bluuebunny/crossref_metadata_2025 huggingface dataset:
Models of Single‐Well Push‐Pull Test With Mixing Effect in the Wellbore
Authors: Wang Quanrong , Shi Wenguang , Zhan Hongbin , Gu Haochen , Chen Kewei
Published: November 2018

The mechanism of solute transport around the wellbore was found to play an important role in the single‐well push‐pull (SWPP) test, but it was grossly overlooked in previous studies. For instance, the mixing effect of injected tracer with water in the wellbore was ignored in analyzing both injection and extraction phases of SWPP. In this study, new models were developed by including such a mixing effect in the wellbore. Two types of boundary conditions at the wellbore were considered: the resident concentration continuity and the flux concentration continuity. To test the assumptions used in the mathematical model, the stochastic modeling, the numerical simulation, and the laboratory‐controlled experiment were executed. Results showed that the SWPP test was sensitive to the mixing effect in both injection and extraction phases. A larger wellbore volume could result in a smaller concentration at the late stage of the extraction phase. Flux concentration continuity was more reasonable in describing solute transport at the wellbore‐aquifer interface than resident concentration continuity, and the difference between them decreased with decreasing radial dispersivity. The MODFLOW/MT3DMS package contained an invalid assumption on the mixing effect for the SWPP test. Stochastic modeling demonstrated that the homogeneous assumption was a good approximation for the reality when the variance of natural logarithm of the autocorrelated hydraulic conductivity field was less than 0.25 (
). The laboratory‐controlled experiment showed that the radial advection‐dispersion equation model of this study worked well for the well‐sorted sand aquifer.
Synergies for Soil Moisture Retrieval Across Scales From Airborne Polarimetric SAR, Cosmic Ray Neutron Roving, and an In Situ Sensor Network
Authors: Fersch B. , Jagdhuber T. , Schrön M. , Völksch I. , Jäger M.
Published: November 2018

The consistent determination of soil moisture across scales is a persistent challenge in hydrology. Several measurement methods exist at distinct scales, each of which is challenging in terms of data processing, removal of vegetation and surface effects, and calibration. While in situ measurements are trusted at the point scale, distributed sensor networks extend the areal representation to the field scale. At this scale, also cosmic ray neutron sensing (CRNS) has become an established method to derive volume‐averaged, root zone soil moisture over several tens of hectometers, but the signal is often biased due to biomass water. With airborne synthetic aperture radar (SAR) remote sensing, it is possible to cover regional scales, but the method is limited to the topmost soil layer and sensitive to vegetation parameters. In this study, the performance and synergistic potential of these complementary methods is investigated for the determination of soil moisture within a 55 km2 Alpine foothill river catchment in Southern Germany. The individual approaches are evaluated and brought into synergy for a 9 ha grassland and several other locations within the catchment. The results indicate that the sensor network data provide valuable information to calibrate the mobile CRNS rover, and to optimize the vegetation removal within the polarimetric SAR retrieval algorithm. The root‐mean‐square errors for polarimetric SAR soil permittivity are 9.32 with the standard agriculture approach, 4.29 with the semi‐stand‐alone approach, and 0.31 with the sensor network optimized approach. Furthermore, the CRNS soil moisture product was improved by considering the remotely sensed cross‐polarized backscatter product as a biomass water proxy.
A High‐Resolution Global Map of Soil Hydraulic Properties Produced by a Hierarchical Parameterization of a Physically Based Water Retention Model
Authors: Zhang Yonggen , Schaap Marcel G. , Zha Yuanyuan
Published: November 2018

A correct quantification of mass and energy exchange processes among Earth's land surface, groundwater, and atmosphere requires an accurate parameterization of soil hydraulic properties. Pedotransfer functions (PTFs) are useful in this regard because they estimate these otherwise difficult to obtain characteristics using texture and other ubiquitous soil data. Most PTFs estimate parameters of empirical hydraulic functions with modest accuracy. In a continued pursuit of improving global‐scale PTF estimates, we evaluated whether improvements can be obtained when estimating parameters of hydraulic functions that make physically based assumptions. To this end, we developed a PTF that estimates the parameters of the Kosugi retention and hydraulic conductivity functions (Kosugi, 1994, https://doi.org/10.1029/93WR02931, 1996, https://doi.org/10.1029/96WR01776), which explicitly assume a lognormal pore size distribution and apply the Young‐Laplace equation to derive a corresponding pressure head distribution. Using a previously developed combination of machine learning and bootstrapping, the developed five hierarchical PTFs allow for estimates under practical data‐poor to data‐rich conditions. Using an independent global data set containing nearly 50,000 samples (118,000 retention points), we demonstrated that the new Kosugi‐based PTFs outperformed two van Genuchten‐based PTFs calibrated on the same data. The new PTFs were applied to a 1 × 1 km2 global map of texture and bulk density, thus producing maps of the parameters, field capacity, wilting point, plant available water, and associated uncertainties. Soil hydraulic parameters exhibit a much larger variability in the Northern Hemisphere than in the Southern Hemisphere, which is likely due to the geographical distribution of climate zones that affect weathering and sedimentation processes.
Light-controlled switching of the spin state of iron(III)
Authors: Shankar Sreejith , Peters Morten , Steinborn Kim , Krahwinkel Bahne , Sönnichsen Frank D. , Grote Dirk , Sander Wolfram , Lohmiller Thomas , Rüdiger Olaf , Herges Rainer
Published: November 2018

Controlled switching of the spin state of transition metal ions, particularly of FeII and FeIII, is a prerequisite to achieve selectivity, efficiency, and catalysis in a number of metalloenzymes. Here we report on an iron(III) porphyrin with a photochromic axial ligand which, upon irradiation with two different wavelengths reversibly switches its spin state between low-spin (S = 1/2) and high-spin (S = 5/2) in solution (DMSO-acetone, 2:598). The switching efficiency is 76% at room temperature. The system is neither oxygen nor water sensitive, and no fatigue was observed after more than 1000 switching cycles. Concomitant with the spin-flip is a change in redox potential by ~60 mV. Besides serving as a simple model for the first step of the cytochrome P450 catalytic cycle, the spin switch can be used to switch the spin-lattice relaxation time T1 of the water protons by a factor of 15.
5D operando tomographic diffraction imaging of a catalyst bed
Authors: Vamvakeros A. , Jacques S. D. M. , Di Michiel M. , Matras D. , Middelkoop V. , Ismagilov I. Z. , Matus E. V. , Kuznetsov V. V. , Drnec J. , Senecal P. , Beale A. M.
Published: November 2018

We report the results from the first 5D tomographic diffraction imaging experiment of a complex Ni–Pd/CeO2–ZrO2/Al2O3 catalyst used for methane reforming. This five-dimensional (three spatial, one scattering and one dimension to denote time/imposed state) approach enabled us to track the chemical evolution of many particles across the catalyst bed and relate these changes to the gas environment that the particles experience. Rietveld analysis of some 2 × 106 diffraction patterns allowed us to extract heterogeneities in the catalyst from the Å to the nm and to the μm scale (3D maps corresponding to unit cell lattice parameters, crystallite sizes and phase distribution maps respectively) under different chemical environments. We are able to capture the evolution of the Ni-containing species and gain a more complete insight into the multiple roles of the CeO2-ZrO2 promoters and the reasons behind the partial deactivation of the catalyst during partial oxidation of methane.
REX1 is the critical target of RNF12 in imprinted X chromosome inactivation in mice
Authors: Gontan Cristina , Mira-Bontenbal Hegias , Magaraki Aristea , Dupont Catherine , Barakat Tahsin Stefan , Rentmeester Eveline , Demmers Jeroen , Gribnau Joost
Published: November 2018

In mice, imprinted X chromosome inactivation (iXCI) of the paternal X in the pre-implantation embryo and extraembryonic tissues is followed by X reactivation in the inner cell mass (ICM) of the blastocyst to facilitate initiation of random XCI (rXCI) in all embryonic tissues. RNF12 is an E3 ubiquitin ligase that plays a key role in XCI. RNF12 targets pluripotency protein REX1 for degradation to initiate rXCI in embryonic stem cells (ESCs) and loss of the maternal copy of Rnf12 leads to embryonic lethality due to iXCI failure. Here, we show that loss of Rex1 rescues the rXCI phenotype observed in Rnf12−/− ESCs, and that REX1 is the prime target of RNF12 in ESCs. Genetic ablation of Rex1 in Rnf12−/− mice rescues the Rnf12−/− iXCI phenotype, and results in viable and fertile Rnf12−/−:Rex1−/− female mice displaying normal iXCI and rXCI. Our results show that REX1 is the critical target of RNF12 in XCI.
Quantitative metaproteomics of medieval dental calculus reveals individual oral health status
Authors: Jersie-Christensen Rosa R. , Lanigan Liam T. , Lyon David , Mackie Meaghan , Belstrøm Daniel , Kelstrup Christian D. , Fotakis Anna K. , Willerslev Eske , Lynnerup Niels , Jensen Lars J. , Cappellini Enrico , Olsen Jesper V.
Published: November 2018

The composition of ancient oral microbiomes has recently become accessible owing to advanced biomolecular methods such as metagenomics and metaproteomics, but the utility of metaproteomics for such analyses is less explored. Here, we use quantitative metaproteomics to characterize the dental calculus associated with the remains of 21 humans retrieved during the archeological excavation of the medieval (ca. 1100–1450 CE) cemetery of Tjærby, Denmark. We identify 3671 protein groups, covering 220 bacterial species and 81 genera across all medieval samples. The metaproteome profiles of bacterial and human proteins suggest two distinct groups of archeological remains corresponding to health-predisposed and oral disease-susceptible individuals, which is supported by comparison to the calculus metaproteomes of healthy living individuals. Notably, the groupings identified by metaproteomics are not apparent from the bioarchaeological analysis, illustrating that quantitative metaproteomics has the potential to provide additional levels of molecular information about the oral health status of individuals from archeological contexts.
High-throughput three-dimensional chemotactic assays reveal steepness-dependent complexity in neuronal sensation to molecular gradients
Authors: Xu Zhen , Fang Peilin , Xu Bingzhe , Lu Yufeng , Xiong Jinghui , Gao Feng , Wang Xin , Fan Jun , Shi Peng
Published: November 2018

Many cellular programs of neural development are under combinatorial regulation by different chemoattractive or chemorepulsive factors. Here, we describe a microfluidic platform that utilizes well-controlled three-dimensional (3D) diffusion to generate molecular gradients of varied steepness in a large array of hydrogel cylinders, allowing high-throughput 3D chemotactic assays for mechanistic dissection of steepness-dependent neuronal chemotaxis. Using this platform, we examine neuronal sensitivity to the steepness of gradient composed of netrin-1, nerve growth factor, or semaphorin3A (Sema3A) proteins, and reveal dramatic diversity and complexity in the associated chemotactic regulation of neuronal development. Particularly for Sema3A, we find that serine/threonine kinase-11 and glycogen synthase kinase-3 signaling pathways are differentially involved in steepness-dependent chemotactic regulation of coordinated neurite repellence and neuronal migration. These results provide insights to the critical role of gradient steepness in neuronal chemotaxis, and also prove the technique as an expandable platform for studying other chemoresponsive cellular systems.
Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection
Authors: Pandey Anish , Cleary David W. , Laver Jay R. , Gorringe Andrew , Deasy Alice M. , Dale Adam P. , Morris Paul D. , Didelot Xavier , Maiden Martin C. J. , Read Robert C.
Published: November 2018

Neisseria lactamica is a harmless coloniser of the infant respiratory tract, and has a mutually-excluding relationship with the pathogen Neisseria meningitidis. Here we report controlled human infection with genomically-defined N. lactamica and subsequent bacterial microevolution during 26 weeks of colonisation. We find that most mutations that occur during nasopharyngeal carriage are transient indels within repetitive tracts of putative phase-variable loci associated with host-microbe interactions (pgl and lgt) and iron acquisition (fetA promotor and hpuA). Recurrent polymorphisms occurred in genes associated with energy metabolism (nuoN, rssA) and the CRISPR-associated cas1. A gene encoding a large hypothetical protein was often mutated in 27% of the subjects. In volunteers who were naturally co-colonised with meningococci, recombination altered allelic identity in N. lactamica to resemble meningococcal alleles, including loci associated with metabolism, outer membrane proteins and immune response activators. Our results suggest that phase variable genes are often mutated during carriage-associated microevolution.
Vibrio cholerae motility exerts drag force to impede attack by the bacterial predator Bdellovibrio bacteriovorus
Authors: Duncan Miles C. , Forbes John C. , Nguyen Y , Shull Lauren M. , Gillette Rebecca K. , Lazinski David W. , Ali Afsar , Shanks Robert M. Q. , Kadouri Daniel E. , Camilli Andrew
Published: November 2018

The bacterial predator Bdellovibrio bacteriovorus is evolved to attack and kill other bacteria, including the human intestinal pathogen Vibrio cholerae. Although B. bacteriovorus exhibit a broad prey range, little is known about the genetic determinants of prey resistance and sensitivity. Here we perform a genetic screen on V. cholerae and identify five pathways contributing to predation susceptibility. We find that the essential virulence regulators ToxR/S increase susceptibility to predation, as mutants of these genes are more resistant to predation. We observe by flow cytometry that lipopolysaccharide is a critical defense, as mutants lacking O-antigen are rapidly attacked by predatory B. bacteriovorus. Using polymer solutions to alter media viscosity, we find that when B. bacteriovorus attacks motile V. cholerae, increased drag forces slow its ability to prey. These results provide insights into key prey resistance mechanisms, and may be useful in the application of B. bacteriovorus in treating infections.
Near-infrared STED nanoscopy with an engineered bacterial phytochrome
Authors: Kamper Maria , Ta Haisen , Jensen Nickels A. , Hell Stefan W. , Jakobs Stefan
Published: November 2018

The near infrared (NIR) optical window between the cutoff for hemoglobin absorption at 650 nm and the onset of increased water absorption at 900 nm is an attractive, yet largely unexplored, spectral regime for diffraction-unlimited super-resolution fluorescence microscopy (nanoscopy). We developed the NIR fluorescent protein SNIFP, a bright and photostable bacteriophytochrome, and demonstrate its use as a fusion tag in live-cell microscopy and STED nanoscopy. We further demonstrate dual color red-confocal/NIR-STED imaging by co-expressing SNIFP with a conventional red fluorescent protein.
Structural insights into the function of type VI secretion system TssA subunits
Authors: Dix Samuel R. , Owen Hayley J. , Sun Ruyue , Ahmad Asma , Shastri Sravanthi , Spiewak Helena L. , Mosby Daniel J. , Harris Matthew J. , Batters Sarah L. , Brooker Thomas A. , Tzokov Svetomir B. , Sedelnikova Svetlana E. , Baker Patrick J. , Bullough Per A. , Rice David W. , Thomas Mark S.
Published: November 2018

The type VI secretion system (T6SS) is a multi-protein complex that injects bacterial effector proteins into target cells. It is composed of a cell membrane complex anchored to a contractile bacteriophage tail-like apparatus consisting of a sharpened tube that is ejected by the contraction of a sheath against a baseplate. We present structural and biochemical studies on TssA subunits from two different T6SSs that reveal radically different quaternary structures in comparison to the dodecameric E. coli TssA that arise from differences in their C-terminal sequences. Despite this, the different TssAs retain equivalent interactions with other components of the complex and position their highly conserved N-terminal ImpA_N domain at the same radius from the centre of the sheath as a result of their distinct domain architectures, which includes additional spacer domains and highly mobile interdomain linkers. Together, these variations allow these distinct TssAs to perform a similar function in the complex.
Increasing compound events of extreme hot and dry days during growing seasons of wheat and maize in China
Authors: Lu You , Hu Hongchang , Li Chao , Tian Fuqiang
Published: November 2018

Compound events of climate extremes such as extremely high temperature and low precipitation during crop growing seasons can greatly affect agricultural production and food security. No study has investigated how Compound Extreme Hot and Dry days (CEHD days) during crop-growing seasons have changed or will change in response to climate warming. Based on observations, we find upward trends in CEHD days during wheat and maize growing seasons in China in the historical period 1980–2015. These trends are remarkably different during wheat and maize growing seasons, pointing to the need for targeted analysis focusing on crop-specific growing seasons. Projections of future temperature and precipitation from the Coordinated Regional Climate Downscaling Experiment show that upward trends will continue into future. On average over China, the frequencies of CEHD days during wheat and maize growing seasons are projected to increase respectively by 168% and 162% in 2036–2050 relatively to 1980–2015 under the RCP8.5 emissions scenario. The projected increases may have serious implications for China’s food production, adding to the need for resilience planning to limit the impacts of growing-season CEHD days.
Coherent Tabletop EUV Ptychography of Nanopatterns
Authors: Truong Nguyen Xuan , Safaei Reza , Cardin Vincent , Lewis Scott M. , Zhong Xiang Li , Légaré François , Denecke Melissa A.
Published: November 2018

Coherent diffraction imaging (CDI) or lensless X-ray microscopy has become of great interest for high spatial resolution imaging of, e.g., nanostructures and biological specimens. There is no optics required in between an object and a detector, because the object can be fully recovered from its far-field diffraction pattern with an iterative phase retrieval algorithm. Hence, in principle, a sub-wavelength spatial resolution could be achieved in a high-numerical aperture configuration. With the advances of ultrafast laser technology, high photon flux tabletop Extreme Ultraviolet (EUV) sources based on the high-order harmonic generation (HHG) have become available to small-scale laboratories. In this study, we report on a newly established high photon flux and highly monochromatic 30 nm HHG beamline. Furthermore, we applied ptychography, a scanning CDI version, to probe a nearly periodic nanopattern with the tabletop EUV source. A wide-field view of about 15 × 15 μm was probed with a 2.5 μm−diameter illumination beam at 30 nm. From a set of hundreds of far-field diffraction patterns recorded for different adjacent positions of the object, both the object and the illumination beams were successfully reconstructed with the extended ptychographical iterative engine. By investigating the phase retrieval transfer function, a diffraction-limited resolution of reconstruction of about 32 nm is obtained.
Imaging the distribution of skin lipids and topically applied compounds in human skin using mass spectrometry
Authors: Sjövall Peter , Skedung Lisa , Gregoire Sébastien , Biganska Olga , Clément Franck , Luengo Gustavo S.
Published: November 2018

The barrier functions of skin against water loss, microbial invasion and penetration of xenobiotics rely, in part, on the spatial distribution of the biomolecular constituents in the skin structure, particularly its horny layer (stratum corneum). However, all skin layers are important to describe normal and dysfunctional skin conditions, and to develop adapted therapies or skin care products. In this work, time-of-flight secondary ion mass spectrometry (ToF-SIMS) combined with scanning electron microscopy (SEM) was used to image the spatial distribution of a variety of molecular species, from stratum corneum down to dermis, in cross-section samples of human abdominal skin. The results demonstrate the expected localization of ceramide and saturated long-chain fatty acids in stratum corneum (SC) and cholesterol sulfate in the upper part of the viable epidermis. The localization of exogenous compounds is demonstrated by the detection and imaging of carvacrol (a constituent of oregano or thyme essential oil) and ceramide, after topical application onto ex vivo human skin. Carvacrol showed pronounced accumulation to triglyceride-containing structures in the deeper parts of dermis. In contrast, the exogenous ceramide was found to be localized in SC. Furthermore, the complementary character of this approach with classical ex vivo skin absorption analysis methods is demonstrated.
Intrinsic disorder in the regulatory N-terminal domain of diacylglycerol acyltransferase 1 from Brassica napus
Authors: Panigrahi Rashmi , Matsui Tsutomu , Song Andrew H. , Caldo Kristian Mark P. , Young Howard S. , Weselake Randall J. , Lemieux M. Joanne
Published: November 2018

Proteins with multifunctional regulatory domains often demonstrate structural plasticity or protein disorder, allowing the binding of multiple regulatory factors and post-translational modifications. While the importance of protein disorder is clear, it also poses a challenge for in vitro characterization. Here, we report protein intrinsic disorder in a plant molecular system, which despite its prevalence is less studied. We present a detailed biophysical characterization of the entire cytoplasmic N-terminal domain of Brassica napus diacylglycerol acyltransferase, (DGAT1), which includes an inhibitory module and allosteric binding sites. Our results demonstrate that the monomeric N-terminal domain can be stabilized for biophysical characterization and is largely intrinsically disordered in solution. This domain interacts with allosteric modulators of DGAT1, CoA and oleoyl-CoA, at micromolar concentrations. While solution scattering studies indicate conformational heterogeneity in the N-terminal domain of DGAT1, there is a small gain of secondary structure induced by ligand binding.
An Algorithm for Enhancing the Image Contrast of Electron Tomography
Authors: Wu Hao , Zhai Xiaobo , Lei Dongsheng , Liu Jianfang , Yu Yadong , Bie Rongfang , Ren Gang
Published: November 2018

Three-dimensional (3D) reconstruction of a single protein molecule is essential for understanding the relationship between the structural dynamics and functions of the protein. Electron tomography (ET) provides a tool for imaging an individual particle of protein from a series of tilted angles. Individual-particle electron tomography (IPET) provides an approach for reconstructing a 3D density map from a single targeted protein particle (without averaging from different particles of this type of protein), in which the target particle was imaged from a series of tilting angles. However, owing to radiation damage limitations, low-dose images (high noise, and low image contrast) are often challenging to be aligned for 3D reconstruction at intermediate resolution (1–3 nm). Here, we propose a computational method to enhance the image contrast, without increasing any experimental dose, for IPET 3D reconstruction. Using an edge-preserving smoothing-based multi-scale image decomposition algorithm, this method can detect the object against a high-noise background and enhance the object image contrast without increasing the noise level or significantly decreasing the image resolution. The method was validated by using both negative staining (NS) ET and cryo-ET images. The successful 3D reconstruction of a small molecule (<100 kDa) indicated that this method can be used as a supporting tool to current ET 3D reconstruction methods for studying protein dynamics via structure determination from each individual particle of the same type of protein.
NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs
Authors: Doña Inmaculada , Barrionuevo Esther , Salas María , Laguna José Julio , Agúndez José , García-Martín Elena , Bogas Gádor , Perkins James Richard , Cornejo-García José Antonio , Torres María José
Published: November 2018

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDs-exacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the current classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n = 138), who had a higher percentage of underlying rhinitis (p < 0.0001) and asthma (p < 0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT.
Trends in Q fever serologic testing by immunofluorescence from four large reference laboratories in the United States, 2012–2016
Authors: Miller Halie K. , Binder Alison M. , Peterson Amy , Theel Elitza S. , Volpe Joseph M. , Couturier Marc Roger , Cherry Cara C. , Kersh Gilbert J.
Published: November 2018

Laboratory testing for Q fever (Coxiella burnetii) is essential for a differential diagnosis, yet little is known about Q fever diagnostic testing practices in the United States. We retrospectively analyzed Q fever immunoglobulin G (IgG) indirect immunofluorescence assay (IFA) testing data between 1/1/2012–10/31/2016 from ARUP, LabCorp, Mayo Medical Laboratories, and Quest Diagnostics. Data included IgG phase I and phase II titers, patient age and sex, and state and date of specimen collection. On average, 12,821 specimens were tested for Q fever annually by the participating laboratories. Of 64,106 total specimens, 84.1% tested negative for C. burnetii-specific antibodies. Positive titers ranged from 16 to 262,144 against both phase I and phase II antigens. Submission of specimens peaked during the summer months, and more specimens were submitted from the West North Central division. Testing occurred more frequently in males (53%) and increased with age. In conclusion, few U.S. Q fever cases are reported, despite large volumes of diagnostic specimens tested. Review of commercial laboratory data revealed a lack of paired serology samples and patterns of serology titers that differ from case reporting diagnostic criteria.
A204E mutation in Nav1.4 DIS3 exerts gain- and loss-of-function effects that lead to periodic paralysis combining hyper- with hypo-kalaemic signs
Authors: Kokunai Yosuke , Dalle Carine , Vicart Savine , Sternberg Damien , Pouliot Valérie , Bendahhou Said , Fournier Emmanuel , Chahine Mohamed , Fontaine Bertrand , Nicole Sophie
Published: November 2018

Periodic paralyses (PP) are characterized by episodic muscle weakness and are classified into the distinct hyperkalaemic (hyperPP) and hypokalaemic (hypoPP) forms. The dominantly-inherited form of hyperPP is caused by overactivity of Nav1.4 — the skeletal muscle voltage-gated sodium channel. Familial hypoPP results from a leaking gating pore current induced by dominant mutations in Nav1.4 or Cav1.1, the skeletal muscle voltage-gated calcium channel. Here, we report an individual with clinical signs of hyperPP and hypokalaemic episodes of muscle paralysis who was heterozygous for the novel p.Ala204Glu (A204E) substitution located in one region of Nav1.4 poor in disease-related variations. A204E induced a significant decrease of sodium current density, increased the window current, enhanced fast and slow inactivation of Nav1.4, and did not cause gating pore current in functional analyses. Interestingly, the negative impact of A204E on Nav1.4 activation was strengthened in low concentration of extracellular K+. Our data prove the existence of a phenotype combining signs of hyperPP and hypoPP due to dominant Nav1.4 mutations. The hyperPP component would result from gain-of-function effects on Nav1.4 and the hypokalemic episodes of paralysis from loss-of-function effects strengthened by low K+. Our data argue for a non-negligible role of Nav1.4 loss-of-function in familial hypoPP.
The thickness-induced magneto-transport and optic properties enhancement in Sb2Te3 flakes
Authors: Huang Shiu-Ming , Chen Kai-Jui , Yan You-Jhih , Yu Shih-Hsun , Chou Mitch
Published: November 2018

The electric and optical properties were studied in Sb2Te3 with different thickness. It reveals the same resistivity at measured temperatures, but shows a larger magnetoresistance ratio at thicker flakes. All measured data conformed to a linear correlation between magnetoresistance ratio which is one-order enhanced, and mobility over a wide mobility range. A higher photocurrent response is observed in thicker flakes. These results support that the thickness enhances the effective carrier mobility which leads to magneto-transport and optic properties enhancement.
Driving the expression of the Salmonella enterica sv Typhimurium flagellum using flhDC from Escherichia coli results in key regulatory and cellular differences
Authors: Albanna Ayman , Sim Martin , Hoskisson Paul A. , Gillespie Colin , Rao Christopher V. , Aldridge Phillip D.
Published: November 2018

The flagellar systems ofEscherichia coliandSalmonella entericaexhibit a significant level of genetic and functional synteny. Both systems are controlled by the flagellar specific master regulator FlhD4C2. Since the early days of genetic analyses of flagellar systems it has been known thatE. coli flhDCcan complement a ∆flhDCmutant inS. enterica. The genomic revolution has identified how genetic changes to transcription factors and/or DNA binding sites can impact the phenotypic outcome across related species. We were therefore interested in asking: using modern tools to interrogate flagellar gene expression and assembly, what would the impact be of replacing theflhDCcoding sequences inS. entericafor theE. coligenes at theflhDC S. enterciachromosomal locus? We show that even though all strains created are motile, flagellar gene expression is measurably lower whenflhDCECare present. These changes can be attributed to the impact of FlhD4C2DNA recognition and the protein-protein interactions required to generate a stable FlhD4C2complex. Furthermore, our data suggests that inE. colithe internal flagellar FliT regulatory feedback loop has a marked difference with respect to output of the flagellar systems. We argue due diligence is required in making assumptions based on heterologous expression of regulators and that even systems showing significant synteny may not behave in exactly the same manner.
Performance of Deep Learning Architectures and Transfer Learning for Detecting Glaucomatous Optic Neuropathy in Fundus Photographs
Authors: Christopher Mark , Belghith Akram , Bowd Christopher , Proudfoot James A. , Goldbaum Michael H. , Weinreb Robert N. , Girkin Christopher A. , Liebmann Jeffrey M. , Zangwill Linda M.
Published: November 2018

The ability of deep learning architectures to identify glaucomatous optic neuropathy (GON) in fundus photographs was evaluated. A large database of fundus photographs (n = 14,822) from a racially and ethnically diverse group of individuals (over 33% of African descent) was evaluated by expert reviewers and classified as GON or healthy. Several deep learning architectures and the impact of transfer learning were evaluated. The best performing model achieved an overall area under receiver operating characteristic (AUC) of 0.91 in distinguishing GON eyes from healthy eyes. It also achieved an AUC of 0.97 for identifying GON eyes with moderate-to-severe functional loss and 0.89 for GON eyes with mild functional loss. A sensitivity of 88% at a set 95% specificity was achieved in detecting moderate-to-severe GON. In all cases, transfer improved performance and reduced training time. Model visualizations indicate that these deep learning models relied on, in part, anatomical features in the inferior and superior regions of the optic disc, areas commonly used by clinicians to diagnose GON. The results suggest that deep learning-based assessment of fundus images could be useful in clinical decision support systems and in the automation of large-scale glaucoma detection and screening programs.
Clinical implications of changes in the diversity of c-MYC copy number variation after neoadjuvant chemotherapy in breast cancer
Authors: Chung Yul Ri , Kim Hyun Jeong , Kim Milim , Ahn Soomin , Park So Yeon
Published: November 2018

Chemotherapy can alter the makeup of a tumor cell population by exerting selection pressure. We examined the change in Shannon index, a mathematical diversity measure used in ecology, for c-MYC copy number variation (CNV) after neoadjuvant chemotherapy and evaluated its clinical significance in breast cancer. Associations between Shannon indices for c-MYC CNV in pre- and post-neoadjuvant chemotherapy breast cancer samples and clinicopathologic features of tumors as well as patient survival were analyzed in 144 patients. A change in c-MYC amplification and copy number gain status was found in 14.3% and 33.6% with most cases showing positive to negative conversion. The chemo-sensitive group showed a significant decrease in Shannon index after neoadjuvant chemotherapy. However, there was no difference in diversity indices between pre- and post-neoadjuvant chemotherapy specimens in the chemo-resistant group. In survival analyses, high Shannon indices for c-MYC CNV in post-neoadjuvant chemotherapy samples as well as those in pre-neoadjuvant chemotherapy samples were revealed as independent prognostic factors for poor disease-free survival not only in the whole group but also in the chemo-resistant subgroup. These findings suggest that a change in Shannon index for c-MYC CNV after neoadjuvant chemotherapy reflects chemo-responsiveness and that Shannon indices after neoadjuvant chemotherapy have a prognostic value in breast cancer patients who receive neoadjuvant chemotherapy.
Influence of dietary supplementation with Bacillus licheniformis and Saccharomyces cerevisiae as alternatives to monensin on growth performance, antioxidant, immunity, ruminal fermentation and microbial diversity of fattening lambs
Authors: Jia Peng , Cui Kai , Ma Tao , Wan Fan , Wang Wenyi , Yang Dong , Wang Yunfei , Guo Baolin , Zhao Lifang , Diao Qiyu
Published: November 2018

Alternatives to antibiotics for improving productivity and maintaining the health of livestock health are urgently needed. The scope of this research was conducted to investigate the effects of two alternatives (Bacillus licheniformis and Saccharomyces cerevisiae) to monensin on growth performance, antioxidant capacity, immunity, ruminal fermentation and microbial diversity of fattening lambs. One hundred and sixty Dorper × Thin-tailed Han sheep (32 ± 3.45 kg BW) were randomly assigned into 5 treatments of n = 32 lambs/group. Lambs in the control group were fed a basal diet (NC) while the other four treatments were fed basal diets supplemented with monensin (PC), Bacillus licheniformis (BL), Saccharomyces cerevisiae (SC), and the combination of Bacillus licheniformis and Saccharomyces cerevisiae with protease (BS), respectively. The experiment lasted for 66 d. Feed intake was recorded every 2 d and lambs were weighed every 20 d. Ten lambs from each group were slaughtered at the end of the trial, and samples of serum and rumen fluid were collected. The results indicated that the dietary regimen did not affect the dry matter intake (DMI). The average daily gain (ADG) of BS treatment was significantly higher than NC group (P < 0.05). Compared with the NC treatment, the other four supplementation treatments increased the concentration of growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin (INS) (P < 0.05). The malondialdehyde (MDA) and total antioxidant capacity (TAOC) showed no significant difference among the 5 treatments while the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of BS group was significantly increased (P < 0.05). The supplementation regimen decreased the concentration of ammonia Nitrogen (NH3-N) and increased the content of microbial crude proteins (MCP) (P < 0.05). The supplementation of antibiotics and probiotics reduced the concentrations of acetate and increased the concentrations of propionate (P < 0.05). The supplementation treatments increased the relative abundance of Lentisphaerae, Fibrobacteres and Tenericutes at the phylum level, whereas at the genus level, they increased the relative abundance of Fibrobacter (P < 0.05). Overall, this study confirmed the facilitating effect of B. licheniformis, S. cerevisiae and their compounds on growth performance, improve the antioxidant capacity and immune function, and beneficially manipulate ruminal fermentation and microbial diversity of fatting lambs.
Semiconductor Hyperbolic Metamaterials at the Quantum Limit
Authors: Montaño Inès , Campione Salvatore , Klem John F. , Beechem Thomas E. , Wolf Omri , Sinclair Michael B. , Luk Ting S.
Published: November 2018

We study semiconductor hyperbolic metamaterials (SHMs) at the quantum limit experimentally using spectroscopic ellipsometry as well as theoretically using a new microscopic theory. The theory is a combination of microscopic density matrix approach for the material response and Green’s function approach for the propagating electric field. Our approach predicts absorptivity of the full multilayer system and for the first time allows the prediction of in-plane and out-of-plane dielectric functions for every individual layer constructing the SHM as well as effective dielectric functions that can be used to describe a homogenized SHM.
Gene prioritization, communality analysis, networking and metabolic integrated pathway to better understand breast cancer pathogenesis
Authors: López-Cortés Andrés , Paz-y-Miño César , Cabrera-Andrade Alejandro , Barigye Stephen J. , Munteanu Cristian R. , González-Díaz Humberto , Pazos Alejandro , Pérez-Castillo Yunierkis , Tejera Eduardo
Published: November 2018

Consensus strategy was proved to be highly efficient in the recognition of gene-disease association. Therefore, the main objective of this study was to apply theoretical approaches to explore genes and communities directly involved in breast cancer (BC) pathogenesis. We evaluated the consensus between 8 prioritization strategies for the early recognition of pathogenic genes. A communality analysis in the protein-protein interaction (PPi) network of previously selected genes was enriched with gene ontology, metabolic pathways, as well as oncogenomics validation with the OncoPPi and DRIVE projects. The consensus genes were rationally filtered to 1842 genes. The communality analysis showed an enrichment of 14 communities specially connected with ERBB, PI3K-AKT, mTOR, FOXO, p53, HIF-1, VEGF, MAPK and prolactin signaling pathways. Genes with highest ranking were TP53, ESR1, BRCA2, BRCA1 and ERBB2. Genes with highest connectivity degree were TP53, AKT1, SRC, CREBBP and EP300. The connectivity degree allowed to establish a significant correlation between the OncoPPi network and our BC integrated network conformed by 51 genes and 62 PPi. In addition, CCND1, RAD51, CDC42, YAP1 and RPA1 were functional genes with significant sensitivity score in BC cell lines. In conclusion, the consensus strategy identifies both well-known pathogenic genes and prioritized genes that need to be further explored.
Dewetting of monolayer water and isopropanol between MoS2 nanosheets
Authors: Wang Beibei , Kalia Rajiv K. , Nakano Aiichiro , Vashishta Priya D.
Published: November 2018

Understanding dewetting of solvent molecules confined to layered material (LM) interfaces is crucial to the synthesis of two-dimensional materials by liquid-phase exfoliation. Here, we examine dewetting behavior of water and isopropanol/water (IPA/H2O) mixtures between molybdenum disulfide (MoS2) membranes using molecular dynamics (MD) simulations. We find that a monolayer of water spontaneously ruptures into nanodroplets surrounded by dry regions. The average speed of receding dry patches is close to the speed of sound in air. In contrast, monolayer mixtures of IPA/H2O between MoS2 membranes slowly transform into percolating networks of nanoislands and nanochannels in which water molecules diffuse inside and IPA molecules stay at the periphery of islands and channels. These contrasting behaviors may explain why IPA/H2O mixtures are much more effective than H2O alone in weakening interlayer coupling and exfoliating MoS2 into atomically thin sheets.
A high-resolution streamflow and hydrological metrics dataset for ecological modeling using a regression model
Authors: Irving Katie , Kuemmerlen Mathias , Kiesel Jens , Kakouei Karan , Domisch Sami , Jähnig Sonja C.
Published: November 2018

Hydrological variables are among the most influential when analyzing or modeling stream ecosystems. However, available hydrological data are often limited in their spatiotemporal scale and resolution for use in ecological applications such as predictive modeling of species distributions. To overcome this limitation, a regression model was applied to a 1 km gridded stream network of Germany to obtain estimated daily stream flow data (m3 s−1) spanning 64 years (1950–2013). The data are used as input to calculate hydrological indices characterizing stream flow regimes. Both temporal and spatial validations were performed. In addition, GLMs using both the calculated and observed hydrological indices were compared, suggesting that the predicted flow data are adequate for use in predictive ecological models. Accordingly, we provide estimated stream flow as well as a set of 53 hydrological metrics at 1 km grid for the stream network of Germany. In addition, we provide an R script where the presented methodology is implemented, that uses globally available data and can be directly applied to any other geographical region.
Brain metastasis DNA methylomes, a novel resource for the identification of biological and clinical features
Authors: Salomon Matthew P. , Orozco Javier I. J. , Wilmott James S. , Hothi Parvinder , Manughian-Peter Ayla O. , Cobbs Charles S. , Scolyer Richard A. , Hoon Dave S. B. , Marzese Diego M.
Published: November 2018

Brain metastases (BM) are one the most lethal and poorly managed clinical complications in cancer patients. These secondary tumors represent the most common intracranial neoplasm in adults, most frequently originating from lung cancer, breast cancer, and cutaneous melanoma. In primary brain tumors, such as gliomas, recent advances in DNA methylation profiling have allowed for a comprehensive molecular classification. Such data provide prognostic information, in addition to helping predict patient response to specific systemic therapies. However, epigenetic alterations of metastatic brain tumors with specific biological and translational relevance still require much further exploration. Using the widely employed Illumina Infinium HumanMethylation 450K platform, we have generated a cohort of genome-wide DNA methylomes from ninety-six needle-dissected BM specimens from patients with lung cancer, breast cancer, and cutaneous melanoma with clinical, pathological, and demographic annotations. This resource offers an unprecedented and unique opportunity to identify novel DNA methylation features influencing the behavior of brain metastasis, and thus accelerate the discovery of BM-specific theranostic epigenetic alterations.
A field amplification enhanced paper-based analytical device with a robust chemiluminescence detection module
Authors: Zhang Xiu-Xiu , Liu Jia-Juan , Cai Yu , Zhao Shuang , Wu Zhi-Yong
Published: November 2018

A field amplification enhanced paper-based analytical device was established with a miniaturized optical detection module for chemiluminescence detection.
Mechanistic insights into HCO2H dehydrogenation and CO2 hydrogenation catalyzed by Ir(Cp*) containing tetrahydroxy bipyrimidine ligand: the role of sodium and proton shuttle
Authors: Wonglakhon Tanakorn , Surawatanawong Panida
Published: November 2018

Catalytic HCO2H dehydrogenation by Ir(Cp*) tetrahydroxy bipyrimidine is influenced not only by the protonation states but also by the involvement of Na+ and the availability of HCO2H as a proton shuttle.
Halogen-free GeO2 conversion: electrochemical reduction vs. complexation in (DTBC)2Ge[Py(CN)n] (n = 0…2) complexes
Authors: Nikolaevskaya Elena N. , Saverina Evgeniya A. , Starikova Alyona A. , Farhati Amel , Kiskin Mikhail A. , Syroeshkin Mikhail A. , Egorov Mikhail P. , Jouikov Viatcheslav V.
Published: November 2018

3,5-di-tert-Butylcatecholate (DTBC) germanium complexes (DTBC)2Ge[Py(CN)n]2 (n = 0…2) have been synthesized from GeO2, DTBC and Py(CN)n.
Spin-crossover compounds based on iron(ii) complexes of 2,6-bis(pyrazol-1-yl)pyridine (bpp) functionalized with carboxylic acid and ethyl carboxylic acid
Authors: García-López Víctor , Palacios-Corella Mario , Abhervé Alexandre , Pellicer-Carreño Isaac , Desplanches Cédric , Clemente-León Miguel , Coronado Eugenio
Published: November 2018

New salts of the iron(ii) bppCOOH and bppCOOEt spin crossover complexes have been studied.
An adhesion based approach for the detection of esophageal cancer
Authors: Noori Mahboubeh S. , Streator Evan S. , Carlson Grady E. , Drozek David S. , Burdick Monica M. , Goetz Douglas J.
Published: November 2018

Selective recognition of esophageal cancer cellsvialigand conjugated microspheres in an endoscopic adhesion assay.