bluuebunny/crossref_metadata_2025 huggingface dataset:
Objectum sexuality: A sexual orientation linked with autism and synaesthesia
Authors: Simner Julia , Hughes James E. A. , Sagiv Noam
Published: December 2019

Objectum-sexuality (OS) is a sexual orientation which has received little attention in the academic literature. Individuals who identify as OS experience emotional, romantic and/or sexual feelings towards inanimate objects (e.g. a bridge, a statue). We tested 34 OS individuals and 88 controls, and provide the first empirical evidence that OS is linked to two separate neurodevelopmental traits - autism and synaesthesia. We show that OS individuals possess significantly higher rates of diagnosed autism and significantly stronger autistic traits compared to controls, as well as a significantly higher prevalence of synaesthesia, and significant synaesthetic traits inherent in the nature of their attractions. Our results suggest that OS may encapsulate autism and synaesthesia within its phenomenology. Our data speak to debates concerning the biological underpinnings of sexuality, to models of autism and synaesthesia, and to psychological and philosophical models of romantic love.
Effective lung-targeted RNAi in mice with peptide-based delivery of nucleic acid
Authors: Kurrikoff Kaido , Freimann Krista , Veiman Kadi-Liis , Peets Elin Madli , Piirsoo Andres , Langel Ülo
Published: December 2019

We have previously developed efficient peptide-based nucleic acid delivery vectors PF14 and NF55, where we have shown that these vectors preferentially transfect lung tissue upon systemic administration with the nucleic acid. In the current work, we have explored the utilization and potential of these vectors for the lung-targeted gene therapy. Accordingly, we assessed the efficacy of these peptides in (i) two different lung disease models – acute lung inflammation and asthma in mice and (ii) using two different nucleic acid cargos – siRNA and pDNA encoding shRNA. Using RNAi against cytokine TNFα, we showed efficient anti-inflammatory effects in both disease models and observed decreased disease symptoms. Our results highlight the potential of our transfection vectors for lung gene therapy.
The Influence of Solar Spectrum and Concentration Factor on the Material Choice and the Efficiency of Multijunction Solar Cells
Authors: Micha Daniel N. , Silvares Junior Ricardo T.
Published: December 2019

In this work, we revisit the theoretical study on the conversion efficiency of series-connected multijunction solar cells. The theoretical method, based on the detailed balance model, is then applied to devices with 2 to 6 junctions under different illumination conditions. As results, (i) we show that the peaks in the efficiency distribution occur for recurrent values of bottom junction bandgap energy corresponding to atmospheric absorption in the solar spectrum, and (ii) we demonstrate that variations in the number of junctions, in the incident solar spectrum, and in the concentration factor lead to changes in the optimum bandgap energy set but that the bottom junction bandgap energy only changes among the recurrent values presented before. Additionally, we highlight that high conversion efficiencies take place for a broad distribution of bandgap energy combination, which make the choice of materials for the device more flexible. Therefore, based on the overall results, we propose more than a hundred III-V, II-VI and IV semiconductor material candidates to compose the bottom junction of highly efficient devices.
Discovery of Several New Families of Saturable Absorbers for Ultrashort Pulsed Laser Systems
Authors: Hussain Syed Asad
Published: December 2019

Saturable Absorber (SA) is a key element of any passive mode-locked laser system to provide ultrashort laser system. So far various materials have been proposed that could be used for this purpose. However, the field is still looking for new ways to make the fabrication process easier and cost-effective. Another challenge in testing mode-locked laser systems using various SA samples is the lack of knowledge in preparing these by laser physicists given this is outside their remit of expertise. In this study, we have proposed a novel method to produce these SAs from plastic materials and glycol. Our new method relies upon increase in thickness up to a value where the modulation depth is enough to give stable ultrashort pulses. Although we have shown this method for four materials; similar approach could be applied to any material. This will open the door of unlimited families of SAs that could be easily prepared and applied without any prior knowledge in material sciences.
Smartphone-based turbidity reader
Authors: Ceylan Koydemir Hatice , Rajpal Simran , Gumustekin Esin , Karinca Doruk , Liang Kyle , Göröcs Zoltan , Tseng Derek , Ozcan Aydogan
Published: December 2019

Water quality is undergoing significant deterioration due to bacteria, pollutants and other harmful particles, damaging aquatic life and lowering the quality of drinking water. It is, therefore, important to be able to rapidly and accurately measure water quality in a cost-effective manner using e.g., a turbidimeter. Turbidimeters typically use different illumination angles to measure the scattering and transmittance of light through a sample and translate these readings into a measurement based on the standard nephelometric turbidity unit (NTU). Traditional turbidimeters have high sensitivity and specificity, but they are not field-portable and require electricity to operate in field settings. Here we present a field-portable and cost effective turbidimeter that is based on a smartphone. This mobile turbidimeter contains an opto-mechanical attachment coupled to the rear camera of the smartphone, which contains two white light-emitting-diodes to illuminate the water sample, optical fibers to transmit the light collected from the sample to the camera, an external lens for image formation, and diffusers for uniform illumination of the sample. Including the smartphone, this cost-effective device weighs only ~350 g. In our mobile turbidimeter design, we combined two illumination approaches: transmittance, in which the optical fibers were placed directly below the sample cuvette at 180° with respect to the light source, and nephelometry in which the optical fibers were placed on the sides of the sample cuvette at a 90° angle with respect to the to the light source. Images of the end facets of these fiber optic cables were captured using the smart phone and processed using a custom written image processing algorithm to automatically quantify the turbidity of each sample. Using transmittance and nephelometric readings, our mobile turbidimeter achieved accurate measurements over a large dynamic range, from 0.3 NTU to 2000 NTU. The accurate performance of our smartphone-based turbidimeter was also confirmed with various water samples collected in Los Angeles (USA), bacteria spiked water samples, as well as diesel fuel contaminated water samples. Having a detection limit of ~0.3 NTU, this cost-effective smartphone-based turbidimeter can be a useful analytical tool for screening of water quality in resource limited settings.
The role of buoyancy in the fate of ultra-high-pressure eclogite
Authors: Chapman Timothy , Clarke Geoffrey L. , Daczko Nathan R.
Published: December 2019

Eclogite facies metamorphism of the lithosphere forms dense mineral assemblages at high- (1.6–2.4 GPa) to ultra-high-pressure (>2.4–12 GPa: UHP) conditions that drive slab-pull forces during its subduction to lower mantle conditions. The relative densities of mantle and lithospheric components places theoretical limits for the re-exposure, and peak conditions expected, of subducted lithosphere. Exposed eclogite terranes dominated by rock denser than the upper mantle are problematic, as are interpretations of UHP conditions in buoyant rock types. Their subduction and exposure require processes that overcame predicted buoyancy forces. Phase equilibria modelling indicates that depths of 50–60 km (P = 1.4–1.8 GPa) and 85–160 km (P = 2.6–5 GPa) present thresholds for pull force in end-member oceanic and continental lithosphere, respectively. The point of no-return for subducted silicic crustal rocks is between 160 and 260 km (P = 5.5–9 GPa), limiting the likelihood of stishovite–wadeite–K-hollandite-bearing assemblages being preserved in equilibrated assemblages. The subduction of buoyant continental crust requires its anchoring to denser mafic and ultramafic lithosphere in ratios below 1:3 for the continental crust to reach depths of UHP conditions (85–160 km), and above 2:3 for it to reach extreme depths (>160 km). The buoyant escape of continental crust following its detachment from an anchored situation could carry minor proportions of other rocks that are denser than the upper mantle. However, instances of rocks returned from well-beyond these limits require exceptional exhumation dynamics, plausibly coupled with the effects of incomplete metamorphism to retain less dense low-P phases.
In Vivo Activity of Amodiaquine against Ebola Virus Infection
Authors: DeWald Lisa Evans , Johnson Joshua C. , Gerhardt Dawn M. , Torzewski Lisa M. , Postnikova Elena , Honko Anna N. , Janosko Krisztina , Huzella Louis , Dowling William E. , Eakin Ann E. , Osborn Blaire L. , Gahagen Janet , Tang Liang , Green Carol E. , Mirsalis Jon C. , Holbrook Michael R. , Jahrling Peter B. , Dyall Julie , Hensley Lisa E.
Published: December 2019

During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral.
Quantifying free behaviour in an open field using k-motif approach
Authors: Könings Marein , Blokpoel Mark , Kapusta Katarzyna , Claassen Tom , Buitelaar Jan K. , Glennon Jeffrey C. , Bielczyk Natalia Z.
Published: December 2019

Quantification and parametrisation of movement are widely used in animal behavioural paradigms. In particular, free movement in controlled conditions (e.g., open field paradigm) is used as a “proxy for indices of baseline and drug-induced behavioural changes. However, the analysis of this is often time- and labour-intensive and existing algorithms do not always classify the behaviour correctly. Here, we propose a new approach to quantify behaviour in an unconstrained environment: searching for frequent patterns (k-motifs) in the time series representing the position of the subject over time. Validation of this method was performed using subchronic quinpirole-induced changes in open field experiment behaviours in rodents. Analysis of this data was performed using k-motifs as features to better classify subjects into experimental groups on the basis of behaviour in the open field. Our classifier using k-motifs gives as high as 94% accuracy in classifying repetitive behaviour versus controls which is a substantial improvement compared to currently available methods including using standard feature definitions (depending on the choice of feature set and classification strategy, accuracy up to 88%). Furthermore, visualisation of the movement/time patterns is highly predictive of these behaviours. By using machine learning, this can be applied to behavioural analysis across experimental paradigms.
Laminin α2, α4, and α5 Chains Positively Regulate Migration and Survival of Oligodendrocyte Precursor Cells
Authors: Suzuki Nobuharu , Hyodo Mai , Hayashi Chikako , Mabuchi Yo , Sekimoto Kaori , Onchi Chinami , Sekiguchi Kiyotoshi , Akazawa Chihiro
Published: December 2019

In the developing central nervous system (CNS), oligodendrocyte precursor cells (OPCs) migrate along blood vessels and are widely distributed in the CNS. Meanwhile, OPCs require survival factors from the extracellular microenvironment. In other tissues, laminins, heterotrimetric (αβγ) extracellular matrix proteins, promote cell migration and survival. However, the expression pattern and functions of laminins in OPC development remain poorly understood. In the present study, we first investigated the expression of laminin α chains, which bind to cell surface receptors such as integrins, in the postnatal murine brain. We found that laminin α1, α2, α4, and α5 chains were expressed around blood vessels and OPCs attached the laminin α chain-positive vessels. We then evaluated the effect of these laminins on OPCs activity using recombinant laminin E8s (LME8s) that are minimally active fragments of the laminin isoforms. OPCs attached on LM211E8, LM411E8, and LM511E8, containing laminin α2, α4, and α5 chains, respectively, through integrin β1. Further, these three LME8s promoted migration of OPCs, and OPC survival was prolonged on either LM411E8 or LM511E8 via the activation of focal adhesion kinase. Together, our findings suggest that laminins expressed surrounding blood vessels positively regulate migration and survival of OPCs through the integrin β1-FAK pathway.
Pressure-induced phase transitions and superconductivity in magnesium carbides
Authors: Kim Sooran , Kim Kyoo , Koo Jahyun , Lee Hoonkyung , Il Min Byung , Kim Duck Young
Published: December 2019

Crystal structure prediction and in silico physical property observations guide experimental synthesis in high-pressure research. Here, we used magnesium carbides as a representative example of computational high-pressure studies. We predicted various compositions of Mg–C compounds up to 150 GPa and successfully reproduced previous experimental results. Interestingly, our proposed MgC2 at high pressure >7 GPa consists of extended carbon bonds, one-dimensional graphene layers, and Mg atomic layers, which provides a good platform to study superconductivity of metal intercalated graphene nano-ribbons. We found that this new phase of MgC2 could be recovered to ambient pressure and exhibited a strong electron-phonon coupling (EPC) strength of 0.6 whose corresponding superconductivity transition temperature reached 15 K. The EPC originated from the cooperation of the out-of-plane and the in-plane phonon modes. The geometry confinement and the hybridization between the Mg s and C pz orbitals significantly affect the coupling of phonon modes and electrons. These results show the importance of the high-pressure route to the synthesis of novel functional materials, which can promote the search for new phases of carbon-based superconductors.
C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis
Authors: Faravelli Giulia , Raimondi Sara , Marchese Loredana , Partridge Frederick A. , Soria Cristina , Mangione P. Patrizia , Canetti Diana , Perni Michele , Aprile Francesco A. , Zorzoli Irene , Di Schiavi Elia , Lomas David A. , Bellotti Vittorio , Sattelle David B. , Giorgetti Sofia
Published: December 2019

The availability of a genetic model organism with which to study key molecular events underlying amyloidogenesis is crucial for elucidating the mechanism of the disease and the exploration of new therapeutic avenues. The natural human variant of β2-microglobulin (D76N β2-m) is associated with a fatal familial form of systemic amyloidosis. Hitherto, no animal model has been available for studying in vivo the pathogenicity of this protein. We have established a transgenic C. elegans line, expressing the human D76N β2-m variant. Using the INVertebrate Automated Phenotyping Platform (INVAPP) and the algorithm Paragon, we were able to detect growth and motility impairment in D76N β2-m expressing worms. We also demonstrated the specificity of the β2-m variant in determining the pathological phenotype by rescuing the wild type phenotype when β2-m expression was inhibited by RNA interference (RNAi). Using this model, we have confirmed the efficacy of doxycycline, an inhibitor of the aggregation of amyloidogenic proteins, in rescuing the phenotype. In future, this C. elegans model, in conjunction with the INVAPP/Paragon system, offers the prospect of high-throughput chemical screening in the search for new drug candidates.
Terminal-Repeat Retrotransposons in Miniature (TRIMs) in bivalves
Authors: Šatović Eva , Luchetti Andrea , Pasantes Juan J. , García-Souto Daniel , Cedilak Andrea , Mantovani Barbara , Plohl Miroslav
Published: December 2019

Terminal repeat retrotransposons in miniature (TRIMs) are small non-autonomous LTR retrotransposons consisting of two terminal direct repeats surrounding a short internal domain. The detection and characterization of these elements has been mainly limited to plants. Here we present the first finding of a TRIM element in bivalves, and among the first known in the kingdom Animalia. Class Bivalvia has high ecological and commercial importance in marine ecosystems and aquaculture, and, in recent years, an increasing number of genomic studies has addressed to these organisms. We have identified biv-TRIM in several bivalve species:Donax trunculus,Ruditapes decussatus, R. philippinarum,Venerupis corrugata, Polititapes rhomboides, Venus verrucosa, Dosinia exoleta, Glycymeris glycymeris, Cerastoderma edule, Magallana gigas, Mytilus galloprovincialis. biv-TRIM has several characteristics typical for this group of elements, exhibiting different variations. In addition to canonically structured elements, solo-TDRs and tandem repeats were detected. The presence of this element in the genome of each species is <1%. The phylogenetic analysis showed a complex clustering pattern of biv-TRIM elements, and indicates the involvement of horizontal transfer in the spreading of this element.
Multiscale Modeling of Fiber Fragmentation Process in Aligned ZnO Nanowires Enhanced Single Fiber Composites
Authors: Marashizadeh Parisa , Abshirini Mohammad , Wang Jingyu , C. Saha Mrinal , Liu Yingtao
Published: December 2019

A three-dimensional multiscale modeling framework is developed to analyze the failure procedure of radially aligned zinc oxide (ZnO) enhanced single fiber composites (SFC) under tensile loading to understand the interfacial improvement between the fiber and the matrix. The model introduces four levels in the computational domain. The nanoscale analysis calculates the size-dependent material properties of ZnO nanowires. The interaction between ZnO nanowires and the matrix is simulated using a properly designed representative volume element at the microscale. At the mesoscale, the interface between the carbon fiber and the surrounding area is modeled using the cohesive zone approach. A combination of ABAQUS Finite element software and the failure criteria modeled in UMAT user subroutine is implemented to simulate the single fiber fragmentation test (SFFT) at the macroscale. The numerical results indicate that the interfacial shear strength of SFC can be improved up to 99% after growing ZnO nanowires on the fiber. The effect of ZnO nanowires geometries on the interfacial shear strength of the enhanced SFC is also investigated. Experimental ZnO nanowires enhanced SFFTs are performed on the fabricated samples to validate the results of the developed multiscale model. A good agreement between the numerical and the experimental results was observed.
Introduction of a CMR-conditional cardiac phantom simulating cardiac anatomy and function and enabling training of interventional CMR procedures
Authors: Bietenbeck Michael , Florian Anca , Chatzantonis Grigorios , Meier Claudia , Korthals Dennis , Martens Sven , Yilmaz Ali
Published: December 2019

Interventional magnetic resonance imaging (MRI) procedures promise to open-up new vistas regarding clinically relevant diagnostic and/or therapeutic procedures in the field of cardiology. However, a number of major limitations and challenges regarding interventional cardiovascular magnetic resonance (CMR) procedures still delay their translation from pre-clinical studies to human application. A CMR-conditional cardiac phantom was constructed using MR-safe or -conditional materials only that is based on a unique modular composition allowing quick replacement of individual components. A maximal flow of 76 ml/sec in the aorta and 111 ml/sec in the pulmonary artery were measured, whereas the maximal flow velocity was 56 cm/sec and 89 cm/sec, respectively. A conventional wedge-pressure catheter was advanced over a MRI-conditional guidewire into the right ventricle and thereafter positioned in the pulmonary artery. Pulmonary artery pressure was measured, obtaining the following values for our cardiac phantom: max/min/mean = 16/10/12 mmHg. The presented CMR-conditional cardiac phantom is the first of its kind that does not only mimic cardiac mechanics with adjustable fluid pressure in a four chamber setup that is closely adapted to that of the human heart, but also enables introduction and testing of interventional tools such as guidewires and catheters.
Electrochemical micro analytical device interfaced with portable potentiostat for rapid detection of chlorpyrifos using acetylcholinesterase conjugated metal organic framework using Internet of things
Authors: Nagabooshanam Shalini , Roy Souradeep , Mathur Ashish , Mukherjee Irani , Krishnamurthy Satheesh , Bharadwaj Lalit M.
Published: December 2019

An Electrochemical micro Analytical Device (EµAD) was fabricated for sensitive detection of organophosphate pesticide chlorpyrifos in the food chain. Gold microelectrode (µE) modified with Zinc based Metal Organic Framework (MOF-Basolite Z1200) and Acetylcholinesterase (AChE) enzyme served as an excellent electro-analytical transducer for the detection of chlorpyrifos. Electrochemical techniques such as Cyclic Voltammetry (CV), Electrochemical Impedance Spectroscopy (EIS) and Differential Pulse Voltammetry (DPV) were performed for electrochemical analysis of the developed EµAD. The sensor needs only 2 µL of the analyte and it was tested within the linear range of 10 to 100 ng/L. The developed EµAD’s limit of detection (LoD) and sensitivity is 6 ng/L and 0.598 µ A/ng L−1/mm2 respectively. The applicability of the device for the detection of chlorpyrifos from the real vegetable sample was also tested within the range specified. The fabricated sensor showed good stability with a shelf-life of 20 days. The EµAD’s response time is of 50 s, including an incubation time of 20 s. The developed EµAD was also integrated with commercially available low-cost, handheld potentiostat (k-Stat) using Bluetooth and the results were comparable with a standard electrochemical workstation.
Estimation of High-Speed Liquid-Jet Velocity Using a Pyro Jet Injector
Authors: Takagaki Naohisa , Kitaguchi Toru , Iwayama Masashi , Shinoda Atsushi , Kumamaru Hiroshige , Honda Itsuro
Published: December 2019

The high-speed liquid-jet velocity achieved using an injector strongly depends on the piston motion, physical property of the liquid, and container shape of the injector. Herein, we investigate the liquid ejection mechanism and a technique for estimating the ejection velocity of a high-speed liquid jet using a pyro jet injector (PJI). We apply a two-dimensional numerical simulation with an axisymmetric approximation using the commercial software ANSYS/FLUENT. To gather the input data applied during the numerical simulation, the piston motion is captured with a high-speed CMOS camera, and the velocity of the piston is measured using motion tracking software. To reproduce the piston motion during the numerical simulation, the boundary-fitted coordinates and a moving boundary method are employed. In addition, we propose a fluid dynamic model (FDM) for estimating the high-speed liquid-jet ejection velocity based on the piston velocity. Using the FDM, we consider the liquid density variation but neglect the effects of the liquid viscosity on the liquid ejection. Our results indicate that the liquid-jet ejection velocity estimated by the FDM corresponds to that predicted by ANSYS/FLUENT for several different ignition-powder weights. This clearly shows that a high-speed liquid-jet ejection velocity can be estimated using the presented FDM when considering the variation in liquid density but neglecting the liquid viscosity. In addition, some characteristics of the presented PJI are observed, namely, (1) a very rapid piston displacement within 0.1 ms after a powder explosion, (2) piston vibration only when a large amount of powder is used, and (3) a pulse jet flow with a temporal pulse width of 0.1 ms.
Nanostructured silver dendrites for photon-induced Cysteine dimerization
Authors: Chang Chia‐Yu , Chen Yu‐Mei , Huang Yu‐Bin , Lai Chin-Hung , Jeng U-Ser , Lai Ying-Huang
Published: December 2019

Under a controlled adsorption environment, L-cysteine molecules can be chemically adsorbed to the dendritic silver (Ag-D) surface by electrochemical methods with different functional groups. It is verified by surface-enhanced Raman spectroscopy that under alkaline conditions (pH = 13.50), the two functional groups of thiol and acid are simultaneously adsorbed on the surface of Ag-D, while NH2 is far from the surface; under acidic conditions (pH = 1.67), adsorption behavior suggests that both NH3+ and COO− are oriented toward the Ag-D surface, and that SH is far from the surface. The structure of L-cysteine adsorption under acidic conditions can be further verified by the addition of an L-cysteine molecule through light-induced coupling reaction to form cystine. Finally, in-situ two-dimensional Raman scattering spectroscopy confirmed the feasibility and uniformity of the coupling reaction.
Diagnostic accuracy of computed tomography angiography for the exclusion of coronary artery disease in candidates for transcatheter aortic valve implantation
Authors: Strong Christopher , Ferreira António , Teles Rui Campante , Mendes Gustavo , Abecasis João , Cardoso Gonçalo , Guerreiro Sara , Freitas Pedro , Santos Ana Coutinho , Saraiva Carla , Brito João , Raposo Luís , Gonçalves Pedro de Araújo , Gabriel Henrique Mesquita , Almeida Manuel de Sousa , Mendes Miguel
Published: December 2019

Coronary CT angiography (CTA) is currently considered a reliable method to exclude obstructive coronary artery disease (CAD) before valvular heart surgery in patients with low pretest probability. However, its role in excluding obstructive CAD before transcatheter aortic valve implantation (TAVI) is less well established. Single-center retrospective study where patients with severe symptomatic aortic stenosis underwent both CTA and invasive coronary angiography (ICA) as part of TAVI planning. CTA exams were conducted on a 64-slice dual source scanner, with a median interval of 45 days to ICA (IQR 25–75 [13–82]). In both tests, obstructive CAD was defined as a ≥50% stenosis in an epicardial vessel ≥2 mm diameter. Per-patient, per-vessel and per-proximal segment analyses were conducted, excluding and including non-evaluable segments. The study included 200 patients (120 women, mean age 83 ± 6 years). The prevalence of obstructive CAD on ICA was 35.5% (n = 71). On a per-patient analysis (assuming non-evaluable segments as stenotic), CTA showed sensitivity of 100% (95% CI, 95–100%), specificity of 42% (95% CI, 33–51%), and positive and negative predictive values of 48% (95% CI, 44–51%) and 100% (95% CI, 92–100%), respectively. CTA was able to exclude obstructive CAD in 54 patients (27%), in whom ICA could have been safely withheld. Despite the high rate of inconclusive tests, pre-procedural CTA is able to safely exclude obstructive CAD in a significant proportion of patients undergoing TAVI, possibly avoiding the need for ICA in roughly one quarter of the cases.
Contribution of protein synthesis depression to poly-β-hydroxybutyrate accumulation in Synechocystis sp. PCC 6803 under nutrient-starved conditions
Authors: Hirai Kazuho , Nojo Miki , Sato Yosuke , Tsuzuki Mikio , Sato Norihiro
Published: December 2019

Poly-β-hydroxybutyrate (PHB) in cyanobacteria, which accumulates as energy and carbon sources through the action of photosynthesis, is expected to substitute for petroleum-based plastics. This study first demonstrated that PHB accumulation was induced, with the appearance of lipid droplets, in sulfur (S)-starved cells of a cyanobacterium, Synechocystis sp. PCC 6803, however, to a lower level than in nitrogen (N)- or phosphorus (P)-starved cells. Concomitantly found was repression of the accumulation of total cellular proteins in the S-starved cells to a similar level to that in N-starved cells, and a severer level than in P-starved cells. Intriguingly, PHB accumulation was induced in Synechocystis even under nutrient-replete conditions, upon repression of the accumulation of total cellular proteins through treatment of the wild type cells with a protein synthesis inhibitor, chloramphenicol, or through disruption of the argD gene for Arg synthesis. Meanwhile, the expression of the genes for PHB synthesis was hardly induced in S-starved cells, in contrast to their definite up-regulation in N- or P-starved cells. It therefore seemed that PHB accumulation in S-starved cells is achieved through severe repression of protein synthesis, but is smaller than in N- or P-starved cells, owing to little induction of the expression of PHB synthesis genes.
Simulation of Glacial Avalanche Hazards in Shyok Basin of Upper Indus
Authors: Gilany Naseem , Iqbal Javed
Published: December 2019

Glacial avalanche hazards can threaten lives and damage infrastructures in high altitude mountainous regions. In April 2012 a gigantic ice plus rock avalanche destroyed military camp at Gyari and killed 139 persons. Antecedent, the objectives of this study are to simulate and model Gyari camp glacial avalanche with reference to its extent, height, momentum, velocity and pressure and, to simulate and model the other potential glacial avalanche prone areas in Shyok basin. To simulate the Gyari camp glacial hazard and other potential glacial avalanche hazards, an empirical process based Glacier Avalanche Model; Rapid Access Mass Movement Simulation (RAMMS) is used. The RAMMS model encompasses the variables like avalanche release height and release area for the conduct of simulation. The model output of Gyari glacial avalanche hazard resulted from a max pressure of 2500 KPa, max velocity of 90 m/s, and the max flow height of 40 m, while the resulted output debris volume calculated was 4.3145 million m3. The calibrated agreement was found in extent and height of actual debris in comparison with RAMMS simulated output. The potential hazardous glacial avalanche prone areas of Shyok basin were simulated by RAMMS model after the model being calibrated to the actual incident of Gyari. The study has resulted in identifying the Siachen glacier conflict zone being more prone to avalanche hazards because of host factors in general and the anthropogenic factor in particular.
Database of adverse events associated with drugs and drug combinations
Authors: Poleksic Aleksandar , Xie Lei
Published: December 2019

Due to the aging world population and increasing trend in clinical practice to treat patients with multiple drugs, adverse events (AEs) are becoming a major challenge in drug discovery and public health. In particular, identifying AEs caused by drug combinations remains a challenging task. Clinical trials typically focus on individual drugs rather than drug combinations and animal models are unreliable. An added difficulty is the combinatorial explosion in the number of possible combinations that can be made using the increasingly large set of FDA approved chemicals. We present a statistical and computational technique for identifying AEs caused by two-drug combinations. Taking advantage of the large and increasing data deposited in FDA’s postmarketing reports, we demonstrate that the task of predicting AEs for 2-drug combinations is amenable to the Likelihood Ratio Test (LRT). Our pAERS database constructed with LRT contains almost 77 thousand associations between pairs of drugs and corresponding AEs caused solely by drug-drug interactions (DDIs). The DDIs stored in pAERS complement the existing data sets. Due to our stringent statistical test, we expect many of the associations in pAERS to be unrecorded or poorly documented in the literature.
Genome-Wide SNP discovery and genomic characterization in avocado (Persea americana Mill.)
Authors: Talavera Alicia , Soorni Aboozar , Bombarely Aureliano , Matas Antonio J. , Hormaza Jose I.
Published: December 2019

Modern crop breeding is based on the use of genetically and phenotypically diverse plant material and, consequently, a proper understanding of population structure and genetic diversity is essential for the effective development of breeding programs. An example is avocado, a woody perennial fruit crop native to Mesoamerica with an increasing popularity worldwide. Despite its commercial success, there are important gaps in the molecular tools available to support on-going avocado breeding programs. In order to fill this gap, in this study, an avocado ‘Hass’ draft assembly was developed and used as reference to study 71 avocado accessions which represent the three traditionally recognized avocado horticultural races or subspecies (Mexican, Guatemalan and West Indian). An average of 5.72 M reads per individual and a total of 7,108 single nucleotide polymorphism (SNP) markers were produced for the 71 accessions analyzed. These molecular markers were used in a study of genetic diversity and population structure. The results broadly separate the accessions studied according to their botanical race in four main groups: Mexican, Guatemalan, West Indian and an additional group of Guatemalan × Mexican hybrids. The high number of SNP markers developed in this study will be a useful genomic resource for the avocado community.
Dynamic, Simultaneous Concentration Mapping of Multiple MRI Contrast Agents with Dual Contrast - Magnetic Resonance Fingerprinting
Authors: Anderson Christian E. , Johansen Mette , Erokwu Bernadette O. , Hu He , Gu Yuning , Zhang Yifan , Kavran Michael , Vincent Jason , Drumm Mitchell L. , Griswold Mark A. , Steinmetz Nicole F. , Li Ming , Clark Heather , Darrah Rebecca J. , Yu Xin , Brady-Kalnay Susann M. , Flask Chris A.
Published: December 2019

Synchronous assessment of multiple MRI contrast agents in a single scanning session would provide a new “multi-color” imaging capability similar to fluorescence imaging but with high spatiotemporal resolution and unlimited imaging depth. This multi-agent MRI technology would enable a whole new class of basic science and clinical MRI experiments that simultaneously explore multiple physiologic/molecular events in vivo. Unfortunately, conventional MRI acquisition techniques are only capable of detecting and quantifying one paramagnetic MRI contrast agent at a time. Herein, the Dual Contrast – Magnetic Resonance Fingerprinting (DC-MRF) methodology was extended for in vivo application and evaluated by simultaneously and dynamically mapping the intra-tumoral concentration of two MRI contrast agents (Gd-BOPTA and Dy-DOTA-azide) in a mouse glioma model. Co-registered gadolinium and dysprosium concentration maps were generated with sub-millimeter spatial resolution and acquired dynamically with just over 2-minute temporal resolution. Mean tumor Gd and Dy concentration measurements from both single agent and dual agent DC-MRF studies demonstrated significant correlations with ex vivo mass spectrometry elemental analyses. This initial in vivo study demonstrates the potential for DC-MRF to provide a useful dual-agent MRI platform.
The Discovery of Twenty-Eight New Encapsulin Sequences, Including Three in Anammox Bacteria
Authors: Tracey John C. , Coronado Maricela , Giessen Tobias W. , Lau Maggie C. Y. , Silver Pamela A. , Ward Bess B.
Published: December 2019

Many prokaryotes encode protein-based encapsulin nanocompartments, including anaerobic ammonium oxidizing (anammox) bacteria. This study expands the list of known anammox encapsulin systems from freshwater species to include the marine genus Scalindua. Two novel systems, identified in “Candidatus Scalindua rubra” and “Candidatus Scalindua sp. SCAELEC01 167” possess different architectures than previously studied freshwater anammox encapsulins. Characterization of the S. rubra encapsulin confirms that it can self-assemble to form compartments when heterologously expressed in Escherichia coli. BLASTp and HMMER searches of additional genomes and metagenomes spanning a range of environments returned 26 additional novel encapsulins, including a freshwater anammox encapsulin identified in “Candidatus Brocadia caroliniensis”. Phylogenetic analysis comparing these 28 new encapsulin sequences and cargo to that of their closest known relatives shows that encapsulins cluster by cargo protein type and therefore likely evolved together. Lastly, prokaryotic encapsulins may be more common and diverse than previously thought. Through searching a small sample size of all public metagenomes and genomes, many new encapsulin systems were unearthed by this study. This suggests that many additional encapsulins likely remain to be discovered.
Comorbidity status in hospitalized elderly in Japan: Analysis from National Database of Health Insurance Claims and Specific Health Checkups
Authors: Nojiri Shuko , Itoh Hiroaki , Kasai Takatoshi , Fujibayashi Kazutoshi , Saito Tomoyuki , Hiratsuka Yoshimune , Okuzawa Atsushi , Naito Toshio , Yokoyama Kazuhito , Daida Hiroyuki
Published: December 2019

The detailed comorbidity status of hospitalized elderly patients throughout Japan has remained largely unknown; therefore, our goal was to rigorously explore this situation and its implications as of the 2015 fiscal year (from April 2015 to March 2016). This study was based on a health insurance claims database, covering all insured policy holders in Japan aged ≥60 years (male: n = 2,135,049, female: 1,969,019) as of the 2015 fiscal year. Comorbidity status was identified by applying principal factor analysis to the database. The factors identified in male patients were [1] myocardial infarction, hypertension, dyslipidemia, and diabetes mellitus; [2] congestive heart failure (CHF), cardiac arrhythmia, and renal failure; [3] Parkinson’s disease, dementia, cerebrovascular disease, and pneumonia; [4] cancer and digestive disorders; and [5] rheumatoid arthritis and hip fracture. However, in female patients, the results obtained for the quaternary and quinary factors were the opposite of those obtained in male patients. In superelderly patients, dementia, cerebrovascular disease, and pneumonia appeared as the tertiary factor, and hip fracture and osteoporosis appeared as the quaternary factor. The comorbidities in the elderly patients suggest the importance of coronary heart disease and its related metabolic disorders; in superelderly patients, fracture and osteoporosis appeared as factors, in addition to dementia and pneumonia.
Electronic structure of the PrNiBi half-Heusler system based on the σGGA + U method
Authors: Mikaeilzadeh L. , Tavana A. , Khoeini F.
Published: December 2019

In this works, we study the electronic structure and magnetic properties of the Pr-Ni-Bi half-Heusler systems based on density functional theory. We use the σ GGA + U scheme to consider the effects of on-site electron-electron interactions. Results show that in contrast to the rough estimation of the total magnetic moment of the unit cell, based on the Slater-Pauling behavior in the half-Heusler systems, this system has an antiferromagnetic ground state because of the localized Pr-f electrons. By increasing the magnitude of the effective U parameter, band-inversion occurs in the band structure of this system, which shows the possibility of topological state occurrence.
The Prognostic Value of Circulating Tumor Cells in Asian Neuroendocrine Tumors
Authors: Hsieh Jason Chia-Hsun , Chen Guan-Yu , Jhou David Da-Wei , Chou Wen-Chi , Yeh Chun-Nan , Hwang Tsann-Long , Lin Hung-Chi , Chu Hui-Chun , Wang Hung-Ming , Yen Tzu-Chen , Chen Jen-Shi , Wu Min-Hsien
Published: December 2019

Circulating tumor cells (CTC) play important roles in various cancers; however, few studies have assessed their clinical utility in neuroendocrine tumors. This study aimed to prospectively evaluate the prognostic value of CTC counts in Asian patients with neuroendocrine tumors before and during anti-cancer therapy. Patients who were diagnosed with unresectable histological neuroendocrine tumors between September 2011 and September 2017 were enrolled. CTC testing was performed before and during anti-cancer therapy using a negative selection protocol. Chromogranin A levels were also assessed. Univariate and multivariate Cox’s proportional hazard model with forward LR model was performed to investigate the impact of independent factors on overall survival and progression-free survival. Kaplan–Meier method with log-rank tests were used to determine the difference among different clinicopathological signatures and CTC cutoff. The baseline CTC detection rate was 94.3% (33/35). CTC counts were associated with cancer stages (I-III vs. IV, P = 0.015), liver metastasis (P = 0.026), and neuroendocrine tumor grading (P = 0.03). The median progression-free survival and overall survivals were 12.3 and 30.4 months, respectively. In multivariate Cox regression model, neuroendocrine tumors grading and baseline CTC counts were both independent prognostic factors for progression-free survival (PFS, P = 0.005 and 0.015, respectively) and overall survival (OS, P = 0.018 and 0.023, respectively). In Kaplan-Meier analysis, lower baseline chromogranin A levels were associated with longer PFS (P = 0.024). Baseline CTC counts are associated with the clinicopathologic features of neuroendocrine tumors and are an independent prognostic factor for this malignancy.
Force spectroscopy-based simultaneous topographical and mechanical characterization to study polymer-to-polymer interactions in coated alginate microspheres
Authors: Virumbrales-Muñoz Maria , Santos-Vizcaino Edorta , Paz Laura , Gallardo-Moreno Amparo Maria , Orive Gorka , Hernandez Rosa Maria , Doblaré Manuel , Gonzalez-Martin Maria Luisa , Fernández Luis Jose , Pedraz Jose Luis , Ochoa Ignacio
Published: December 2019

Cell-laden hydrogel microspheres have shown encouraging outcomes in the fields of drug delivery, tissue engineering or regenerative medicine. Beyond the classical single coating with polycations, many other different coating designs have been reported with the aim of improving mechanical properties and in vivo performance of the microspheres. Among the most common strategies are the inclusion of additional polycation coatings and the covalent bonding of the semi-permeable membranes with biocompatible crosslinkers such as genipin. However, it remains challenging to characterize the effects of the interactions between the polycations and the hydrogel microspheres over time in vitro. Here we use a force spectroscopy-based simultaneous topographical and mechanical characterization to study polymer-to-polymer interactions in alginate microspheres with different coating designs, maintaining the hydrogels in liquid. In addition to classical topography parameters, we explored, for the first time, the evolution of peak/valley features along the z axis via thresholding analysis and the cross-correlation between topography and stiffness profiles with resolution down to tens of nanometers. Thus, we demonstrated the importance of genipin crosslinking to avoid membrane detachment in alginate microspheres with double polycation coatings. Overall, this methodology could improve hydrogel design rationale and expedite in vitro characterization, therefore facilitating clinical translation of hydrogel-based technologies.
Seizure localization using pre ictal phase-amplitude coupling in intracranial electroencephalography
Authors: Cámpora Nuria E. , Mininni Camilo J. , Kochen Silvia , Lew Sergio E.
Published: December 2019

Understanding changes in brain rhythms provides useful information to predict the onset of a seizure and to localize its onset zone in epileptic patients. Brain rhythms dynamics in general, and phase-amplitude coupling in particular, are known to be drastically altered during epileptic seizures. However, the neural processes that take place before a seizure are not well understood. We analysed the phase-amplitude coupling dynamics of stereoelectroencephalography recordings (30 seizures, 5 patients) before and after seizure onset. Electrodes near the seizure onset zone showed higher phase-amplitude coupling. Immediately before the beginning of the seizure, phase-amplitude coupling dropped to values similar to the observed in electrodes far from the seizure onset zone. Thus, our results bring accurate information to detect epileptic events during pre-ictal periods and to delimit the zone of seizure onset in patients undergoing epilepsy surgery.
Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector
Authors: Giel-Moloney M. , Esteban M. , Oakes B. H. , Vaine M. , Asbach B. , Wagner R. , Mize G. J. , Spies A. G. , McElrath J. , Perreau M. , Roger T. , Ives A. , Calandra T. , Weiss D. , Perdiguero B. , Kibler K. V. , Jacobs B. , Ding S. , Tomaras G. D. , Montefiori D. C. , Ferrari G. , Yates N. L. , Roederer M. , Kao S. F. , Foulds K. E. , Mayer B. T. , Bennett C. , Gottardo R. , Parrington M. , Tartaglia J. , Phogat S. , Pantaleo G. , Kleanthous H. , Pugachev K. V.
Published: December 2019

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.