cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Cytotoxic-T-Lymphocyte-Mediated Elimination of Target Cells Transduced with Engineered Adeno-Associated Virus Type 2 Vector In Vivo
Creators: name: Asokan, A.
name: DiPrimio, N.
name: Goudy, K.
name: Hirsch, M.
name: Tisch, R.
name: Li, C.
name: Samulski, R. J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: A recent clinical trial in patients with hemophilia B has suggested that adeno-associated virus (AAV) capsid-specific cytotoxic T lymphocytes (CTLs) eliminated AAV-transduced hepatocytes and resulted in therapeutic failure. AAV capsids elicit a CTL response in animal models; however, these capsid-specific CTLs fail to kill AAV-transduced target cells in mice. To better model the human clinical trial data in mice, we introduced an immunodominant epitope derived from ovalbumin (OVA; SIINFEKL) into the AAV capsid and tested CTL-mediated killing of AAV2-transduced target tissues in vivo. Initially, in vitro experiments demonstrated both classical class I and cross-presentation of the OVA antigen, following endogenous expression or AAV2-OVA vector transduction, respectively. Furthermore, an OVA-specific CTL response was elicited after muscular or systemic injection of the AAV2-OVA vector. Finally, CTL reactivity was enhanced in mice with established SIINFEKL-specific immunity after AAV2-OVA/α1 anti-trypsin (AAT) administration. Most importantly, these OVA-specific CTLs decreased AAT expression in mice treated with AAV2-OVA/AAT vector that followed a time course mimicking uncoating kinetics of AAV2 transduction in OVA-immunized mice. These results demonstrate that AAV capsid-derived antigens elicit CD8+ CTL reactivity, and these CTLs eliminated AAV-transduced target cells in mice. Notably, this model system can be exploited to study the kinetics of capsid presentation from different serotypes of AAV and permit the design of novel strategies to block CTL-mediated killing of AAV-transduced cells.
Dynamic orbitals in high-harmonic generation from CO molecules
Creators: name: Zhang, Bin
name: Yuan, Jianmin
name: Zhao, Zengxiu
Publisher: name: arXiv
Year: 2014
Subjects: subject: Atomic Physics (physics.atom-ph)
subject: FOS: Physical sciences

description: We identify that both the dynamic core polarization and dynamic orbital deformation are important in the orientation-dependent high-harmonic generation of CO molecules subjected to intense few cycle laser fields. These polarization dynamics allow for the observation of strong orientation effects and dynamic minimum in the harmonic spectra. The generated attosecond pulses can be greatly affected by these multielectron effects. This work sheds light on future development of dynamic orbital imaging on attosecond time scale.
description: 5 pages, 4 figures
Disruption of LANA in Rhesus Rhadinovirus Generates a Highly Lytic Recombinant Virus
Creators: name: Wen, K. W.
name: Damania, B.
name: Dittmer, D. P.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Rhesus monkey rhadinovirus (RRV) is a gammaherpesvirus that is closely related to human Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). RRV is the closest relative to KSHV that has a fully sequenced genome and serves as an in vitro and an in vivo model system for KSHV. The latency-associated nuclear antigen (LANA) protein of both KSHV and RRV plays key roles in the establishment and maintenance of these herpesviruses. We have constructed a RRV recombinant virus (RRVΔLANA/GFP) in which the RRV LANA open reading frame has been disrupted with a green fluorescent protein (GFP) expression cassette generated by homologous recombination. The integrity of the recombinant virus was confirmed by diagnostic PCR, restriction digestion, Southern blot analysis, and whole-genome sequencing. We compared the single-step and multistep replication kinetics of RRVΔLANA/GFP, RRV-GFP, wild-type (WT) RRV H26-95, and a revertant virus using traditional plaque assays, as well as real-time quantitative PCR-based genome quantification assays. The RRVΔLANA/GFP recombinant virus exhibited significantly higher lytic replicative properties compared to RRV-GFP, WT RRV, or the revertant virus. This was observed upon de novo infection and in the absence of chemical inducers such as phorbol esters. In addition, by using a quantitative real-time PCR-based viral array, we are the first to report differences in global viral gene expression between WT and recombinant viruses. The RRVΔLANA/GFP virus displayed increased lytic gene transcription at all time points postinfection compared to RRV-GFP. Moreover, we also examined several cellular genes that are known to be repressed by KSHV LANA and report that these genes are derepressed during de novo lytic infection with the RRVΔLANA/GFP virus compared to RRV-GFP. Finally, we also demonstrate that the RRVΔLANA/GFP virus fails to establish latency in B cells, as measured by the loss of GFP-positive cells and intracellular viral genomes.
Phonon Transport in Single-Layer Transition Metal Dichalcogenides: a First-Principles Study
Creators: name: Gu, Xiaokun
name: Yang, Ronggui
Publisher: name: arXiv
Year: 2014
Subjects: subject: Materials Science (cond-mat.mtrl-sci)
subject: FOS: Physical sciences

description: Two-dimensional transition metal dichalcogenides (TMDCs) are finding promising electronic and optical applications due to their unique properties. In this letter, we systematically study the phonon transport and thermal conductivity of eight semiconducting single-layer TMDCs, MX2 (M=Mo, W, Zr and Hf, X=S and Se), by using the first-principles-driven phonon Boltzmann transport equation approach. The validity of the single-mode relaxation time approximation to predict the thermal conductivity of TMDCs is assessed by comparing the results with the iterative solution of the phonon Boltzmann transport equation. We find that the phononic thermal conductivities of 2H-type TMDCs are above 50 W/mK at room temperature while the thermal conductivity values of the 1T-type TMDCs are much lower, when the size of the sample is 1 μm. A very high thermal conductivity value of 142 W/mK was found in single-layer WS2. The large atomic weight difference between W and S leads to a very large phonon bandgap which in turn forbids the scattering between acoustic and optical phonon modes and thus resulting in very long phonon relaxation time.
description: 21 pages, 7 figures
Multilingualism and multiscriptism in TEI publishing: DH2022
Creators: name: Wang, Yifan
name: Nagasaki, Kiyonori
name: Ohmukai, Ikki
name: Shimoda, Masahiro
Publisher: name: Zenodo
Year: 2022
Subjects: language
script
typography
multilingualization

description: In the conference DH2022 Tokyo held in this July, the book of abstracts has been published entirely through the XSL-FO pipeline based on ADHO’s DHConvalidator and TEI to PDF Book Creator. The texts of the abstracts were converted by each author with DHConvalidator, which generates a format not always expected by the original TEI to PDF Book Creator. Moreover, while the text body is mostly written in English and some other languages which are accepted in CFP, it also embraces a large number of words and phrases in various Asian languages, reflecting the theme of the conference and authors’ regional backgrounds. Thus, we needed to adapt the original stylesheets to multi-script typography by a large expansion of linguistic and typographical templates as well as extensive annotation. Our modification involves extraction and annotation of Asian language fragments in TEI documents, locale-oriented typeface differentiation, adjustment for typographical conventions, and mixed script typesetting. We will share our methodology and decisions we applied to the actual book, hoping that it serves as a case study that leads to dissemination of attention to, and better practices in, non-Latin and/or multi-script publication in the TEI community.
Nonequilibrium scaling explorations on a 2D Z(5)-symmetric model
Creators: name: da Silva, Roberto
name: Fernandes, Henrique A.
name: de Felicio, J. R. Drugowich
Publisher: name: arXiv
Year: 2014
Subjects: subject: Statistical Mechanics (cond-mat.stat-mech)
subject: FOS: Physical sciences

description: We have investigated the dynamic critical behavior of the two-dimensional Z(5)-symmetric spin model by using short-time Monte Carlo (MC) simulations. We have obtained estimates of some critical points in its rich phase diagram and included, among the usual critical lines the study of first-order (weak) transition by looking into the order-disorder phase transition. Besides, we also investigated the soft-disorder phase transition by considering empiric methods. A study of the behavior of $β/νz$ along the self-dual critical line has been performed and special attention has been devoted to the critical bifurcation point, or FZ (Fateev-Zamolodchikov) point. Firstly, by using a refinement method and taking into account simulations out-of-equilibrium, we were able to localize parameters of this point. In a second part of our study, we turned our attention to the behavior of the model at the early stage of its time evolution in order to find the dynamic critical exponent z as well as the static critical exponents $β$ and $% ν$ of the FZ-point on square lattices. The values of the static critical exponents and parameters are in good agreement with the exact results, and the dynamic critical exponent $z\approx 2.28$ very close of the 4-state Potts model ($z\approx 2.29$).
description: 11 pages, 7 figures
Enhancement of Adeno-Associated Virus Infection by Mobilizing Capsids into and Out of the Nucleolus
Creators: name: Johnson, J. S.
name: Samulski, R. J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Adeno-associated virus (AAV) serotypes are being tailored for numerous therapeutic applications, but the parameters governing the subcellular fate of even the most highly characterized serotype, AAV2, remain unclear. To understand how cellular conditions control capsid trafficking, we have tracked the subcellular fate of recombinant AAV2 (rAAV2) vectors using confocal immunofluorescence, three-dimensional infection analysis, and subcellular fractionation. Here we report that a population of rAAV2 virions enters the nucleus and accumulates in the nucleolus after infection, whereas empty capsids are excluded from nuclear entry. Remarkably, after subcellular fractionation, virions accumulating in nucleoli were found to retain infectivity in secondary infections. Proteasome inhibitors known to enhance transduction were found to potentiate nucleolar accumulation. In contrast, hydroxyurea, which also increases transduction, mobilized virions into the nucleoplasm, suggesting that two separate pathways influence vector delivery in the nucleus. Using a small interfering RNA (siRNA) approach, we then evaluated whether nucleolar proteins B23/nucleophosmin and nucleolin, previously shown to interact with AAV2 capsids, affect trafficking and transduction efficiency. Similar to effects observed with proteasome inhibition, siRNA-mediated knockdown of nucleophosmin potentiated nucleolar accumulation and increased transduction 5- to 15-fold. Parallel to effects from hydroxyurea, knockdown of nucleolin mobilized capsids to the nucleoplasm and increased transduction 10- to 30-fold. Moreover, affecting both pathways simultaneously using drug and siRNA combinations was synergistic and increased transduction over 50-fold. Taken together, these results support the hypothesis that rAAV2 virions enter the nucleus intact and can be sequestered in the nucleolus in stable form. Mobilization from the nucleolus to nucleoplasmic sites likely permits uncoating and subsequent gene expression or genome degradation. In summary, with these studies we have refined our understanding of AAV2 trafficking dynamics and have identified cellular parameters that mobilize virions in the nucleus and significantly influence AAV infection.
Gene Mapping and Phylogenetic Analysis of the Complete Genome from 30 Single-Stranded RNA Male-Specific Coliphages (Family Leviviridae)
Creators: name: Genthner, F. J.
name: Vinje, J.
name: Gentry, J.
name: Friedman, S. D.
name: Sobsey, M. D.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Male-specific single-stranded RNA (FRNA) coliphages belong to the family Leviviridae. They are classified into two genera (Levivirus and Allolevivirus), which can be subdivided into four genogroups (genogroups I and II in Levivirus and genogroups III and IV in Allolevivirus). Relatively few strains have been completely characterized, and hence, a detailed knowledge of this virus family is lacking. In this study, we sequenced and characterized the complete genomes of 19 FRNA strains (10 Levivirus strains and 9 Allolevivirus strains) and compared them to the 11 complete genome sequences available in GenBank. Nucleotide similarities among strains of Levivirus genogroups I and II were 75% to 99% and 83 to 94%, respectively, whereas similarities among strains of Allolevivirus genogroups III and IV ranged from 70 to 96% and 75 to 95%, respectively. Although genogroup I strain fr and genogroup III strains MX1 and M11 share only 70 to 78% sequence identity with strains in their respective genogroups, phylogenetic analyses of the complete genome and the individual genes suggest that strain fr should be grouped in Levivirus genogroup I and that the MX1 and M11 strains belong in Allolevivirus genogroup III. Strains within each genus share >50% sequence identity, whereas between the two genera, strains have <40% nucleotide sequence identity. Overall, amino acid composition, nucleotide similarities, and replicase catalytic domain location contributed to phylogenetic assignments. A conserved eight-nucleotide signature at the 3′ end of the genome distinguishes leviviruses (5′ ACCACCCA 3′) from alloleviviruses (5′ TCCTCCCA 3′).
A study protocol for development and validation of a clinical prediction model for frailty (ModulEn): a new European commitment to tackling frailty
Creators: name: Apóstolo, Joao
name: Bobrowicz-Campos, Elzbieta
name: Moreno-Casbas, Teresa
name: Teixeira-Santos, Luisa
name: Sánchez De Madariaga, Ricardo
name: Casado-Ramírez, Elvira
name: Couto, Filipa
name: Coelho, Adriana Neves
name: Parola, Vitor
name: Gil, Isabel María
name: Pascual-Carrasco, Mario
name: Almeida, Maria De Lurdes
name: ModulEn Consortium
Publisher: name: Universita' degli Studi di Salerno
Year: 2019
Subjects: Older adults
Frailty
Circadian health
Predictive model
Citizen engagement
Digital solutions

description: There is a growing need to implement and evaluate the technological solutions that allow the early detection of age-related frailty and enable assessment of the predictive values of frailty components. The broad use of these solutions may ensure an efficient and sustainable response of health and social care systems to the challenges related to demographic aging. In this paper, we present the protocol of the ModulEn study that aims to develop and validate a predictive model for frailty. For this purpose, the sample composed by older adults aged 65-80 years and recruited from the community will be invited to use an electronic device ACM Kronowise® 2.0. This device allows proactive and continuous monitoring of circadian health, physical activity, and sleep and eating habits. It will be used during a period of seven to ten days. The participants will also be given the questionnaires evaluating the variables of interest, including frailty level, as well as their experience and satisfaction with the device use. Data provided from these two sources will be combined and the relevant associations will be identified. In our view, the implications of this study' findings for clinical practice include the possibility to develop and validate tools for timely prevention of frailty progress. In the long term, the ModulEn may contribute to the critical reduction of frailty burden in Europe.
Invariant classification of second-order conformally flat superintegrable systems
Creators: name: Capel, Joshua
name: Kress, Jonathan
Publisher: name: arXiv
Year: 2014
Subjects: subject: Mathematical Physics (math-ph)
subject: FOS: Physical sciences
subject: 20C35, 81R05, 22E70, 14M99

description: In this paper we continue the work of Kalnins et al in classifying all second-order conformally-superintegrable (Laplace-type) systems over conformally flat spaces, using tools from algebraic geometry and classical invariant theory. The results obtained show, through Staeckel equivalence, that the list of known nondegenerate superintegrable systems over three-dimensional conformally flat spaces is complete. In particular, a 7-dimensional manifold is determined such that each point corresponds to a conformal class of superintegrable systems. This manifold is foliated by the nonlinear action of the conformal group in three-dimensions. Two systems lie in the same conformal class if and only if they lie in the same leaf of the foliation. This foliation is explicitly described using algebraic varieties formed from representations of the conformal group. The proof of these results rely heavily on Groebner basis calculations using the computer algebra software packages Maple and Singular.
General and Target-Specific RNA Binding Properties of Epstein-Barr Virus SM Posttranscriptional Regulatory Protein
Creators: name: Swaminathan, S.
name: Han, Z.
name: Dittmer, D. P.
name: Verma, D.
name: Hilscher, C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Epstein-Barr virus (EBV) SM protein is an essential nuclear shuttling protein expressed by EBV early during the lytic phase of replication. SM acts to increase EBV lytic gene expression by binding EBV mRNAs and enhancing accumulation of the majority of EBV lytic cycle mRNAs. SM increases target mRNA stability and nuclear export, in addition to modulating RNA splicing. SM and its homologs in other herpesvirus have been hypothesized to function in part by binding viral RNAs and recruiting cellular export factors. Although activation of gene expression by SM is gene specific, it is unknown whether SM binds to mRNA in a specific manner or whether its RNA binding is target independent. SM-mRNA complexes were isolated from EBV-infected B-lymphocyte cell lines induced to permit lytic EBV replication, and a quantitative measurement of mRNAs corresponding to all known EBV open reading frames was performed by real-time quantitative reverse transcription-PCR. The results showed that although SM has broad RNA binding properties, there is a clear hierarchy of affinities among EBV mRNAs with respect to SM complex formation. In vitro binding assays with two of the most highly SM-associated transcripts suggested that SM binds preferentially to specific sequences or structures present in noncoding regions of some EBV mRNAs. Furthermore, the presence of these sequences conferred responsiveness to SM. These data are consistent with a mechanism of action similar to that of hnRNPs, which exert sequence-specific effects on gene expression despite having multiple degenerate consensus binding sites common to a large number of RNAs.
A spin-boson theory for charge photogeneration in organic molecules: Role of quantum coherence
Creators: name: Yao, Yao
Publisher: name: arXiv
Year: 2014
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: The charge photogeneration process in organic molecules is investigated by a quantum heat engine model, in which two molecules are modeled by a two-spin system sandwiched between two bosonic baths at their own temperatures. The two baths represent the photon emission source and the phonon environment, respectively. We utilize the time-dependent density matrix renormalization group algorithm to investigate the ultrafast quantum thermodynamical processes of the model. We find that the transient energy flow through the two spins behaves a two-stage effect: The first stage shows a coherent dynamics which represents the ultrafast delocalization and dissociation of the charge-transfer state, and in the second stage a steady current is establish. The photo-to-charge conversion is highly efficient with the maximum efficiency being $93\%$ with optimized model parameters. The survival entanglement between the two spins is found to be mostly responsible for the hyper efficiency.
description: 9 pages, 8 figures
OLED devices optimization for lighting application
Creators: name: Aprano, Salvatore
Publisher: name: Universita degli studi di Salerno
Year: 2017
Subjects: subject: ING-INF/01 ELETTRONICA
subject: Oled
subject: Organic electronics
subject: Light sources

description: 2015 - 2016
description: In this work a potential new OLED application is presented: a large-area purple OLED for horticultural application, which combines red and blue light emissions in a unique device. The main issue of this thesis is to demonstrate the effectiveness of the proposed OLED structure by using theoretical models created during the three years of the Ph.D. studies and applied to commercial materials. The core of this dissertation is the third chapter, where the reader is brought to the optimization of the final purple OLED structure after several experiments, which confirm either the basic concepts explained in the two previous chapters, either a mathematical model for a fine-tuning of the blue emission layer. Behind the proposed device architecture and material employed, there is the concept of “hybrid OLEDs with triplet harvesting”, where a proper combined use of fluorescent and phosphorescent emitting materials allows a theoretical internal quantum efficiency of 100%. The last chapter is focused on the study and the realization of metal grids on the indium-tin-oxide (ITO), which is the most used material as transparent and conductive anode for the OLED devices. Despite ITO owns good property of transmittance (transparency), because of its limited conductivity, a lateral voltage drop occurs, preventing a homogeneous emission when the dimensions of the devices exceeds few square centimetres. To overcome this problem, it is presented a new mathematical model which, unlike the most established literature models do, takes into account both the electrical influence of the metal grid and that one of the ITO. Finally, with a good agreement with the experimental data, the theoretical model is used to predict optical and electrical behaviour of different hexagonal metal grid on ITO. It worth to underline that all the approaches implemented in this work to achieve a large-area purple OLED, have a general validity. Indeed, the entire know-how in this thesis it has been successfully used, in the last three years, to make several different OLED devices, different for colour emission, size and performances. [edited by Author]
A minimal model for two-component dark matter
Creators: name: Esch, Sonja
name: Klasen, Michael
name: Yaguna, Carlos E.
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Physics - Phenomenology (hep-ph)
subject: FOS: Physical sciences

description: We propose and study a new minimal model for two-component dark matter. The model contains only three additional fields, one fermion and two scalars, all singlets under the Standard Model gauge group. Two of these fields, one fermion and one scalar, are odd under a $Z_2$ symmetry that renders them simultaneously stable. Thus, both particles contribute to the observed dark matter density. This model resembles the union of the singlet scalar and the singlet fermionic models but it contains some new features of its own. We analyze in some detail its dark matter phenomenology. Regarding the relic density, the main novelty is the possible annihilation of one dark matter particle into the other, which can affect the predicted relic density in a significant way. Regarding dark matter detection, we identify a new contribution that can lead either to an enhancement or to a suppression of the spin-independent cross section for the scalar dark matter particle. Finally, we define a set of five benchmarks models compatible with all present bounds and examine their direct detection prospects at planned experiments. A generic feature of this model is that both particles give rise to observable signals in 1-ton direct detection experiments. In fact, such experiments will be able to probe even a subdominant dark matter component at the percent level.
description: 18 pages, 10 figures
Herd Immunity to GII.4 Noroviruses Is Supported by Outbreak Patient Sera
Creators: name: Baric, R. S.
name: Lindesmith, L. C.
name: Donaldson, E. F.
name: Vinje, J.
name: Saxe, L.
name: Cannon, J. L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Noroviruses (NoVs) of genogroup II, cluster 4 (GII.4), are the most common cause of outbreaks of acute gastroenteritis worldwide. During the past 13 years, GII.4 NoVs caused four seasons of widespread activity globally, each associated with the emergence of a new strain. In this report, we characterized the most recent epidemic strain, GII.4-2006 Minerva, by comparing virus-like particle (VLP) antigenic relationships and histo-blood group antigen (HBGA) binding profiles with strains isolated earlier. We also investigated the seroprevalence and specificity of GII.4 antibody in the years prior to, during, and following the GII.4 pandemic of 1995 and 1996 using a large collection of acute- and convalescent-phase serum pairs (n = 298) collected from 34 outbreaks. In a surrogate neutralization assay, we measured the blockade of HBGA binding using a panel of GII.4 VLPs representing strains isolated in 1987, 1997, 2002, and 2006 and a GII.3 VLP representing a strain isolated in the mid-1990s. Serum titers required for 50% HBGA blockade were compared between populations. In general, blockade of GII.4 VLP-HBGA binding was greater with convalescent-phase outbreak sera collected near the time of origin of the VLP strain. Heterotypic genotypes did not contribute to herd immunity against GII.4 NoVs based on their inability to block GII.4 VLP binding to HBGA. However, previous exposure to GII.4 NoV followed by infection by GII.3 NoV appeared to evoke an immune response to GII.4 NoV. These results support the hypothesis that herd immunity is a driving force for GII.4 evolution in the U.S. population. The data also suggest that complex patterns of cross-protection may exist across NoV genotypes in humans.
Human Cytomegalovirus IE1-72 Protein Interacts with p53 and Inhibits p53-Dependent Transactivation by a Mechanism Different from That of IE2-86 Protein
Creators: name: Huang, E.-S.
name: Zhang, Z.
name: Cai, H.
name: Cha, C.-Y.
name: Hwang, E.-S.
name: Huong, S.-M.
name: Huang, D. Y.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Infection of host cells with human cytomegalovirus (HCMV) induces cell cycle dysregulation. Two HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, are promiscuous transactivators that have been implicated in the dysregulatory events. Cellular p53 protein is accumulated to high levels in HCMV-infected cells, but the indicative marker of p53 transcriptional activity, p21, is markedly decreased. Both IE1-72 and IE2-86 were able to transactivate the p53 promoter and interact with p53 protein in DNA-transfected or HCMV-infected cells. HCMV UL84, a multiregulatory protein expressed in early periods of HCMV infection, also interacted with p53. HCMV IE1-72 prevented or disrupted p53 binding to p53-specific DNA sequences, while IE2-86 and/or UL84 enhanced p53 binding and induced supershift of this DNA-protein complex. Both HCMV IE1-72 and IE2-86 were able to inhibit p53-dependent transcriptional activation in plasmid-transfected cells. IE1-72, rather than IE2-86, was found to be responsible for p21 downregulation in HCMV-infected HEL cells. DNA transfection analysis using IE1-72 mutants revealed that exon 2/3 and the zinc finger region of IE1-72 are essential for IE1-72's effect on the repression of p53-dependent transcriptional activation. These data suggest that HCMV IE1-72 and/or IE2-86 transactivates the p53 promoter and induces p53 accumulation, but HCMV IE1-72 represses the p53 transactivation activity by a unique binding hindrance mechanism different from that of IE2-86. Thus, various modes of viral IE proteins and p53 interactions might result in multiple outcomes, such as stimulation of cellular DNA synthesis, cell cycle progression and cell cycle arrest, and prevention of program cell death.
title: Improving pesticide regulation by use of impact analyses: A case study for bees
Creators: name: Miles, Mark
name: Alix, Anne
name: Becker, Roland
name: Coulson, Mike
name: Dinter, Axel
name: Oger, Laurent
name: Pilling, Ed
name: Sharples, Amanda
name: Weyman, Gabe
Publisher: name: Julius Kühn-Institut
Year: 2018

description: When changes to regulatory guidance for risk assessment are proposed it is necessary to undertake an impact analysis to assess whether they bring the desired improvement to a risk assessment and reliability of the outcomes to inform decision making. In particular impact analyses should estimate the chances of getting both false negative (concluding low risk where more research is needed) and false positive outcomes (concluding high risks where the product is of low risk). Such analyses are also used to inform on future product development costs and workload for regulatory authorities.
In this paper, we present the findings from an impact analysis conducted on the proposed EFSA bee guidance document (2013) and discuss whether the proposed guidance would provide for a cost effective and tiered approach toward the protection of bees due to the potential risks posed by the use of plant protection products. Following on from this a second impact assessment is presented based on new data generated by ECPA member companies regarding the assessment of chronic risk to bees. Critical areas are discussed and suggestions for the improvement of assess the risk assessment for plant protection products (PPP) to bees are presented.
description: Julius-Kühn-Archiv, Nr. 462 (2018): Hazards of pesticides to bees 13th International Symposium of the ICP-PR Bee Protection Group 18. - 20. October 2017, València (Spain) - Proceedings -
Kaposi's Sarcoma-Associated Herpesvirus Encodes a Viral Deubiquitinase
Creators: name: Wang, L.
name: Damania, B.
name: Gonzalez, C. M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically linked to Kaposi's sarcoma, primary effusion lymphomas, and multicentric Castleman's disease. Like other herpesviruses, KSHV can exist in either a lytic or a latent phase during its life cycle. We report that the lytic protein encoded by KSHV open reading frame 64 (Orf64) is a viral deubiquitinase (DUB) enzyme capable of deubiquitinating cellular proteins in vitro and in vivo. Orf64 DUB activity is effective against lysine 48 (K48)- and lysine 63 (K63)-linked ubiquitin chains. Thus, KSHV Orf64 is a viral DUB that does not show specificity toward K48 or K63 ubiquitin linkages. Orf64 DUB activity lies within the first 205 residues of the protein, and deubiquitination is dependent on a cysteine at position 29, since mutation of this residue ablated this activity. Cell fractionation studies revealed that the N terminus and the full-length protein localized to both the nuclear and cytoplasmic compartments. The function of Orf64 was tested by short interfering RNA (siRNA) knockdown studies on latently infected cells that were induced into lytic replication. We found that depletion of Orf64 by siRNA resulted in decreased viral lytic transcription and lytic protein expression. These experiments indicate that Orf64 plays a role in KSHV lytic replication.
Multiphoton transitions for delay-zero calibration in attosecond spectroscopy
Creators: name: Herrmann, Jens
name: Lucchini, Matteo
name: Chen, Shaohao
name: Wu, Mengxi
name: Ludwig, André
name: Kasmi, Lamia
name: Schafer, Kenneth J.
name: Gallmann, Lukas
name: Gaarde, Mette B.
name: Keller, Ursula
Publisher: name: arXiv
Year: 2014
Subjects: subject: Atomic Physics (physics.atom-ph)
subject: FOS: Physical sciences

description: The exact delay-zero calibration in an attosecond pump-probe experiment is important for the correct interpretation of experimental data. In attosecond transient absorption spectroscopy the determination of the delay-zero exclusively from the experimental results is not straightforward and may introduce significant errors. Here, we report the observation of quarter-laser-cycle (4ω) oscillations in a transient absorption experiment in helium using an attosecond pulse train overlapped with a precisely synchronized, moderately strong infrared pulse. We demonstrate how to extract and calibrate the delay-zero with the help of the highly nonlinear 4ω signal. A comparison with the solution of the time-dependent Schrödinger equation is used to confirm the accuracy and validity of the approach. Moreover, we study the mechanisms behind the quarter-laser-cycle and the better-known half-laser-cycle oscillations as a function of experimental parameters. This investigation yields an indication of the robustness of our delay-zero calibration approach.
description: 15 pages, 10 figures
Major Coexisting Human Immunodeficiency Virus Type 1 env Gene Subpopulations in the Peripheral Blood Are Produced by Cells with Similar Turnover Rates and Show Little Evidence of Genetic Compartmentalization
Creators: name: Price, R. W.
name: Schnell, G. L.
name: Patel-Chhabra, M.
name: Ince, W. L.
name: Eron, J. J.
name: Harrington, P. R.
name: Menezes, P.
name: Swanstrom, R. I.
name: Burch, C. L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: A distinctive feature of chronic human immunodeficiency virus type 1 (HIV-1) infection is the presence of multiple coexisting genetic variants, or subpopulations, that comprise the HIV-1 population detected in the peripheral blood. Analysis of HIV-1 RNA decay dynamics during the initiation of highly active antiretroviral therapy (HAART) has been a valuable tool for modeling the life span of infected cells that produce the bulk HIV-1 population. However, different HIV-1 target cells may have different turnover rates, and it is not clear whether the bulk HIV-1 RNA decay rate actually represents a composite of the decay rates of viral subpopulations compartmentalized in different cellular subsets with different life spans. Using heteroduplex tracking assays targeting the highly variable V3 or V4-V5 regions of the HIV-1 env gene in eight subjects, we found that all detectable coexisting HIV-1 variants in the peripheral blood generally decayed at similar rates during the initiation of HAART, suggesting that all of the variants were produced by cells with similar life spans. Furthermore, single genome amplification and coreceptor phenotyping revealed that in two subjects coexisting HIV-1 variants with distinct CXCR4 or CCR5 coreceptor phenotypes decayed with similar rates. Also, in nine additional subjects, recombination and a lack of genetic compartmentalization between X4 and R5 variants were observed, suggesting an overlap in host cell range. Our results suggest that the HIV-1 env subpopulations detectable in the peripheral blood are produced by cells with similar life spans and are not genetically isolated within particular cell types.
Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication
Creators: name: Roy, D.
name: Gershburg, E.
name: Whitehurst, C. B.
name: Dittmer, D. P.
name: Wang, F.-Z.
name: Pagano, J. S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Although many drugs inhibit the replication of Epstein-Barr virus (EBV) in cell culture systems, there is still no drug that is effective and approved for use in primary EBV infection. More recently, maribavir (MBV), an l-ribofuranoside benzimidazole, has been shown to be a potent and nontoxic inhibitor of EBV replication and to have a mode of action quite distinct from that of acyclic nucleoside analogs such as acyclovir (ACV) that is based primarily on MBV's ability to block the phosphorylation of target proteins by EBV and human cytomegalovirus protein kinases. However, since the antiviral mechanisms of the drug are complex, we have carried out a comprehensive analysis of the effects of MBV on the RNA expression levels of all EBV genes with a quantitative real-time reverse transcription-PCR-based array. We show that in comparisons with ACV, the RNA expression profiles produced by the two drugs are entirely different, with MBV causing a pronounced inhibition of multiple viral mRNAs and with ACV causing virtually none. The results emphasize the different modes of action of the two drugs and suggest that the action of MBV may be linked to indirect effects on the transcription of EBV genes through the interaction of BGLF4 with multiple viral proteins.
Novel Influenza Virus NS1 Antagonists Block Replication and Restore Innate Immune Function
Creators: name: Basu, D.
name: Walkiewicz, M. P.
name: Auble, D. T.
name: Engel, D. A.
name: Frieman, M.
name: Baric, R. S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: The innate immune system guards against virus infection through a variety of mechanisms including mobilization of the host interferon system, which attacks viral products mainly at a posttranscriptional level. The influenza virus NS1 protein is a multifunctional facilitator of virus replication, one of whose actions is to antagonize the interferon response. Since NS1 is required for efficient virus replication, it was reasoned that chemical inhibitors of this protein could be used to further understand virus-host interactions and also serve as potential new antiviral agents. A yeast-based assay was developed to identify compounds that phenotypically suppress NS1 function. Several such compounds exhibited significant activity specifically against influenza A virus in cell culture but had no effect on the replication of another RNA virus, respiratory syncytial virus. Interestingly, cells lacking an interferon response were drug resistant, suggesting that the compounds block interactions between NS1 and the interferon system. Accordingly, the compounds reversed the inhibition of beta interferon mRNA induction during infection, which is known to be caused by NS1. In addition, the compounds blocked the ability of NS1 protein to inhibit double-stranded RNA-dependent activation of a transfected beta interferon promoter construct. The effects of the compounds were specific to NS1, because they had no effect on the ability of the severe acute respiratory syndrome coronavirus papainlike protease protein to block beta interferon promoter activation. These data demonstrate that the function of NS1 can be modulated by chemical inhibitors and that such inhibitors will be useful as probes of biological function and as starting points for clinical drug development.
Experimental Evidences of Quantum Phase Transition in a Spin Cluster Compound
Creators: name: Chakraborty, Tanmoy
name: Singh, Harkirat
name: Mitra, Chiranjib
Publisher: name: arXiv
Year: 2014
Subjects: subject: Strongly Correlated Electrons (cond-mat.str-el)
subject: FOS: Physical sciences

description: Experimental realization of magnetic field induced quantum phase transition (QPT) is reported for NH4CuPO4.H2O, a two spin cluster material with isotropic Heisenberg interaction. Experimental magnetization and specific heat data have been collected as a function of temperature and magnetic field. Experimental data have been analyzed in terms of Heisenberg dimer model. Two quantum complementary observables representing local and non-local properties of the spins are constructed using the experimental data and a clear evidence of QPT is observed through partial quantum information sharing when the magnetic field is swept through a particular value. Signature of QPT is also observed when specific heat is measured as a function of magnetic field at low temperature. Furthermore, using the experimental specific heat data, magnetic energy values are calculated and their variations are captured as a function of magnetic field and temperature.
Quantitating the Multiplicity of Infection with Human Immunodeficiency Virus Type 1 Subtype C Reveals a Non-Poisson Distribution of Transmitted Variants
Creators: name: Cohen, M. S.
name: Chu, H.
name: Williamson, C.
name: Hide, W.
name: Athreya, G. S.
name: Fiscus, S.
name: Bhattacharya, T.
name: Haynes, B. F.
name: Galvin, S.
name: Hahn, B. H.
name: Treurnicht, F. K.
name: Salazar-Gonzalez, J. F.
name: Swanstrom, R.
name: Shaw, G. M.
name: Thebus, R.
name: Hoffman, I.
name: Mapanje, C.
name: Karim, S. A.
name: Giorgi, E. E.
name: Seoighe, C.
name: Mlisana, K.
name: Anderson, J. A.
name: Keele, B. F.
name: Kazembe, P.
name: Abrahams, M.-R.
name: Ping, L.-H.
name: Korber, B. T.
name: Wood, N.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.
Reducing the Risk of Adeno-Associated Virus (AAV) Vector Mobilization with AAV Type 5 Vectors
Creators: name: Hewitt, F. C.
name: Li, C.
name: Gray, S. J.
name: Samulski, R. J.
name: Cockrell, S.
name: Washburn, M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Current adeno-associated virus (AAV) gene therapy vectors package a transgene flanked by the terminal repeats (TRs) of AAV type 2 (AAV2). Although these vectors are replication deficient, wild-type (wt) AAV2 prevalent in the human population could lead to replication and packaging of a type 2 TR (TR2)-flanked transgene in trans during superinfection by a helper virus, leading to “mobilization” of the vector genome from treated cells. More importantly, it appears likely that the majority of currently characterized AAV serotypes as well as the majority of new novel isolates are capable of rescuing and replicating AAV2 vector templates. To investigate this possibility, we flanked a green fluorescent protein transgene with type 2 and, the most divergent AAV serotype, type 5 TRs (TR2 or TR5). Consistent with AAV clades, AAV5 specifically replicated TR5 vectors, while AAV2 and AAV6 replicated TR2-flanked vectors. To exploit this specificity, we created a TR5 vector production system for Cap1 to Cap5. Next, we showed that persisting recombinant AAV genomes flanked by TR2s or TR5s were mobilized in vitro after addition of the cognate AAV Rep (as well as Rep6 for TR2) and adenoviral helper. Finally, we showed that a cell line containing a stably integrated wt AAV2 genome resulted in mobilization of a TR2-flanked vector but not a TR5-flanked vector upon adenoviral superinfection. Based on these data and the relative prevalence of wt AAV serotypes in the population, we propose that TR5 vectors have a significantly lower risk of mobilization and should be considered for clinical use.
Replicon Particles of Venezuelan Equine Encephalitis Virus as a Reductionist Murine Model for Encephalitis
Creators: name: Johnston, R. E.
name: Konopka, J. L.
name: Schafer, A.
name: Whitmore, A. C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) were used to model the initial phase of VEE-induced encephalitis in the mouse brain. VRP can target and infect cells as VEE, but VRP do not propagate beyond the first infected cell due to the absence of the structural genes. Direct intracranial inoculation of VRP into mice induced acute encephalitis with signs similar to the neuronal phase of wild-type VEE infection and other models of virus-induced encephalitis. Using the previously established VRP-mRNP tagging system, a new method to distinguish the host responses in infected cells from those in uninfected bystander cell populations, we detected a robust and rapid innate immune response in the central nervous system (CNS) by infected neurons and uninfected bystander cells. Moreover, this innate immune response in the CNS compromised blood-brain barrier integrity, created an inflammatory response, and directed an adaptive immune response characterized by proliferation and activation of microglia cells and infiltration of inflammatory monocytes, in addition to CD4+ and CD8+ T lymphocytes. Taken together, these data suggest that a naïve CNS has an intrinsic potential to induce an innate immune response that could be crucial to the outcome of the infection by determining the composition and dynamics of the adaptive immune response. Furthermore, these results establish a model for neurotropic virus infection to identify host and viral factors that contribute to invasion of the brain, the mechanism(s) whereby the adaptive immune response can clear the infection, and the role of the host innate response in these processes.
Quantum Mechanics of a Rotating Billiard
Creators: name: Jha, Nandan
name: Jain, Sudhir R.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Chaotic Dynamics (nlin.CD)
subject: Quantum Physics (quant-ph)
subject: FOS: Physical sciences

description: Integrability of a square billiard is spontaneously broken as it rotates about one of its corners. The system becomes quasi-integrable where the invariant tori are broken with respect to a certain parameter, $λ= 2E/ω^{2}$ where E is the energy of the particle inside the billiard and $ω$ is the angular frequency of rotation of billiard. We study the system classically and quantum mechanically in view of obtaining a correspondence in the two descriptions. Classical phase space in Poincaré surface of section shows transition from regular to chaotic motion as the parameter $λ$ is decreased. In the Quantum counterpart, the spectral statistics shows a transition from Poisson to Wigner distribution as the system turns chaotic with decrease in $λ$. The wavefunction statistics however show breakdown of time-reversal symmetry as $λ$ decreases.