bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical evaluation of tissue stops on 3D-printed custom trays
Authors: Deng Kehui , Chen Hu , Li Rong , Li Linlin , Wang Yong , Zhou Yongsheng , Sun Yuchun
Published: February 2019

This study evaluated the quality of impressions taken using three-dimensional (3D)-printed custom trays with different tissue stops to optimize the custom tray designs. Different custom trays were designed and printed based on six edentulous patients. These trays were divided into four groups based on the tissue-stop designs: 3DP trays (3D-printed trays without tissue stops), 3DPS trays (3D-printed trays with saddle-shaped tissue stops), 3DPM trays (3D-printed trays with marginal-band tissue stops) and 3DPIM trays (3D-printed trays with inner marginal-band tissue stops). Final impressions were taken using these trays, of which, the 3DP and 3DPIM trays were preborder-moulded. The finished complete dentures were used to take impressions that were set as the reference group to analyse the accuracy of the final impressions. The impressions taken using the 3DP custom trays (preborder-moulded) were used as a reference to analyse the extensions of the impressions taken using the other three custom trays. Randomized block or Friedman tests were used to evaluate each group’s statistical significance. The results revealed that the 3DPIM custom trays with the inner marginal-band tissue stop facilitated the preborder-moulding process and improved the accuracy and extension of the impression.
Experimental Evidence of Rainbow Trapping and Bloch Oscillations of Torsional Waves in Chirped Metallic Beams
Authors: Arreola-Lucas A. , Báez G. , Cervera F. , Climente A. , Méndez-Sánchez R. A. , Sánchez-Dehesa J.
Published: February 2019

The Bloch oscillations (BO) and the rainbow trapping (RT) are two apparently unrelated phenomena, the former arising in solid state physics and the latter in metamaterials. A Bloch oscillation, on the one hand, is a counter-intuitive effect in which electrons start to oscillate in a crystalline structure when a static electric field is applied. This effect has been observed not only in solid state physics but also in optical and acoustical structured systems since a static electric field can be mimicked by a chirped structure. The RT, on the other hand, is a phenomenon in which the speed of a wave packet is slowed down in a dielectric structure; different colors then arrive to different depths within the structure thus separating the colors also in time. Here we show experimentally the emergence of both phenomena studying the propagation of torsional waves in chirped metallic beams. Experiments are performed in three aluminum beams in which different structures were machined: one periodic and two chirped. For the smaller value of the chirping parameter the wave packets, with different central frequencies, are back-scattered at different positions inside the corrugated beam; the packets with higher central frequencies being the ones with larger penetration depths. This behavior represents the mechanical analogue of the rainbow trapping effect. This phenomenon is the precursor of the mechanical Bloch oscillations, which are here demonstrated for a larger value of the chirping parameter. It is observed that the oscillatory behavior observed at small values of the chirp parameter is rectified according to the penetration length of the wave packet.
Multilayer fabrication of unobtrusive poly(dimethylsiloxane) nanobrush for tunable cell adhesion
Authors: Chae Soo Sang , Jung Joo Hyun , Choi Won Jin , Park Joung Kyu , Baik Hong Koo , Jung Jongjin , Ko Hyuk Wan
Published: February 2019

Precise modulation of polymer brush in its thickness and grafting density can cause unexpected cell behaviors and regulated bioactivities. Herein, a nanoscale poly(dimethylsiloxane) (PDMS) brush was employed to use as a controllable material for cell adhesion. Facile fabrication of ultrathin monolayer PDMS nanobrush on an underlying substrate facilitated regaining cell adhesion through long-range cell attractive forces such as the van der Waals forces. We showed that cell adhesion is diminished by increasing the number of nanobrush layers, causing a gradual decrease of the effectiveness of the long-range force. The result demonstrates that ultrathin PDMS nanobrush can either promote or inhibit cell adhesion, which is required for various biomedical fields such as tissue-engineering, anti-fouling coating, and implantable biomaterials and sensors.
Gene silencing based on RNA-guided catalytically inactive Cas9 (dCas9): a new tool for genetic engineering in Leptospira
Authors: Fernandes L. G. V. , Guaman L. P. , Vasconcellos S. A. , Heinemann Marcos B. , Picardeau M. , Nascimento A. L. T. O.
Published: February 2019

Leptospirosis is a worldwide zoonosis caused by pathogenic bacteria of the genus Leptospira, which also includes free-living saprophyte strains. Many aspects of leptospiral basic biology and virulence mechanisms remain unexplored mainly due to the lack of effective genetic tools available for these bacteria. Recently, the type II CRISPR/Cas system from Streptococcus pyogenes has been widely used as an efficient genome engineering tool in bacteria by inducing double-strand breaks (DSBs) in the desired genomic targets caused by an RNA-guided DNA endonuclease called Cas9, and the DSB repair associated machinery. In the present work, plasmids expressing heterologous S. pyogenes Cas9 in L. biflexa cells were generated, and the enzyme could be expressed with no apparent toxicity to leptospiral cells. However, L. biflexa cells were unable to repair RNA-guided Cas9-induced DSBs. Thus, we used a catalytically dead Cas9 (dCas9) to obtain gene silencing rather than disruption, in a strategy called CRISPR interference (CRISPRi). We demonstrated complete gene silencing in L. biflexa cells when both dCas9 and single-guide RNA (sgRNA) targeting the coding strand of the β-galactosidase gene were expressed simultaneously. Furthermore, when the system was applied for silencing the dnaK gene, no colonies were recovered, indicating that DnaK protein is essential in Leptospira. In addition, flagellar motor switch FliG gene silencing resulted in reduced bacterial motility. To the best of our knowledge, this is the first work applying the CRISPRi system in Leptospira and spirochetes in general, expanding the tools available for understanding leptospiral biology.
Analysis of SMALP co-extracted phospholipids shows distinct membrane environments for three classes of bacterial membrane protein
Authors: Teo Alvin C. K. , Lee Sarah C. , Pollock Naomi L. , Stroud Zoe , Hall Stephen , Thakker Alpesh , Pitt Andrew R. , Dafforn Timothy R. , Spickett Corinne M. , Roper David I.
Published: February 2019

Biological characterisation of membrane proteins lags behind that of soluble proteins. This reflects issues with the traditional use of detergents for extraction, as the surrounding lipids are generally lost, with adverse structural and functional consequences. In contrast, styrene maleic acid (SMA) copolymers offer a detergent-free method for biological membrane solubilisation to produce SMA-lipid particles (SMALPs) containing membrane proteins together with their surrounding lipid environment. We report the development of a reverse-phase LC-MS/MS method for bacterial phospholipids and the first comparison of the profiles of SMALP co-extracted phospholipids from three exemplar bacterial membrane proteins with different topographies: FtsA (associated membrane protein), ZipA (single transmembrane helix), and PgpB (integral membrane protein). The data showed that while SMA treatment per se did not preferentially extract specific phospholipids from the membrane, SMALP-extracted ZipA showed an enrichment in phosphatidylethanolamines and depletion in cardiolipins compared to the bulk membrane lipid. Comparison of the phospholipid profiles of the 3 SMALP-extracted proteins revealed distinct lipid compositions for each protein: ZipA and PgpB were similar, but in FtsA samples longer chain phosphatidylglycerols and phosphatidylethanolamines were more abundant. This method offers novel information on the phospholipid interactions of these membrane proteins.
Synergic effects of oxygen supply and antioxidants on pancreatic β-cell spheroids
Authors: Myasnikova Dina , Osaki Tatsuya , Onishi Kisaki , Kageyama Tatsuto , Zhang Molino Binbin , Fukuda Junji
Published: February 2019

Diabetes is one of the most common metabolic disorders, and is characterized by the inability to secrete/sense insulin and abnormal blood glucose concentration. Many researchers have concentrated their efforts on improving islet transplantation, in particular by fabricating bioartificial pancreatic islets in vitro. One of the critical points for the success of this research direction is the improvement of culture conditions, such as oxygen supply, in the engineering of bioartificial pancreatic islets to ensure their viability and functionality after transplantation. In this work, we fabricated microwell spheroid culture devices made of oxygen-permeable polydimethylsiloxane (PDMS), with which hypoxia in the core of bioartificial islets was alleviated and glucose-stimulated insulin secretion was increased ~2.5-fold compared to a device with the same configuration but made of non-oxygen-permeable plastic. We also demonstrated that antioxidants, such as ascorbic acid-2-phosphate (AA2P), could neutralize islet damage caused by increased reactive oxygen species (ROS) in the cell culture environment. These results suggest that supply of oxygen together with removal of ROS may lead to a better approach to prepare highly viable and functional bioartificial pancreatic islets.
Prognostic nomogram of hypoxia-related genes predicting overall survival of colorectal cancer–Analysis of TCGA database
Authors: Lee Joon-Hyop , Jung Sohee , Park Won Seo , Choe Eun Kyung , Kim Eunyoung , Shin Rumi , Heo Seung Chul , Lee Jae Hyun , Kim Kwangsoo , Chai Young Jun
Published: February 2019

Hypoxia-related gene (HRG) expression is associated with survival outcomes of colorectal cancer (CRC). Our aim was developing a nomogram predicting CRC overall survival (OS) with HRGs and clinicopathological factors. The Cancer Genome Atlas (TCGA) database was used as discovery cohort and two Gene Expression Omnibus databases (GSE39582 and GSE41258) served as validation cohorts. A genetic risk score model prognosticating OS was developed using mRNA expression level of HRGs. Nomogram predicting OS was developed using genetic risk score model and clinicopathological variables. The genetic risk score model included four HRGs (HSPA1L, PUM1, UBE2D2, and HSP27) and successfully prognosticated OS of discovery and two validation cohorts (p < 0.001 for TCGA discovery set, p < 0.003 for the GSE39582 and p = 0.042 for the GSE41258 datasets). Nomogram included genetic risk score, age, and TNM stage. Harrell’s concordance indexes of the nomogram were higher than those of TNM stage alone in the discovery set (0.77 vs. 0.69, p < 0.001), GSE39582 (0.65 vs. 0.63, p < 0.001), and GSE41258 datasets (0.78 vs. 0.77, p < 0.001). Our nomogram successfully predicted OS of CRC patients. The mRNA expression level of the HRGs might be useful as an ancillary marker for prognosticating CRC outcome.
Fibroblast growth factor receptor signaling in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Jerchel Isabel S. , Hoogkamer Alex Q. , Ariës Ingrid M. , Boer Judith M. , Besselink Nicolle J. M. , Koudijs Marco J. , Pieters Rob , den Boer Monique L.
Published: February 2019

The FGF receptor signaling pathway is recurrently involved in the leukemogenic processes. Oncogenic fusions of FGFR1 with various fusion partners were described in myeloid proliferative neoplasms, and overexpression and mutations of FGFR3 are common in multiple myeloma. In addition, fibroblast growth factors are abundant in the bone marrow, and they were shown to enhance the survival of acute myeloid leukemia cells. Here we investigate the effect of FGFR stimulation on pediatric BCP-ALL cells in vitro, and search for mutations with deep targeted next-generation sequencing of mutational hotspots in FGFR1, FGFR2, and FGFR3. In 481 primary BCP-ALL cases, 28 samples from 19 unique relapsed BCP-ALL cases, and twelve BCP-ALL cell lines we found that mutations are rare (4/481 = 0.8%, 0/28 and 0/12) and do not affect codons which are frequently mutated in other malignancies. However, recombinant ligand FGF2 reduced the response to prednisolone in several BCP-ALL cell lines in vitro. We therefore conclude that FGFR signaling can contribute to prednisolone resistance in BCP-ALL cells, but that activating mutations in this receptor tyrosine kinase family are very rare.
Epithelial Cells and Fibroblasts from the Human Female Reproductive Tract Accumulate and Release TFV and TAF to Sustain Inhibition of HIV Infection of CD4+ T cells
Authors: Shen Zheng , Rodriguez-Garcia Marta , Patel Mickey V. , Bodwell Jack , Wira Charles R.
Published: February 2019

Tenofovir (TFV) treatment of female reproductive tract (FRT) cells results in differential accumulation of intracellular Tenofovir diphosphate (TFV-DP) in different cell types, with greater concentrations in epithelial cells (100-fold) and fibroblasts (10-fold) than in CD4+ T cells. The possibility that TFV-DP accumulation and retention in epithelial cells and fibroblasts may alter TFV availability and protection of CD4+ T cells against HIV infection, prompted us to evaluate TFV and/or Tenofovir alafenamide (TAF) release from FRT cells. Endometrial, endocervical and ectocervical polarized epithelial cells and fibroblasts were pre-loaded with TFV or TAF, and secretions tested for their ability to inhibit HIV infection of activated blood CD4+ T cells. Epithelial cell basolateral secretions (1, 2 and 3 days post-loading), but not apical secretions, suppressed HIV infection of CD4+ T cells, as did secretions from pre-loaded fibroblasts from each site. Intracellular TFV-DP levels in epithelial cells following preloading with TFV or TAF correlated directly with ARV protection of CD4+ T cells from HIV infection. When added apically to epithelial cells, TFV/TAF was released basolaterally, in part through Multidrug Resistant Protein transporters, taken up by fibroblasts and released into secretions to partially protect CD4+ T cells. These findings demonstrate that epithelial cells and fibroblasts release TFV/TAF for use by CD4+ T cells and suggest that the tissue environment plays a major role in the sustained protection against HIV infection.
Permeability regain and aqueous phase migration during hydraulic fracturing shut-ins
Authors: Li Shuai , Lei Qun , Wang Xin , Cai Bo , Liu Guangfeng , Wang Long
Published: February 2019

Hydraulic fracturing has become a key technology to economically extract oil and gas from unconventional reservoirs. During hydraulic fracturing, fluid loss and water invasion into formation can cause serious permeability reduction near fracture face. At the same time, field practice also showed that well shut-ins after hydraulic fracturing could significantly increase hydrocarbon outputs, whereas the inner mechanism still remains unknown. In this paper, firstly, we studied permeability reduction after water invasion and permeability enhancement after well shut-ins using a core flooding system. Then, to investigate the inner mechanism, we studied aqueous phase migration during shut-ins using nuclear magnetic resonance (NMR) method. Results showed that fluids invasion reduce matrix permeability while well shut-ins can improve permeability and this improvement depends on the length of shut-ins time. NMR results showed that aqueous phases mainly distribute in macropores and mesopores after water invasion, while in shut-ins period, these invaded aqueous phases redistribute and migrate from larger pore spaces to smaller ones. Aqueous phase redistribution and migration during shut-ins period can remove near fracture water-block, reduce capillary discontinuity and increase the relative permeability of hydrocarbon phase, and this is the reason for permeability enhancement and hydrocarbon output increase after well shut-ins.
Development of a new High Resolution Melting (HRM) assay for identification and differentiation of Mycobacterium tuberculosis complex samples
Authors: Landolt Patricia , Stephan Roger , Scherrer Simone
Published: February 2019

The rapid identification and differentiation of members of the Mycobacterium tuberculosis complex (MTBC) is essential to assess the potential zoonotic risk. Different available molecular methods are time consuming since they depend on cultivation of mycobacteria. High Resolution Melting (HRM) is a low cost, rapid and easy to perform single-tube method not limited to cultured samples. In this study, a HRM assay specifically targeting gyrB was developed to simultaneously identify and differentiate Mycobacterium (M.) tuberculosis, M. microti and M. bovis/M. caprae. To evaluate the performance of this assay, 38 MTBC isolates and 25 directly extracted clinical specimens were analysed. HRM results of all 38 (100%) examined isolates correlated with the results obtained with the commercially available GenoType MTBC test (Hain Lifescience). From the 25 clinical specimens tested, species identification by HRM showed concordant results with the previously used identification methods in 23 samples (92%). The assay demonstrated a good analytical sensitivity, specificity and reproducibility and can be used directly on clinical specimens.
The Regenerative Potential of Amniotic Fluid Stem Cell Extracellular Vesicles: Lessons Learned by Comparing Different Isolation Techniques
Authors: Antounians Lina , Tzanetakis Areti , Pellerito Ornella , Catania Vincenzo D. , Sulistyo Adrienne , Montalva Louise , McVey Mark J. , Zani Augusto
Published: February 2019

Extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs) mediate anti-apoptotic, pro-angiogenic, and immune-modulatory effects in multiple disease models, such as skeletal muscle atrophy and Alport syndrome. A source of potential variability in EV biological functions is how EV are isolated from parent cells. Currently, a comparative study of different EV isolation strategies using conditioned medium from AFSCs is lacking. Herein, we examined different isolation strategies for AFSC-EVs, using common techniques based on differential sedimentation (ultracentrifugation), solubility (ExoQuick, Total Exosome Isolation Reagent, Exo-PREP), or size-exclusion chromatography (qEV). All techniques isolated AFSC-EVs with typical EV morphology and protein markers. In contrast, AFSC-EV size, protein content, and yield varied depending on the method of isolation. When equal volumes of the different AFSC-EV preparations were used as treatment in a model of lung epithelial injury, we observed a significant variation in how AFSC-EVs were able to protect against cell death. AFSC-EV enhancement of cell survival appeared to be dose dependent, and largely uninfluenced by variation in EV-size distributions, relative EV-purity, or their total protein content. The variation in EV-mediated cell survival obtained with different isolation strategies emphasizes the importance of testing alternative isolation techniques in order to maximize EV regenerative capacity.
Non-alcoholic fatty liver disease and cerebral small vessel disease in Korean cognitively normal individuals
Authors: Jang Hyemin , Kang Danbee , Chang Yoosoo , Kim Yeshin , Lee Jin San , Kim Ko Woon , Jang Young Kyoung , Kim Hee Jin , Na Duk L. , Shin Hee Young , Kang Mira , Guallar Eliseo , Cho Juhee , Seo Sang Won
Published: February 2019

We aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and cerebral small vessel disease (CSVD) burden, especially according to the NAFLD severity. A total of 1,260 participants were included. The CSVD burden was assessed with white matter hyperintensities (WMH), lacunes, and microbleeds (MBs) on brain MRI. An ultrasound diagnosis of fatty liver was made based on standard criteria, and the Fibrosis-4 (FIB-4) index was used to classify participants with NAFLD with having a high-intermediate (FIB-4 ≥1.45) or low (FIB-4 < 1.45) probability of advanced fibrosis. A multivariable logistic regression analysis was used to assess the association between NAFLD and the presence of moderate to severe WMH, lacunes, and MBs. NAFLD had a significant association only with moderate to severe WMH (OR: 1.64, 95% CI: 1.10–2.42), even after controlling for cardiometabolic risk factors. A linear trend test showed a significant association between the severity of NAFLD fibrosis and the presence of moderate to severe WMH (p for trend <0.001). Our findings suggest that NAFLD, especially NAFLD with fibrosis, has a significant association with the presence of moderate to severe WMH in cognitively normal individuals, and NAFLD severity predicted more frequent moderate to severe WMH.
In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds
Authors: Albanna Mohammed , Binder Kyle W. , Murphy Sean V. , Kim Jaehyun , Qasem Shadi A. , Zhao Weixin , Tan Josh , El-Amin Idris B. , Dice Dennis D. , Marco Julie , Green Jason , Xu Tao , Skardal Aleksander , Holmes James H. , Jackson John D. , Atala Anthony , Yoo James J.
Published: February 2019

The early treatment and rapid closure of acute or chronic wounds is essential for normal healing and prevention of hypertrophic scarring. The use of split thickness autografts is often limited by the availability of a suitable area of healthy donor skin to harvest. Cellular and non-cellular biological skin-equivalents are commonly used as an alternative treatment option for these patients, however these treatments usually involve multiple surgical procedures and associated with high costs of production and repeated wound treatment. Here we describe a novel design and a proof-of-concept validation of a mobile skin bioprinting system that provides rapid on-site management of extensive wounds. Integrated imaging technology facilitated the precise delivery of either autologous or allogeneic dermal fibroblasts and epidermal keratinocytes directly into an injured area, replicating the layered skin structure. Excisional wounds bioprinted with layered autologous dermal fibroblasts and epidermal keratinocytes in a hydrogel carrier showed rapid wound closure, reduced contraction and accelerated re-epithelialization. These regenerated tissues had a dermal structure and composition similar to healthy skin, with extensive collagen deposition arranged in large, organized fibers, extensive mature vascular formation and proliferating keratinocytes.
Solution of Cross-Kerr Interaction Combined with Parametric Amplification
Authors: Khorasani Sina
Published: February 2019

We present a full operator approach to treatment of the cross-Kerr interaction combined with parametric amplification. It is shown that this problem can be exactly integrated using the method of higher-order operators. While the initial basis is infinite-dimensional, an orthogonal transformation can reduce the problem exactly into a six-dimensional basis which can be integrated conveniently.
Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer
Authors: Martin Nikolas Tim , Roy Dominic Guy , Workenhe Samuel Tekeste , van den Wollenberg Diana J. M. , Hoeben Rob C. , Mossman Karen Louise , Bell John Cameron , Bourgeois-Daigneault Marie-Claude
Published: February 2019

The use of oncolytic viruses (OVs) for cancer treatment is emerging as a successful strategy that combines the direct, targeted killing of the cancer with the induction of a long-lasting anti-tumor immune response. Using multiple aggressive murine models of triple-negative breast cancer, we have recently demonstrated that the early administration of oncolytic Maraba virus (MRB) prior to surgical resection of the primary tumor is sufficient to minimize the metastatic burden, protect against tumor rechallenge, cure a fraction of the mice and sensitize refractory tumors to immune checkpoint blockade without the need for further treatment. Here, we apply our surgical model to other OVs: Vesicular stomatitis virus (VSV), Adenovirus (Ad), Reovirus (Reo) and Herpes simplex virus (HSV) and show that all of the tested OVs could positively change the outcome of the treated animals. The growth of the primary and secondary tumors was differently affected by the various OVs and most of the viruses conferred survival benefits in this neoadjuvant setting despite the absence of direct treatment following rechallenge. This study establishes that OV-therapy confers long-term protection when administered in the pre-operative window of opportunity.
Amplified Spontaneous Emission in Paper
Authors: Hoinka N. M. , Fuhrmann-Lieker T.
Published: February 2019

Industrially produced copy paper is presented as a novel optical material for narrow-band stimulated emission. Fluorescent brightening agents (FBA) such as Calcofluor White provide enough gain to exceed the threshold for amplified spontaneous emission. By applying an additional dye such as Coumarin 307, or simply a highlighter pen, the emission line can be shifted from blue (~440 nm), towards turquoise (>480 nm), up to orange (590 nm) which can be useful for spectroscopic applications. These properties are demonstrated in two papers, a commercial copy paper and a FBA-stained calligraphy paper.
Four-dimensional joint visualization of electrode degradation and liquid water distribution inside operating polymer electrolyte fuel cells
Authors: White Robin T. , Eberhardt Sebastian H. , Singh Yadvinder , Haddow Tylynn , Dutta Monica , Orfino Francesco P. , Kjeang Erik
Published: February 2019

Understanding of degradation mechanisms present in polymer electrolyte fuel cells (PEFCs) is important to continue the integration of this clean energy technology into everyday life. Further comprehension of the interaction between various components during fuel cell operation is also critical in this context. In this work, a four-dimensional operando X-ray computed tomography method is developed for combined visualization of all PEFC components as well as transient water distribution residing in the cell, which results as a by-product of the electrochemical reaction. Time resolved, identical-location visualization through degradation stages is uniquely enabled by the non-invasive and non-destructive qualities of this method. By applying an accelerated stress test that targets cathode catalyst layer (CCL) corrosion, novel observations resulting from morphological changes of the CCL such as reduction in the water volume in the adjacent gas diffusion layer, CCL crack formation and propagation, membrane swelling, as well as quantification of local carbon loss is achieved. Additionally, insight into features that contribute to reduced fuel cell performance is enabled by the use of this specialized imaging technique, such as increased membrane undulation causing delamination and separation of the CCL from the microporous layer, which greatly affects liquid water pathways and overall device performance.
Revisit Population-based and Family-based Genotype Imputation
Authors: Liu Ching-Ti , Deng Xuan , Fisher Virginia , Heard-Costa Nancy , Xu Hanfei , Zhou Yanhua , Vasan Ramachandran S. , Cupples L. Adrienne
Published: February 2019

Genome-Wide Association (GWA) with population-based imputation (PBI) has been successful in identifying common variants associated with complex diseases; however, much heritability remains to be explained and low frequency variants (LFV) may contribute. To identify LFV, a study of unrelated individuals may no longer be as efficient as a family study, where rare population variants can be frequent in families. Family-based imputation (FBI) provides an opportunity to evaluate LFV. To compare the performance of PBI and FBI, we conducted extensive simulations, generating genotypes using SeqSIMLA from various reference panels for families. We masked genotype information for variants unavailable in Framingham 550 K GWA genotype data in less informative subjects selected by GIGI-Pick. We implemented IMPUTE2 with duoHMM in SHAPEIT (Impute2_duoHMM) for PBI, MERLIN and GIGI for FBI and PedBLIMP for a hybrid approach. In general, FBI in both MERLIN and GIGI outperformed other approaches with imputation accuracy greater than 0.99 for the squared correlation and imputation quality scores (IQS) especially for LFV, although imputation accuracy from MERLIN depends on pedigree splitting for larger families. PBI performed worst with the exception of good imputation accuracy for common variants when a closely ancestry matched reference is used. In summary, linkage disequilibrium (LD) information from large available genotype resources provides good imputation for common variants with well-selected reference panels without requiring densely sequenced data in family members, while imputation of LFV with FBI benefits more from information on inheritance patterns within families yielding better imputation.
Fractal conceptualization of intumescent fire barriers, toward simulations of virtual morphologies
Authors: Okyay Gizem , Naik Anil D. , Samyn Fabienne , Jimenez Maude , Bourbigot Serge
Published: February 2019

By limiting the heat spread during a fire hazard, intumescent coatings are important components of passive protection systems. They swell due to heat induced reactions of micro constituents and are transformed into carbonaceous porous-like media, known as intumescent chars. Their multiscale inner structures, key elements of performance, are costly to predict by recurrent and large scale fire testing while numerical simulations are challenging due to complex kinetics. Hence, we propose a novel approach using the fractal theory and the random nature of events to conceptualize the coating expansion. Experimental specimens were obtained from fire protective coatings exposed to bench scale hydrocarbon fire. Mass fractals were evidenced in the slices of 3D sample volumes reconstructed from X-ray microtomography. Consequently, geometrical building blocks were simulated by random walk, active walk, aggregation-like and site percolation: physical-chemical modes of action were inherent in the attribution of the randomness. It is a first demonstration to conceptualize different types of intumescent actions by a generalized approach with dimensionless parameters at multiscale, thus eliminating the simulation of complex kinetics to obtain a realistic morphology. Also, fractal results brought new evidence to former chemical analyses on fire test residues trying to explain the kinetics of expansion. Expected outcomes are to predict virtually the reaction of fire protective systems hence to speed-up the assessment of fire performance through computed properties of virtual volumes.
Long-term in vitro 3D hydrogel co-culture model of inflammatory bowel disease
Authors: Dosh Rasha H. , Jordan-Mahy Nicola , Sammon Christopher , Le Maitre Christine L.
Published: February 2019

Thein vitrostudy of the pathogenesis of inflammatory bowel disease (IBD) requires a cell model which closely reflects the characteristics of thein vivointestinal epithelium. This study aimed to investigate the application of L-pNIPAM hydrogel as a scaffold to develop a long-term 3D co-culture model of Caco-2 and HT29-MTX cells under conditions analogous to inflammation, to determine its potential use in studying IBD. Monocultures and co-cultures were layered on L-pNIPAM hydrogel scaffolds and maintained under dynamic culture conditions for up to 12 weeks. Treatments with IL-1β, TNFα, and hypoxia for 1 week were used to create an inflammatory environment. Following prolonged culture, the metabolic activity of Caco-2 monoculture and 90% Caco-2/10% HT29-MTX co-cultures on L-pNIPAM hydrogels were increased, and finger-like structures, similar in appearance to villi were observed. Following treatment with IL-1β, TNFα and hypoxia, ALP and ZO-1 were decreased, MUC2 increased, and MUC5AC remained unchanged. ADAMTS1 was increased in response to hypoxia. Caspase 3 expression was increased in response to TNFα and hypoxic conditions. In conclusion, L-pNIPAM hydrogel supported long-term co-culture within a 3D model. Furthermore, stimulation with factors seen during inflammation recapitulated features seen during IBD.
Development of Orthogonal Linear Separation Analysis (OLSA) to Decompose Drug Effects into Basic Components
Authors: Mizuno Tadahaya , Kinoshita Setsuo , Ito Takuya , Maedera Shotaro , Kusuhara Hiroyuki
Published: February 2019

Drugs have multiple, not single, effects. Decomposition of drug effects into basic components helps us to understand the pharmacological properties of a drug and contributes to drug discovery. We have extended factor analysis and developed a novel profile data analysis method: orthogonal linear separation analysis (OLSA). OLSA contracted 11,911 genes to 118 factors from transcriptome data of MCF7 cells treated with 318 compounds in a Connectivity Map. Ontology of the main genes constituting the factors detected significant enrichment of the ontology in 65 of 118 factors and similar results were obtained in two other data sets. In further analysis of the Connectivity Map data set, one factor discriminated two Hsp90 inhibitors, geldanamycin and radicicol, while clustering analysis could not. Doxorubicin and other topoisomerase inhibitors were estimated to inhibit Na+/K+ATPase, one of the suggested mechanisms of doxorubicin-induced cardiotoxicity. Based on the factor including PI3K/AKT/mTORC1 inhibition activity, 5 compounds were predicted to be novel inducers of autophagy, and other analyses including western blotting revealed that 4 of the 5 actually induced autophagy. These findings indicate the potential of OLSA to decompose the effects of a drug and identify its basic components.
On-target and off-target effects of novel orthosteric and allosteric activators of GPR84
Authors: Mancini Sarah J. , Mahmud Zobaer Al , Jenkins Laura , Bolognini Daniele , Newman Robert , Barnes Matt , Edye Michelle E. , McMahon Stephen B. , Tobin Andrew B. , Milligan Graeme
Published: February 2019

Many members of the G protein-coupled receptor family, including examples with clear therapeutic potential, remain poorly characterised. This often reflects limited availability of suitable tool ligands with which to interrogate receptor function. In the case of GPR84, currently a target for the treatment of idiopathic pulmonary fibrosis, recent times have seen the description of novel orthosteric and allosteric agonists. Using 2-(hexylthiol)pyrimidine-4,6 diol (2-HTP) and di(5,7-difluoro-1H-indole-3-yl)methane (PSB-16671) as exemplars of each class, in cell lines transfected to express either human or mouse GPR84, both ligands acted as effective on-target activators and with high co-operativity in their interactions. This was also the case in lipopolysaccharide-activated model human and mouse immune cell lines. However in mouse bone-marrow-derived neutrophils, where expression of GPR84 is particularly high, the capacity of PSB-16671 but not of 2-HTP to promote G protein activation was predominantly off-target because it was not blocked by an antagonist of GPR84 and was preserved in neutrophils isolated from GPR84 deficient mice. These results illustrate the challenges of attempting to study and define functions of poorly characterised receptors using ligands that have been developed via medicinal chemistry programmes, but where assessed activity has been limited largely to the initially identified target.
Fabrication of dual-functional composite yarns with a nanofibrous envelope using high throughput AC needleless and collectorless electrospinning
Authors: Valtera Jan , Kalous Tomas , Pokorny Pavel , Batka Ondrej , Bilek Martin , Chvojka Jiri , Mikes Petr , Kostakova Eva Kuzelova , Zabka Petr , Ornstova Jana , Beran Jaroslav , Stanishevsky Andrei , Lukas David
Published: February 2019

Nanotechnologies allow the production of yarns containing nanofibres for use in composites, membranes and biomedical materials. Composite yarns with a conventional thread core for mechanical strength and a nanofibrous envelope for functionality, e.g. biological, catalytic, have many advantages. Until now, the production of such yarns has been technologically difficult. Here, we show an approach to composite yarn production whereby a plume of nanofibers generated by high throughput AC needleless and collectorless electrospinning is wound around a classic thread. In the resulting yarn, nanofibres can form up to 80% of its weight. Our yarn production speed was 10 m/min; testing showed this can be increased to 60 m/min. After the yarn was embedded into knitwear, scanning electron microscope images revealed an intact nanofibrous envelope of the composite yarn. Our results indicate that this production method could lead to the widespread production and use of composite nanofibrous yarns on an industrial scale.
Investigating the Effects of Stove Emissions on Ocular and Cancer Cells
Authors: Karakoçak Bedia Begüm , Patel Sameer , Ravi Nathan , Biswas Pratim
Published: February 2019

More than a third of the world’s population relies on solid fuels for cooking and heating, with major health consequences. Although solid fuel combustion emissions are known to increase the prevalence of illnesses such as chronic obstructive pulmonary disease and lung cancer, however, their effect on the eyes is underexplored. This study assesses the acute toxicity of solid fuel combustion emissions on healthy ocular cells and a cancer cell line. Three healthy ocular cell lines (corneal, lens, and retinal epithelial cells) and a cancer cell line (Chinese hamster ovary cells) were exposed to liquid and gas phase emissions from applewood and coal combustion. Following the exposure, real-time cell attachment behavior was monitored for at least 120 hours with electrical cell impedance spectroscopy. The viability of the cells, amount of apoptotic cells, and generation of reactive oxygen species (ROS) were quantified with MTT, ApoTox-Glo, and ROS-Glo H2O2 assays, respectively. The results showed that coal emissions compromised the viability of ocular cells more than applewood emissions. Interestingly, the cancer cells, although their viability was not compromised, generated 1.7 to 2.7 times more ROS than healthy cells. This acute exposure study provides compelling proof that biomass combustion emissions compromise the viability of ocular cells and increase ROS generation. The increased ROS generation was fatal for ocular cells, but it promoted the growth of cancer cells.
Enhanced nonreciprocal transmission through a saturable cubic-quintic nonlinear dimer defect
Authors: Wasay Muhammad Abdul , Lyra M. L. , Ham B. S.
Published: February 2019

The transmission properties through a saturable cubic-quintic nonlinear defect attached to lateral linear chains is investigated. Particular attention is directed to the possible non-reciprocal diode-like transmission when the parity-symmetry of the defect is broken. Distinct cases of parity breaking are considered including asymmetric linear and nonlinear responses. The spectrum of the transmission coefficient is analytically computed and the influence of the degree of saturation analyzed in detail. The transmission of Gaussian wave-packets is also numerically investigated. Our results unveil that spectral regions with high transmission and enhanced diode-like operation can be achieved.
Light Emitting Spin Active Electronic States in Ultra-Thin Mn Doped CdSe Layered Nanosheets
Authors: Halder O. , Satpati B. , Rajput P. , Mohapatra N. , Jha S. N. , Suffczyński J. , Pacuski W. , Rath S.
Published: February 2019

The layered nanosheets exhibit a variety of physical and optical properties originating from amalgamation of intra- and inter- layer electronic interactions, which makes them promising materials for advanced devices with varsatile controlling channels. In particular, the dilute magnetic semiconductor multilayered nanosheets have promising optical, electrical and magnetic properties that have been less explored so far. Here, the spin permissible optical properties from solvothermally grown Mn doped CdSe (thickness ~2.26 nm) multilayered nanosheets are reported on. The presence of multi-phase magnetic orderings with a sharp ferromagnetic transition at temperature ~48 K pertinent to the stabilization and co-existence of Mn2+and Mn3+based local phases have been observed from the (Cd,Mn)Se layered nanosheets corroborating to the x-ray absorption near edge structure, electron paramagnetic resonance, Raman scattering and magnetic measurements. The optical absorption and photoluminescence (PL) studies at room temperature affirm wide array of optical properties in the visible regime corresponding to the band edge and intriguing dopant-phase mediated spin approved transitions. The circularly polarized magneto-PL and life time analysis exhibits the spin-polarized fast radiative transitions confirming the presence of spin-active electronic states.
A metagenomic survey of soil microbial communities along a rehabilitation chronosequence after iron ore mining
Authors: Gastauer Markus , Vera Mabel Patricia Ortiz , de Souza Kleber Padovani , Pires Eder Soares , Alves Ronnie , Caldeira Cecílio Frois , Ramos Silvio Junio , Oliveira Guilherme
Published: February 2019

Microorganisms are useful environmental indicators, able to deliver essential insights to processes regarding mine land rehabilitation. To compare microbial communities from a chronosequence of mine land rehabilitation to pre-disturbance levels from references sites covered by native vegetation, we sampled non-rehabilitated, rehabilitating and reference study sites from the Urucum Massif, Southwestern Brazil. From each study site, three composed soil samples were collected for chemical, physical, and metagenomics analysis. We used a paired-end library sequencing technology (NextSeq 500 Illumina); the reads were assembled using MEGAHIT. Coding DNA sequences (CDS) were identified using Kaiju in combination with non-redundant NCBI BLAST reference sequences containing archaea, bacteria, and viruses. Additionally, a functional classification was performed by EMG v2.3.2. Here, we provide the raw data and assembly (reads and contigs), followed by initial functional and taxonomic analysis, as a base-line for further studies of this kind. Further investigation is needed to fully understand the mechanisms of environmental rehabilitation in tropical regions, inspiring further researchers to explore this collection for hypothesis testing.
Argumentation in Chemistry Education: An Overview
Authors: Erduran Sibel
Published: February 2019

The chapter is an introduction to the book by highlighting the role of argumentation in chemistry education. Argumentation is typically defined as the justification of claims with evidence. There is now a substantial body of work in this area as evidenced by content review of key journals and the presence of books dedicated to this theme. The chapter starts with a concrete example from a practical chemistry lesson activity to illustrate why argumentation is needed in chemistry teaching and learning. The relevance and current status of argumentation for the chemistry curriculum are subsequently discussed. The intention in this book is to contextualise argumentation in chemistry education by drawing on accounts from research, curriculum policy and practice. The chapter concludes with an overview of the content of the chapters.
Teaching and Learning Chemistry through Argumentation
Authors: Aydeniz Mehmet
Published: February 2019

This chapter focuses on teaching and learning of chemistry through argumentation. It focuses on chemistry educators’ uptake of argumentation, provides a summary and critique of argumentation studies conducted in the field of chemical education across K-16 classrooms, and discusses implications of the findings reported in these studies for practice and future argumentation studies in chemistry education. One critical piece of this chapter is a discussion on the nature of chemical knowledge and how to promote the philosophy of chemistry in argumentation-based teaching and learning. This chapter also provides a sample argumentation task that can be adopted and used by high school chemistry teachers, professors of introductory chemistry courses and pre-service teacher educators.
Research and Practice on Science Teachers’ Continuous Professional Development in Argumentation
Authors: Zembal-Saul Carla , Vaishampayan Abha
Published: February 2019

This contribution interrogates shifts in the landscape of science education research and practice that have had a substantial influence on teacher learning in argumentation. Existing research on the specialized knowledge and practices unique to science teaching is summarized. From this, the question of why argumentation is uncommon in school science when there has been significant attention to research and practice in this area for decades is raised. In light of this dilemma, argumentation is considered in the context of current reform endeavors that foreground productive participation in scientific practices for understanding and using disciplinary core ideas in chemistry (and other domains of science) to construct evidence-based explanations for natural phenomena. The demands of supporting teacher development in argumentation is further explored using conceptual, epistemic, and social lenses. Once this terrain is mapped, the literature on science teachers’ learning needs is examined, and promising approaches for teacher learning and development are described. The chapter concludes with what the authors believe to be one of the most pressing considerations moving forward with the continuous professional development of science teachers – that of equitable opportunities and access to high quality science learning experiences for every student.
Argumentation in Organic Chemistry Education
Authors: Pabuccu Aybuke
Published: February 2019

This chapter firstly presents some of the findings from the other studies to better understand the difficulties that college students encountered in learning organic chemistry. Secondly, it presents studies on argumentation in organic chemistry education. Research on argumentation in the context of some specific science topics, like organic chemistry, is rather scarce. One possible reason of this tendency could be the fact that promoting students’ argumentation about organic chemistry topics seems much more difficult than the other chemistry topics, so that researchers usually prefer to use other methods besides argumentation to promote students’ understanding about organic chemistry concepts. Also, for teachers and students, it may appear that there is not much to debate in organic chemistry and so organic chemistry topics are conventionally based on memorization. Thirdly, example activities to support the incorporation of argumentation in organic chemistry lessons will also be presented. Unlike regular organic chemistry activities, these activities are not only aimed at helping students understand organic chemistry concepts, but also to develop their ability to reason with evidence and justifications. Finally, the effects of the incorporation of argumentation into the organic chemistry classroom on transforming organic chemistry education and my own reflections as a teacher educator are discussed.