pinecone/core-2020-05-10-deduplication huggingface dataset:
A Shine-Dalgarno-like Sequence Mediates in Vitro Ribosomal Internal Entry and Subsequent Scanning for Translation Initiation of Coxsackievirus B3 RNA

AbstractTranslation initiation of coxsackievirus B3 (CVB3) RNA is directed by an internal ribosome entry site (IRES) within the 5′ untranslated region. However, the details of ribosome-template recognition and subsequent translation initiation are still poorly understood. In this study, we have provided evidence to support the hypothesis that 40S ribosomal subunits bind to CVB3 RNA via basepairing with 18S rRNA in a manner analogous to that of the Shine-Dalgarno (S-D) sequence in prokaryotic systems. We also identified a new site within both the 18S rRNA and the polpyrimidine-tract sequence of the IRES that allows them to form stronger sequence complementation. All these data were obtained from in vitro translation experiments using mutant RNAs containing either an antisense IRES core sequence at the original position or site-directed mutations or deletions in the polypyrimidine tract of the IRES. The mutations significantly reduced translation efficiency but did not abolish protein synthesis, suggesting that the S-D-like sequence is essential, but not sufficient for ribosome binding. To determine how ribosomes reach the initiation codon after internal entry, we created additional mutants: when the authentic initiation codon at nucleotide (nt) 742 was mutated, a 180-nt downstream in-frame AUG codon at nt 922 is able to produce a truncated smaller protein. When this mutation was introduced into the full-length cDNA of CVB3, the derived viruses were still infectious. However, their infectivity was much weaker than that of the wild-type CVB3. In addition, when a stable stem-loop was inserted upstream of the initiation codon in the bicistronic RNA, translation was strongly inhibited. These data suggest that ribosomes reach the initiation codon from the IRES likely by scanning along the viral RNA
Paramyxoviruses SV5 and HPIV2 Assemble STAT Protein Ubiquitin Ligase Complexes from Cellular Components

AbstractSignal transducer and activator of transcription (STAT) proteins are normally long-lived, but infection with certain Paramyxoviruses results in efficient loss of IFN-responsive STAT1 or STAT2. Expression of a virus-encoded protein called “V” is sufficient to mediate the destruction of STAT proteins. STAT degradation is blocked by proteasome inhibitors, strongly implicating the ubiquitin (Ub)-proteasome targeting system. We demonstrate that cellular expression of V proteins from simian virus 5 (SV5) and type II human parainfluenza virus (HPIV2) induces polyubiquitylation of STAT1 and STAT2 targets. In vitro, the V proteins catalyze Ub transfer in an ATP-dependent process that requires both Ub-activating (E1) and Ub-conjugating (E2) activities. Furthermore, SV5 and HPIV2 V-interacting protein partners were isolated by affinity purification from human cells and reveal a complex of associated cellular proteins. This complex includes both STAT1 and STAT2, and the damaged DNA binding protein, DDB1. In addition, a protein related to a family of cellular Ub ligase complex subunits, cullin 4A (Cul4A), associated with the V proteins. The roles of both DDB1 and Cul4A in STAT1 degradation by SV5 infection were analyzed using small interfering RNAs. These findings demonstrate the assembly of a V-dependent degradation complex that includes STAT1, STAT2, DDB1, and Cul4A. In agreement with prior nomenclature on SCF-type cellular E3 enzymes, we refer to this complex as VDC
CD4-Independent Protective Cytotoxic T Cells Induced in Early Life by a Non-Replicative Delivery System Based on Virus-like Particles

AbstractThe relative immaturity of the neonatal immune system limits CD4+ Th1 and cytotoxic T lymphocyte (CTL) responses, and represents a significant challenge for the development of vaccines against intracellular pathogens. In this report, we demonstrate the ability of a non-replicative delivery system based on parvovirus-like particles (VLP) to induce CTL responses in the neonatal period. A single immunization of 1-week-old BALB/c mice with recombinant VLP carrying a CD8+ T cell determinant from lymphocytic choriomeningitis virus (VLP-LCMV) induced antigen-specific CD8+ cytotoxic T cells that were similar to those elicited by adult immunization, as assessed by cytotoxic activity, interferon (IFN)-γ secretion, cytotoxic precursor cell frequencies, in vitro avidity for antigen and protective activity against viral challenge. These CTL responses are elicited within 2 weeks of a single immunization, in the absence of adjuvant and independently of the presence and help of CD4+ T cells, highlighting the potential of VLP as candidate vaccine vectors in early life
Thymidine Kinase of Herpes Simplex Virus Type 1 Strain KOS Lacks Mutator Activity

AbstractThe effect of thymidine kinase (TK) encoded by herpes simplex virus type 1(HSV-1) strain KOS in DNA replication fidelity was examined by two different mutagenesis assays. Mutagenesis assay of the LacZ reporter gene present in recombinant tkLTRZ1, which contained the integrated LacZ gene in the tk locus, revealed a less than 0.05% mutation frequency of the LacZ gene regardless of whether the viruses were propagated in TK-expressing cells or control cells, conflicting an earlier report that a HSV-1 TK+ strain replicated a 0.5% mutation frequency of the LacZ gene (R. B. Pyles and R. L. Thompson, 1994, J. Virol. 68, 4514–4524). Furthermore, TK-proficient and -deficient recombinant viruses replicated with similar mutation frequencies (0.027 and 0.026%, respectively) of the LacZ gene, which was integrated in the polymerase locus. Results of SupF mutagenesis assay demonstrated that neither the spectra of mutation nor the mutation frequencies of SupF gene, which was integrated in the tk locus of recombinant, were significantly different (P > 0.05) in progeny viruses grown in TK-expressing cells and control cells. Therefore, both LacZ and SupF mutagenesis assays demonstrated that TK of the HSV-1 strain KOS did not have detectable mutator activity
Displaying Epidermal Growth Factor on Spleen Necrosis Virus-Derived Targeting Vectors

AbstractTargeted gene transfer into human cells has previously been achieved with spleen necrosis virus (SNV)-derived vector particles harboring envelope (Env) proteins which carry single chain Fv (scFv) domains derived from antibodies. Such cell targeting vectors have been found to directly transduce human cells expressing the cell surface molecules recognized by the respective scFv. In an attempt to achieve targeted gene transfer into epidermal growth factor receptor (EGFR)-positive human cells, SNV vector particles carrying a surface (SU) envelope protein N-terminally modified with the EGF domain and the wildtype transmembrane protein were generated. However, direct transduction of EGFR-positive cells was not detected. Canine D17 cells, which can be infected by wildtype SNV, were also not transduced. Infectivity of D17 cells was restored by removal of the EGF modification via cleavage of a factor Xa site located between the EGF domain and the SU protein or by blocking the EGFRs on the cell surface by EGF treatment. The properties of SNV-EGF vector particles as described here are similar to those of murine leukemia virus-derived vector particles harboring envelope proteins modified with a growth factor-derived domain. It seems therefore that, although scFv-modified SNV allows direct cell targeting, EGF-modified SNV allows only indirect cell targeting
A Transcriptional Initiator Overlaps with a Conserved YY1 Binding Site in the Long Control Region of Human Papillomavirus Type 16

AbstractA single promoter has so far been found in the long control region (LCRs) of human papillomavirus-16 (HPV-16). Multiple promoters exist in the LCRs of several other papillomaviruses, which are spliced to become mRNAs for late and some early genes. Here we have investigated whether such promoters exist in the LCR of HPV-16. In in vitro transcription experiments, we detected a strong transcript starting 280 bp downstream from the 3′ end of the L1 gene between a nuclear matrix attachment region and the epithelial-specific enhancer. Promoter activity coincides with a GCCATTTT motif, which binds the transcription factor YY1 (YY1-7436). The A of this motif is the first nucleotide of the transcripts and identifies YY1-7436 as an initiator. Genomic segments with YY1-7436 initiate expression of a luciferase reporter gene in transfection experiments. Mutational analysis of YY1-7436 suggests, however, that promoter function originates from another factor but YY1, which can contact overlapping sequences. Promoter activity of YY1-7436 is modulated by upstream A-T-rich sequences, which bind the basal transcription factor TFIID, and it is stimulated by the viral E2 protein binding to a downstream E2 binding site. In differentiating W12 cells, which contain episomal HPV-16 copies, we detected transcripts including LCR sequences downstream of YY1-7436, which were differentially spliced to early and late genes. However, we could not detect 5′ ends mapping to YY1-7436, but we detected two novel HPV-16 promoters within the L1 gene. Conservation of the arrangement of the YY1 and E2 binding sites suggests a role in important biological functions, which, however, is difficult to confirm in every type of cell culture. The study of W12 cells complements the examination of YY1-7436 and points to yet undetected promoters upstream of the LCR
A New Packaging Cell Line for SV40 Vectors That Eliminates the Generation of T-Antigen-Positive, Replication-Competent Recombinants

AbstractSimian virus 40 (SV40) vectors are efficient vehicles for gene delivery to hematopoietic and hepatic cells. To ensure their replication incompetence and because of safety considerations, it is critical that the vectors do not contain T-antigen sequences. Available packaging cell lines for T-antigen replacement vectors, COS and CMT4, contain considerable sequence identity with the vectors, leading to homologous recombination and reacquisition of the T-antigen gene. We constructed a packaging cell line, COT18, with minimal sequence identity to the vector. Vector stocks produced by passaging on COT18 had high transducing activity and undetectable levels of T-antigen-positive, replication-competent contaminants. This cell line provides a means for the preparation of safe SV40 vector stocks
Quantum chaos and holographic tensor models

A class of tensor models were recently outlined as potentially calculable examples of holography: their perturbative large-N behavior is similar to the Sachdev-Ye-Kitaev (SYK) model, but they are fully quantum mechanical (in the sense that there is no quenched disorder averaging). These facts make them intriguing tentative models for quantum black holes. In this note, we explicitly diagonalize the simplest non-trivial Gurau-Witten tensor model and study its spectral and late-time properties. We find parallels to (a single sample of) SYK where some of these features were recently attributed to random matrix behavior and quantum chaos. In particular, the spectral form factor exhibits a dip-ramp plateau structure after a running time average, in qualitative agreement with SYK. But we also observe that even though the spectrum has a unique ground state, it has a huge (quasi-?)degeneracy of intermediate energy states, not seen in SYK. If one ignores the delta function due to the degeneracies however, there is level repulsion in the unfolded spacing distribution hinting chaos. Furthermore, there are gaps in the spectrum. The system also has a spectral mirror symmetry which we trace back to the presence of a unitary operator with which the Hamiltonian anticommutes. We use it to argue that to the extent that the model exhibits random matrix behavior, it is controlled not by the Dyson ensembles, but by the BDI (chiral orthogonal) class in the Altland-Zirnbauer classification
Non-Locality and Quantum Theory: New Experimental Evidence

Starting from the late 60’s many experiments have been performed to verify the violation Bell’s inequality by Einstein-Podolsky-Rosen (EPR) type correlations. The idea of these experiments being that: (i) Bell’s inequality is a consequence of locality, hence its experimental violation is an indication of non locality; (ii) this violation is a typical quantum phenomenon because any classical system making local choices (either deterministic or random) will produce correlations satisfying this inequality. Both statements (i) and (ii) have been criticized by quantum probability on theoretical grounds (not discussed in the present paper) and the experiment discussed below has been devised to support these theoretical arguments. We emphasize that the goal of our experiment is not to reproduce classically the EPR correlations but to prove that there exist perfectly local classical dynamical systems violating Bell’s inequality. The conclusions of the present experiment are: (I)  no contradiction between quantum theory and locality can be deduced from the violation of Bell’s inequality. \ud
(II)  The Copenhagen interpretation of quantum theory becomes quite reasonable and not metaphyisic if interpreted at the light of the chameleon effect.  \ud
(III)  One can realize quantum entanglement by classical computers. \ud
\ud
In section (7) we prove that our experiment also provides a classical analogue of the type of logical (i.e. independent of statistics) incompatibilities pointed out by Greenberger, Home and Zeilinger
Scalar Field Dark Matter

This work is a review of the last results of research on the Scalar Field Dark Matter model of the Universe at cosmological and at galactic level. We present the complete solution to the scalar field cosmological scenario in which the dark matter is modeled by a scalar field $\Phi$ with the scalar potential $V(\Phi)=V_{0}(cosh {(\lambda \sqrt{\kappa_{0}}\Phi)}-1)$ and the dark energy is modeled by a scalar field $\Psi$, endowed with the scalar potential $\tilde{V}(\Psi)= \tilde{V_{0}}(\sinh{(\alpha \sqrt{\kappa_{0}}\Psi)})^{\beta}$, which together compose the 95% of the total matter energy in the Universe. The model presents successfully deals with the up to date cosmological observations, and is a good candidate to treat the dark matter problem at the galactic level
Revisiting the calculations of inflationary perturbations

We present a new approximation scheme that allows us to increase the accuracy of analytical predictions of the power spectra of inflationary perturbations for two specific classes of inflationary models. Among these models are chaotic inflation with a monomial potential, power-law inflation and natural inflation (inflation at a maximum). After reviewing the established first order results we calculate the amplitudes and spectral indices for these classes of models at higher orders in the slow-roll parameters for scalar and tensorial perturbations
Conformal symmetry and deflationary gas universe

We describe the ``deflationary'' evolution from an initial de Sitter phase to
a subsequent Friedmann-Lema\^{\i}tre-Robertson-Walker (FLRW) period as a
specific non-equilibrium configuration of a self-interacting gas. The
transition dynamics corresponds to a conformal, timelike symmetry of an
``optical'' metric, characterized by a refraction index of the cosmic medium
which continously decreases from a very large initial value to unity in the
FLRW phase.Comment: 10 pages, to appear in "Exact Solutions and Scalar Fields in Gravity:
  Recent Developments", ed. by A. Macias, J. Cervantes-Cota, and C.
  L\"ammerzahl, Kluwer Academic Publishers 200
Integration of simulation and multimedia in automatically generated Internet courses

The final publication is available at Springer via http://dx.doi.org/10.1007/0-306-47532-4_5This paper describes the automatic generation of simulation-based Internet courses by means of an object-oriented continuous simulation language (OOCSMP), and a compiler for this language (C-OOL). Several multimedia extensions added to the language are also described. These extensions provide the student with a better understanding of the simulated models. The paper finally describes a course developed using the multimedia extensions
Using simulation and virtual reality for distance education

The final publication is available at Springer via http://dx.doi.org/10.1007/0-306-47533-2_19This paper describes the construction of virtual reality simulations for distance education through the Internet. This is accomplished by means of an object oriented continuous simulation language, called OOCSMP, and a Java generating compiler for this language called C-OOL. This compiler is also able to create VRML worlds. The behaviour of the VRML world is specified in the OOCSMP models. Change of simulation parameters is possible at run time by means of a Java interface, generated by the compiler. An example of the simulation of the inner Solar System is presented.This paper has been sponsored by the Spanish Interdepartmental
Commission of Science and Technology (CICYT), project number
TEL1999-0181
Modelling water resource allocation: a case study on agriculture versus hydropower production

In this paper we propose an economic model for the optimum allocation of water within a given area with the following features. First, the introduction of the institutional, geographical and time scheme under which the water rights are granted. Secondly, the establishment of a modelling framework for these characteristics which influence and are, in turn, influenced by two particular circumstances, namely the irregular conditions of the upstream flows and the possible new requirements of some of the users. Particular attention is paid to the influence of the time and space variables on both the water demand and supply conditions. The application of the model to a specific case confirms the potential of the analysis as a basis for achieving improvements in water allocation from the former administrative-based rules to new flexible and tradable water rights. In both case, gains are obtained from the exchange and we can note the implications of the time and space variables on the optimal allocations.
The Physics of Cluster Mergers

Clusters of galaxies generally form by the gravitational merger of smaller clusters and groups. Major cluster mergers are the most energetic events in the Universe since the Big Bang. Some of the basic physical properties of mergers will be discussed, with an emphasis on simple analytic arguments rather than numerical simulations. Semi-analytic estimates of merger rates are reviewed, and a simple treatment of the kinematics of binary mergers is given. Mergers drive shocks into the intracluster medium, and these shocks heat the gas and should also accelerate nonthermal relativistic particles. X-ray observations of shocks can be used to determine the geometry and kinematics of the merger. Many clusters contain cooling flow cores; the hydrodynamical interactions of these cores with the hotter, less dense gas during mergers are discussed. As a result of particle acceleration in shocks, clusters of galaxies should contain very large populations of relativistic electrons and ions. Electrons with Lorentz factors gamma~300 (energies E = gamma m_e c^2 ~ 150 MeV) are expected to be particularly common. Observations and models for the radio, extreme ultraviolet, hard X-ray, and gamma-ray emission from nonthermal particles accelerated in these mergers are described
Dynamic Adaptation of Parallel Codes: Toward Self-Adaptable Components for the Grid

International audienceOne of the challenges that come from the emergence of Grid architectures is to invent new programming techniques for these new platforms. As we explain in this chapter, we think that the architecture of the applications should reflect both the parallel and the distributed aspects of Grid architectures. It results in applications built as assemblies of parallel components. Since Grid architectures are known to be highly dynamic, using resources efficiently on such architectures is a challenging problem. Software must be able to react dynamically to the changes of the underlying execution environment. In order to help developers to create software for the Grid, we are investigating a model for the adaptation of parallel components. This chapter focuses on the adaptation mechanisms that are provided as a meta-level for components. We describe how a generic platform can help to develop efficient Grid software. First experimental results show the gain that can be expected from the use of such a platform
Complementing Computational Protocol Analysis with Formal Specifications

The computational proof model of Bellare and Rogaway for cryptographic protocol analysis is complemented by providing a formal specification of the actions of the adversary and the protocol entities. This allows a matching model to be used in both a machine-generated analysis and a human-generated computational proof. Using a protocol of Jakobsson and Pointcheval as a case study, it is demonstrated that flaws in the protocol could have been found with this approach, providing evidence that the combination of human and computer analysis can be more effective than either alone. As well as finding the known flaw, previously unknown flaws in the protocol are discovered by the automatic analysis
Threat modelling for web services based web applications

Threat analysis of a web application can lead to a wide variety of identified threats. Some of these threats will be very specific to the application; others will be more related to the underlying infrastructural software, such as the web or application servers, the database, the directory server and so forth. This paper analyzes the threats that can be related to the use of web services technology in a web application. It is part of a series of papers, written by different academic teams, that each focus on one particular technological building block for web applications.status: publishe
Social capital, social norms and the New Institutional Economics

Douglass North (1990) describes institutions as the rules of the game that set limits on human behavior, now a universally-accepted definition. North and others especially underline the crucial role of informal social norms.  They predict that, like all rules of the game, social norms should affect the economic prosperity enjoyed by individuals and countries – that they should have a crucial impact, for example, on economic and political development.  In fact, substantial evidence demonstrates that social norms prescribing cooperative or trustworthy behavior have a significant impact on whether societies can overcome obstacles to contracting and collective action that would otherwise hinder their development.  Much of this evidence comes from outside the new institutional economics, emerging instead from scholarly research in the field of “social capital.”  A review of this evidence, and its implications for our understanding of the role of social norms and institutions, is therefore the focus of this chapter.
Weka: A machine learning workbench for data mining

The Weka workbench is an organized collection of state-of-the-art machine learning algorithms and data preprocessing tools. The basic way of interacting with these methods is by invoking them from the command line. However, convenient interactive graphical user interfaces are provided for data exploration, for setting up large-scale experiments on distributed computing platforms, and for designing configurations for streamed data processing. These interfaces constitute an advanced environment for experimental data mining. The system is written in Java and distributed under the terms of the GNU General Public License