Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiviral Activity of Bay 41-4109 on Hepatitis B Virus in Humanized Alb-uPA/SCID Mice

Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2. 15 cells constitutively expressing HBV, displayed an IC(50) of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy.
Sink-oriented dynamic location service for shortest path relay with energy efficient global grid

Portable wireless devices are increasing in popularity. Mechanisms that allow information to be efficiently obtained through mobile WSNs are of significant interest. However, a mobile sink introduces many challenges to data dissemination in large WSNs. For example, it is important to efficiently identify the locations of mobile sinks and disseminate information from multi-source nodes to the multi-mobile sinks. In particular, a stationary dissemination path may no longer to effective in mobile sink applications, due to sink mobility. In this paper, we propose a Sink-oriented Dynamic Location Service (SDLS) approach to handle sink mobility. In SDLS, we propose an Eight-Direction Anchor (EDA) system that acts as a location service server. EDA prevents intensive energy consumption at the border sensor nodes and thus provides energy balancing to all the sensor nodes. Then we propose a Location-based Shortest Relay (LSR) that efficiently forwards (or relays) data from a source node to a sink with minimal delay path. Our results demonstrate that SDLS not only provides an efficient and scalable location service, but also reduces the average data communication overhead in scenarios with multiple and moving sinks and sources.
Initiation of Electron Transport Chain Activity in the Embryonic Heart Coincides with the Activation of Mitochondrial Complex 1 and the Formation of Supercomplexes

Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx-1, -3, and -4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes.
Cell-laden hinged microplates for measuring the contractile forces of cardiomyocytes

We report a method to measure contractile forces of cardiomyocytes at cellular level using microplates; pairs of single-cell sized plates are connected by a flexible hinge at the center. Cardiomyocytes repeatedly contract and relax, and thereby fold and stretch the microplates at the flexible hinge. By measuring the change of the bending angle in folded microplates, we can estimate contractile forces of cardiomyocytes. We believe that this method is a useful tool to study the biomechanics of cardiomyocytes.
On Performance Evaluation of Reliable Topology Control Algorithms in Mobile Ad Hoc Networks

Energy consumption and network connectivity are two of the important research issues that are yet to be resolved in mobile ad hoc networks (MANETs). As taken advantage of in static networks, reliable topology control algorithms are also considered to be a good approach for mobile networks. However, a more adequate evaluation of these algorithms regarding mobility is still needed. In this paper, we evaluate the performance of some well-known topology control algorithms with various scenarios and measurements. The results show that Local Tree-based Reliable Topology (LTRT), a recently proposed algorithm, is the most scalable method and provides the most benefit in terms of redundant connectivity.
Development of the environmental ethics’ attitude scale: The study of validity and reliability

The purpose of this study is to develop a environmental ethics’ attitude scale which is valid and reliable about to determine students’ attitudes towards environmental ethics. The working group of the research has been comprised of 406 Science and Anatolia high school students living in Kars province in the academic year of 2013-2014. These students were determined by the convenience sampling method. An exploratory and confirmatory factor analysis was performed on the data. As a result of these analysis, the findings revealed that the scale show the four factor structure. Considering the matter content of the factors have been tried to be named. Cronbach Alpha coefficient for the first factor was found . 98, for the second factor was found . 72, for the third factor was found . 82 and for the fourth factor was found . 80. Cronbach Alpha internal consistency coefficient for the whole scale was found to be . 87.
Fluorescent Fusion Proteins of Soluble Guanylyl Cyclase Indicate Proximity of the Heme Nitric Oxide Domain and Catalytic Domain

Background To examine the structural organisation of heterodimeric soluble guanylyl cyclase (sGC) Förster resonance energy transfer (FRET) was measured between fluorescent proteins fused to the amino- and carboxy-terminal ends of the sGC β1 and α subunits. Methodology/Principal Findings Cyan fluorescent protein (CFP) was used as FRET donor and yellow fluorescent protein (YFP) as FRET acceptor. After generation of recombinant baculovirus, fluorescent-tagged sGC subunits were co-expressed in Sf9 cells. Fluorescent variants of sGC were analyzed in vitro in cytosolic fractions by sensitized emission FRET. Co-expression of the amino-terminally tagged α subunits with the carboxy-terminally tagged β1 subunit resulted in an enzyme complex that showed a FRET efficiency of 10% similar to fluorescent proteins separated by a helix of only 48 amino acids. Because these findings indicated that the amino-terminus of the α subunits is close to the carboxy-terminus of the β1 subunit we constructed fusion proteins where both subunits are connected by a fluorescent protein. The resulting constructs were not only fluorescent, they also showed preserved enzyme activity and regulation by NO. Conclusions/Significance Based on the ability of an amino-terminal fragment of the β1 subunit to inhibit activity of an heterodimer consisting only of the catalytic domains (αcatβcat), Winger and Marletta (Biochemistry 2005, 44:4083–90) have proposed a direct interaction of the amino-terminal region of β1 with the catalytic domains. In support of such a concept of “trans” regulation of sGC activity by the H-NOX domains our results indicate that the domains within sGC are organized in a way that allows for direct interaction of the amino-terminal regulatory domains with the carboxy-terminal catalytic region. In addition, we constructed “fluorescent-conjoined” sGC's by fusion of the α amino-terminus to the β1 carboxy-terminus leading to a monomeric, fluorescent and functional enzyme complex. To our knowledge this represents the first example where a fluorescent protein links two different subunits of a higher ordered complex to yield a stoichometrically fixed functionally active monomer.
Partition Theorems and Computability Theory

The connections between mathematical logic and combinatorics have a rich history. This paper focuses on one aspect of this relationship: understanding the strength, measured using the tools of computability theory and reverse mathematics, of various partition theorems. To set the stage, recall two of the most fundamental combinatorial principles, Konig’s Lemma and Ramsey’s Theorem. We denote the set of natural numbers by ω and the set of finite sequences of natural numbers by ω. We also identify each n ∈ ω with its set of predecessors, so n = {0, 1, 2, . , n− 1}.
Curli Fibers Mediate Internalization ofEscherichia coli by Eukaryotic Cells

ABSTRACT Curli fibers are adhesive surface fibers expressed byEscherichia coli and Salmonella enterica that bind several host extracellular matrix and contact phase proteins and were assumed to have a role in pathogenesis. The results presented here suggest that one such role is internalization into host cells. AnE. coli K-12 strain transformed with a low-copy vector containing the gene cluster encoding curli fibers (csgoperon) was internalized by several lines of eukaryotic cells. The internalization could be correlated with a high level of curli fiber expression and was abolished by disruption of the csgoperon. The ability to be internalized by eukaryotic cells could be conferred even by the curli fiber gene cluster of a noninvasive K-12 strain, but the homologous csg cluster from a virulent septicemic E. coli isolate mediated a higher level of internalization. The finding that curli fibers promote bacterial internalization indicates a new role for curli fibers in pathogenesis.
Sustainability: Planning’s Saving Grace or Road to Perdition?

This article explores the concept—sustainability—as a transcendental ideal of planning purpose and value. The article critically argues that sustainability largely has been captured and deployed under a narrative of sustainable development in a manner that stifles the potential for substantive social and environmental change, all of which constitutes new purpose, legitimacy, and authority for the discipline of planning and its practitioners while potentially sustaining or creating adverse social and environmental injustices. These are injustices that planning traditionally attempted to address but now often obscures under the primacy of the economic imperative within dominant institutional interpretations of the sustainable development narrative.
PR‐924, a selective inhibitor of the immunoproteasome subunit LMP‐7, blocks multiple myeloma cell growth both in vitro and in vivo

PR‐924 is an LMP‐7‐selective tripeptide epoxyketone proteasome inhibitor that covalently modifies proteasomal N‐terminal threonine active sites. In the present study, we show that PR‐924 inhibits growth and triggers apoptosis in multiple myeloma (MM) cell lines and primary patient MM cells, without significantly affecting normal peripheral blood mononuclear cells. PR‐924‐induced apoptosis in MM cells is associated with activation of caspase‐3, caspase‐8, caspase‐9, BID, PARP and cytochrome–c release. In vivo administration of PR‐924 inhibits tumour growth in human plasmacytoma xenografts. Results from SCID‐hu model show a significant reduction in the shIL‐6R levels in mice treated with PR‐924 versus vehicle‐control. PR‐924 treatment was well tolerated as evidenced by the lack of weight loss. Importantly, treatment of tumour‐bearing mice with PR‐924, but not vehicle alone, prolonged survival. Our preclinical findings therefore validate immunoproteasome LMP‐7 subunit as a novel therapeutic target in MM.
Stochastic Canonical Correlation Analysis

We study the sample complexity of canonical correlation analysis (CCA), \ie, the number of samples needed to estimate the population canonical correlation and directions up to arbitrarily small error. With mild assumptions on the data distribution, we show that in order to achieve $\epsilon$-suboptimality in a properly defined measure of alignment between the estimated canonical directions and the population solution, we can solve the empirical objective exactly with $N(\epsilon, \Delta, \gamma)$ samples, where $\Delta$ is the singular value gap of the whitened cross-covariance matrix and $1/\gamma$ is an upper bound of the condition number of auto-covariance matrices. Moreover, we can achieve the same learning accuracy by drawing the same level of samples and solving the empirical objective approximately with a stochastic optimization algorithm; this algorithm is based on the shift-and-invert power iterations and only needs to process the dataset for $\mathcal{O}\left(\log \frac{1}{\epsilon} \right)$ passes. Finally, we show that, given an estimate of the canonical correlation, the streaming version of the shift-and-invert power iterations achieves the same learning accuracy with the same level of sample complexity, by processing the data only once.
Text-linguistic comments on metaphor identification

It seems to me very important that proponents of psychological approaches to and theories of metaphor should turn their attention to real textual and discoursal data. Equally important is that linguistic approaches to and theories of metaphor should be tested against the psychological realities of text processing. To the extent that the metaphor identification project bridges this gap it is to be welcomed. However, since the phenomenon of metaphor is complex and somewhat intractable, it seems doubtful that there can be any quick fixes by which long sections of literary texts can be rapidly and reliably coded for their metaphorical potential. Any method for coding or tagging of potential metaphors has of course to take into account the purpose of such coding. The writers of the articles in this issue talk sometimes about the goal as ‘the exact description and measurement or quantification of metaphor in discourse’ (Crisp et al., 2002: 65). But other participants in the project seem a little unsure about the extent to which various metaphorical features are to be coded, and this, one supposes, could be because the kind of research for which the coding is to be used is at present less than clear.
Série Scientifique Scientific Series a Nonparametric Copula Based Test for Conditional Independence with Applications to Granger Causality a Nonparametric Copula Based Test for Conditional Independence with Applications to Granger Causality

CIRANO Le CIRANO est un organisme sans but lucratif constitué en vertu de la Loi des compagnies du Québec. Le financement de son infrastructure et de ses activités de recherche provient des cotisations de ses organisations-membres, d'une subvention d'infrastructure du Ministère du Développement économique et régional et de la Recherche, de même que des subventions et mandats obtenus par ses équipes de recherche. CIRANO is a private non-profit organization incorporated under the Québec Companies Act. Its infrastructure and research activities are funded through fees paid by member organizations, an infrastructure grant from the Ministère du Développement économique et régional et de la Recherche, and grants and research mandates obtained by its research teams. Le CIRANO collabore avec de nombreux centres et chaires de recherche universitaires dont on peut consulter la liste sur son site web. Les cahiers de la série scientifique (CS) visent à rendre accessibles des résultats de recherche effectuée au CIRANO afin de susciter échanges et commentaires. Ces cahiers sont écrits dans le style des publications scientifiques. Les idées et les opinions émises sont sous l'unique responsabilité des auteurs et ne représentent pas nécessairement les positions du CIRANO ou de ses partenaires. This paper presents research carried out at CIRANO and aims at encouraging discussion and comment. The observations and viewpoints expressed are the sole responsibility of the authors. They do not necessarily represent positions of CIRANO or its partners. Résumé Le présent document propose un nouveau test non paramétrique d'indépendance conditionnelle, lequel est fondé sur la comparaison des densités de la copule de Bernstein suivant la distance de Hellinger. Le test est facile à réaliser, du fait qu'il n'implique pas de fonction de pondération dans les variables utilisées et peut être appliqué dans des conditions générales puisqu'il n'y a pas de restriction sur l'étendue des données. En fait, dans le cas de la copule non paramétrique, l'application du test ne requiert qu'une largeur de bande. Nous démontrons que les variables utilisées pour le test jouent asymptotiquement un rôle crucial sous l'hypothèse nulle. Nous établissons aussi les propriétés des pouvoirs locaux et justifions la validité de la technique bootstrap (technique d'auto-amorçage) que nous utilisons dans les contextes où les échantillons sont de taille finie. Une étude par simulation illustre l'ampleur adéquate et la puissance du test. Nous démontrons la pertinence empirique de notre démarche en mettant l'accent sur les liens de causalité de Granger et en recourant à …
Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B‐chronic lymphocytic leukaemia cells

B‐chronic lymphocytic leukaemia (B‐CLL) is characterized by the accumulation of long‐lived CD5+ B lymphocytes. The effect of mitoxantrone, a topoisomerase II inhibitor, on B‐CLL cells was studied. Treatment of B‐CLL cells for 48 h with mitoxantrone (0.5 μg/ml) induced a decrease in cell viability as determined by MTT assay. The IC50 calculated for the cells of three patients was 0.7 μg/ml for two of them and 1.4 μg/ml for the third. In all three patients the maximum effect was observed with 2 μg/ml. An additive cytotoxic effect was observed when mitoxantrone (0.5 μg/ml) was combined with fludarabine (5 μg/ml). Mitoxantrone induced DNA fragmentation and the proteolytic cleavage of poly(ADP‐ribose) polymerase (PARP), a marker of the activation of caspases, in all the patients studied, demonstrating that the cytotoxic effect of mitoxantrone was due to induction of apoptosis. These results suggest that mitoxantrone, and possibly other topoisomerase II inhibitors, may be used in the chemotherapy of B‐CLL, and that combination of mitoxantrone with fludarabine or other drugs could improve the effectiveness of the treatment.
A Long-Chain Flavodoxin Protects Pseudomonas aeruginosa from Oxidative Stress and Host Bacterial Clearance

Long-chain flavodoxins, ubiquitous electron shuttles containing flavin mononucleotide (FMN) as prosthetic group, play an important protective role against reactive oxygen species (ROS) in various microorganisms. Pseudomonas aeruginosa is an opportunistic pathogen which frequently has to face ROS toxicity in the environment as well as within the host. We identified a single ORF, hereafter referred to as fldP (for flavodoxin from P . aeruginosa), displaying the highest similarity in length, sequence identity and predicted secondary structure with typical long-chain flavodoxins. The gene was cloned and expressed in Escherichia coli. The recombinant product (FldP) could bind FMN and exhibited flavodoxin activity in vitro. Expression of fldP in P. aeruginosa was induced by oxidative stress conditions through an OxyR-independent mechanism, and an fldP-null mutant accumulated higher intracellular ROS levels and exhibited decreased tolerance to H2O2 toxicity compared to wild-type siblings. The mutant phenotype could be complemented by expression of a cyanobacterial flavodoxin. Overexpression of FldP in a mutT-deficient P. aeruginosa strain decreased H2O2-induced cell death and the hypermutability caused by DNA oxidative damage. FldP contributed to the survival of P. aeruginosa within cultured mammalian macrophages and in infected Drosophila melanogaster, which led in turn to accelerated death of the flies. Interestingly, the fldP gene is present in some but not all P. aeruginosa strains, constituting a component of the P. aeruginosa accessory genome. It is located in a genomic island as part of a self-regulated polycistronic operon containing a suite of stress-associated genes. The collected results indicate that the fldP gene encodes a long-chain flavodoxin, which protects the cell from oxidative stress, thereby expanding the capabilities of P. aeruginosa to thrive in hostile environments.
Are Caricatures Special? Evidence of Peak Shift in Face Recognition

It has been shown that it is possible to obtain faster and more accurate recognition for a caricatured face than for a veridical face. This could suggest that there is something special about the transformations that produce caricatures. An experiment was conducted to investigate whether there are other circumstances in which improved recognition occurs away from the veridical face. A peak-shift paradigm was employed, using images generated from morphing between two faces, where participants learned to respond to a target and learned not to respond to a similar non-target. When tested on the whole range of morphed faces, the response profile showed a shift in the peak of the responses away from the learned nontarget face. From this it was concluded that the advantage seen with caricatures is not special but a result of a shift in the peak of responses away from more typical faces.
DNA Conjugation by the Staudinger Ligation: New Thymidine Analogues

Two novel modified 2′-deoxyuridine triphosphates carrying an azide functionality linked to the nucleobase were synthesized. For probing the sterical influence on enzymatic incorporation and Staudinger ligation, differently sized flexible linkers were chosen. Both nucleotides can completely replace natural thymidine in primer extension as well as polymerase chain reaction (PCR) using PYROCOCCUS WOESEI DNA polymerase. For PCR with larger gene fragments as template, however, the longer linker disturbs the DNA polymerase and yields less product. For azide-labeled primer extension products, subsequent conjugation of suitably functionalized phosphines via Staudinger ligation was achieved, for example for the conjugation of biotin as an affinity tag.