all patients with FLE were classified, based on their responses to AEDs treatment, into drug-responsive and drug-refractory groups. The amplitude of low-frequency fluctuation (ALFF) was calculated amongst the three groups in order to detect regional neural function integration. The responsive group showed decreased ALFF only in the left ventromedial prefrontal cortex (vmPFC), while the refractory group showed decreased ALFF in the left vmPFC, right superior frontal gyrus (SFG), and supramarginal gyrus (SMG) relative to healthy controls. In addition, both the responsive and refractory groups showed increased ALFF in the precuneus and postcentral gyrus when compared to the healthy controls. Furthermore, the refractory group exhibited significantly decreased ALFF in the left vmPFC, right SFG and SMG, relative to the responsive group. Focal spontaneous activity, as assessed by ALFF, was associated with response to antiepileptic treatment in patients with FLE. Patients with refractory frontal lobe epilepsy exhibited decreased intrinsic brain activity. Our findings provide novel neuroimaging evidence into the mechanisms of medically-intractable FLE at the brain level.
The levels of the NMDA receptor co-agonist D-serine are reduced in the substantia nigra of MPTP-lesioned macaques and in the cerebrospinal fluid of Parkinson’s disease patients
Authors: Nuzzo Tommaso , Punzo Daniela , Devoto Paola , Rosini Elena , Paciotti Silvia , Sacchi Silvia , Li Qin , Thiolat Marie-Laure , Véga Celine , Carella Massimo , Carta Manolo , Gardoni Fabrizio , Calabresi Paolo , Pollegioni Loredano , Bezard Erwan , Parnetti Lucilla , Errico Francesco , Usiello Alessandro
Published: June 2019

Dysfunction of NMDA receptor (NMDAR)-mediated transmission is supposed to contribute to the motor and non-motor symptoms of Parkinson’s Disease (PD), and to L-DOPA-induced dyskinesia. Besides the main agonist L-glutamate, two other amino acids in the atypical D-configuration, D-serine and D-aspartate, activate NMDARs. In the present work, we investigated the effect of dopamine depletion on D-amino acids metabolism in the brain of MPTP-lesioned Macaca mulatta, and in the serum and cerebrospinal fluid of PD patients. We found that MPTP treatment increases D-aspartate and D-serine in the monkey putamen while L-DOPA rescues both D-amino acids levels. Conversely, dopaminergic denervation is associated with selective D-serine reduction in the substantia nigra. Such decrease suggests that the beneficial effect of D-serine adjuvant therapy previously reported in PD patients may derive from the normalization of endogenous D-serine levels and consequent improvement of nigrostriatal hypoglutamatergic transmission at glycine binding site. We also found reduced D-serine concentration in the cerebrospinal fluid of L-DOPA-free PD patients. These results further confirm the existence of deep interaction between dopaminergic and glutamatergic neurotransmission in PD and disclose a possible direct influence of D-amino acids variations in the changes of NMDAR transmission occurring under dopamine denervation and L-DOPA therapy.
Colourimetric analysis of thermally altered human bone samples
Authors: Krap Tristan , Ruijter Jan M. , Nota Kevin , Karel Joyce , Burgers A. Lieke , Aalders Maurice C. G. , Oostra Roelof-Jan , Duijst Wilma
Published: June 2019

At this moment, no method is available to objectively estimate the temperature to which skeletal remains have been exposed during a fire. Estimating this temperature can provide crucial information in a legal investigation. Exposure of bone to heat results in observable and measurable changes, including a change in colour. To determine the exposure temperature of experimental bone samples, heat related changes in colour were systemically studied by means of image analysis. In total 1138 samples of fresh human long bone diaphysis and epiphysis, varying in size, were subjected to heat ranging from room temperature to 900 °C for various durations and in different media. The samples were scanned with a calibrated flatbed scanner and photographed with a Digital Single Lens Reflex camera. Red, Green, Blue values and Lightness, A-, and B-coordinates were collected for statistical analysis. Cluster analysis showed that discriminating thresholds for Lightness and B-coordinate could be defined and used to construct a model of decision rules. This model enables the user to differentiate between seven different temperature clusters with relatively high precision and accuracy. The proposed decision model provides an objective, robust and non-destructive method for estimating the exposure temperature of heated bone samples.
A genetically encoded fluorescent temperature sensor derived from the photoactive Orange Carotenoid Protein
Authors: Maksimov Eugene G. , Yaroshevich Igor A. , Tsoraev Georgy V. , Sluchanko Nikolai N. , Slutskaya Ekaterina A. , Shamborant Olga G. , Bobik Tatiana V. , Friedrich Thomas , Stepanov Alexey V.
Published: June 2019

The heterogeneity of metabolic reactions leads to a non-uniform distribution of temperature in different parts of the living cell. The demand to study normal functioning and pathological abnormalities of cellular processes requires the development of new visualization methods. Previously, we have shown that the 35-kDa photoswitchable Orange Carotenoid Protein (OCP) has a strong temperature dependency of photoconversion rates, and its tertiary structure undergoes significant structural rearrangements upon photoactivation, which makes this protein a nano-sized temperature sensor. However, the determination of OCP conversion rates requires measurements of carotenoid absorption, which is not suitable for microscopy. In order to solve this problem, we fused green and red fluorescent proteins (TagGFP and TagRFP) to the structure of OCP, producing photoactive chimeras. In such chimeras, electronic excitation of the fluorescent protein is effectively quenched by the carotenoid in OCP. Photoactivation of OCP-based chimeras triggers rearrangements of complex geometry, permitting measurements of the conversion rates by monitoring changes of fluorescence intensity. This approach allowed us to determine the local temperature of the microenvironment. Future directions to improve the OCP-based sensor are discussed.
Excision and transfer of an integrating and conjugative element in a bacterial species with high recombination efficiency
Authors: Weiss Evelyn , Spicher Carolin , Haas Rainer , Fischer Wolfgang
Published: June 2019

Horizontal transfer of mobile genetic elements, such as integrating and conjugative elements (ICEs), plays an important role in generating diversity and maintaining comprehensive pan-genomes in bacterial populations. The human gastric pathogen Helicobacter pylori, which is known for its extreme genetic diversity, possesses highly efficient transformation and recombination systems to achieve this diversity, but it is unclear to what extent these systems influence ICE physiology. In this study, we have examined the excision/integration and horizontal transfer characteristics of an ICE (termed ICEHptfs4) in these bacteria. We show that transfer of ICEHptfs4 DNA during mating between donor and recipient strains is independent of its conjugation genes, and that homologous recombination is much more efficient than site-specific integration into the recipient chromosome. Nevertheless, ICEHptfs4 excision by site-specific recombination occurs permanently in a subpopulation of cells and involves relocation of a circularization-dependent promoter. Selection experiments for excision indicate that the circular form of ICEHptfs4 is not replicative, but readily reintegrates by site-specific recombination. Thus, although ICEHptfs4 harbours all essential transfer genes, and typical ICE functions such as site-specific integration are active in H. pylori, canonical ICE transfer is subordinate to the more efficient general DNA uptake and homologous recombination machineries in these bacteria.
Epoxidation Kinetics of High-Linolenic Triglyceride Catalyzed by Solid Acidic-Ion Exchange Resin
Authors: Kousaalya Adhimoolam Bakthavachalam , Beyene Shiferaw D. , Ayalew Beshah , Pilla Srikanth
Published: June 2019

Epoxidation of high-linolenic perilla oil was carried out in the presence of solid acidic ion-exchange resin at varying reaction temperatures for 8 h. A pseudo two-phase kinetic model that captures the differences in reactivity of double bonds at various positions in the fatty acid of a triglyceride molecule during both epoxy formation and cleavage was developed. The proposed model is based on the Langmuir-Hinshelwood-Hougen-Watson (L-H-H-W) postulates and considers the adsorption of formic acid on the catalyst as the rate-determining step. To estimate the kinetic rate constants of various reactions, genetic algorithm was used to fit experimentally obtained iodine and epoxy values of epoxidized perilla oil. A re-parametrized form of Arrhenius equation was used in the proposed model to facilitate the precise estimation of parameters with least computational effort. The obtainment of the least error between experimentally determined and theoretically predicted iodine and epoxy values indicates the robustness of the proposed model.
Nitric oxide and ROS mediate autophagy and regulate Alternaria alternata toxin-induced cell death in tobacco BY-2 cells
Authors: Sadhu Abhishek , Moriyasu Yuji , Acharya Krishnendu , Bandyopadhyay Maumita
Published: June 2019

Synergistic interaction of nitric oxide (NO) and reactive oxygen species (ROS) is essential to initiate cell death mechanisms in plants. Though autophagy is salient in either restricting or promoting hypersensitivity response (HR)-related cell death, the crosstalk between the reactive intermediates and autophagy during hypersensitivity response is paradoxical. In this investigation, the consequences of Alternaria alternata toxin (AaT) in tobacco BY-2 cells were examined. At 3 h, AaT perturbed intracellular ROS homeostasis, altered antioxidant enzyme activities, triggered mitochondrial depolarization and induced autophagy. Suppression of autophagy by 3-Methyladenine caused a decline in cell viability in AaT treated cells, which indicated the vital role of autophagy in cell survival. After 24 h, AaT facilitated Ca2+ influx with an accumulation of reactive oxidant intermediates and NO, to manifest necrotic cell death. Inhibition of NO accumulation by 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) decreased the level of necrotic cell death, and induced autophagy, which suggests NO accumulation represses autophagy and facilitates necrotic cell death at 24 h. Application of N-acetyl-L-cysteine at 3 h, confirmed ROS to be the key initiator of autophagy, and together with cPTIO for 24 h, revealed the combined effects of NO and ROS is required for necrotic HR cell death.
High-energy, high-resolution, fly-scan X-ray phase tomography
Authors: Wang Hongchang , Atwood Robert C. , Pankhurst Matthew James , Kashyap Yogesh , Cai Biao , Zhou Tunhe , Lee Peter David , Drakopoulos Michael , Sawhney Kawal
Published: June 2019

High energy X-ray phase contrast tomography is tremendously beneficial to the study of thick and dense materials with poor attenuation contrast. Recently, the X-ray speckle-based imaging technique has attracted widespread interest because multimodal contrast images can now be retrieved simultaneously using an inexpensive wavefront modulator and a less stringent experimental setup. However, it is time-consuming to perform high resolution phase tomography with the conventional step-scan mode because the accumulated time overhead severely limits the speed of data acquisition for each projection. Although phase information can be extracted from a single speckle image, the spatial resolution is deteriorated due to the use of a large correlation window to track the speckle displacement. Here we report a fast data acquisition strategy utilising a fly-scan mode for near field X-ray speckle-based phase tomography. Compared to the existing step-scan scheme, the data acquisition time can be significantly reduced by more than one order of magnitude without compromising spatial resolution. Furthermore, we have extended the proposed speckle-based fly-scan phase tomography into the previously challenging high X-ray energy region (120 keV). This development opens up opportunities for a wide range of applications where exposure time and radiation dose are critical.
Do you understand the words that are comin outta my mouth? Voice assistant comprehension of medication names
Authors: Palanica Adam , Thommandram Anirudh , Lee Andrew , Li Michael , Fossat Yan
Published: June 2019

This study investigated the speech recognition abilities of popular voice assistants when being verbally asked about commonly dispensed medications by a variety of participants. Voice recordings of 46 participants (12 of which had a foreign accent in English) were played back to Amazon’s Alexa, Google Assistant, and Apple’s Siri for the brand- and generic names of the top 50 most dispensed medications in the United States. A repeated measures ANOVA indicated that Google Assistant achieved the highest comprehension accuracy for both brand medication names (M = 91.8%, SD = 4.2) and generic medication names (M = 84.3%, SD = 11.2), followed by Siri (brand names M = 58.5%, SD = 11.2; generic names M = 51.2%, SD = 16.0), and the lowest accuracy by Alexa (brand names M = 54.6%, SD = 10.8; generic names M = 45.5%, SD = 15.4). An interaction between voice assistant and participant accent was also found, demonstrating lower comprehension performance overall for those with a foreign accent using Siri (M = 48.8%, SD = 11.8) and Alexa (M = 41.7%, SD = 12.7), compared to participants without a foreign accent (Siri M = 57.0%, SD = 11.7; Alexa M = 53.0%, SD = 10.9). No significant difference between participant accents were found for Google Assistant. These findings show a substantial performance lead for Google Assistant compared to its voice assistant competitors when comprehending medication names, but there is still room for improvement.
GECKO is a genetic algorithm to classify and explore high throughput sequencing data
Authors: Thomas Aubin , Barriere Sylvain , Broseus Lucile , Brooke Julie , Lorenzi Claudio , Villemin Jean-Philippe , Beurier Gregory , Sabatier Robert , Reynes Christelle , Mancheron Alban , Ritchie William
Published: June 2019

Comparative analysis of high throughput sequencing data between multiple conditions often involves mapping of sequencing reads to a reference and downstream bioinformatics analyses. Both of these steps may introduce heavy bias and potential data loss. This is especially true in studies where patient transcriptomes or genomes may vary from their references, such as in cancer. Here we describe a novel approach and associated software that makes use of advances in genetic algorithms and feature selection to comprehensively explore massive volumes of sequencing data to classify and discover new sequences of interest without a mapping step and without intensive use of specialized bioinformatics pipelines. We demonstrate that our approach called GECKO for GEnetic Classification using k-mer Optimization is effective at classifying and extracting meaningful sequences from multiple types of sequencing approaches including mRNA, microRNA, and DNA methylome data.
Thermococcus sp. 9°N DNA polymerase exhibits 3′-esterase activity that can be harnessed for DNA sequencing
Authors: LinWu Shiuan-Woei , Tu Yu-Hsuan , Tsai Ting-Yueh , Maestre-Reyna Manuel , Liu Mu-Sen , Wu Wen-Jin , Huang Jyun-Yuan , Chi Hung-Wen , Chang Wei-Hsin , Chiou Chung-Fan , Wang Andrew H.-J. , Lee Johnsee , Tsai Ming-Daw
Published: June 2019

It was reported in 1995 that T7 and Taq DNA polymerases possess 3′-esterase activity, but without follow-up studies. Here we report that the 3′-esterase activity is intrinsic to the Thermococcus sp. 9°N DNA polymerase, and that it can be developed into a continuous method for DNA sequencing with dNTP analogs carrying a 3′-ester with a fluorophore. We first show that 3′-esterified dNTP can be incorporated into a template-primer DNA, and solve the crystal structures of the reaction intermediates and products. Then we show that the reaction can occur continuously, modulated by active site residues Tyr409 and Asp542. Finally, we use 5′-FAM-labeled primer and esterified dNTP with a dye to show that the reaction can proceed to ca. 450 base pairs, and that the intermediates of many individual steps can be identified. The results demonstrate the feasibility of a 3′-editing based DNA sequencing method that could find practical applications after further optimization.
Enhanced photo-sensitivity in a Si photodetector using a near-field assisted excitation
Authors: Yatsui T. , Okada S. , Takemori T. , Sato T. , Saichi K. , Ogamoto T. , Chiashi S. , Maruyama S. , Noda M. , Yabana K. , Iida K. , Nobusada K.
Published: June 2019

Silicon is an indispensable material in electric device technology. However, Si is an indirect bandgap material; therefore, its excitation efficiency, which requires phonon assistance, is low under propagating far-field light. To improve the excitation efficiency, herein we performed optical near-field excitation, which is confined in a nano-scale, where the interband transitions between different wave numbers are excited according to the uncertainty principle; thus, optical near-field can directly excite the carrier in the indirect bandgap. To evaluate the effect of optical near-field confined in a nano-scale, we fabricate the lateral Si p–n junction with Au nanoparticles as sources to generate the field confinement. We observed a 47.0% increase in the photo-sensitivity rate. In addition, by using the thin lateral p–n junction, which eliminates the far-field excitation, we confirmed a 42.3% increase in the photo-sensitivity rate.
A radical capture mechanism for immediate Csp2–H bond hydroxylation via a heterogeneous Cu–graphene catalyst
Authors: Sun Wei , Gao Lingfeng , Zheng Gengxiu
Published: June 2019

A radical capture mechanism via a synergistic heterogeneous Cu2O–rGO catalyst for Csp2–H bond immediate hydroxylation has been developed.
Electrodepositing a 3D porous rGO electrode for efficient hydrogel electrolyte integration towards 1.6 V flexible symmetric supercapacitors
Authors: Song Kaizheng , Jiang Yuqi , Pang Xiang , Li Yuanyuan , Liu Jinping
Published: June 2019

A reduced graphene oxide electrode with a 3D hierarchical architecture achieves 3D penetration of hydrogel, giving rise to a high-performance quasi-solid-state supercapacitor.
Piroxicam–clonixin drug–drug cocrystal solvates with enhanced hydration stability
Authors: Li Duanxiu , Li Jiong , Deng Zongwu , Zhang Hailu
Published: June 2019

Piroxicam and clonixin can form drug–drug crystalline complexes with the help of suitable solvent molecules.
Dual metal-free polymer reactive sites for the efficient degradation of diclofenac by visible light-driven oxygen reduction to superoxide radical and hydrogen peroxide
Authors: Zhang Qianxin , Tan Cuiwen , Zheng Xiaoshan , Chen Ping , Zhuo Meihui , Chen Tiansheng , Xie Zhijie , Wang Fengliang , Liu Haijin , Liu Yang , Zhang Xiangdan , Lv Wenying , Liu Guoguang
Published: June 2019

Hydrogen peroxide (H2O2) and superoxide radical (O2˙−) play a critical role in environmental remediation technologies.
Temperature dependence of the vibrational spectrum of porphycene: a qualitative failure of classical-nuclei molecular dynamics
Authors: Litman Yair , Behler Jörg , Rossi Mariana
Published: June 2019

Approximate quantum dynamics succeed in predicting a temperature-dependent blue-shift of the high-frequency stretch bands that arise from vibrational coupling between low-frequency thermally activated modes and high-frequency quantized ones. Classical nuclei molecular dynamics fail and instead predict a red-shift.
Modeling multidimensional spectral lineshapes from first principles: application to water-solvated adenine
Authors: Segarra-Martí Javier , Segatta Francesco , Mackenzie Tristan A. , Nenov Artur , Rivalta Ivan , Bearpark Michael J. , Garavelli Marco
Published: June 2019

We theoretically describe spectral lineshape from first principles, providing insight into solvent–solute interactions in terms of static and dynamic disorder and how these shape experimental signals in linear and non-linear optical spectroscopies.
Laboratory-scale near-edge X-ray absorption fine structure spectroscopy with a laser-induced plasma source
Authors: Müller Matthias , Schellhorn Meike , Mann Klaus
Published: June 2019

A compact spectrometer for laboratory NEXAFS measurements, allowing quantitative chemical analysis in the soft X-ray spectral range (250–1000 eV).
2-Azaanthracenes: a chronology of synthetic approaches and bright prospects for practical applications
Authors: Taniya Olga S. , Kopchuk Dmitry S. , Khasanov Albert F. , Kovalev Igor S. , Santra Sougata , Rahman Matiur , Zyryanov Grigory V. , Majee Adinath , Charushin Valery N. , Chupakhin Oleg N.
Published: June 2019

This review aims to summarize the common synthetic approaches towards 2-azaanthracenes in chronological order, as well as systematize information on the areas of application of 2-azaanthracenes.
The reactivity of CO on bimetallic Ni3M clusters (M = Sc, Ti, V, Cr, Mn, Fe, Co, Cu, Rh, Ru, Ag, Pd and Pt) by density functional theory
Authors: Roy Ghanashyam , Chattopadhyay Asoke Prasun
Published: June 2019

Surface C and O overlap with bimetallic clusters in σ, π and δ-type bonding; for example, C is a σ-donor at −15.23 eV and a π-donor at −9.29 eV, and O is a δ-acceptor at −7.76 eV in Ni3Fe clusters.
Chirality-activated mechanoluminescence from aggregation-induced emission enantiomers with high contrast mechanochromism and force-induced delayed fluorescence
Authors: Chen Yitong , Xu Chao , Xu Bingjia , Mao Zhu , Li Jian-An , Yang Zhan , Peethani Naga Raju , Liu Cong , Shi Guang , Gu Feng Long , Zhang Yi , Chi Zhenguo
Published: June 2019

A pair of AIE enantiomers exhibit chirality-activated mechanoluminescence and circularly polarized luminescence, as well as force-induced multiple-variations in emission properties.
The rapid microwave-assisted hydrothermal synthesis of NASICON-structured Na3V2O2x(PO4)2F3−2x(0 <x≤ 1) cathode materials for Na-ion batteries
Authors: Burova Daria , Shakhova Iaroslava , Morozova Polina , Iarchuk Anna , Drozhzhin Oleg A. , Rozova Marina G. , Praneetha S. , Murugan Vadivel , Tarascon Jean-Marie , Abakumov Artem M.
Published: June 2019

NASICON-structured Na3V2O2x(PO4)2F3−2x(0 <x≤ 1) solid solutions have been prepared using a microwave-assisted hydrothermal (MW-HT) technique.
Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent
Authors: Yin Jie , Yin Guangfu , Pu Ximing , Huang Zhongbing , Yao Dajin
Published: June 2019

As desirable contrast agents for magnetic resonance imaging (MRI), ultrasmall superparamagnetic iron oxides (USPIOs) modified with targeting ligands are considered to be the most effective strategies to achieve better imaging contrast at lower dose.
Tetrathiafulvalene: effective organic anodic materials for WO3-based electrochromic devices
Authors: Kim Yong Min , Li Xinlin , Kim Keon-Woo , Kim Se Hyun , Moon Hong Chul
Published: June 2019

Tetrathiafulvalene (TTF) is employed as an effective electrolyte-soluble anodic species for achieving low-voltage tungsten trioxide (WO3)-based electrochromic devices (ECDs).
Fe3O4/SO3H@zeolite-Y as a novel multi-functional and magnetic nanocatalyst for clean and soft synthesis of imidazole and perimidine derivatives
Authors: Kalhor Mehdi , Zarnegar Zohre
Published: June 2019

Fe3O4/SO3H@zeolite-Y was applied as a novel, effective and environmentally friendly magnetic nanocatalyst for the synthesis of imidazole and perimidine scaffolds.
Rapid microwave activation of waste palm into hierarchical porous carbons for supercapacitors using biochars from different carbonization temperatures as catalysts
Authors: Liu Chaozheng , Chen Weimin , Li Meichun , Hong Shu , Li Wanzhao , Pan Mingzhu , Wu Qinglin , Mei Changtong
Published: June 2019

A rapid, simple and cost-effective approach to prepare hierarchical porous carbons (PCs) for supercapacitors is reported by microwave activation of abundant and low-cost waste palm, biochar (BC) and KOH.
Charge transport enhancement in supramolecular oligothiophene assemblies using Pt(ii) centers as a guide
Authors: Ruiz-Carretero Amparo , Atoini Youssef , Han Tianyan , Operamolla Alessandra , Ippolito Stefano , Valentini Cataldo , Carrara Serena , Sinn Stephan , Prasetyanto Eko Adi , Heiser Thomas , Samorì Paolo , Farinola Gianluca , De Cola Luisa
Published: June 2019

The self-assembly properties of a series of square planar Pt(ii) complexes have been related to their charge transport properties, finding higher mobility values in the complexes placing the Pt centers in closer proximity.
Electrochemically scalable production of bilayer fluorographene nanosheets for solid-state supercapacitors
Authors: Lv Jiangquan , Zeng Peng , Abbas Syed Comail , Guan Xiangfeng , Luo Peihui , Chen Dagui , Wang Yaobing
Published: June 2019

We propose a scalable electrochemical approach to exfoliate FGi into bilayer FG nanosheets for the first time using a designed Li-ion battery.
Facile synthesis of novel elastomers with tunable dynamics for toughness, self-healing and adhesion
Authors: Chen Liang , Sun Tao Lin , Cui Kunpeng , King Daniel R. , Kurokawa Takayuki , Saruwatari Yoshiyuki , Gong Jian Ping
Published: June 2019

We propose a universal strategy to design novel advanced elastomers with excellent properties through dynamic linear rheology.
A highly flexible tactile sensor with an interlocked truncated sawtooth structure based on stretchable graphene/silver/silicone rubber composites
Authors: Wang Yancheng , Zhu Lingfeng , Mei Deqing , Zhu Wandong
Published: June 2019

A highly flexible and sensitive tactile sensor with an interlocked truncated sawtooth structure and stretchable conductive composites is demonstrated.
Establishment of a non-small-cell lung cancer-liver metastasis patient-derived tumor xenograft model for the evaluation of patient-tailored chemotherapy
Authors: Yang Xue , Meng Gaopei
Published: June 2019

In order to optimize patient-tailored chemotherapy, a non-small-cell lung cancer (NSCLC)-liver metastasis patient-derived tumor xenograft (PDTX) model is developed. Computed tomography (CT)-guided NSCLC percutaneous biopsy was subcutaneously inoculated into the flank of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice (PDTX F1) and allowed to reach 500 mm3 volume. Then, the tumors were re-transplanted into Balb/c nude mice and liver metastasis was confirmed (PDTX F2), which were further assigned into doxorubicin (DOX), docetaxel (DTX), and non-treatment control group. H&E staining and Keratin 20 (CK20) staining were applied to determine the consistency of PDTX models and primary tumors. Tumor growth curve, body weight, and the expression of p65 nuclear factor (NF)-κB and the secretion of interferon (IFN)-γ were investigated. The successive transplant procedure can induce the NSCLC-liver metastasis PDTX model, and morphological and structural characteristics of PDTX models (F2) were in accordance with primary tumors. DOX and DTX could delay tumor growth, activate the NF-κB pathway, and promote IFN-γ secretion in the PDTX models. The NSCLC-liver metastasis PDTX model is established and provides a powerful mean to assess chemotherapeutic efficacy.
MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway
Authors: Huang Zhengping , Xing Shan , Liu Meng , Deng Weiming , Wang Yunqing , Huang Zhixiang , Huang Yukai , Huang Xuechan , Wu Chiwei , Guo Xin , Pan Xia , Jiang Jiawei , Feng Fan , Li Tianwang
Published: June 2019

Behavior alterations in fibroblast-like synoviocytes (FLS) contribute to a pivotal role in pathogenesis of rheumatoid arthritis (RA). MiRNAs are closely involved in a variety of pathologic conditions. In the present study, we aimed to screen for the aberrant expression of miRNAs in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to further identify the altered expression of miR-26a-5p in RA-FLS and to investigate the role of miR-26a-5p in RA. The altered expression of miR-26a-5p in RA-FLS was screened by microarray analysis and confirmed by quantitative real time PCR. The effect of miR-26a-5p on proliferation, cell cycle, apoptosis, and invasion in RA-FLS were studied. The verification of miR-26a-5p target mRNA and downstream signaling pathway was elucidated by bioinformatics analysis, dual luciferase reporter assay, and western blot. Expression of miR-26a-5p was higher in RA-FLS than in fibroblast-like synoviocytes from osteoarthritis patients and trauma patients. Overexpression of miR-26a-5p RA-FLS promoted cells proliferation, G1/S transition, cells invasion, and resisted apoptosis in RA-FLS, whereas it led to contrary effects when inhibiting the expression of miR-26a-5p. The 3′UTR of tensin homolog (PTEN) was directly targetted by miR-26a-5p and activation of phosphoinositide 3-kinase (PI3K)/AKT pathway was observed when overexpression of miR-26a-5p. Our study suggested that miR-26a-5p has a complementary role in cells proliferation, invasion, and apoptosis of RA-FLS, which may be attributed to its activation effect on PI3K/AKT signaling pathway via targetting PTEN. MiR-26a-5p is likely to be a clinically helpful target for novel therapeutic strategies in RA.
High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways
Authors: Shan Lizhen , Yang Di , Zhu Danjie , Feng Fabo , Li Xiaolin
Published: June 2019

Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. A high glucose niche-mediated disc cell apoptosis is an implicate causative factor for the spine degenerative diseases related with DM. However, the effects of a high glucose niche on disc annulus fibrosus (AF) cell apoptosis and the potential signaling transduction pathway is unclear. The present study is to investigate the effects of high glucose on disc AF cell apoptosis and the role of two potential signaling pathways in this process. Rat AF cells were cultured in baseline medium or medium with different concentrations (0.1 and 0.2 M) of glucose for 3 days. Flow cytometry was used to assess the degree of apoptosis. Activity of caspase 3/9 was evaluated by chemical kit. Expression of pro-apoptotic and anti-apoptotic molecules was analyzed by real-time polymerase chain reaction and Western blot. In addition, activity of the C-Jun NH2-terminal kinases (JNK) pathway and p38 mitogen-activated protein kinase (MAPK) pathway was evaluated by Western blot. Compared with the control group, high glucose culture increased cell apoptosis ratio and caspase-3/9 activity, up-regulated expression of bax, caspase-3, cleaved caspase-3 and cleaved PARP, and down-regulated expression of bcl-2 in a glucose concentration-dependent manner. Additionally, high glucose culture increased expression of the p-JNK and p-p38 MAPK in a concentration-dependent manner. Further results showed that inhibition of the JNK or p38 MAPK pathway attenuated the effects of high glucose on AF cell apoptosis. Together, high glucose promoted disc AF cell apoptosis through regulating the JNK pathway and p38 MAPK pathway in a glucose concentration-dependent manner.
Broadband FIR absorption spectra of low‐density polyethylene sheets containing six different antioxidants and estimation of their contents by chemometric analysis
Authors: Ogishima Takaaki , Kuroda Chiaki , Hirai Naoshi , Ohki Yoshimichi
Published: June 2019

Antioxidants are usually added to polymeric insulating materials to suppress oxidative degradation. However, the details of antioxidant added to a polymer are often not disclosed. On the other hand, compared to mid‐infrared absorption spectroscopy, terahertz (THz) absorption spectroscopy, and far‐infrared (FIR) absorption spectroscopy have not been performed so often. Based on the above backgrounds, six different kinds of antioxidants were added into low‐density polyethylene sheets with four different contents, and their THz and FIR absorption spectra were measured. As a result, it has become clear that each antioxidant shows its specific absorption peaks, by which the antioxidants can be identified. Furthermore, the antioxidant content can be estimated by the absorption intensity of the specific peak. A chemometric analysis can make the estimation more accurately than a simple comparison of absorption intensity.
Frequency support from photovoltaic power plants using offline maximum power point tracking and variable droop control
Authors: Jibji‐Bukar Fyali , Anaya‐Lara Olimpo
Published: June 2019

With higher penetration of converter‐connected renewable energy sources (RES) into power systems, the successful operation of the system is challenged by significant reductions in system inertia. Presently, given the dominant share of the conventional synchronous power plant, RES power plants are not demanded to provide ancillary services. However, as RES connections increase, RES power plants will play a major role in power system operation, contributing to frequency control. This study demonstrates that photovoltaic power plants (PVPPs) can provide effectively different types of frequency support based on a power reserve and an offline maximum power point tracking (MPPT) technique. An innovative method to de‐load the PVPP without significantly increasing the MPPT complexity is proposed. Results from different PVPP frequency support methods, under varying levels of photovoltaic penetration, are presented which demonstrate their capability to provide inertia support comparable to that of synchronous generators. A new variable droop control method, which releases maximum power during the inertial response and returns to fixed droop gain value after a specified time is also presented. The results from using the variable droop show that the frequency nadir and the rate‐of‐change‐of‐frequency can be significantly reduced and some power reserve still maintained after a frequency event.