bluuebunny/crossref_metadata_2025 huggingface dataset:
Coulomb-driven single defect engineering for scalable qubits and spin sensors in diamond
Authors: Lühmann Tobias , John Roger , Wunderlich Ralf , Meijer Jan , Pezzagna Sébastien
Published: October 2019

Qubits based on colour centres in diamond became a prominent system for solid-state quantum information processing and sensing. But the deterministic creation of qubits and the control of their environment are still critical issues, preventing the development of a room-temperature quantum computer. We report on the high creation yield of NV centres of 75% (a tenfold enhancement) by charge-assisted defect engineering, together with an improvement of their spin coherence. The method strongly favours the formation and negative charge state of the NV centres with respect to intrinsic diamond, while it hinders the formation of competing and perturbing defects such as di-vacancies or NVH complexes. We evidence spectrally the charge state tuning of the implantation-induced vacancies from V0 to V−, key element of this Coulomb-driven engineering. The generality of the method is demonstrated using several donors (phosphorous, oxygen and sulphur) and applying it to other centres (SnV and MgV) in diamond.
Dynamic modulation of the lipid translocation groove generates a conductive ion channel in Ca2+-bound nhTMEM16
Authors: Khelashvili George , Falzone Maria E. , Cheng Xiaolu , Lee Byoung-Cheol , Accardi Alessio , Weinstein Harel
Published: October 2019

Both lipid and ion translocation by Ca2+-regulated TMEM16 transmembrane proteins utilizes a membrane-exposed hydrophilic groove. Several conformations of the groove are observed in TMEM16 protein structures, but how these conformations form, and what functions they support, remains unknown. From analyses of atomistic molecular dynamics simulations of Ca2+-bound nhTMEM16 we find that the mechanism of a conformational transition of the groove from membrane-exposed to occluded from the membrane involves the repositioning of transmembrane helix 4 (TM4) following its disengagement from a TM3/TM4 interaction interface. Residue L302 is a key element in the hydrophobic TM3/TM4 interaction patch that braces the open-groove conformation, which should be changed by an L302A mutation. The structure of the L302A mutant determined by cryogenic electron microscopy (cryo-EM) reveals a partially closed groove that could translocate ions, but not lipids. This is corroborated with functional assays showing severely impaired lipid scrambling, but robust channel activity by L302A.
Synthetic asters as elastic and radial skeletons
Authors: Xie Qingqiao , Chen Xixi , Wu Tianli , Wang Tiankuo , Cao Yi , Granick Steve , Li Yuchao , Jiang Lingxiang
Published: October 2019

The radial geometry with rays radiated from a common core occurs ubiquitously in nature for its symmetry and functions. Herein, we report a class of synthetic asters with well-defined core-ray geometry that can function as elastic and radial skeletons to harbor nano- and microparticles. We fabricate the asters in a single, facile, and high-yield step that can be readily scaled up; specifically, amphiphilic gemini molecules self-assemble in water into asters with an amorphous core and divergently growing, twisted crystalline ribbons. The asters can spontaneously position microparticles in the cores, along the radial ribbons, or by the outer rims depending on particle sizes and surface chemistry. Their mechanical properties are determined on single- and multiple-aster levels. We further maneuver the synthetic asters as building blocks to form higher-order structures in virtue of aster-aster adhesion induced by ribbon intertwining. We envision the astral structures to act as rudimentary spatial organizers in nanoscience for coordinated multicomponent systems, possibly leading to emergent, synergistic functions.
In situ nuclear-glass corrosion under geological repository conditions
Authors: Debure Mathieu , Linard Yannick , Martin Christelle , Claret Francis
Published: October 2019

Silicate glasses are durable materials but laboratory experiments reveal that elements that derive from their environment may induce high corrosion rates and reduce their capacity to confine high-level radioactive waste. This study investigates nuclear-glass corrosion in geological media using an in situ diffusion experiment and multi-component diffusion modelling. The model highlights that the pH imposed by the Callovo–Oxfordian (COx) claystone host rock supports secondary-phase precipitation and increases glass corrosion compared with pure water. Elements from the COx rock (mainly Mg and Fe) form secondary phases with Si provided by the glass, which delay the establishment of a passivating interface. The presence of elements (Mg and Fe) that sustain glass alteration does not prevent a significant decrease in the glass-alteration rate, mainly due to the limited species transport that drives system reactivity. These improvements in the understanding of glass corrosion in its environment provide further insights for predictive modelling over larger timescales and space.
ColPortal, an integrative multiomic platform for analysing epigenetic interactions in colorectal cancer
Authors: Esteban-Gil Angel , Pérez-Sanz Fernando , García-Solano José , Alburquerque-González Begoña , Parreño-González María Antonia , Legaz-García María del Carmen , Fernández-Breis Jesualdo Tomás , Rodriguez-Braun Edith , Pimentel Paola , Tuomisto Anne , Mäkinen Markus , Slaby Ondrej , Conesa-Zamora Pablo
Published: October 2019

Colorectal cancer (CRC) is the third leading cause of cancer mortality worldwide. Different pathological pathways and molecular drivers have been described and some of the associated markers are used to select effective anti-neoplastic therapy. More recent evidence points to a causal role of microbiota and altered microRNA expression in CRC carcinogenesis, but their relationship with pathological drivers or molecular phenotypes is not clearly established. Joint analysis of clinical and omics data can help clarify such relations. We present ColPortal, a platform that integrates transcriptomic, microtranscriptomic, methylomic and microbiota data of patients with colorectal cancer. ColPortal also includes detailed information of histological features and digital histological slides from the study cases, since histology is a morphological manifestation of a complex molecular change. The current cohort consists of Caucasian patients from Europe. For each patient, demographic information, location, histology, tumor staging, tissue prognostic factors, molecular biomarker status and clinical outcomes are integrated with omics data. ColPortal allows one to perform multiomics analyses for groups of patients selected by their clinical data.
STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse
Authors: Gomez-Cabrero David , Tarazona Sonia , Ferreirós-Vidal Isabel , Ramirez Ricardo N. , Company Carlos , Schmidt Andreas , Reijmers Theo , Paul Veronica von Saint , Marabita Francesco , Rodríguez-Ubreva Javier , Garcia-Gomez Antonio , Carroll Thomas , Cooper Lee , Liang Ziwei , Dharmalingam Gopuraja , van der Kloet Frans , Harms Amy C. , Balzano-Nogueira Leandro , Lagani Vincenzo , Tsamardinos Ioannis , Lappe Michael , Maier Dieter , Westerhuis Johan A. , Hankemeier Thomas , Imhof Axel , Ballestar Esteban , Mortazavi Ali , Merkenschlager Matthias , Tegner Jesper , Conesa Ana
Published: October 2019

Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation. Hence, we lack formal analysis methods and comprehensive multi-omics datasets that can be leveraged to develop true multi-layered models for dynamic cellular systems. Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.
The Personal Genome Project-UK, an open access resource of human multi-omics data
Authors: Chervova Olga , Conde Lucia , Guerra-Assunção José Afonso , Moghul Ismail , Webster Amy P. , Berner Alison , Larose Cadieux Elizabeth , Tian Yuan , Voloshin Vitaly , Jesus Tiago F. , Hamoudi Rifat , Herrero Javier , Beck Stephan
Published: October 2019

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few resources that recruits its participants under open consent and makes the resulting multi-omics data freely and openly available. As part of this resource, we describe the PGP-UK multi-omics reference panel consisting of ten genomic, methylomic and transcriptomic data. Specifically, we outline the data processing, quality control and validation procedures which were implemented to ensure data integrity and exclude sample mix-ups. In addition, we provide a REST API to facilitate the download of the entire PGP-UK dataset. The data are also available from two cloud-based environments, providing platforms for free integrated analysis. In conclusion, the genotype-validated PGP-UK multi-omics human reference panel described here provides a valuable new open access resource for integrated analyses in support of personal and medical genomics.
High-speed and Large-scale Privacy Amplification Scheme for Quantum Key Distribution
Authors: Tang Bang-Ying , Liu Bo , Zhai Yong-Ping , Wu Chun-Qing , Yu Wan-Rong
Published: October 2019

State-of-art quantum key distribution (QKD) systems are performed with several GHz pulse rates, meanwhile privacy amplification (PA) with large scale inputs has to be performed to generate the final secure keys with quantified security. In this paper, we propose a fast Fourier transform (FFT) enhanced high-speed and large-scale (HiLS) PA scheme on commercial CPU platform without increasing dedicated computational devices. The long input weak secure key is divided into many blocks and the random seed for constructing Toeplitz matrix is shuffled to multiple sub-sequences respectively, then PA procedures are parallel implemented for all sub-key blocks with correlated sub-sequences, afterwards, the outcomes are merged as the final secure key. When the input scale is 128 Mb, our proposed HiLS PA scheme reaches 71.16 Mbps, 54.08 Mbps and 39.15 Mbps with the compression ratio equals to 0.125, 0.25 and 0.375 respectively, resulting achievable secure key generation rates close to the asymptotic limit. HiLS PA scheme can be applied to 10 GHz QKD systems with even larger input scales and the evaluated throughput is around 32.49 Mbps with the compression ratio equals to 0.125 and the input scale of 1 Gb, which is ten times larger than the previous works for QKD systems. Furthermore, with the limited computational resources, the achieved throughput of HiLS PA scheme is 0.44 Mbps with the compression ratio equals to 0.125, when the input scale equals up to 128 Gb. In theory, the PA of the randomness extraction in quantum random number generation (QRNG) is same as the PA procedure in QKD, and our work can also be efficiently performed in high-speed QRNG.
A Clearing Technique to Enhance Endogenous Fluorophores in Skin and Soft Tissue
Authors: Foster Deshka S. , Nguyen Alan T. , Chinta Malini , Salhotra Ankit , Jones R. Ellen , Mascharak Shamik , Titan Ashley L. , Ransom R. Chase , da Silva Oscar L. , Foley Eliza , Briger Emma , Longaker Michael T.
Published: October 2019

Fluorescent proteins are used extensively in transgenic animal models to label and study specific cell and tissue types. Expression of these proteins can be imaged and analyzed using fluorescent and confocal microscopy. Conventional confocal microscopes cannot penetrate through tissue more than 4–6 μm thick. Tissue clearing procedures overcome this challenge by rendering thick specimens into translucent tissue. However, most tissue clearing techniques do not satisfactorily preserve expression of endogenous fluorophores. Using simple adjustments to the BABB (Benzoic Acid Benzyl Benzoate) clearing methodology, preservation of fluorophore expression can be maintained. Modified BABB tissue clearing is a reliable technique to clear skin and soft tissue specimens for the study of dermal biology, wound healing and fibrotic pathologies.
Experimental characterisation of the bound acoustic surface modes supported by honeycomb and hexagonal hole arrays
Authors: Starkey Timothy A. , Kyrimi Vicky , Ward Gareth P. , Sambles J. Roy , Hibbins Alastair P.
Published: October 2019

The Dirac point and associated linear dispersion exhibited in the band structure of bound (non-radiative) acoustic surface modes supported on a honeycomb array of holes is explored. An aluminium plate with a honeycomb lattice of periodic sub-wavelength perforations is characterised by local pressure field measurements above the sample surface to obtain the full band-structure of bound modes. The local pressure fields of the bound modes at the K and M symmetry points are imaged, and the losses at frequencies near the Dirac frequency are shown to increase monotonically as the mode travels through the K point at the Dirac frequency on the honeycomb lattice. Results are contrasted with those from a simple hexagonal array of similar holes, and both experimentally obtained dispersion relations are shown to agree well with the predictions of a numerical model.
MC-SleepNet: Large-scale Sleep Stage Scoring in Mice by Deep Neural Networks
Authors: Yamabe Masato , Horie Kazumasa , Shiokawa Hiroaki , Funato Hiromasa , Yanagisawa Masashi , Kitagawa Hiroyuki
Published: October 2019

Automated sleep stage scoring for mice is in high demand for sleep research, since manual scoring requires considerable human expertise and efforts. The existing automated scoring methods do not provide the scoring accuracy required for practical use. In addition, the performance of such methods has generally been evaluated using rather small-scale datasets, and their robustness against individual differences and noise has not been adequately verified. This research proposes a novel automated scoring method named “MC-SleepNet”, which combines two types of deep neural networks. Then, we evaluate its performance using a large-scale dataset that contains 4,200 biological signal records of mice. The experimental results show that MC-SleepNet can automatically score sleep stages with an accuracy of 96.6% and kappa statistic of 0.94. In addition, we confirm that the scoring accuracy does not significantly decrease even if the target biological signals are noisy. These results suggest that MC-SleepNet is very robust against individual differences and noise. To the best of our knowledge, evaluations using such a large-scale dataset (containing 4,200 records) and high scoring accuracy (96.6%) have not been reported in previous related studies.
Author Correction: Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized controlled trial
Authors: Bajerska Joanna , Chmurzynska Agata , Muzsik Agata , Krzyżanowska Patrycja , Mądry Edyta , Malinowska Anna M. , Walkowiak Jarosław
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
C. elegans protein interaction network analysis probes RNAi validated pro-longevity effect of nhr-6, a human homolog of tumor suppressor Nr4a1
Authors: Akhoon Bashir A. , Gupta Shishir K. , Tiwari Sudeep , Rathor Laxmi , Pant Aakanksha , Singh Nivedita , Gupta Shailendra K. , Dandekar Thomas , Pandey Rakesh
Published: October 2019

Protein-protein interaction (PPI) studies are gaining momentum these days due to the plethora of various high-throughput experimental methods available for detecting PPIs. Proteins create complexes and networks by functioning in harmony with other proteins and here in silico network biology hold the promise to reveal new functionality of genes as it is very difficult and laborious to carry out experimental high-throughput genetic screens in living organisms. We demonstrate this approach by computationally screening C. elegans conserved homologs of already reported human tumor suppressor and aging associated genes. We select by this nhr-6, vab-3 and gst-23 as predicted longevity genes for RNAi screen. The RNAi results demonstrated the pro-longevity effect of these genes. Nuclear hormone receptor nhr-6 RNAi inhibition resulted in a C. elegans phenotype of 23.46% lifespan reduction. Moreover, we show that nhr-6 regulates oxidative stress resistance in worms and does not affect the feeding behavior of worms. These findings imply the potential of nhr-6 as a common therapeutic target for aging and cancer ailments, stressing the power of in silico PPI network analysis coupled with RNAi screens to describe gene function.
Adipose-derived mesenchymal stem cells regenerate radioiodine-induced salivary gland damage in a murine model
Authors: Kim Ji Won , Kim Jeong Mi , Choi Mi Eun , Kim Seok-Ki , Kim Young-Mo , Choi Jeong-Seok
Published: October 2019

After radioiodine (RI) therapy, patients with thyroid cancer frequently suffer from painful salivary gland (SG) swelling, xerostomia, taste alterations, and oral infections. This study was aimed to determine whether adipose-derived mesenchymal stem cells (AdMSCs) might restore RI-induced SG dysfunction in a murine model. Forty -five mice were divided into three groups; a PBS sham group, a RI+ PBS sham group (0.01 mCi/g mouse, orally), and an RI+AdMSCs (1 × 105 cells/150 uL, intraglandular injection on experimental day 28) treated group. At 16 weeks after RI treatment, body weights, SG weight, salivary flow rates (SFRs), and salivary lag times were measured. Morphologic and histologic examinations and immunohistochemistry (IHC) were performed and the activities of amylase and EGF in saliva were also measured. Changes in salivary 99mTc pertechnetate excretion were followed by SPECT and TUNEL assays were performed. The body and SG weights were similar in the AdMSCs and sham groups. Hematoxylin and eosin staining revealed the AdMSCs group had more mucin-containing acini than the RI group. Furthermore, AdMSCs treatment resulted in tissue remodeling and elevated expressions of epithelial (AQP5) and endothelial (CD31) markers, and increased SFRs. The activities of amylase and EGF were higher in the AdMSCs group than in the RI treated group. 99mTc pertechnetate excretions were similar in the AdMSCs and sham group. Also, TUNEL positive apoptotic cell numbers were less in the AdMSCs group than in the RI group. Local delivery of AdMSCs might regenerate SG damage induced by RI.
Identification of suitable controls for miRNA quantification in T-cells and whole blood cells in sepsis
Authors: Hirschberger Simon , Hübner Max , Strauß Gabriele , Effinger David , Bauer Michael , Weis Sebastian , Giamarellos-Bourboulis Evangelos J. , Kreth Simone
Published: October 2019

Complex immune dysregulation is a hallmark of sepsis. The occurring phases of immunosuppression and hyperinflammation require rapid detection and close monitoring. Reliable tools to monitor patient’s immune status are yet missing. Currently, microRNAs are being discussed as promising new biomarkers in sepsis. However, no suitable internal control for normalization of miRNA expression by qPCR has been validated so far, thus hampering their potential benefit. We here present the first evaluation of endogenous controls for miRNA analysis in human sepsis. Novel candidate reference miRNAs were identified via miRNA microArray. TaqMan qPCR assays were performed to evaluate these microRNAs in T-cells and whole blood cells of sepsis patients and healthy controls in two independent cohorts. In T-cells, U48 and miR-320 proved suitable as endogenous controls, while in whole blood cells, U44 and miR-942 provided best stability values for normalization of miRNA quantification. Commonly used snRNA U6 exhibited worst stability in all sample groups. The identified internal controls have been prospectively validated in independent cohorts. The critical importance of housekeeping gene selection is emphasized by exemplary quantification of imuno-miR-150 in sepsis patients. Use of appropriate internal controls could facilitate research on miRNA-based biomarker-use and might even improve treatment strategies in the future.
The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing
Authors: Valbuena Gabriel N. , Apostolidou Sophia , Roberts Rhiannon , Barnes Julie , Alderton Wendy , Harper Lauren , Jacobs Ian , Menon Usha , Keun Hector C.
Published: October 2019

Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2–5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.
Whole mitochondrial genome sequencing highlights mitochondrial impact in gastric cancer
Authors: Cavalcante Giovanna Chaves , Marinho Anderson N. R. , Anaissi Ana Karyssa , Vinasco-Sandoval Tatiana , Ribeiro-dos-Santos André , Vidal Amanda Ferreira , de Araújo Gilderlanio S. , Demachki Samia , Ribeiro-dos-Santos Ândrea
Published: October 2019

Mitochondria are organelles that perform major roles in cellular operation. Thus, alterations in mitochondrial genome (mtGenome) may lead to mitochondrial dysfunction and cellular deregulation, influencing carcinogenesis. Gastric cancer (GC) is one of the most incident and mortal types of cancer in Brazil, particularly in the Amazon region. Here, we sequenced and compared the whole mtGenome extracted from FFPE tissue samples of GC patients (tumor and internal control – IC) and cancer-free individuals (external control – EC) from this region. We found 3-fold more variants and up to 9-fold more heteroplasmic regions in tumor when compared to paired IC samples. Moreover, tumor presented more heteroplasmic variants when compared to EC, while IC and EC showed no significant difference when compared to each other. Tumor also presented substantially more variants in the following regions: MT-RNR1, MT-ND5, MT-ND4, MT-ND2, MT-DLOOP1 and MT-CO1. In addition, our haplogroup results indicate an association of Native American ancestry (particularly haplogroup C) to gastric cancer development. To the best of our knowledge, this is the first study to sequence the whole mtGenome from FFPE samples and to apply mtGenome analysis in association to GC in Brazil.
Intestinal helminth infection enhances bacteria-induced recruitment of neutrophils to the airspace
Authors: Long Shao Rong , Lanter Bernard B. , Pazos Michael A. , Mou Hongmei , Barrios Juliana , Su Chien-Wen , Wang Zhong Quan , Walker W. Allan , Hurley Bryan P. , Shi Hai Ning
Published: October 2019

Intestinal helminth infections elicit Th2-type immunity, which influences host immune responses to additional threats, such as allergens, metabolic disease, and other pathogens. Th2 immunity involves a shift of the CD4+ T-cell population from type-0 to type-2 (Th2) with increased abundance of interleukin (IL)-4 and IL-13. This study sought to investigate if existing gut-restricted intestinal helminth infections impact bacterial-induced acute airway neutrophil recruitment. C57BL/6 mice were divided into four groups: uninfected; helminth-Heligmosomoides polygyrus infected; Pseudomonas aeruginosa infected; and coinfected. Mice infected with H. polygyrus were incubated for 2 weeks, followed by P. aeruginosa intranasal inoculation. Bronchial alveolar lavage, blood, and lung samples were analyzed. Interestingly, infection with gut-restricted helminths resulted in immunological and structural changes in the lung. These changes include increased lung CD4+ T cells, increased Th2 cytokine expression, and airway goblet cell hyperplasia. Furthermore, coinfected mice exhibited significantly more airspace neutrophil infiltration at 6 hours following P. aeruginosa infection and exhibited an improved rate of survival compared with bacterial infected alone. These results suggest that chronic helminth infection of the intestines can influence and enhance acute airway neutrophil responses to P. aeruginosa infection.
Fractal properties in sensorimotor variability unveil internal adaptations of the organism before symptomatic functional decline
Authors: Torre Kjerstin , Vergotte Grégoire , Viel Éric , Perrey Stéphane , Dupeyron Arnaud
Published: October 2019

If health can be defined as adaptability, then measures of adaptability are crucial. Convergent findings across clinical areas established the notion that fractal properties in bio-behavioural variability characterize the healthy condition of the organism, and its adaptive capacities in general. However, ambiguities remain as to the significance of fractal properties: the literature mainly discriminated between healthy vs. pathological states, thereby loosing perspective on the progression in between, and overlooking the distinction between adaptability and effective adaptations of the organism. Here, we design an experimental tapping paradigm involving gradual feedback deprivation in groups of healthy subjects and one deafferented man as a pathological-limit case. We show that distinct types of fractal properties in sensorimotor behaviour characterize, on the one hand impaired functional ability, and on the other hand internal adaptations for maintaining performance despite the imposed constraints. Findings may prove promising for early detection of internal adaptations preceding symptomatic functional decline.
Studying electronic properties in GaN without electrical contacts using γ-γ vs e−-γ Perturbed Angular Correlations
Authors: Barbosa M. B. , Correia J. G. , Lorenz K. , Vianden R. , Araújo J. P.
Published: October 2019

The potential use of combined e−-γ vs γ-γ Perturbed Angular Correlations (PAC) experiments as a possible alternative to study electronic properties of materials and/or samples where Hall effect measurements are difficult to perform due to low-quality ohmic contacts is here demonstrated using Si- and Zn-doped GaN samples as a showcase example. To do so, the lattice site of implanted 181Hf/181Ta and the recombination of Ta ionized and excited electronic states were studied as a function of temperature and sample doping in GaN. By combining the γ-γ and e−-γ PAC results with Density Functional Theory simulations, it was possible to assign a single stable site with a double-donor character for Ta in GaN. A metastable charge state was also identified at particular temperatures using e−-γ PAC. A thermally activated process was observed for the electronic recombination at high temperatures with activation energies of 15(2) meV and 12(1) meV for the Si- and Zn-doped samples, respectively, and attributed to Si shallow donors present in both samples. A reduced number of available electrons was observed in the Zn-doped sample due to donor compensation by the Zn acceptors. At low temperatures, it is suggested that the recombination process occurs via Variable Range Hopping. The doping characteristics of both samples were successfully distinguished.
Correlation of axial length and myopic macular degeneration to levels of molecular factors in the aqueous
Authors: Wong Chee Wai , Yanagi Yasuo , Tsai Andrew Shih Hsiang , Shihabuddeen Waseem Ahamed , Cheung Ning , Lee Shu Yen , Jonas Jost B. , Cheung Chui Ming Gemmy
Published: October 2019

To elucidate the molecular processes associated with the development of myopic macular degeneration (MMD), we measured the intraocular concentrations of molecular factors in emmetropic and myopic eyes. This is a retrospective clinic-based case-control study that included eyes undergoing routine cataract surgery whereby aqueous humour samples were obtained. We measured the concentrations of pigment epithelium derived factor(PEDF), matrix metalloproteinase 2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-2), vascular endothelial growth factor isoform A(VEGF-A), interleukin 8(IL-8), interleukin 6(IL-6), C-reactive protein(CRP), angiopoietin 2(Ang2), and amphiregulin. 38 eyes (axial length (AL): 22.4–32.4 mm), including 12 highly myopic (HM) eyes (AL ≥ 26.5 mm) without MMD and 12 HM eyes with MMD but without neovascularization were included. Eyes with MMD were found to have significantly lower VEGF-A levels (p = 0.007) and higher MMP-2 levels (p = 0.02) than control eyes after adjusting for age and gender. MMP-2 levels correlated positively (r = 0.58, p = 0.002), while VEGF-A levels correlated negatively with longer axial length (r = −0.75, p < 0.001). Both the concentrations of VEGF-A (P = 0.25) and MMP-2 (P = 0.69) were not significantly associated with MMD after adjusting for AL. These findings suggest that the predominant mechanism underlying the development of non-neovascular MMD may be axial elongation, driven in part by MMP-2 related mechanisms.
Single-walled carbon nanotube supported Pt-Ru bimetallic superb
nanocatalyst for the hydrogen generation from the methanolysis of methylamine-borane at
mild conditions
Authors: Sogut Eda Gokirmak , Acidereli Hilal , Kuyuldar Esra , Karatas Yasar , Gulcan Mehmet , Sen Fatih
Published: October 2019

Several metal nanoparticle based catalysts have been synthesized for
catalyzing the hydrogen production process by hydrolysis of methylamine-borane
(MeAB). However, there was only one study that catalyzes the producing of hydrogenvia the methanolysis of MeAB, and it was
carried out by our research group. For this reason, in this work, a new catalyst
system entitled by single-walled carbon nanotube (SWCNT) supported bimetallic
platinum-ruthenium nanoparticles were developed and called as PtRu@SWCNT. These NPs
were characterized by several techniques (XRD, XPS, Raman, and TEM), and they were
performed for the methanolysis of MeAB with high catalytic activity. The prepared
PtRu@SWCNT NPs were also tested in the methanolysis of MeAB at different parameters
including different temperatures, catalyst and substrate concentrations, and
reusability performance. Experimental results revealed that the new PtRu@SWCNT NPs
had excellent catalytic activity and reusability for removing of hydrogen from the
methanolysis of MeAB at ambient conditions. According to the obtained data, the
turnover frequency is 136.25 mole H2/mole PtRu × min, and the
activation energy (Ea) is 17.29 kJ/mole. More than 99% of conversion was observed at
room temperature.
Paper Stacks for Uniform Rehydration of Dried Reagents in Paper Microfluidic Devices
Authors: Das Debayan , Dsouza Andrea , Kaur Navjot , Soni Shruti , Toley Bhushan J.
Published: October 2019

Spatially uniform reconstitution of dried reagents is critical to the function of paper microfluidic devices. Advancing fluid fronts in paper microfluidic devices drive (convect) and concentrate rehydrated reagents to the edges, causing steep chemical gradients and imperfect mixing. This largely unsolved problem in paper microfluidics is exacerbated by increasing device dimensions. In this article, we demonstrate that mixing of dried reagents with a rehydrating fluid in paper microfluidics may be significantly enhanced by stacking paper layers having different wicking rates. Compared to single-layer paper membranes, stacking reduced the “non-reactive area”, i.e. area in which the reconstituted reagents did not interact with the rehydrating fluid, by as much as 97% in large (8 cm × 2 cm) paper membranes. A paper stack was designed to collect ~0.9 ml liquid sample and uniformly mix it with dried reagents. Applications of this technology are demonstrated in two areas: (i) collection and dry storage of sputum samples for tuberculosis testing, and (ii) salivary glucose detection using an enzymatic assay and colorimetric readout. Maximizing the interaction of liquids with dried reagents is central to enhancing the performance of all paper microfluidic devices; this technique is therefore likely to find important applications in paper microfluidics.
Genetic characterization of a novel picornavirus in Algerian bats: co-evolution analysis of bat-related picornaviruses
Authors: Zeghbib Safia , Herczeg Róbert , Kemenesi Gábor , Zana Brigitta , Kurucz Kornélia , Urbán Péter , Madai Mónika , Földes Fanni , Papp Henrietta , Somogyi Balázs , Jakab Ferenc
Published: October 2019

Bats are reservoirs of numerous zoonotic viruses. The Picornaviridae family comprises important pathogens which may infect both humans and animals. In this study, a bat-related picornavirus was detected from Algerian Minioptreus schreibersii bats for the first time in the country. Molecular analyses revealed the new virus originates to the Mischivirus genus. In the operational use of the acquired sequence and all available data regarding bat picornaviruses, we performed a co-evolutionary analysis of mischiviruses and their hosts, to authentically reveal evolutionary patterns within this genus. Based on this analysis, we enlarged the dataset, and examined the co-evolutionary history of all bat-related picornaviruses including their hosts, to effectively compile all possible species jumping events during their evolution. Furthermore, we explored the phylogeny association with geographical location, host-genus and host-species in both data sets.
Molecular signatures of retinal ganglion cells revealed through single cell profiling
Authors: Laboissonniere Lauren A. , Goetz Jillian J. , Martin Gregory M. , Bi Ran , Lund Terry J. S. , Ellson Laura , Lynch Madison R. , Mooney Bailey , Wickham Hannah , Liu Peng , Schwartz Gregory W. , Trimarchi Jeffrey M.
Published: October 2019

Retinal ganglion cells can be classified into more than 40 distinct subtypes, whether by functional classification or transcriptomics. The examination of these subtypes in relation to their physiology, projection patterns, and circuitry would be greatly facilitated through the identification of specific molecular identifiers for the generation of transgenic mice. Advances in single cell transcriptomic profiling have enabled the identification of molecular signatures for cellular subtypes that are only rarely found. Therefore, we used single cell profiling combined with hierarchical clustering and correlate analyses to identify genes expressed in distinct populations of Parvalbumin-expressing cells and functionally classified RGCs. RGCs were manually isolated based either upon fluorescence or physiological distinction through cell-attached recordings. Microarray hybridization and RNA-Sequencing were employed for the characterization of transcriptomes and in situ hybridization was utilized to further characterize gene candidate expression. Gene candidates were identified based upon cluster correlation, as well as expression specificity within physiologically distinct classes of RGCs. Further, we identified Prph, Ctxn3, and Prkcq as potential candidates for ipRGC classification in the murine retina. The use of these genes, or one of the other newly identified subset markers, for the generation of a transgenic mouse would enable future studies of RGC-subtype specific function, wiring, and projection.
A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin
Authors: Lee Jong Bong , Radhi Masar , Cipolla Elena , Gandhi Raj D. , Sarmad Sarir , Zgair Atheer , Kim Tae Hwan , Feng Wanshan , Qin Chaolong , Adrower Cecilia , Ortori Catherine A. , Barrett David A. , Kagan Leonid , Fischer Peter M. , de Moor Cornelia H. , Gershkovich Pavel
Published: October 2019

Although adenosine and its analogues have been assessed in the past as potential drug candidates due to the important role of adenosine in physiology, only little is known about their absorption following oral administration. In this work, we have studied the oral absorption and disposition pathways of cordycepin, an adenosine analogue. In vitro biopharmaceutical properties and in vivo oral absorption and disposition of cordycepin were assessed in rats. Despite the fact that numerous studies showed efficacy following oral dosing of cordycepin, we found that intact cordycepin was not absorbed following oral administration to rats. However, 3′-deoxyinosine, a metabolite of cordycepin previously considered to be inactive, was absorbed into the systemic blood circulation. Further investigation was performed to study the conversion of 3′-deoxyinosine to cordycepin 5′-triphosphate in vitro using macrophage-like RAW264.7 cells. It demonstrated that cordycepin 5′-triphosphate, the active metabolite of cordycepin, can be formed not only from cordycepin, but also from 3′-deoxyinosine. The novel nucleoside rescue metabolic pathway proposed in this study could be responsible for therapeutic effects of adenosine and other analogues of adenosine following oral administration. These findings may have importance in understanding the physiology and pathophysiology associated with adenosine, as well as drug discovery and development utilising adenosine analogues.
18F-FIMP: a LAT1-specific PET probe for discrimination between tumor tissue and inflammation
Authors: Nozaki Satoshi , Nakatani Yuka , Mawatari Aya , Shibata Nina , Hume William E. , Hayashinaka Emi , Wada Yasuhiro , Doi Hisashi , Watanabe Yasuyoshi
Published: October 2019

Positron emission tomography (PET) imaging can assist in the early-phase diagnostic and therapeutic evaluation of tumors. Here, we report the radiosynthesis, small animal PET imaging, and biological evaluation of a L-type amino acid transporter 1 (LAT1)-specific PET probe, 18F-FIMP. This probe demonstrates increased tumor specificity, compared to existing tumor-specific PET probes (18F-FET, 11C-MET, and 18F-FDG). Evaluation of probes by in vivo PET imaging, 18F-FIMP showed intense accumulation in LAT1-positive tumor tissues, but not in inflamed lesions, whereas intense accumulation of 18F-FDG was observed in both tumor tissues and in inflamed lesions. Metabolite analysis showed that 18F-FIMP was stable in liver microsomes, and mice tissues (plasma, urine, liver, pancreas, and tumor). Investigation of the protein incorporation of 18F-FIMP showed that it was not incorporated into protein. Furthermore, the expected mean absorbed dose of 18F-FIMP in humans was comparable or slightly higher than that of 18F-FDG and indicated that 18F-FIMP may be a safe PET probe for use in humans. 18F-FIMP may provide improved specificity for tumor diagnosis, compared to 18F-FDG, 18F-FET, and 11C-MET. This probe may be suitable for PET imaging for glioblastoma and the early-phase monitoring of cancer therapy outcomes.
GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome
Authors: Seppa Kadri , Toots Maarja , Reimets Riin , Jagomäe Toomas , Koppel Tuuliki , Pallase Maia , Hasselholt Stine , Krogsbæk Mikkelsen Maiken , Randel Nyengaard Jens , Vasar Eero , Terasmaa Anton , Plaas Mario
Published: October 2019

Wolfram syndrome (WS) is a rare neurodegenerative disorder that is mainly characterized by diabetes mellitus, optic nerve atrophy, deafness, and progressive brainstem degeneration. Treatment with GLP-1 receptor agonists has shown a promising anti-diabetic effect in WS treatment in both animal models and in human patients. Since previous research has tended to focus on investigation of the WS first symptom, diabetes mellitus, the aim of the present study was to examine liraglutide effect on WS-associated neurodegeneration. We took 9-month-old Wfs1 knock-out (KO) animals that already had developed glucose intolerance and treated them with liraglutide for 6 months. Our research results indicate that 6-month liraglutide treatment reduced neuroinflammation and ameliorated endoplasmic reticulum (ER) stress in the inferior olive of the aged WS rat model. Liraglutide treatment also protected retinal ganglion cells from cell death and optic nerve axons from degeneration. According to this, the results of the present study provide novel insight that GLP-1 receptor agonist liraglutide has a neuroprotective effect in the WS rat model.
Trait-based community assembly of epiphytic diatoms in saline astatic ponds: a test of the stress-dominance hypothesis
Authors: Ács Éva , Földi Angéla , Vad Csaba Ferenc , Trábert Zsuzsa , Kiss Keve Tihamér , Duleba Mónika , Borics Gábor , Grigorszky István , Botta-Dukát Zoltán
Published: October 2019

The stress dominance hypothesis (SDH) postulates that strong environmental gradients drive trait convergence in communities over limiting similarity. Previous studies, conducted mostly with terrestrial plant communities, found controversial evidence for this prediction. We provide here the first test for SDH for epiphytic diatoms. We studied community assembly in diatom communities of astatic ponds. These water bodies serve as a good model system for testing SDH because they exhibit stress gradients of various environmental factors. Functional diversity of diatom communities was assessed based on four traits: (1) combined trait reflecting the trade-off between stress tolerance and competitive dominance, (2) cell size, (3) oxygen requirement and (4) N-uptake strategy. According to our results, salinity, pH and the width of the macrophyte belt appeared as significant predictors of the trait convergence/divergence patterns presumably acting through influencing the availability of carbon dioxide and turbidity. Lower trait diversity was found in turbid, more saline and more alkaline ponds and functional diversity was higher in transparent, less saline and less alkaline ponds. Overall, our results supported the stress dominance hypothesis. In habitats representing increased environmental stress, environmental filtering was the most important community assembly rule, while limiting similarity became dominant under more favourable conditions.
From taxonomic deflation to newly detected cryptic species: Hidden diversity in a widespread African squeaker catfish
Authors: Jirsová Dagmar , Štefka Jan , Blažek Radim , Malala John O. , Lotuliakou David E. , Mahmoud Zuheir N. , Jirků Miloslav
Published: October 2019

Cryptic genetic diversity and erroneous morphological species determination represent frequent problems in biodiversity research. Here, examination of 138 specimens of Synodontis (Mochokidae, Siluriformes) from the Nile River and Lake Turkana revealed the presence of both S. schall-like and S. frontosus-like morphotypes, with a phenotypic gradient between them. We concluded phylogenetic and population genetic analyses based on two mitochondrial and one nuclear marker including 131 coxI (565 bp), 96 cytb (973 bp) and 19 RAG2 (896 bp) sequences from the Nile-Turkana population, plus additional GenBank data of Synodontis spp. Whilst nuclear data were inconclusive, mitochondrial sequences suggested that both morphotypes and intermediate forms are conspecific. The results imply probable synonymy of S. frontosus with S. schall. Conversely, a strong biogeographical signal was revealed among widely distributed and supposedly conspecific S. schall-like catfish of the Nilo-Sudanian ichthyological province. Synodontis schall sensu stricto (=Eastern clade), as defined by type locality in the Nile, is apparently restricted to the eastern part of the Nilo-Sudanian ichthyological province (e.g. Nile, Turkana, Chad). Synodontis schall Western clade (Senegambia, Niger, Chad) most probably represents a cryptic taxon, unrecognized thus far due to the absence of distinctive morphological differences.
Asian and African lineage Zika viruses show differential replication and innate immune responses in human dendritic cells and macrophages
Authors: Österlund Pamela , Jiang Miao , Westenius Veera , Kuivanen Suvi , Järvi Riia , Kakkola Laura , Lundberg Rickard , Melén Krister , Korva Miša , Avšič – Županc Tatjana , Vapalahti Olli , Julkunen Ilkka
Published: October 2019

Zika virus (ZIKV) infections in humans are considered to be mild or subclinical. However, during the recent epidemics in the Pacific Islands and the Americas, the infection was associated with Quillain-Barré syndrome and congenital infections with fetal brain abnormalities, including microcephaly. Thus, more detailed understanding of ZIKV-host cell interactions and regulation of innate immune responses by strains of differential evolutionary origin is required. Here, we characterized the infection and immune responses triggered by two epidemic Asian/American lineage viruses, including an isolate from fetal brains, and a historical, low passage 1947 African lineage virus in human monocyte-derived dendritic cells (DCs) and macrophages. The epidemic Asian/American ZIKV replicated well and induced relatively good antiviral responses in human DCs whereas the African strain replicated less efficiently and induced weaker immune responses. In macrophages both the African and Asian strains showed limited replication and relatively weak cytokine gene expression. Interestingly, in macrophages we observed host protein degradation, especially IRF3 and STAT2, at early phases of infection with both lineage viruses, suggesting an early proteasomal activation in phagocytic cells. Our data indicates that ZIKV evolution has led to significant phenotypic differences in the replication characteristics leading to differential regulation of host innate immune responses.
A Dual-modality Smartphone Microendoscope for Quantifying the Physiological and Morphological Properties of Epithelial Tissues
Authors: Hong Xiangqian , Lu Tongtong , Fruzyna Liam , Yu Bing
Published: October 2019

We report a nonconcurrent dual-modality fiber-optic microendoscope (named SmartME) that integrates quantitative diffuse reflectance spectroscopy (DRS) and high-resolution fluorescence imaging (FLI) into a smartphone platform. The FLI module has a spatial resolution of ~3.5 µm, which allows the determination of the nuclear-cytoplasmic ratio (N/C) of epithelial tissues. The DRS has a spectral resolution of ~2 nm and can measure the total hemoglobin concentration (THC) and scattering properties of epithelial tissues with mean errors of 4.7% and 6.9%, respectively, which are comparable to the errors achieved with a benchtop spectrometer. Our preliminary in vivo studies from a single healthy human subject demonstrate that the SmartME can noninvasively quantify the tissue parameters of normal human oral mucosa tissues, including labial mucosa tissue, gingival tissue, and tongue dorsum tissue. The THCs of the three oral mucosa tissues are significantly different from each other (p ≤ 0.003). The reduced scattering coefficients of the gingival and labial tissues are significantly different from those of the tongue dorsum tissue (p < 0.001) but are not significantly different from each other. The N/Cs for all three tissue types are similar. The SmartME has great potential to be used as a portable, cost-effective, and globally connected tool to quantify the THC and scattering properties of tissues in vivo.