bluuebunny/crossref_metadata_2025_split huggingface dataset:
Label-free, multi-scale imaging of ex-vivo mouse brain using spatial light interference microscopy
Authors: Min Eunjung , Kandel Mikhail E. , Ko CheMyong J , Popescu Gabriel , Jung Woonggyu , Best-Popescu Catherine 
Published: December 2016

AbstractBrain connectivity spans over broad spatial scales, from nanometers to centimeters. In order to understand the brain at multi-scale, the neural network in wide-field has been visualized in detail by taking advantage of light microscopy. However, the process of staining or addition of fluorescent tags is commonly required, and the image contrast is insufficient for delineation of cytoarchitecture. To overcome this barrier, we use spatial light interference microscopy to investigate brain structure with high-resolution, sub-nanometer pathlength sensitivity without the use of exogenous contrast agents. Combining wide-field imaging and a mosaic algorithm developed in-house, we show the detailed architecture of cells and myelin, within coronal olfactory bulb and cortical sections, and from sagittal sections of the hippocampus and cerebellum. Our technique is well suited to identify laminar characteristics of fiber tract orientation within white matter, e.g. the corpus callosum. To further improve the macro-scale contrast of anatomical structures, and to better differentiate axons and dendrites from cell bodies, we mapped the tissue in terms of its scattering property. Based on our results, we anticipate that spatial light interference microscopy can potentially provide multiscale and multicontrast perspectives of gross and microscopic brain anatomy.
Global microbial carbonate proliferation after the end-Devonian mass extinction: Mainly controlled by demise of skeletal bioconstructors
Authors: Yao Le , Aretz Markus , Chen Jitao , Webb Gregory E. , Wang Xiangdong 
Published: December 2016

AbstractMicrobial carbonates commonly flourished following mass extinction events. The end-Devonian (Hangenberg) mass extinction event is a first-order mass extinction on the scale of the ‘Big Five’ extinctions. However, to date, it is still unclear whether global microbial carbonate proliferation occurred after the Hangenberg event. The earliest known Carboniferous stromatolites on tidal flats are described from intertidal environments of the lowermost Tournaisian (Qianheishan Formation) in northwestern China. With other early Tournaisian microbe-dominated bioconstructions extensively distributed on shelves, the Qianheishan stromatolites support microbial carbonate proliferation after the Hangenberg extinction. Additional support comes from quantitative analysis of the abundance of microbe-dominated bioconstructions through the Famennian and early Tournaisian, which shows that they were globally distributed (between 40° latitude on both sides of the palaeoequator) and that their abundance increased distinctly in the early Tournaisian compared to the latest Devonian (Strunian). Comparison of variations in the relative abundance of skeleton- versus microbe-dominated bioconstructions across the Hangenberg and ‘Big Five’ extinctions suggests that changes in abundance of skeletal bioconstructors may play a first-order control on microbial carbonate proliferation during extinction transitions but that microbial proliferation is not a general necessary feature after mass extinctions.
Effect of high-flux, low-energy He+ ion irradiation on Ta as a plasma-facing material
Authors: Novakowski T. J. , Tripathi J. K. , Hassanein A. 
Published: December 2016

AbstractThe goal of this work is to assess Ta as a potential plasma-facing material for future fusion reactors in terms of its response to high-flux, low-energy He+ ion irradiation. Ta samples were irradiated with 100 eV He+ ions at various fluences up to 3.5 × 1025 ions m−2 while simultaneously heated at constant temperatures in the range 823–1223 K. SEM studies show that irradiated Ta surfaces undergo significant morphology changes that have a strong dependence on both ion fluence and sample temperature. Optical reflectivity complements SEM and demonstrates a vertical growth of surface structures with increasing fluence. Ex situ XPS and XRD both show significant oxidation of the irradiated Ta surfaces, giving further qualitative information on the extent of surface modification. Overall, these irradiation-induced structures on Ta are similar to early-stage “fuzz” structures observed in W. However, Ta exhibits a higher fluence threshold for structure formation. While Ta may have less desirable bulk properties (e.g., thermal conductivity) when compared to W, its higher resilience to He+ ion-induced surface modification suggests that surface thermal and mechanical properties may not degrade as quickly in extreme fusion environments; this quality may be a redeeming factor for Ta as a plasma-facing material.
Real-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji
Authors: Dunne Eileen M. , Mantanitobua Silivia , Singh Shalini P. , Reyburn Rita , Tuivaga Evelyn , Rafai Eric , Tikoduadua Lisi , Porter Barbara , Satzke Catherine , Strachan Janet E. , Fox Kimberly K. , Jenkins Kylie M. , Jenney Adam , Baro Silo , Mulholland E. Kim , Kama Mike , Russell Fiona M. 
Published: December 2016

AbstractAs part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Of 266 samples tested, pathogens were identified in 47 (17.7%). S. pneumoniae was the most common pathogen detected (n = 17) followed by N. meningitidis (n = 13). The use of qPCR significantly increased detection of IB-VPD pathogens (P = 0.0001): of 35 samples that were qPCR positive for S. pneumoniae, N. meningitidis, and H. influenzae, only 10 were culture positive. This was particularly relevant for N. meningitidis, as only 1/13 cases was culture positive. Molecular serotyping by microarray was used to determine pneumococcal serotypes from 9 of 16 (56%) of samples using DNA directly extracted from CSF specimens. Results indicate that qPCR significantly increases detection of S. pneumoniae, N. meningitidis, and H. influenzae in CSF, and that application of molecular diagnostics is a feasible way to enhance local and global surveillance for IB-VPD.
Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering
Authors: Rogozhnikov Dmitry , O’Brien Paul J. , Elahipanah Sina , Yousaf Muhammad N. 
Published: December 2016

AbstractThere has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.
Circulating tumor cell detection in hepatocellular carcinoma based on karyoplasmic ratios using imaging flow cytometry
Authors: Liu Zixin , Guo Weixing , Zhang Dandan , Pang Yanan , Shi Jie , Wan Siqin , Cheng Kai , Wang Jiaqi , Cheng Shuqun 
Published: December 2016

AbstractCirculating tumor cells (CTCs) originate from tumor tissues and are associated with cancer prognosis. However, existing technologies for CTC detection are limited owing to a lack of specific or accurate biomarkers. Here, we developed a new method for CTC detection based on the karyoplasmic ratio, without biomarkers. Consecutive patients with liver cancer or non-cancer liver diseases were recruited. CTCs in blood samples were analyzed by imaging flow cytometry based on the karyoplasmic ratio as well as EpCAM and CD45. Microvascular invasion (MVI), tumor recurrence, and survival were recorded for all patients. A total of 56.2 ± 23.8/100,000 cells with high karyoplasmic ratios (HKR cells) were detected in cancer patients, which was higher than the number of HKR cells in the non-cancer group (7.6 ± 2.2/100,000). There was also a difference in HKR cells between liver cancer patients with and without MVI. Based on a receiver operating characteristic curve analysis, the threshold was 21.8 HKR cells per 100,000 peripheral blood mononuclear cells, and the area under the curve was higher than those of traditional methods (e.g., CD45 and EpCAM staining). These results indicate that the new CTC detection method was more sensitive and reliable than existing methods. Accordingly, it may improve clinical CTC detection.
Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population
Authors: Ostrowski Jerzy , Paziewska Agnieszka , Lazowska Izabella , Ambrozkiewicz Filip , Goryca Krzysztof , Kulecka Maria , Rawa Tomasz , Karczmarski Jakub , Dabrowska Michalina , Zeber-Lubecka Natalia , Tomecki Roman , Kluska Anna , Balabas Aneta , Piatkowska Magdalena , Paczkowska Katarzyna , Kierkus Jaroslaw , Socha Piotr , Lodyga Michal , Rydzewska Grazyna , Klopocka Maria , Mierzwa Grazyna , Iwanczak Barbara , Krzesiek Elzbieta , Bak-Drabik Katarzyna , Walkowiak Jaroslaw , Klincewicz Beata , Radwan Piotr , Grzybowska-Chlebowczyk Urszula , Landowski Piotr , Jankowska Agnieszka , Korczowski Bartosz , Starzynska Teresa , Albrecht Piotr , Mikula Michal 
Published: December 2016

AbstractMost inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.
The presence of Anf/Hesx1 homeobox gene in lampreys suggests that it could play an important role in emergence of telencephalon
Authors: Bayramov Andrey V. , Ermakova Galina V. , Eroshkin Fedor M. , Kucheryavyy Alexandr V. , Martynova Natalia Y. , Zaraisky Andrey G. 
Published: December 2016

AbstractAccumulated evidence indicates that the core genetic mechanisms regulating early patterning of the brain rudiment in vertebrates are very similar to those operating during development of the anterior region of invertebrate embryos. However, the mechanisms underlying the morphological differences between the elaborate vertebrate brain and its simpler invertebrate counterpart remain poorly understood. Recently, we hypothesized that the emergence of the most anterior unit of the vertebrate brain, the telencephalon, could be related to the appearance in vertebrates’ ancestors of a unique homeobox gene, Anf/Hesx1(further Anf), which is absent from all invertebrates and regulates the earliest steps of telencephalon development in vertebrates. However, the failure of Anf to be detected in one of the most basal extant vertebrate species, the lamprey, seriously compromises this hypothesis. Here, we report the cloning of Anf in three lamprey species and demonstrate that this gene is indeed expressed in embryos in the same pattern as in other vertebrates and executes the same functions by inhibiting the expression of the anterior general regulator Otx2 in favour of the telencephalic regulator FoxG1. These results are consistent with the hypothesis that the Anf homeobox gene may have been important in the evolution of the telencephalon.
High step‐up DC–DC converter with switched‐capacitor and its zero‐voltage switching realisation
Authors: He Liangzong , Zheng Zhipeng 
Published: December 2016

As generally acknowledged, the high step‐up DC–DC converter is widely used in the sustainable energy system as the front‐end stage of the DC–AC converter. Therefore, a novel high step‐up DC–DC converter is proposed in this study. The proposed converter with network of switched‐inductor and switched‐capacitor can achieve high voltage gain under low duty cycle. Meanwhile, the active switches and diodes suffer from low voltage stress. More importantly, an auxiliary resonant circuit with lower losses and cost is employed to realise zero‐voltage switching (ZVS) turned‐on and ZVS turned‐off for the active switches, resulting in high conversion efficiency. Firstly, the operation principle and steady‐state performance are discussed in detail. Then, prototype with power rating of 200 W is built to verify the performance of the proposed converter. The maximum efficiency of the prototype can be up to 96%, and the experimental results agree with the theoretical analysis and the simulation results well.
Inhibition of radiation-induced glioblastoma invasion by genetic and pharmacological targeting of MDA-9/Syntenin
Authors: Kegelman Timothy P. , Wu Bainan , Das Swadesh K. , Talukdar Sarmistha , Beckta Jason M. , Hu Bin , Emdad Luni , Valerie Kristoffer , Sarkar Devanand , Furnari Frank B. , Cavenee Webster K. , Wei Jun , Purves Angela , De Surya K. , Pellecchia Maurizio , Fisher Paul B. 
Published: December 2016

SignificanceIn the setting of glioblastoma multiforme (GBM), invasion of cells into normal brain and the unlikeliness of complete surgical removal contributes to GBM lethality and recurrence. “Gold standard” GBM treatment includes adjuvant radiotherapy. Unfortunately, cells surviving radiation demonstrate increased invasion and therapeutic resistance. Melanoma differentiation-associated gene 9 (MDA-9/Syntenin) expression is elevated in patient-derived tumors and GBM cell lines, which correlates with decreased survival and poor response to radiation. Genetic suppression of MDA-9/Syntenin sensitizes GBM to radiation by inhibiting radiation-induced invasion gains and signaling changes. Additionally, intraperitoneal administration of a small-molecule MDA-9/Syntenin inhibitor, PDZ1i, developed using innovative fragment-based drug design and NMR approaches, improved survival of brain tumor-bearing mice. Survival was enhanced further when used with radiation, supporting MDA-9/Syntenin as a therapeutic target for this deadly disease.
Comparative analysis of stakeholder experiences with an online approach to prioritizing patient-centered research topics
Authors: Khodyakov Dmitry , Grant Sean , Meeker Daniella , Booth Marika , Pacheco-Santivanez Nathaly , Kim Katherine K 
Published: December 2016

Objective: Little evidence exists about effective and scalable methods for meaningful stakeholder engagement in research. We explored patient/caregiver experiences with a high-tech online engagement approach for patient-centered research prioritization, compared their experiences with those of professional stakeholders, and identified factors associated with favorable participant experiences.
Methods: We conducted 8 online modified-Delphi (OMD) panels. Panelists participated in 2 rating rounds with a statistical feedback/online discussion round in between. Panels focused on weight management/obesity, heart failure, and Kawasaki disease. We recruited a convenience sample of adults with any of the 3 conditions (or parents/guardians of Kawasaki disease patients), clinicians, and researchers. Measures included self-reported willingness to use OMD again, the panelists’ study participation and online discussion experiences, the system’s perceived ease of use, and active engagement metrics.
Results: Out of 349 panelists, 292 (84%) completed the study. Of those, 46% were patients, 36% were clinicians, and 19% were researchers. In multivariate models, patients were not significantly more actively engaged (Odds ratio (OR) = 1.69, 95% confidence interval (CI), 0.94–3.05) but had more favorable study participation (β = 0.49; P ≤ .05) and online discussion (β = 0.18; P ≤ .05) experiences and were more willing to use OMD again (β = 0.36; P ≤ .05), compared to professional stakeholders. Positive perceptions of the OMD system’s ease of use (β = 0.16; P ≤ .05) and favorable study participation (β = 0.26; P ≤ .05) and online discussion (β = 0.57; P ≤ .05) experiences were also associated with increased willingness to use OMD in the future. Active engagement was not associated with online experience indices or willingness to use OMD again.
Conclusion: Online approaches to engaging large numbers of stakeholders are a promising and efficient adjunct to in-person meetings.
Spatiotemporal Dynamics of the Bacterial Microbiota on LacustrineCladophora Glomerata(Chlorophyta)
Authors: Braus Michael J. , Graham Linda E. , Whitman Thea L. 
Published: December 2016

ABSTRACTThe branched periphytic green algaCladophora glomerata,often abundant in nearshore waters of lakes and rivers worldwide, plays important ecosystem roles, some mediated by epibiotic microbiota that benefit from host-provided surface, organic C, and O2. Previous microscopy and high throughput sequencing studies have indicated surprising epibiont taxonomic and functional diversity, but have not included adequate consideration of sample replication or the potential for spatial and temporal variation. Here we report the results of 16S rRNA amplicon-based phylum-to-genus taxonomic analysis ofCladophora-associated bacterial epibiota sampled in replicate from three microsites and at six times during the open-water season of 2014, from the same lake locale (Picnic Point, Lake Mendota, Dane Co., WI, USA) explored by high throughput sequencing studies in two previous years. Statistical methods were used to test null hypotheses that the bacterial community: 1) is homogeneous across microsites tested, and 2) does not change over the course of a growth season or among successive years. Results indicated a dynamic microbial community that is more strongly influenced by sampling day during the growth season than by microsite variation. A surprising diversity of bacterial genera known to be associated with the key function of methane-oxidation (methanotrophy)-including relatively high-abundance ofCrenothrix, Methylomonas,andMethylocaldum–showed intra-seasonal and inter-annual variability possibly related to temperature differences, and microsite preferences possibly related to variation in methane abundance. By contrast, a core assemblage of bacterial genera seems to persist over a growth season and from year-to-year, possibly transmitted by a persistent attached host resting stage.
Infectious Disease Dynamics Inferred from Genetic Data via Sequential Monte Carlo
Authors: Smith R. A. , Ionides E. L. , King A. A. 
Published: December 2016

AbstractGenetic sequences from pathogens can provide information about infectious disease dynamics that may supplement or replace information from other epidemiological observations. Currently available methods first estimate phylogenetic trees from sequence data, then estimate a transmission model conditional on these phylogenies. Outside limited classes of models, existing methods are unable to enforce logical consistency between the model of transmission and that underlying the phylogenetic reconstruction. Such conflicts in assumptions can lead to bias in the resulting inferences. Here, we develop a general, statistically efficient, plug-and-play method to jointly estimate both disease transmission and phylogeny using genetic data and, if desired, other epidemiological observations. This method explicitly connects the model of transmission and the model of phylogeny so as to avoid the aforementioned inconsistency. We demonstrate the feasibility of our approach through simulation and apply it to estimate stage-specific infectiousness in a subepidemic of HIV in Detroit, Michigan. In a supplement, we prove that our approach is a valid sequential Monte Carlo algorithm. While we focus on how these methods may be applied to population-level models of infectious disease, their scope is more general. These methods may be applied in other biological systems where one seeks to infer population dynamics from genetic sequences, and they may also find application for evolutionary models with phenotypic rather than genotypic data.
From static to temporal network theory – applications to functional brain connectivity
Authors: Thompson William Hedley , Brantefors Per , Fransson Peter 
Published: December 2016

AbstractNetwork neuroscience has become an established paradigm to tackle questions related to the functional and structural connectome of the brain. Recently, there has been a growing interest to examine the temporal dynamics of the brain's network activity. While different approaches to capture fluctuations in brain connectivity have been proposed, there have been few attempts to quantify these fluctuations using temporal network theory. Temporal network theory is an extension of network theory that has been successfully applied to the modeling of dynamic processes in economics, social sciences and engineering. The objective of this paper is twofold: (i) to present a detailed description of the central tenets and outline measures from temporal network theory; (ii) apply these measures to a resting-state fMRI dataset to illustrate their utility. Further, we discuss the interpretation of temporal network theory in the context of the dynamic functional brain connectome. All the temporal network measures and plotting functions described in this paper are freely available as a python package Teneto.