bluuebunny/crossref_metadata_2025 huggingface dataset:
Privacy, Cybersecurity, and GATS Article XIV: A New Frontier for Trade and Internet Regulation?
Authors: Mishra Neha
Published: May 2019

Measures restricting data flows outside one's borders, including mandatory data/server localization measures, are not only a barrier to trade, but also largely ineffective in achieving better internet security or trust. Nevertheless, governments deploy such measures, primarily on grounds of cybersecurity and privacy, potentially violating their obligations under the General Agreement on Trade in Services (GATS). In this article, I investigate whether GATS-inconsistent measures may be justified under GATS Art. XIV when aimed at ensuring privacy or cybersecurity, and, if so, whether GATS Art. XIV effectively balances trade and internet policy. As the internet governance framework is complex and somewhat ambiguous, applying GATS Art. XIV to cybersecurity/privacy measures necessitates balancing of trade liberalization principles and domestic internet policy. This exercise can be effective in weeding out data localization measures disguised as privacy/cybersecurity measures, particularly by employing relevant technical and factual evidence. However, given the lack of binding international law/norms on these issues, GATS Art. XIV has a limited role, particularly in cases involving direct conflict between multistakeholder/transnational internet norms and domestic internet policies, or where the measures are founded on contentious standards/benchmarks on privacy/cybersecurity. Ultimately, ensuring free and secure data flows requires a multidimensional policy response, including strengthening linkages between trade law and internet governance.
Childhood Victimization by Adults and Peers and Health-Risk Behaviors in Adulthood
Authors: Cerezo M. Ángeles , Pérez-García Elena
Published: May 2019

Victimization experienced in childhood has been linked with health-risk behaviors (HRBs) in adulthood. The purpose of this cross-sectional survey was to provide data regarding the HRBs using the ISPCAN Child Abuse Screening Tool Retrospective version (ICAST-R), Spanish version. This aimed to broaden existing knowledge by assessing both being victimized by adults and by peers in a Spanish general population of 348, aged 18–35. Age and timing of the reported victimization were also considered. Victimization: physical, psychological, sexual abuse by adults and/or peers showed a prevalence of 44.54%. Of these, 41.29% reported abuse by both. Children victimized by adults, regardless of type, were significantly associated to be psychologically abused by their peers (p < .001). Moreover, psychological maltreatment by adults was significantly associated with two peer victimizations: Physical and psychological (p < .001 in both). Regarding HRBs, peer victimized groups showed significantly higher levels of severity than non-victimized, with a higher proportion reporting attempted suicide (p < .05) and psychological or psychiatric treatment (p < .05). Participants victimized only by adults reported higher number of HRBs (p < .01), their victimization was associated to more severe abuse of drugs/alcohol (p ≤ .05), and suicide attempts (p < .05). Those victimized by adults and peers received treatment in higher proportion than non-victims (p < .001). Participants reporting victimization since before 5 years to age of 17, compared with non-victimized, showed more substance abuse (p < .05), attempted suicide (p < .01) and receipt of treatment (p < .05). These findings highlight the relevance of ICAST-R in studying HRBs.
Remote Western Arctic Nutrients Fuel Remineralization in Deep Baffin Bay
Authors: Lehmann N. , Kienast M. , Granger J. , Bourbonnais A. , Altabet M. A. , Tremblay J.‐É.
Published: May 2019

The oceanic nitrogen cycle is critically important for the partitioning of greenhouse gases between ocean and atmosphere. Baffin Bay connects ocean regions that are major sources (North Atlantic) and sinks (North Pacific and western Arctic) of biologically available nitrogen and further harbors supersaturation of nitrous oxide and a coincident deficit in nitrate in the deep basin. Isotopic tracer profiles of both nitrogen species presented here provide novel insights into the origin and cycling of reactive nitrogen in Baffin Bay, highlighting the connectivity between different Arctic systems and horizontal components of basin‐scale nutrient transport. Baffin Bay bottom water properties are derived from export production in northern Baffin Bay, which is largely fueled by Pacific‐derived nutrients. In situ remineralization at depth gives rise to benthic denitrification, evidenced by a pronounced accumulation of nitrous oxide with a distinctively high site preference (<44‰) in the deep basin. Nutrients supplied to Baffin Bay are hence stripped from surface waters and trapped at depth over long timescales, where sedimentary denitrification further adds to the N removal capacity of the Arctic Ocean.
A Numerical Study on the 3‐D Approach of the Equatorial Plasma Bubble Seeded by the Prereversal Vertical Drift
Authors: Sousasantos J. , Kherani E. A. , Sobral J. H. A. , Abdu M. A. , Moraes A. O. , Oliveira C. B. A.
Published: May 2019

Numerical studies concerning equatorial plasma bubble (EPB) seeding source mechanisms have been performed for the last decades. Density perturbations, gravity waves, shear instabilities among others were used in the literature. In all the cases the prereversal vertical drift has a central role, being a necessary condition in addition to all these seeding mechanisms. Notwithstanding, since the prereversal vertical drift presents an asymmetric distribution, this longitudinal variation was hypothesized to act as a seeding source mechanism. This mechanism is capable of providing both contributions: elevate the ionosphere and seed the collisional interchange instability. Two‐dimensional investigation was already done, showing the validity of this hypothesis in a bidimensional scenario. Nonetheless, the inclusion of the parallel dynamics could alter the outcome of such analysis, once the component of the conductivity along the geomagnetic field direction causes a load effect reducing the growth rate and shifting its altitude of maximization, thus a 3‐D model was developed, named MATPLAB_3D (Mathematical Plasma Bubble Model 3D), and the hypothesis was tested. A progressive approach was performed starting with an oversimplified configuration and concluding with a more realistic profile of prereversal vertical drift obtained using the SAMI2 model. The numerical simulations revealed the existence of a quasi‐gaussian seeding source. Also, in case of a prereversal vertical drift varying within 20–60 m/s, the seeded instability evolves into an EPB structure with a longitudinal extension of ~2° within ~22 min. This EPB maps to low latitude regions and presents secondary structures in its west side. This result further suggests that even though a decrease in the EPB growth due to the inclusion of the parallel conductivity occurred, the hypothesis remains valid.
Control of Convection in High‐Resolution Simulations of Tropical Cyclogenesis
Authors: Raymond D. J. , Kilroy G.
Published: May 2019

Three idealized high‐resolution simulations of tropical storm formation from a weak vortex are analyzed. The three simulations include a case using warm rain microphysics, a similar case in which surface friction is omitted, and a case in which ice microphysics is used. The goal is to understand the mechanisms controlling the intensity and distribution of convection in the formation process in each of these cases. Simulations of convection in weak temperature gradient convective models show that a combination of low to middle tropospheric moist convective instability, the saturation fraction or column relative humidity, and the surface moist entropy flux explain a high percentage of the variance in precipitation and lower tropospheric vertical mass flux. Tropical cyclones differ from other convective environments in that intense frictional convergence occurs in the boundary layer. Adding a measure of convective inhibition to account for this process enables the lower tropospheric mass flux to be predicted even in the core regions of the simulated tropical cyclones. These results are pertinent to the development of more accurate convective parameterizations for large‐scale models.
Burning Fossil Fuels Worsens Drought
Authors: Duncombe Jenessa
Published: May 2019

Tree rings help scientists trace the influence of greenhouse gas emissions on 20th-century drought conditions.
The Role of MJO Propagation, Lifetime, and Intensity on Modulating the Temporal Evolution of the MJO Extratropical Response
Authors: Zheng C. , Chang E. K. M.
Published: May 2019

The Madden‐Julian Oscillation (MJO) is the dominant mode of tropical intraseasonal variability. Many studies have found that the MJO has significant impacts on extratropical weather. Since the MJO can act as a tropical heat source that excites Rossby waves, midlatitude weather is modulated by the MJO due to the Rossby waves that propagate into the midlatitude and modulate the midlatitude circulation. Heat sources of individual MJO events are different since each event has different eastward propagation speed, lifetime, intensity, and structure. The background flow is also different for each event. These result in different Rossby waves and different extratropical response for each MJO event. In this study, the role of MJO propagation speed, lifetime, and intensity on modulating the structure and temporal evolution of the MJO extratropical response is systematically explored by using an idealized general circulation model. By adding the MJO‐associated heating into the general circulation model as an external forcing, the extratropical response in the Reanalysis is captured reasonably by the model. However, large ensemble model simulations show that the response in the Reanalysis is not robust. Experiments with MJO events of different propagation speed, lifetime, and intensity show that to excite a strong extratropical response, the MJO has to propagate through specific phases (Phases 1–3 and 5–7). The intensity, timing, and duration of the extratropical response strongly depend on when the MJO is initiated and when the MJO decays. The extratropical impacts of slow‐ and fast‐propagating MJO also have significant differences, especially on intensity and duration.
Effects of LiDAR DEM Smoothing and Conditioning Techniques on a Topography‐Based Wetland Identification Model
Authors: O'Neil Gina L. , Saby Linnea , Band Lawrence E. , Goodall Jonathan L.
Published: May 2019

Accurate and widely available wetland inventories are needed for wetland conservation and environmental planning. We propose an open source, automated wetland identification model that relies primarily on light detection and ranging (LiDAR) digital elevation models (DEMs). LiDAR DEMs are increasingly available and provide the resolution needed to map detailed topographic metrics and areas of likely soil saturation, but the choice of smoothing and conditioning techniques can significantly impact the accuracy of hydrologic parameter extraction. So far, the effect of these preprocessing steps on wetland delineation has not been thoroughly analyzed. We test the response of a Random Forest wetland classifier, using topographic wetness index, curvature, and cartographic depth‐to‐water index as input variables, to combinations of smoothing techniques (none, mean, median, Gaussian, and Perona‐Malik) and conditioning techniques (Fill, Impact Reduction Approach, and A* least‐cost path analysis) for four sites in Virginia, USA. The Random Forest model was configured to account for imbalanced data sets, and manually surveyed wetlands were used for verification. Applying Perona‐Malik smoothing and A* conditioning yielded the highest accuracy across all sites and considerably reduced model runtime. We found that models could be further improved by individualizing the smoothing method and scale to each input variable. Using only topographic information, the wetland identification model could accurately detect wetlands in all sites (81‐91% recall). Model overprediction varied across sites, represented by precision scores ranging from 22 to 69%. In its current form, the wetland model shows strong potential to support wetland field surveying by identifying likely wetland areas.
Correction: Effect of behavioral change intervention around new-born care practices among most marginalized women in self-help groups in rural India: analyses of three cross-sectional surveys between 2013 and 2016
Authors: Saggurti Niranjan , Porwal Akash , Atmavilas Yamini , Walia Monika , Das Rajshree , Irani Laili
Published: May 2019

This article was originally published under a standard License to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.
Structural basis for functional interactions in dimers of SLC26 transporters
Authors: Chang Yung-Ning , Jaumann Eva A. , Reichel Katrin , Hartmann Julia , Oliver Dominik , Hummer Gerhard , Joseph Benesh , Geertsma Eric R.
Published: May 2019

The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. The family shares a 7 + 7 transmembrane segments inverted repeat architecture with the SLC4 and SLC23 families, but holds a regulatory STAS domain in addition. While the only experimental SLC26 structure is monomeric, SLC26 proteins form structural and functional dimers in the lipid membrane. Here we resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize its functional relevance by combining PELDOR/DEER distance measurements and biochemical studies with MD simulations and spin-label ensemble refinement. Our structural model reveals a unique interface different from the SLC4 and SLC23 families. The functionally relevant STAS domain is no prerequisite for dimerization. Characterization of heterodimers indicates that protomers in the dimer functionally interact. The combined structural and functional data define the framework for a mechanistic understanding of functional cooperativity in SLC26 dimers.
TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells
Authors: Arhatte Malika , Gunaratne Gihan S. , El Boustany Charbel , Kuo Ivana Y. , Moro Céline , Duprat Fabrice , Plaisant Magali , Duval Hélène , Li Dahui , Picard Nicolas , Couvreux Anais , Duranton Christophe , Rubera Isabelle , Pagnotta Sophie , Lacas-Gervais Sandra , Ehrlich Barbara E. , Marchant Jonathan S. , Savage Aaron M. , van Eeden Fredericus J. M. , Wilkinson Robert N. , Demolombe Sophie , Honoré Eric , Patel Amanda
Published: May 2019

Mutations in the polycystins cause autosomal dominant polycystic kidney disease (ADPKD). Here we show that transmembrane protein 33 (TMEM33) interacts with the ion channel polycystin-2 (PC2) at the endoplasmic reticulum (ER) membrane, enhancing its opening over the whole physiological calcium range in ER liposomes fused to planar bilayers. Consequently, TMEM33 reduces intracellular calcium content in a PC2-dependent manner, impairs lysosomal calcium refilling, causes cathepsins translocation, inhibition of autophagic flux upon ER stress, as well as sensitization to apoptosis. Invalidation of TMEM33 in the mouse exerts a potent protection against renal ER stress. By contrast, TMEM33 does not influence pkd2-dependent renal cystogenesis in the zebrafish. Together, our results identify a key role for TMEM33 in the regulation of intracellular calcium homeostasis of renal proximal convoluted tubule cells and establish a causal link between TMEM33 and acute kidney injury.
Decoding individual differences in STEM learning from functional MRI data
Authors: Cetron Joshua S. , Connolly Andrew C. , Diamond Solomon G. , May Vicki V. , Haxby James V. , Kraemer David J. M.
Published: May 2019

Traditional tests of concept knowledge generate scores to assess how well a learner understands a concept. Here, we investigated whether patterns of brain activity collected during a concept knowledge task could be used to compute a neural ‘score’ to complement traditional scores of an individual’s conceptual understanding. Using a novel data-driven multivariate neuroimaging approach—informational network analysis—we successfully derived a neural score from patterns of activity across the brain that predicted individual differences in multiple concept knowledge tasks in the physics and engineering domain. These tasks include an fMRI paradigm, as well as two other previously validated concept inventories. The informational network score outperformed alternative neural scores computed using data-driven neuroimaging methods, including multivariate representational similarity analysis. This technique could be applied to quantify concept knowledge in a wide range of domains, including classroom-based education research, machine learning, and other areas of cognitive science.
Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans
Authors: Ashton P. M. , Thanh L. T. , Trieu P. H. , Van Anh D. , Trinh N. M. , Beardsley J. , Kibengo F. , Chierakul W. , Dance D. A. B. , Rattanavong S. , Davong V. , Hung L. Q. , Chau N. V. V. , Tung N. L. N. , Chan A. K. , Thwaites G. E. , Lalloo D. G. , Anscombe C. , Nhat L. T. H. , Perfect J. , Dougan G. , Baker S. , Harris S. , Day J. N.
Published: May 2019

Cryptococcus neoformans (C. neoformans var. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformans from HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformans reveals a recent exponential population expansion, consistent with the increase in the number of susceptible hosts. In our study population, this expansion has been driven by three sub-clades of the C. neoformans VNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub-clades account for 91% of clinical isolates sequenced in our study. Combining the genome data with clinical information, we find that the VNIa-93 sub-clade, the most common sub-clade in Uganda and Malawi, was associated with better outcomes than VNIa-4 and VNIa-5, which predominate in Southeast Asia. This study lays the foundation for further work investigating the dominance of VNIa-4, VNIa-5 and VNIa-93 and the association between lineage and clinical phenotype.
Author Correction: Efficient electron transfer across hydrogen bond interfaces by proton-coupled and -uncoupled pathways
Authors: Cheng Tao , Shen Dong Xue , Meng Miao , Mallick Suman , Cao Lijiu , Patmore Nathan J. , Zhang Hong Li , Zou Shan Feng , Chen Huo Wen , Qin Yi , Wu Yi Yang , Liu Chun Y.
Published: May 2019

The original version of this Article contained errors in the symbols displayed in the eighteenth sentence of the third paragraph of the ‘Determination of Hab and kET data for the Mo2 dimers’ section of the Results, and the third sentence of the Discussion. This has been corrected in both the PDF and HTML versions of the Article.
Universal behavior of the apparent fragility in ultraslow glass forming systems
Authors: Drozd-Rzoska Aleksandra
Published: May 2019

Despite decades of studies on the grand problem of the glass transition the question of well-defined universal patterns, including the key problem of the previtreous behavior of the primary (structural) relaxation time, remains elusive. This report shows the universal previtreous behavior of the apparent fragility, i.e. the steepness index mP (T > Tg) = d log10τ(T)/d( Tg/T). It is evidenced that mP(T) = 1(T − T*), for T → Tg and  T*= Tg − Δ T*. Basing on this finding, the new 3-parameter dependence for portraying the previtreous behavior of the primary relaxation time has been derived: τ(T) = CΩ((T − T*)/T)−Ω × [exp((T − T*)/T)]Ω. The universality of obtained relations is evidenced for glass formers belonging to low molecular weight liquids, polymers (melt and solid), plastic crystals, liquid crystals, resins and relaxors. They exhibit clear preferences either for the VFT or for the critical-like descriptions, if recalled already used modeling. The novel relation can obey even above the dynamic crossover temperature, with the power exponent Ω ranging between ~17 (liquid crystals) to ~57 (glycerol), what may indicate the impact of symmetry on the previtreous effect. Finally, the emerging similarity to the behavior in the isotropic phase of nematic liquid crystals is recalled.
Immunoprofiling of Colitis-associated and Sporadic Colorectal Cancer and its Clinical Significance
Authors: Soh Jae Seung , Jo Su In , Lee Hyejin , Do Eun-ju , Hwang Sung Wook , Park Sang Hyoung , Ye Byong Duk , Byeon Jeong-Sik , Yang Suk-Kyun , Kim Ji Hun , Yang Dong-Hoon , Kim Sang-Yeob , Myung Seung-Jae
Published: May 2019

Immunoprofiling is useful for predicting prognosis in various malignancies and provides targets for immunotherapy. Quantitative multispectral imaging system, which allows simultaneous detection of multiple immune markers, is a novel method for examining the tumor immune environment. We compared the expression levels of various surface markers in immune cells between colitis-associated cancer (CAC) and sporadic colorectal cancer (CRC) and evaluated the clinical usefulness of immunoprofiling in CRC. Tumor specimens from 24 CAC patients and 48 sporadic CRC patients, matched by age, sex, and tumor location to CAC, were included in the analysis. The expression levels of CD3, CD8, Foxp3, and programmed death-ligand 1 (PD-L1) in immune cells at the invasive margins of tumor tissues were evaluated by quantitative multispectral imaging. The CAC group had significantly less levels of cells expressing CD3, CD8, Foxp3, or PD-L1 (all, p < 0.01). In the CAC group, patients whose immune cells had high expression of CD3+ and CD8+ had better overall survival. The immune profiling patterns of CAC patients were significantly distinct from those of sporadic CRC patients, suggesting that CAC and sporadic CRC have distinct disease phenotypes. Immunoprofiling can be helpful for evaluation of clinical prognosis in CAC.
Untargeted metabolomics reveals N, N, N-trimethyl-L-alanyl-L-proline betaine (TMAP) as a novel biomarker of kidney function
Authors: Velenosi Thomas J. , Thomson Benjamin K. A. , Tonial Nicholas C. , RaoPeters Adrien A. E. , Mio Megan A. , Lajoie Gilles A. , Garg Amit X. , House Andrew A. , Urquhart Bradley L.
Published: May 2019

The diagnosis and prognosis of chronic kidney disease (CKD) currently relies on very few circulating small molecules, which can vary by factors unrelated to kidney function. In end-stage renal disease (ESRD), these same small molecules are used to determine dialysis dose and dialytic clearance. Therefore, we aimed to identify novel plasma biomarkers to estimate kidney function in CKD and dialytic clearance in ESRD. Untargeted metabolomics was performed on plasma samples from patients with a single kidney, non-dialysis CKD, ESRD and healthy controls. For ESRD patients, pre- and post-dialysis plasma samples were obtained from several dialysis modalities. Metabolomics analysis revealed over 400 significantly different features in non-dialysis CKD and ESRD plasma compared to controls while less than 35 features were significantly altered in patients with a single kidney. N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP, AUROC = 0.815) and pyrocatechol sulfate (AUROC = 0.888) outperformed creatinine (AUROC = 0.745) in accurately identifying patients with a single kidney. Several metabolites accurately predicted ESRD; however, when comparing pre-and post-hemodialysis, TMAP was the most robust biomarker of dialytic clearance for all modalities (AUROC = 0.993). This study describes TMAP as a novel potential biomarker of kidney function and dialytic clearance across several hemodialysis modalities.
Laser-PIXE using laser-accelerated proton beams
Authors: Barberio M. , Antici P.
Published: May 2019

Laser-driven proton acceleration is a field of growing interest, in particular for its numerous applications, including in the field of materials science. A benefit of these laser-based particle sources is their potential for a relative compactness in addition to some characteristics at the source that differ from those of conventional, radio-frequency based proton sources. These features include, e.g., a higher brilliance, a shorter duration, and a larger energy spread. Recently, the use of laser-accelerated protons has been proposed in the field of Cultural Heritage, as alternative source for the Particle Induced X-ray Emission diagnostic (“laser-PIXE”), a particular ion beam analysis (IBA) technique that allows to precisely analyse the chemical composition of the material bulk. In this paper we study the feasibility of the laser-PIXE using laser-accelerated proton beams. We focus on materials specifically of interest for the Cultural Heritage domain. Using Geant4 simulations, we show that the laser-PIXE allows analysing a larger volume than conventional PIXE, profiting from the large energy spread of laser-accelerated protons. Furthermore, for specific materials, the large energy spread allows investigating multilayer materials, providing an advantage compared to conventional PIXE technologies.
Node centrality measures are a poor substitute for causal inference
Authors: Dablander Fabian , Hinne Max
Published: May 2019

Network models have become a valuable tool in making sense of a diverse range of social, biological, and information systems. These models marry graph and probability theory to visualize, understand, and interpret variables and their relations as nodes and edges in a graph. Many applications of network models rely on undirected graphs in which the absence of an edge between two nodes encodes conditional independence between the corresponding variables. To gauge the importance of nodes in such a network, various node centrality measures have become widely used, especially in psychology and neuroscience. It is intuitive to interpret nodes with high centrality measures as being important in a causal sense. Using the causal framework based on directed acyclic graphs (DAGs), we show that the relation between causal influence and node centrality measures is not straightforward. In particular, the correlation between causal influence and several node centrality measures is weak, except for eigenvector centrality. Our results provide a cautionary tale: if the underlying real-world system can be modeled as a DAG, but researchers interpret nodes with high centrality as causally important, then this may result in sub-optimal interventions.
Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis
Authors: Awanye Amaka M. , Chang Chun-Mien , Wheeler Jun X. , Chan Hannah , Marsay Leanne , Dold Christina , Rollier Christine S. , Bird Louise E. , Nettleship Joanne E. , Owens Raymond J. , Pollard Andrew J. , Derrick Jeremy P.
Published: May 2019

Outer membrane vesicle (OMV)- based vaccines have been used to provide strain-specific protection against capsular group B Neisseria meningitidis infections, but the full breadth of the immune response against the components of the OMV has not been established. Sera from adults vaccinated with an OMV vaccine were used to screen 91 outer membrane proteins (OMPs) incorporated in an antigen microarray panel. Antigen-specific IgG levels were quantified pre-vaccination, and after 12 and 18 weeks. These results were compared with IgG levels from mice vaccinated with the same OMV vaccine. The repertoires of highly responding antigens in humans and mice overlapped, but were not identical. The highest responding antigens to human IgG comprised four integral OMPs (PorA, PorB, OpcA and PilQ), a protein which promotes the stability of PorA and PorB (RmpM) and two lipoproteins (BamC and GNA1162). These observations will assist in evaluating the role of minor antigen components within OMVs in providing protection against meningococcal infection. In addition, the relative dominance of responses to integral OMPs in humans emphasizes the importance of this subclass and points to the value of maintaining conformational epitopes from integral membrane proteins in vaccine formulations.
Giant bowing of the band gap and spin-orbit splitting energy in GaP1−xBix dilute bismide alloys
Authors: Bushell Zoe L. , Broderick Christopher A. , Nattermann Lukas , Joseph Rita , Keddie Joseph L. , Rorison Judy M. , Volz Kerstin , Sweeney Stephen J.
Published: May 2019

Using spectroscopic ellipsometry measurements on GaP1−xBix/GaP epitaxial layers up to x = 3.7% we observe a giant bowing of the direct band gap ($${E}_{g}^{{\rm{\Gamma }}}$$

E

g

Γ

) and valence band spin-orbit splitting energy (ΔSO). $${E}_{g}^{{\rm{\Gamma }}}$$

E

g

Γ

(ΔSO) is measured to decrease (increase) by approximately 200 meV (240 meV) with the incorporation of 1% Bi, corresponding to a greater than fourfold increase in ΔSO in going from GaP to GaP0.99Bi0.01. The evolution of $${E}_{g}^{{\rm{\Gamma }}}$$

E

g

Γ

and ΔSO with x is characterised by strong, composition-dependent bowing. We demonstrate that a simple valence band-anticrossing model, parametrised directly from atomistic supercell calculations, quantitatively describes the measured evolution of $${E}_{g}^{{\rm{\Gamma }}}$$

E

g

Γ

and ΔSO with x. In contrast to the well-studied GaAs1−xBix alloy, in GaP1−xBix substitutional Bi creates localised impurity states lying energetically within the GaP host matrix band gap. This leads to the emergence of an optically active band of Bi-hybridised states, accounting for the overall large bowing of $${E}_{g}^{{\rm{\Gamma }}}$$

E

g

Γ

and ΔSO and in particular for the giant bowing observed for x ≲ 1%. Our analysis provides insight into the action of Bi as an isovalent impurity, and constitutes the first detailed experimental and theoretical analysis of the GaP1−xBix alloy band structure.
Computational prediction and in vitro validation of VEGFR1 as a novel protein target for 2,3,7,8-tetrachlorodibenzo-p-dioxin
Authors: Chitrala Kumaraswamy Naidu , Yang Xiaoming , Busbee Brandon , Singh Narendra P. , Bonati Laura , Xing Yongna , Nagarkatti Prakash , Nagarkatti Mitzi
Published: May 2019

The toxic manifestations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, primarily depend on its ability to activate aryl hydrocarbon receptor (AhR), which is a ligand-dependent transcription factor belonging to the superfamily of basic-helix-loop-helix DNA-binding proteins. In the present study, we aimed to identify novel protein receptor targets for TCDD using computational and in vitro validation experiments. Interestingly, results from computational methods predicted that Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) could be one of the potential targets for TCDD in both mouse and humans. Results from molecular docking studies showed that human VEGFR1 (hVEGFR1) has less affinity towards TCDD compared to the mouse VEGFR1 (mVEGFR1). In vitro validation results showed that TCDD can bind and phosphorylate hVEGFR1. Further, results from molecular dynamic simulation studies showed that hVEGFR1 interaction with TCDD is stable throughout the simulation time. Overall, the present study has identified VEGFR1 as a novel target for TCDD, which provides the basis for further elucidating the role of TCDD in angiogenesis.
Large apparent growth increases in boreal forests inferred from tree-rings are an artefact of sampling biases
Authors: Duchesne Louis , Houle Daniel , Ouimet Rock , Caldwell Liam , Gloor Manuel , Brienen Roel
Published: May 2019

Tree rings are thought to be a powerful tool to reconstruct historical growth changes and have been widely used to assess tree responses to global warming. Demographic inferences suggest, however, that typical sampling procedures induce spurious trends in growth reconstructions. Here we use the world’s largest single tree-ring dataset (283,536 trees from 136,621 sites) from Quebec, Canada, to assess to what extent growth reconstructions based on these - and thus any similar - data might be affected by this problem. Indeed, straightforward growth rate reconstructions based on these data suggest a six-fold increase in radial growth of black spruce (Picea mariana) from ~0.5 mm yr−1 in 1800 to ~2.5 mm yr−1 in 1990. While the strong correlation (R2 = 0.98) between this increase and that of atmospheric CO2 could suggest a causal relationship, we here unambiguously demonstrate that this growth trend is an artefact of sampling biases caused by the absence of old, fast-growing trees (cf. “slow-grower survivorship bias”) and of young, slow-growing trees (cf. “big-tree selection bias”) in the dataset. At the moment, we cannot envision how to remedy the issue of incomplete representation of cohorts in existing large-scale tree-ring datasets. Thus, innovation will be needed before such datasets can be used for growth rate reconstructions.
Acidic Stress Triggers Sodium-Coupled Bicarbonate Transport and Promotes Survival in A375 Human Melanoma Cells
Authors: Yang Oscar C. Y. , Loh Shih-Hurng
Published: May 2019

Melanoma cells preserve intracellular pH (pHi) within a viable range despite an acidic ambient pH that typically falls below pH 7.0. The molecular mechanisms underlying this form of acidic preservation in melanoma remain poorly understood. Previous studies had demonstrated that proton transporters including the monocarboxylate transporter (MCT), the sodium hydrogen exchanger (NHE), and V-Type ATPase mediate acid extrusion to counter intracellular acidification in melanoma cells. In this report, the expression and function of the Sodium-Coupled Bicarbonate Transporter (NCBT) family of base loaders were further characterized in melanoma cell lines. NCBT family members were found to be expressed in three different melanoma cell lines – A375, MeWo, and HS695T – and included the electrogenic sodium-bicarbonate cotransporter isoforms 1 and 2 (NBCe1 and NBCe2), the electroneutral sodium-bicarbonate cotransporter (NBCn1), and the sodium-dependent chloride-bicarbonate exchanger (NDCBE). These transporters facilitated 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS)-dependent pHirecovery in melanoma cells, in response to intracellular acidification induced by ammonium chloride prepulse. Furthermore, the expression of NCBTs were upregulated via chronic exposure to extracellular acidification. Given the current research interest in the NCBTs as a molecular driver of tumourigenesis, characterising NCBT in melanoma provides impetus for developing novel therapeutic targets for melanoma treatment.
Cisplatin Pharmacodynamics Following Endobronchial Ultrasound-Guided Transbronchial Needle Injection into Lung Tumors
Authors: Mori Vitor , Roy Gregory S. , Bates Jason H. T. , Kinsey C. Matthew
Published: May 2019

Intratumoral delivery of cisplatin by endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) has recently emerged as a therapy for treating peribronchial lung cancers. It remains unclear, however, where best to inject drug into a tumor, and at how many sites, so current cisplatin delivery strategies remain empirical. Motivated by the need to put EBUS-TBNI treatment of lung cancer on a more objective footing, we developed a computational model of cisplatin pharmacodynamics following EBUS-TBNI. The model accounts for diffusion of cisplatin within and between the intracellular and extracellular spaces of a tumor, as well as clearance of cisplatin from the tumor via the vasculature and clearance from the body via the kidneys. We matched the tumor model geometry to that determined from a thoracic CT scan of a patient with lung cancer. The model was calibrated by fitting its predictions of cisplatin blood concentration versus time to measurements made up to 2 hrs following EBUS-TBNI of cisplatin into the patient’s lung tumor. This gave a value for the systemic volume of distribution for cisplatin of 12.2 L and a rate constant of clearance from the tumor into the systemic compartment of 1.46 × 10−4 s−1. Our model indicates that the minimal dose required to kill all cancerous cells in a lung tumor can be reduced by roughly 3 orders of magnitude if the cisplatin is apportioned between 5 optimally spaced locations throughout the tumor rather than given as a single bolus to the tumor center. Our findings suggest that optimizing the number and location of EBUS-TBNI sites has a dramatic effect on the dose of cisplatin required for efficacious treatment of lung cancer.
Multiple stressors interact primarily through antagonism to drive changes in the coral microbiome
Authors: Maher Rebecca L. , Rice Mallory M. , McMinds Ryan , Burkepile Deron E. , Vega Thurber Rebecca
Published: May 2019

Perturbations in natural systems generally are the combination of multiple interactions among individual stressors. However, methods to interpret the effects of interacting stressors remain challenging and are biased to identifying synergies which are prioritized in conservation. Therefore we conducted a multiple stressor experiment (no stress, single, double, triple) on the coralPocillopora meandrinato evaluate how its microbiome changes compositionally with increasing levels of perturbation. We found that effects of nutrient enrichment, simulated predation, and increased temperature are antagonistic, rather than synergistic or additive, for a variety of microbial community diversity measures. Importantly, high temperature and scarring alone had the greatest effect on changing microbial community composition and diversity. Using differential abundance analysis, we found that the main effects of stressors increased the abundance of opportunistic taxa, and two-way interactions among stressors acted antagonistically on this increase, while three-way interactions acted synergistically. These data suggest that: (1) multiple statistical analyses should be conducted for a complete assessment of microbial community dynamics, (2) for some statistical metrics multiple stressors do not necessarily increase the disruption of microbiomes over single stressors in this coral species, and (3) the observed stressor-induced community dysbiosis is characterized by a proliferation of opportunists rather than a depletion of a proposed coral symbiont of the genusEndozoicomonas.
Characterization of microbial communities in the chicken oviduct and the origin of chicken embryo gut microbiota
Authors: Lee Sangwon , La Tae-Min , Lee Hong-Jae , Choi In-Soo , Song Chang-Seon , Park Seung-Yong , Lee Joong-Bok , Lee Sang-Won
Published: May 2019

The transferred microbiota from mother to baby constitutes the initial infant gastrointestinal microbiota and has an important influence on the development and health of infants in human. However, the reproductive tract microbiota of avian species and its inheritance have rarely been studied. We aimed to characterize the microbial community in the chicken reproductive tract and determine the origin of the chicken embryo gut microbiota. Microbiota in four different portions of chicken oviduct were determined using 16S rRNA metagenomic approach with the IonTorrent platform. Additionally, we analyzed the mother hen’s magnum and cloaca, descendent egg, and embryo gut microbiota. The microbial composition and relative abundance of bacterial genera were stable throughout the entire chicken reproductive tract, without significant differences between the different parts of the oviduct. The chicken reproductive tract showed a relatively high abundance of Lactobacillus species. The number of bacterial species in the chicken reproductive tract significantly increased following sexual maturation. Core genera analysis detected 21 of common genera in the maternal magnum and cloaca, descendent egg shell, egg white, and embryo gut. Some elements of the maternal oviduct microbiota appear to be transferred to the embryo through the egg white and constitute most of the embryo gut bacterial population.
Contrasting endemism in pond-dwelling cyclic parthenogens: the Daphnia curvirostris species group (Crustacea: Cladocera)
Authors: Kotov Alexey A. , Taylor Derek J.
Published: May 2019

Pond-dwelling cyclic parthenogens are often proposed to be highly vagile. However, the Holarctic biogeography of parthenogens has been hampered by very limited sampling in the eastern Palearctic. Here we examine the geographic boundaries, diversity, and connectivity across the Palearctic for theDaphnia curvirostriscomplex (Cladocera: Daphniidae). Nuclear (HSP90) and mitochondrial (ND2) sequence data supported the existence of five main clades (most of which corresponded to presumptive species) with one eastern Palearctic clade being novel to this study (the average mitochondrial genetic divergence from known species was 19.2%).D.curvirostriss.s. was geographically widespread in the Palearctic, with a population genetic signature consistent with postglacial expansion. The Eastern Palearctic had local nine endemic species and/or subclades (other Holarctic regions lacked more than one endemic subclade). Even though several endemic species appeared to have survived Pleistocene glaciation in the eastern Palearctic, much of the Palearctic has been recolonized byD.curvirostriss.str. from a Western Palearctic refugium. A disjunct population in Mexico also shared its haplotypes withD.curvirostriss.str., consistent with a recent introduction. The only apparently endemic North American lineage was detected in a thermally disturbed pond system in northwestern Alaska. Our results for pond-dwelling cyclic parthenogens further support the hypothesis that the Eastern Palearctic is a diversity hotspot for freshwater invertebrates.
Reversal of established liver fibrosis by IC-2-engineered mesenchymal stem cell sheets
Authors: Itaba Noriko , Kono Yohei , Watanabe Kaori , Yokobata Tsuyoshi , Oka Hiroyuki , Osaki Mitsuhiko , Kakuta Hiroki , Morimoto Minoru , Shiota Goshi
Published: May 2019

Chronic hepatitis viral infection, alcoholic intoxication, and obesity cause liver fibrosis, which progresses to decompensated liver cirrhosis, a disease for which medical demands cannot be met. Since there are currently no approved anti-fibrotic therapies for established liver fibrosis, the development of novel modalities is required to improve patient prognosis. In this study, we clarified the anti-fibrotic effects of cell sheets produced from human bone marrow-derived mesenchymal stem cells (MSCs) incubated on a temperature-sensitive culture dish with the chemical compound IC-2. Orthotopic transplantation of IC-2-engineered MSC sheets (IC-2 sheets) remarkably reduced liver fibrosis induced by chronic CCl4 administration. Further, the marked production of fibrolytic enzymes such as matrix metalloproteinase (MMP)-1 and MMP-14, as well as thioredoxin, which suppresses hepatic stellate cell activation, was observed in IC-2 sheets. Moreover, the anti-fibrotic effect of IC-2 sheets was much better than that of MSC sheets. Finally, knockdown experiments revealed that MMP-14 was primarily responsible for the reduction of liver fibrosis. Here, we show that IC-2 sheets could be a promising therapeutic option for established liver fibrosis.
Comparison of the trabecular meshwork length between open and closed angle with evaluation of the scleral spur location
Authors: Choi Wungrak , Lee Min woo , Kang Hyun Goo , Lee Hye Sun , Bae Hyoung Won , Kim Chan Yun , Seong Gong Je
Published: May 2019

This study analysed the trabecular meshwork (TM) length in open and closed angle patients and presented a better method for locating the scleral spur using Schwalbe’s line method in anterior segment optical coherence tomography (AS-OCT). Patients who underwent AS-OCT at Yonsei University Gangnam Severance Hospital we enrolled; 58 and 57 open and closed angle eyes, respectively. We measured the distance from the scleral spur to Schwalbe’s line as the TM length and compared it between open and closed angle patients, and to previous studies. TM length was applied to locate the scleral spur using Schwalbe’s line method. Mean TM lengths were 811 ± 83 μm and 575 ± 96 μm in the open and closed angle groups, respectively (p < 0.001). Comparing the actual TM heights using Schwalbe’s line method with an updated reference distance significantly increased accuracy to locate the scleral spur (open: 811 μm, closed: 575 μm) when compared with the 1000 μm reference distance (p < 0.001). TM length was significantly different between open and closed angle patients. Further, the reference distance for Schwalbe’s line method should be distinguished according to open and closed angle eyes in order that the scleral spur can be located properly.
Nanostraw membrane stamping for direct delivery of molecules into adhesive cells
Authors: Zhang Bowen , Shi Yiming , Miyamoto Daisuke , Nakazawa Koji , Miyake Takeo
Published: May 2019

Delivering ions and molecules into living cells has become an important challenge in medical and biological fields. Conventional molecular delivery, however, has several issues such as physical and chemical damage to biological cells. Here, we present a method of directly delivering molecules into adhesive cells with an Au-based nanostraw membrane stamp that can physically inject a target molecule into the cytoplasm through a nanostraw duct. We successfully delivered calcein target molecules into adhesive cells with high efficiency (85%) and viability (90%). Furthermore, we modeled the molecular flow through Au nanostraws and then demonstrated the control of calcein flow by changing the concentration and geometry of Au nanostraws. Our Au membrane stamping provides a new way of accessing the cytoplasm to modulate cellular functions via injected molecules.
Increased biomass and lipid production of Ettlia sp. YC001 by optimized C and N sources in heterotrophic culture
Authors: Kim Minsik , Lee Bongsoo , Kim Hee Su , Nam Kibok , Moon Myounghoon , Oh Hee-Mock , Chang Yong Keun
Published: May 2019

The culture conditions and media composition for the heterotrophic culture of an axenic strain of Ettlia sp. YC001 were firstly optimized using the Plackett-Burman design (PBD) and response surface methodology (RSM). The strain successfully showed higher productivity in the basal media without any light illumination at 32.2 to 33.3 °C. The PBD results showed that the most effective components for biomass productivity of Ettlia sp. were fructose and yeast extract for sources of C and N, respectively. The RSM results showed an optimal level of 72.2 g/L for fructose and 21.5 g/L for yeast extract, resulting in 46.1 g/L biomass with a lipid content of 13.8% over a course of 9 days. Using a 5 L scaled-up fermentation system for 6 days, the production of biomass and lipids was 7.21 g/L/day and 1.18 g/L/day, respectively. Consequently, heterotrophic cultivation of Ettlia sp. YC001 provided much higher production of biomass and lipids than those of autotrophic cultivation. As further research, the use of substitute substrates instead of fructose and yeast extract should be developed to reduce production costs.
Cost-effective fibrinolytic enzyme production by Bacillus subtilis WR350 using medium supplemented with corn steep powder and sucrose
Authors: Wu Rui , Chen Guiguang , Pan Shihan , Zeng Jingjing , Liang Zhiqun
Published: May 2019

The goal of this study was to develop a cheap and simple medium and to optimize fermentation parameters for fibrinolytic enzyme production by Bacillus subtilis WR350. A low-cost medium containing 35 g/L sucrose, 20 g/L corn steep powder and 2 g/L MgSO4·7H2O was developed via single-factor and orthogonal experiments. A cheap nitrogen source, corn steep powder, was used to replace the soy peptone present in the initial medium. The highest fibrinolytic activity of 5865 U/mL was achieved using the optimized medium in a 100-L fermenter with an aeration rate of 1.0 vvm and an agitation speed of 200 rpm. The resulting enzyme yield was among the highest described in the literature with respect to fibrinolytic activity, as determined by the fibrin plate method. Techno-economic evaluation indicated that the cost of the optimized medium was only 8.5% of the cost of the initial medium, and the total fermentation cost of fibrinolytic enzyme production using the optimized medium was 23.35% of the cost of using the initial medium.