bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Sclerosis patients carry an increased burden of exceedingly rare genetic variants in the inflammasome regulatory genes
Authors: Vidmar Lovro , Maver Ales , Drulović Jelena , Sepčić Juraj , Novaković Ivana , Ristič Smiljana , Šega Saša , Peterlin Borut 
Published: June 2019

AbstractThe role of rare genetic variation and the innate immune system in the etiology of multiple sclerosis (MS) is being increasingly recognized. Recently, we described several rare variants in the NLRP1 gene, presumably conveying an increased risk for familial MS. In the present study we aimed to assess rare genetic variation in the inflammasome regulatory network. We performed whole exome sequencing of 319 probands, comprising patients with familial MS, sporadic MS and control subjects. 62 genes involved in the NLRP1/NLRP3 inflammasome regulation were screened for potentially pathogenic rare genetic variation. Aggregate mutational burden was analyzed, considering the variants’ predicted pathogenicity and frequency in the general population. We demonstrate an increased (p = 0.00004) variant burden among MS patients which was most pronounced for the exceedingly rare variants with high predicted pathogenicity. These variants were found in inflammasome genes (NLRP1/3, CASP1), genes mediating inflammasome inactivation via auto and mitophagy (RIPK2, MEFV), and genes involved in response to infection with DNA viruses (POLR3A, DHX58, IFIH1) and to type-1 interferons (TYK2, PTPRC). In conclusion, we present new evidence supporting the importance of rare genetic variation in the inflammasome signaling pathway and its regulation via autophagy and interferon-β to the etiology of MS.
Differential expression profiling of long non-coding RNA GAS5 and miR-126-3p in human cancer cells in response to sorafenib
Authors: Faranda Teresa , Grossi Ilaria , Manganelli Michele , Marchina Eleonora , Baiocchi Gianluca , Portolani Nazario , Crosatti Marialuisa , De Petro Giuseppina , Salvi Alessandro 
Published: June 2019

AbstractLong non-coding RNAs (lncRNAs) and microRNAs are involved in numerous physio-pathological conditions included cancer. To better understand the molecular mechanism of the oral antitumor multikinase inhibitor sorafenib, we profiled the expression of a panel of lncRNAs and miRNAs by qPCR array in a sorafenib-treated hepatocellular carcinoma (HCC) cell line. Among the most affected ncRNAs, we found that sorafenib mediated the dysregulation of the lncRNAs GAS5, HOTTIP and HOXA-AS2 and the miR-126-3p, in a panel of human cancer cell lines (HCC, renal and breast carcinomas). By luciferase gene reporter assay, we discovered that GAS5 may act as a sponge for miR-126-3p in HCC cells. The expression level of GAS5 and miR-126-3p was verified in human liquid and/or solid biopsies from HCC patients. miR-126-3p expression in HCC tissues was decreased respect to their correspondent peritumoral tissues. The levels of plasmatic circulating miR-126-3p and GAS5 were significantly higher and lower in HCC patients compared to healthy subjects, respectively. This study highlighted the capability of sorafenib to modulate the expression of a wide range of ncRNAs and specifically, GAS5 and miR-126-3p were involved in the response to sorafenib of different cancer cell types.
Brain wave classification using long short-term memory network based OPTICAL predictor
Authors: Kumar Shiu , Sharma Alok , Tsunoda Tatsuhiko 
Published: June 2019

AbstractBrain-computer interface (BCI) systems having the ability to classify brain waves with greater accuracy are highly desirable. To this end, a number of techniques have been proposed aiming to be able to classify brain waves with high accuracy. However, the ability to classify brain waves and its implementation in real-time is still limited. In this study, we introduce a novel scheme for classifying motor imagery (MI) tasks using electroencephalography (EEG) signal that can be implemented in real-time having high classification accuracy between different MI tasks. We propose a new predictor, OPTICAL, that uses a combination of common spatial pattern (CSP) and long short-term memory (LSTM) network for obtaining improved MI EEG signal classification. A sliding window approach is proposed to obtain the time-series input from the spatially filtered data, which becomes input to the LSTM network. Moreover, instead of using LSTM directly for classification, we use regression based output of the LSTM network as one of the features for classification. On the other hand, linear discriminant analysis (LDA) is used to reduce the dimensionality of the CSP variance based features. The features in the reduced dimensional plane after performing LDA are used as input to the support vector machine (SVM) classifier together with the regression based feature obtained from the LSTM network. The regression based feature further boosts the performance of the proposed OPTICAL predictor. OPTICAL showed significant improvement in the ability to accurately classify left and right-hand MI tasks on two publically available datasets. The improvements in the average misclassification rates are 3.09% and 2.07% for BCI Competition IV Dataset I and GigaDB dataset, respectively. The Matlab code is available at https://github.com/ShiuKumar/OPTICAL.
Design of Scalable Optical Decoder based on Hexagonal Plasmonic Modes induced on Topological Insulator Surface States
Authors: Srivastava Siddharth , Jain Priyanshu , Maiti Tanmoy 
Published: June 2019

AbstractIn the present work, optical decoder based on hexagonal plasmonic lens encrypted on topological insulator is designed. Using Finite Difference Time Domain (FDTD) simulation we have shown 2D optical lattice of scalar vortices in hexagonal plasmonic lens using surface states of topological insulator (Bi1.5Sb0.5Te1.8Se1.2). To ensure feasible and flexible physical dimensions, scaling of the optical device is proposed via increasing area density of vortices. This is numerically obtained by changing radius of hexagonal lens or decreasing incident wavelength. Using these scalable optical vortex lattices, a device scheme is proposed for storing or decoding information. Advantage of scaling in optical devices without any additional processing step shows the promise of this technology for future devices. Simulation results are further validated by detailed theoretical calculation of electric field intensity and phase distribution.
3DμF - Interactive Design Environment for Continuous Flow Microfluidic Devices
Authors: Sanka Radhakrishna , Lippai Joshua , Samarasekera Dinithi , Nemsick Sarah , Densmore Douglas 
Published: June 2019

AbstractThe design of microfluidic Lab on a Chip (LoC) systems is an onerous task requiring specialized skills in fluid dynamics, mechanical design drafting, and manufacturing. Engineers face significant challenges during the labor-intensive process of designing microfluidic devices, with very few specialized tools that help automate the process. Typical design iterations require the engineer to research the architecture, manually draft the device layout, optimize for manufacturing processes, and manually calculate and program the valve sequences that operate the microfluidic device. The problem compounds when engineers not only have to test the functionality of the chip but are also expected to optimize them for the robust execution of biological assays. In this paper, we present an interactive tool for designing continuous flow microfluidic devices. 3DμF is the first completely open source interactive microfluidic system designer that readily supports state of the art design automation algorithms. Through various case studies, we show 3DμF can be used to reproduce designs from literature, provide metrics for evaluating microfluidic design complexity and showcase how 3DμF is a platform for integrating a wide assortment of engineering techniques used in the design of microfluidic devices as a part of the standard design workflow.
Screening of Candida albicans GRACE library revealed a unique pattern of biofilm formation under repression of the essential gene ILS1
Authors: Costa Anna Carolina Borges Pereira , Omran Raha Parvizi , Correia-Mesquita Tuana Oliveira , Dumeaux Vanessa , Whiteway Malcolm 
Published: June 2019

AbstractCandida albicans biofilm formation is governed by a regulatory circuit comprising nine transcription factors which control a network of target genes. However, there are still unknown genes contributing to biofilm features. Thus, the GRACE library was screened to identify genes involved in mature biofilm development. Twenty-nine conditional mutants were selected for a second screening revealing three groups of genes: twenty- two conditional mutants were defective for normal growth and unable to form biofilms; six strains, conditionally defective in genes ARC40, ARC35, ORF19.2438, SKP1, ERG6, and ADE5,7 that are likely essential or involved in general cell processes, grew normally as free-floating cells but produced less biofilm; finally, the conditional strain for a putative essential isoleucyl- tRNA synthetase gene, ILS1, was unable to grow as yeast-phase cells but was capable of producing a tridimensional biofilm structure in spite of reduced metabolic activity. This unique biofilm still relied on the classical biofilm genes, while it differentially induced groups of genes involved in adhesion, protein synthesis, cell wall organization, and protein folding. Although the conditional mutant repressed genes annotated for morphology and homeostasis processes affecting morphology and metabolism, the dynamic cell growth enabled the formation of a complex biofilm community independent of ILS1.
Self-compensation in chlorine-doped CdTe
Authors: Orellana Walter , Menéndez-Proupin Eduardo , Flores Mauricio A. 
Published: June 2019

AbstractDefect energetics, charge transition levels, and electronic band structures of several Cl-related complexes in CdTe are studied using density-functional theory calculations. We investigate substitutional chlorine (ClTe and ClCd) and complexes formed by ClTe with the cadmium vacancy (ClTe-VCd and 2ClTe-VCd) and the TeCd antisite (ClTe-TeCd). Our calculations show that none of the complexes studied induce deep levels in the CdTe band gap. Moreover, we find that ClTe-VCd and ClTe are the most stable Cl-related centers in n-type and p-type CdTe, under Te-rich growth conditions, showing shallow donor and acceptor properties, respectively. This result suggests that the experimentally-observed Fermi level pinning near midgap would be originated in self-compensation. We also find that the formation of the ClTe-TeCd complex passivates the deep level associated to the Te antisite in neutral charge state.
Negative Capacitance as Universal Digital and Analog Performance Booster for Complementary MOS Transistors
Authors: Saeidi Ali , Jazaeri Farzan , Stolichnov Igor , Enz Christian C. , Ionescu Adrian M. 
Published: June 2019

AbstractBoltzmann electron energy distribution poses a fundamental limit to lowering the energy dissipation of conventional MOS devices, a minimum increase of the gate voltage, i.e. 60 mV, is required for a 10-fold increase in drain-to-source current at 300 K. Negative Capacitance (NC) in ferroelectric materials is proposed in order to address this physical limitation of CMOS technology. A polarization destabilization in ferroelectrics causes an effective negative permittivity, resulting in a differential voltage amplification and a reduced subthreshold swing when integrated into the gate stack of a transistor. The novelty and universality of this approach relate to the fact that the gate stack is not anymore a passive part of the transistor and contributes to signal amplification. In this paper, we experimentally validate NC as a universal performance booster: (i) for complementary MOSFETs, of both n- and p-type in an advanced CMOS technology node, and, (ii) for both digital and analog significant enhancements of key figures of merit for information processing (subthreshold swing, overdrive, and current efficiency factor). Accordingly, a sub-thermal swing down to 10 mV/decade together with an enhanced current efficiency factor up to 105 V−1 is obtained in both n- and p-type MOSFETs at room temperature by exploiting a PZT capacitor as the NC booster. As a result of the subthreshold swing reduction and overdrive improvement observed by NC, the required supply voltage to provide the same on-current is reduced by approximately 50%.
Engineering mouse cationic trypsinogen for rapid and selective activation by cathepsin B
Authors: Demcsák Alexandra , Geisz Andrea , Sahin-Tóth Miklós 
Published: June 2019

AbstractIntra-pancreatic activation of trypsin is an early event in pancreatitis. Trypsinogen can be activated to trypsin either through autoactivation (trypsin-mediated trypsinogen activation) or by the lysosomal protease cathepsin B (CTSB). Experimental separation of CTSB-mediated activation from autoactivation in mice is possible through knocking in mutations that render trypsinogen sensitive to CTSB but resistant to trypsin. Here we present biochemical studies on novel mouse cationic trypsinogen (isoform T7) mutants engineered for selective CTSB activation. First, we demonstrated that mutation K24G, which alters the activation site Lys in T7 trypsinogen, abolished autoactivation while activation by CTSB was stimulated 4-fold at pH 4.0. Interestingly, CTSB-mediated activation of the K24G mutant became more sensitive to inhibition by increasing pH. Next, Ala-scanning of the five Asp residues preceding the activation site Lys revealed that mutation D22A accelerated CTSB-mediated activation by 2-fold. Finally, combination of mutations D22A and K24G resulted in a trypsinogen mutant that exhibited 14-fold increased activation by CTSB and normal pH sensitivity. We conclude that we successfully engineered a mouse T7 trypsinogen mutant (D22A,K24G), which is robustly activated by CTSB but cannot undergo autoactivation. These studies set the stage for the generation of a preclinical mouse model of CTSB-dependent pancreatitis.
A novel potent autophagy inhibitor ECDD-S27 targets vacuolar ATPase and inhibits cancer cell survival
Authors: Paha Jiraporn , Kanjanasirirat Phongthon , Munyoo Bamroong , Tuchinda Patoomratana , Suvannang Naravut , Nantasenamat Chanin , Boonyarattanakalin Kanokthip , Kittakoop Prasat , Srikor Sirawit , Kongklad Gunganist , Rangkasenee Noppawan , Hongeng Suradej , Utaisincharoen Pongsak , Borwornpinyo Suparerk , Ponpuak Marisa 
Published: June 2019

AbstractAutophagy is a conserved lysosomal-dependent cellular degradation process and its dysregulation has been linked to numerous diseases including neurodegeneration, infectious diseases, and cancer. Modulation of autophagy is therefore considered as an attractive target for disease intervention. We carried out a high-content image analysis screen of natural product-derived compounds to discover novel autophagy modulating molecules. Our screen identified ECDD-S27 as the most effective compound for increasing the number of autophagic vacuoles inside cells. The structure of ECDD-S27 revealed that it is a derivative of cleistanthin A, a natural arylnaphthalene lignan glycoside found in plants. ECDD-S27 increases the number of autophagic vacuoles by inhibiting the autophagic flux and is able to restrict the survival of different cancer cells at low nanomolar concentrations. Molecular docking and SERS analysis showed that ECDD-S27 may potentially target the V-ATPase. Upon treatment of various cancer cells with ECDD-S27, the V-ATPase activity is potently inhibited thereby resulting in the loss of lysosomal acidification. Taken together, these data indicated that ECDD-S27 retards the autophagy pathway by targeting the V-ATPase and inhibits cancer cell survival. The observed antitumor activity without cytotoxicity to normal cells suggests the therapeutic potential warranting further studies on lead optimization of the compound for cancer treatment.
The extracellular matrix proteoglycan lumican improves survival and counteracts cardiac dilatation and failure in mice subjected to pressure overload
Authors: Mohammadzadeh Naiyereh , Lunde Ida G. , Andenæs Kine , Strand Mari E. , Aronsen Jan Magnus , Skrbic Biljana , Marstein Henriette S. , Bandlien Caroline , Nygård Ståle , Gorham Joshua , Sjaastad Ivar , Chakravarti Shukti , Christensen Geir , Engebretsen Kristin V. T. , Tønnessen Theis 
Published: June 2019

AbstractLeft ventricular (LV) dilatation is a key step in transition to heart failure (HF) in response to pressure overload. Cardiac extracellular matrix (ECM) contains fibrillar collagens and proteoglycans, important for maintaining tissue integrity. Alterations in collagen production and cross-linking are associated with cardiac LV dilatation and HF. Lumican (LUM) is a collagen binding proteoglycan with increased expression in hearts of patients and mice with HF, however, its role in cardiac function remains poorly understood. To examine the role of LUM in pressure overload induced cardiac remodeling, we subjected LUM knock-out (LUMKO) mice to aortic banding (AB) and treated cultured cardiac fibroblasts (CFB) with LUM. LUMKO mice exhibited increased mortality 1–14 days post-AB. Echocardiography revealed increased LV dilatation, altered hypertrophic remodeling and exacerbated contractile dysfunction in surviving LUMKO 1–10w post-AB. LUMKO hearts showed reduced collagen expression and cross-linking post-AB. Transcriptional profiling of LUMKO hearts by RNA sequencing revealed 714 differentially expressed transcripts, with enrichment of cardiotoxicity, ECM and inflammatory pathways. CFB treated with LUM showed increased mRNAs for markers of myofibroblast differentiation, proliferation and expression of ECM molecules important for fibrosis, including collagens and collagen cross-linking enzyme lysyl oxidase. In conclusion, we report the novel finding that lack of LUM attenuates collagen cross-linking in the pressure-overloaded heart, leading to increased mortality, dilatation and contractile dysfunction in mice.
Deep transcriptome analysis using RNA-Seq suggests novel insights into molecular aspects of fat-tail metabolism in sheep
Authors: Bakhtiarizadeh Mohammad Reza , Salehi Abdolreza , Alamouti Ali A. , Abdollahi-Arpanahi Rostam , Salami Seyed Alireza 
Published: June 2019

AbstractFat-tail content of sheep breeds is varied and the molecular mechanisms regulating fat-tail development have not been well characterized. Aiming at better identifying the important candidate genes and their functional pathways contributing to fat deposition in the tail, a comparative transcriptome analysis was performed between fat- (Lori-Bakhtiari) and thin-tailed (Zel) Iranian sheep breeds using RNA-seq. The experiment was conducted on six male lambs (three lambs per each breed) at seven months of age. Four different combinations of aligners and statistical methods including Hisat2 + edgeR, Hisat2 + DESeq2, STAR + edgeR and STAR + DESeq2 were used to identify the differentially expressed genes (DEGs). The DEGs were selected for functional enrichment analysis and protein-protein interaction (PPI) network construction. Module analysis was also conducted to mine the functional sub-networks from the PPI network. In total, 264 genes including 80 up- and 184 down-regulated genes were identified as DEGs. The RNA-Seq results were validated by Q-RT-PCR. Functional analysis of DEGs and the module analysis of PPI network demonstrated that in addition to pathways affecting lipid metabolism, a series of enriched functional terms related to “response to interleukin”, “MAPK signaling pathways”, “Wnt signaling pathway”, “ECM-receptor interaction”, “regulation of actin cytoskeleton”, and “response to cAMP” might contribute to the deposition of fat in tails of sheep. Overall results using RNA-Seq analysis characterized important candidate genes involved in the fatty acid metabolism and regulation of fat deposition, suggesting novel insights into molecular aspects of fat-tail metabolism in sheep. Selected DEGs should be further investigated as potential markers associated with the fat-tail development in sheep breeds.
Scheelite type Sr1−xBaxWO4 (x = 0.1, 0.2, 0.3) for possible application in Solid Oxide Fuel Cell electrolytes
Authors: Afif Ahmed , Zaini Juliana , Rahman Seikh Mohammad Habibur , Eriksson Sten , Islam Md Aminul , Azad Abul Kalam 
Published: June 2019

AbstractPolycrystalline scheelite type Sr1−xBaxWO4 (x = 0.1, 0.2 & 0.3) materials were synthesized by the solid state sintering method and studied with respect to phase stability and ionic conductivity under condition of technological relevance for SOFC applications. All compounds crystallized in the single phase of tetragonal scheelite structure with the space group of I41/a. Room temperature X-ray diffraction and subsequent Rietveld analysis confirms its symmetry, space group and structural parameters. SEM illustrates the highly dense compounds. Significant mass change was observed to prove the proton uptake at higher temperature by TG-DSC. All compound shows lower conductivity compared to the traditional BCZY perovskite structured materials. SBW with x = 0.3 exhibit the highest ionic conductivity among all compounds under wet argon condition which is 1.9 × 10−6 S cm−1 at 1000 °C. Since this scheelite type compounds show significant conductivity, the new series of SBW could serve in IT-SOFC as proton conducting electrolyte.
Seebeck-voltage-triggered self-biased photoelectrochemical water splitting using HfOx/SiOx bi-layer protected Si photocathodes
Authors: Jung Jin-Young , Woong Kim Dae , Kim Dong-Hyung , Joo Park Tae , Wehrspohn Ralf B. , Lee Jung-Ho 
Published: June 2019

AbstractThe use of a photoelectrochemical device is an efficient method of converting solar energy into hydrogen fuel via water splitting reactions. One of the best photoelectrode materials is Si, which absorbs a broad wavelength range of incident light and produces a high photocurrent level (~44 mA·cm−2). However, the maximum photovoltage that can be generated in single-junction Si devices (~0.75 V) is much lower than the voltage required for a water splitting reaction (>1.6 V). In addition, the Si surface is electrochemically oxidized or reduced when it comes into direct contact with the aqueous electrolyte. Here, we propose the hybridization of the photoelectrochemical device with a thermoelectric device, where the Seebeck voltage generated by the thermal energy triggers the self-biased water splitting reaction without compromising the photocurrent level at 42 mA cm−2. In this hybrid device p-Si, where the surface is protected by HfOx/SiOx bilayers, is used as a photocathode. The HfOx exhibits high corrosion resistance and protection ability, thereby ensuring stability. On applying the Seebeck voltage, the tunneling barrier of HfOx is placed at a negligible energy level in the electron transfer from Si to the electrolyte, showing charge transfer kinetics independent of the HfOx thickness. These findings serve as a proof-of-concept of the stable and high-efficiency production of hydrogen fuel by the photoelectrochemical-thermoelectric hybrid devices.