cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Murine Hepatitis Virus Replicase Protein nsp10 Is a Critical Regulator of Viral RNA Synthesis
Creators: name: Denison, M. R.
name: Donaldson, E. F.
name: Sims, A. C.
name: Baric, R. S.
name: Graham, R. L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Coronavirus replication requires proteolytic processing of the large polyprotein encoded by ORF1a/ab into putative functional intermediates and eventually ∼15 mature proteins. The C-terminal ORF1a protein nsp10 colocalizes with viral replication complexes, but its role in transcription/replication is not well defined. To investigate the role of nsp10 in coronavirus transcription/replication, alanine replacements were engineered into a murine hepatitis virus (MHV) infectious clone in place of conserved residues in predicted functional domains or charged amino acid pairs/triplets, and rescued viruses were analyzed for mutant phenotypes. Of the 16 engineered clones, 5 viable viruses were rescued, 3 mutant viruses generated no cytopathic effect but were competent to synthesize viral subgenomic RNAs, and 8 were not viable. All viable mutants showed reductions in growth kinetics and overall viral RNA synthesis, implicating nsp10 as being a cofactor in positive- or negative-strand synthesis. Viable mutant nsp10-E2 was compromised in its ability to process the nascent polyprotein, as processing intermediates were detected in cells infected with this virus that were not detectable in wild-type infections. Mapping the mutations onto the crystal structure of severe acute respiratory syndrome virus nsp10 identified a central core resistant to mutation. Mutations targeting residues in or near either zinc-binding finger generated nonviable phenotypes, demonstrating that both domains are essential to nsp10 function and MHV replication. All mutations resulting in viable phenotypes mapped to loops outside the central core and were characterized by a global decrease in RNA synthesis. These results demonstrate that nsp10 is a critical regulator of coronavirus RNA synthesis and may play an important role in polyprotein processing.
Analysis of Competence Level and the Attendance of the Lecturer in Its Effects on Students Grade Using Fuzzy Quantification Theory
Creators: name: Mustafidah, Hindayati
name: Suwarsito
Publisher: name: arXiv
Year: 2014
Subjects: subject: Computers and Society (cs.CY)
subject: FOS: Computer and information sciences

description: It known that teachers as educators should have competence that shows its quality so that the lecture material provided can be absorbed by the student. The competencies in this term include the pedagogic, professional, personality, and social. The competence that owned by lecturer can be obtained from the results of the assessment conducted by the student through the filling of the questionnaire. This study conducted an analysis of the level of the lecturer competence of the relationship between the present of lecturer in classroom with a percentage of the value of passing students in courses using fuzzy quantification theory. Based on the results of the four competencies acquired professional competence that contributes most of 79.45% in contributed the attendance of lecturer will it affect the percentage of passing students in courses that are shown with a percentage of the graduation minimum B.
description: 5 pages, 1 figure, 5 tables, 4 equations, published with International Journal of Computer Science Issues (IJCSI)
High resolution numerical-relativity simulations for the merger of binary magnetized neutron stars
Creators: name: Kiuchi, Kenta
name: Kyutoku, Koutarou
name: Sekiguchi, Yuichiro
name: Shibata, Masaru
name: Wada, Tomohide
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: General Relativity and Quantum Cosmology (gr-qc)
subject: FOS: Physical sciences

description: We perform high-resolution magnetohydrodynamics simulations of binary neutron star mergers in numerical relativity on the Japanese supercomputer K. The neutron stars and merger remnants are covered by a grid spacing of 70\,m, which yields the highest-resolution results among those derived so far. By an in-depth resolution study, we clarify several amplification mechanisms of magnetic fields during the binary neutron star merger for the first time. First, the Kelvin-Helmholtz instability developed in the shear layer at the onset of the merger significantly amplifies the magnetic fields. A hypermassive neutron star (HMNS) formed after the merger is then subject to the nonaxisymmetric magnetorotational instability, which amplifies the magnetic field in the HMNS. These two amplification mechanisms cannot be found with insufficient-resolution runs. We also show that the HMNS eventually collapses to a black hole surrounded by an accretion torus which is strongly magnetized at birth.
description: 5 pages, 4 figures, to be appeared in PRD rapid communication
title: Essere, nulla e linguaggio. Rudolf Carnap e Martin Heidegger
Creators: name: Torrente , Chiara
Publisher: name: Roma Tre-Press
Year: 2012

description: Nel contributo si tenta di aprire un dialogo tra l'ontologia e il concetto di linguaggio di Heidegger e la posizione del neopositivista Carnap, il quale proprio a partire da un testo heideggeriano, Che cos'è metafisica?, intendeva mostrare come i problemi filosofici siano perlopiù pseudoproblemi, questioni fondate su proposizioni prive di senso, poiché legate a una carenza logica della lingua.

description: B@belonline vol. 13 Chaos/Kosmos
Nuclear Import and Export of Venezuelan Equine Encephalitis Virus Nonstructural Protein 2
Creators: name: Johnston, R. E.
name: Montgomery, S. A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Many RNA viruses, which replicate predominantly in the cytoplasm, have nuclear components that contribute to their life cycle or pathogenesis. We investigated the intracellular localization of the multifunctional nonstructural protein 2 (nsP2) in mammalian cells infected with Venezuelan equine encephalitis virus (VEE), an important, naturally emerging zoonotic alphavirus. VEE nsP2 localizes to both the cytoplasm and the nucleus of mammalian cells in the context of infection and also when expressed alone. Through the analysis of a series of enhanced green fluorescent protein fusions, a segment of nsP2 that completely localizes to the nucleus of mammalian cells was identified. Within this region, mutation of the putative nuclear localization signal (NLS) PGKMV diminished, but did not obliterate, the ability of the protein to localize to the nucleus, suggesting that this sequence contributes to the nuclear localization of VEE nsP2. Furthermore, VEE nsP2 specifically interacted with the nuclear import protein karyopherin-α1 but not with karyopherin-α2, -3, or -4, suggesting that karyopherin-α1 transports nsP2 to the nucleus during infection. Additionally, a novel nuclear export signal (NES) was identified, which included residues L526 and L528 of VEE nsP2. Leptomycin B treatment resulted in nuclear accumulation of nsP2, demonstrating that nuclear export of nsP2 is mediated via the CRM1 nuclear export pathway. Disruption of either the NLS or the NES in nsP2 compromised essential viral functions. Taken together, these results establish the bidirectional transport of nsP2 across the nuclear membrane, suggesting that a critical function of nsP2 during infection involves its shuttling between the cytoplasm and the nucleus.
Frobenius and the derived centers of algebraic theories
Creators: name: Dwyer, William G.
name: Szymik, Markus
Publisher: name: arXiv
Year: 2014
Subjects: subject: Algebraic Topology (math.AT)
subject: Category Theory (math.CT)
subject: Rings and Algebras (math.RA)
subject: FOS: Mathematics

description: We show that the derived center of the category of simplicial algebras over every algebraic theory is homotopically discrete, with the abelian monoid of components isomorphic to the center of the category of discrete algebras. For example, in the case of commutative algebras in characteristic $p$, this center is freely generated by Frobenius. Our proof involves the calculation of homotopy coherent centers of categories of simplicial presheaves as well as of Bousfield localizations. Numerous other classes of examples are discussed.
description: 40 pages
Boosting photocatalytic activity using carbon nitride based 2D/2D van der Waals heterojunctions
Creators: Laishram, Devika
Publisher: name: University of Alberta Library
Year: 2022

The surging demand for energy and staggering pollutants in the environment have geared the scientific community to explore sustainable pathways that are economically feasible and environmentally compelling. In this context, harnessing solar energy using semiconductor materials to generate charge pairs to drive photoredox reactions has been envisioned as a futuristic approach. Numerous inorganic crystals with promising nanoregime properties investigated in the past decade have yet to demonstrate practical application due to limited photon absorption and sluggish charge separation kinetics. Two-dimensional semiconductors with tunable optical and electronic properties and quasi-resistance-free lateral charge transfer mechanisms have shown great promise in photocatalysis. Polymeric graphitic carbon nitride (g-C3N4) is among the most promising candidates due to fine-tuned band edges and the feasibility of optimizing the optical properties via materials genomics. Constructing a two-dimensional (2D)/2D van der Waals (vdW) heterojunction by allies of 2D carbon nitride sheets and other 2D semiconductors has demonstrated enhanced charge separation with improved visible photon absorption, and the performance is not restricted by the lattice matching of constituting materials. With the advent of new 2D semiconductors over the recent past, the 2D/2D heterojunction assemblies are gaining momentum to design high performance photocatalysts for numerous applications. This review aims to highlight recent advancements and key understanding in carbon nitride based 2D/2D heterojunctions and their applications in photocatalysis, including small molecules activation, conversion, and degradations. We conclude with a forward-looking perspective discussing the key challenges and opportunity areas for future research.
Processing of Open Reading Frame 1a Replicase Proteins nsp7 to nsp10 in Murine Hepatitis Virus Strain A59 Replication
Creators: name: Denison, M. R.
name: Deming, D. J.
name: Baric, R. S.
name: Graham, R. L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Coronaviruses express open reading frame 1a (ORF1a) and ORF1b polyproteins from which 16 nonstructural proteins (nsp) are derived. The highly conserved region at the carboxy terminus of ORF1a is processed by the nsp5 proteinase (Mpro) into mature products, including nsp7, nsp8, nsp9, and nsp10, proteins with predicted or identified activities involved in RNA synthesis. Although continuous translation and proteolytic processing of ORF1ab by Mpro is required for replication, it is unknown whether specific cleavage events within the polyprotein are dispensable. We determined the requirement for the nsp7 to nsp10 proteins and their processing during murine hepatitis virus (MHV) replication. Through use of an MHV reverse genetics system, in-frame deletions of the coding sequences for nsp7 to nsp10, or ablation of their flanking Mpro cleavage sites, were made and the effects upon replication were determined. Viable viruses were characterized by analysis of Mpro processing, RNA transcription, and growth fitness. Deletion of any of the regions encoding nsp7 to nsp10 was lethal. Disruption of the cleavage sites was lethal with the exception of that of the nsp9-nsp10 site, which resulted in a mutant virus with attenuated replication. Passage of the attenuated nsp9-nsp10 cleavage mutant increased fitness to near-wild-type kinetics without reversion to a virus capable of processing nsp9-nsp10. We also confirmed the presence of a second cleavage site between nsp7 and nsp8. In order to determine whether a distinct function could be attributed to preprocessed forms of the polyprotein, including nsp7 to nsp10, the genes encoding nsp7 and nsp8 were rearranged. The mutant virus was not viable, suggesting that the uncleaved protein may be essential for replication or proteolytic processing.
Pfaffian formulas for spanning tree probabilities
Creators: name: Panova, Greta
name: Wilson, David B.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Probability (math.PR)
subject: Combinatorics (math.CO)
subject: FOS: Mathematics
subject: 60C05, 82B20, 05C05, 05C50

description: We show that certain topologically defined uniform spanning tree probabilities for graphs embedded in an annulus can be computed as linear combinations of Pfaffians of matrices involving the line-bundle Green's function, where the coefficients count cover-inclusive Dyck tilings of skew Young diagrams.
description: 18 pages
Signaling Cascades Triggered by Bacterial Metabolic End Products during Reactivation of Kaposi's Sarcoma-Associated Herpesvirus
Creators: name: Morris, T. L.
name: Webster-Cyriaque, J.
name: Arnold, R. R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: The present studies explore the role of polymicrobial infection in the reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) and analyze signaling pathways activated upon this induction. We hypothesized that activation of the cellular stress-activated mitogen-activated protein kinase (MAPK) p38 pathway would play a key role in the bacterium-mediated disruption of viral latency similar to that of previously reported results obtained with other inducers of gammaherpesvirus lytic replication. KSHV within infected BCBL-1 cells was induced to replicate following exposure to metabolic end products from gram-negative or -positive bacteria that were then simultaneously exposed to specific inhibitors of signal transduction pathways. We have determined that bacterium-mediated induction of lytic KSHV infection is significantly reduced by the inhibition of the p38 MAPK pathway. In contrast, inhibition of the phosphatidylinositol 3-kinase pathway did not impair induction of lytic replication or p38 phosphorylation. Protein kinase C, though activated, was not the major pathway used for bacterium-induced viral reactivation. Furthermore, hyperacetylation of histones 3 and 4 was detected. Collectively, our results show that metabolic end products from these pathogens induce lytic replication of KSHV in BCBL-1 cells primarily via the activation of a stress-activated MAPK pathway. Importantly, we demonstrate for the first time a mechanism by which polymicrobial bacterial infections result in KSHV reactivation and pathogenesis.
Expression of MAP-2, GFAP, and Calcium in CA3 Area of a Modified Organotypic Hippocampal Slice Culture Treated with Kainic Acid
Creators: name: Husna, Machlusil
name: Kusworini Handono, drkusworini@gmail.com
name: Hidayat Sujuti, hidayatsujuti@gmail.com
name: Aulanni'am, Aulanni'am
name: Rukmigarsari, Ettie
Publisher: name: figshare
Year: 2022
Subjects: subject: Neuroscience
subject: 110904 Neurology and Neuromuscular Diseases
subject: FOS: Clinical medicine

description: Neurodegeneration due to neurotoxicity is one of the phenomena in temporal lobe epilepsy. Experimentally, hippocampal excitotoxicity process can occur due to kainic acid exposure, especially in the CA3 area. Neuronal death, astrocyte reactivity and increased calcium also occur in hippocampal excitotoxicity, but few studies have investigated immediate effect after kainic acid exposure. The organotypic hippocampal slice culture (OHSC) is a useful model for studying the neurodegeneration process, but there are still many protocol differences. In this study, minor modifications were made in the OHSC protocol.
title: Weight differences of honey bees after administration of sublethal doses of dimethoate
Creators: name: Kling, Annette
name: Schmitzer, Stephan
Publisher: name: Julius Kühn-Institut
Year: 2018

description: Background: The aim of this work was to assess honey bee body weight as a possible further parameter to detect effects in a 10 day chronic feeding study according to OECD 2451 following exposure to sublethal concentrations of a plant protection product (i.e. dimethoate). This investigation is based on the assumption that weight differences might be caused by chronic feeding of dimethoate. Two set of tests in two different laboratories (Lab 1 and Lab 2) were conducted in order to investigate possible weight changes of complete adult honey bees and/or parts of their body (honey stomach and intestine) following treatment of dimethoate. Bees were weighed before and after chronic feeding of sub-lethal concentrations of dimethoate.
Results: Differences in the number of bees which lost weight following treatment of sublethal concentrations of dimethoate was found in Lab 1, but could not confirmed in Lab 2. The difference in weight between the control group and the dimethoate treatment could only be detected as a statistical significant difference in one lab at the highest concentration (0.4 mg/kg). Assessment of weight changes of parts of the bee body (honey stomach and intestine) shows a very high variation (CV) which makes interpretation of the data of the total body weight questionable.
Conclusion: The results of the two laboratories were contradictory and no conclusive assessment can be done following the two sets of experiments. Assessment of bee body weight within a 10-day chronic feeding study is considered questionable for the detection of sublethal effects. Further work with other active ingredients is needed to clarify if body weight change of honey bees can be used as a parameter for sublethal effects.
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 -
Surface-Exposed Adeno-Associated Virus Vp1-NLS Capsid Fusion Protein Rescues Infectivity of Noninfectious Wild-Type Vp2/Vp3 and Vp3-Only Capsids but Not That of Fivefold Pore Mutant Virions
Creators: name: Agbandje-McKenna, M.
name: Johnson, J. S.
name: Gurda-Whitaker, B.
name: Grieger, J. C.
name: Samulski, R. J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Over the past 2 decades, significant effort has been dedicated to the development of adeno-associated virus (AAV) as a vector for human gene therapy. However, understanding of the virus with respect to the functional domains of the capsid remains incomplete. In this study, the goal was to further examine the role of the unique Vp1 N terminus, the N terminus plus the recently identified nuclear localization signal (NLS) (J. C. Grieger, S. Snowdy, and R. J. Samulski, J. Virol 80:5199-5210, 2006), and the virion pore at the fivefold axis in infection. We generated two Vp1 fusion proteins (Vp1 and Vp1NLS) linked to the 8-kDa chemokine domain of rat fractalkine (FKN) for the purpose of surface exposure upon assembly of the virion, as previously described (K. H. Warrington, Jr., O. S. Gorbatyuk, J. K. Harrison, S. R. Opie, S. Zolotukhin, and N. Muzyczka, J. Virol 78:6595-6609, 2004). The unique Vp1 N termini were found to be exposed on the surfaces of these capsids and maintained their phospholipase A2 (PLA2) activity, as determined by native dot blot Western and PLA2 assays, respectively. Incorporation of the fusions into AAV type 2 capsids lacking a wild-type Vp1, i.e., Vp2/Vp3 and Vp3 capsid only, increased infectivity by 3- to 5-fold (Vp1FKN) and 10- to 100-fold (Vp1NLSFKN), respectively. However, the surface-exposed fusions did not restore infectivity to AAV virions containing mutations at a conserved leucine (Leu336Ala, Leu336Cys, or Leu336Trp) located at the base of the fivefold pore. EM analyses suggest that Leu336 may play a role in global structural changes to the virion directly impacting downstream conformational changes essential for infectivity and not only have local effects within the pore, as previously suggested.
Water-splitting photoelectrodes consisting of heterojunctions of carbon nitride with a p-type low bandgap double perovskite oxide
Creators: Laishram, Devika
Publisher: name: University of Alberta Library
Year: 2022

Quinary and senary non-stoichiometric double perovskites such as Ba2Ca0.66Nb1.34−xFexO6−δ (BCNF) have been utilized for gas sensing, solid oxide fuel cells and thermochemical CO2 reduction. Herein, we examined their potential as narrow bandgap semiconductors for use in solar energy harvesting. A cobalt co-doped BCNF, Ba2Ca0.66Nb0.68Fe0.33Co0.33O6−δ (BCNFCo), exhibited an optical absorption edge at ∼800 nm, p-type conduction and a distinct photoresponse up to 640 nm while demonstrating high thermochemical stability. A nanocomposite of BCNFCo and g-C3N4 (CN) was prepared via a facile solvent-assisted exfoliation/blending approach using dichlorobenzene and glycerol at a moderate temperature. The exfoliation of g-C3N4 followed by wrapping on perovskite established an effective heterojunction between the materials for charge separation. The conjugated 2D sheets of CN enabled better charge migration resulting in increased photoelectrochemical performance. A blend composed of 40 wt% perovskites and CN performed optimally, whilst achieving a photocurrent density as high as 1.5 mA cm−2 for sunlight-driven water-splitting with a Faradaic efficiency as high as ∼88%.
Unique Signaling Properties of CTAR1 in LMP1-Mediated Transformation
Creators: name: Raab-Traub, N.
name: Mainou, B. A.
name: Everly, D. N.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene is considered the EBV oncogene as it is necessary for EBV-mediated transformation of B lymphocytes and itself transforms rodent fibroblasts. LMP1 activates the NF-κB, phosphatidylinositol 3-kinase (PI3K)-Akt, mitogen-activated protein kinase, and Jun N-terminal protein kinase signaling pathways through its two signaling domains, carboxyl-terminal activating regions 1 and 2 (CTAR1 and CTAR2). CTAR1 and CTAR2 induce signal transduction pathways through their direct (CTAR1) or indirect (CTAR2) recruitment of tumor necrosis factor receptor-associated factors (TRAFs). CTAR1 is necessary for LMP1-mediated transformation as well as activation of PI3K signaling and induction of cell cycle markers associated with G1/S transition. In this study, activation of PI3K-Akt signaling and deregulation of cell cycle markers were mapped to the TRAF-binding domain within CTAR1 and to the residues between CTAR1 and CTAR2. LMP1 CTAR1 also activated the MEK1/2-extracellular signal-regulated kinase 1/2 signaling pathway, and this activation was necessary for LMP1-induced transformation of Rat-1 fibroblasts. Dominant-negative forms of TRAF2 and TRAF3 inhibited but did not fully block LMP1-mediated transformation. These findings identify a new signaling pathway that is uniquely activated by the TRAF-binding domain of LMP1 and is required for transformation.
A measurement based software quality framework
Creators: name: Kelemen, Zádor Dániel
name: Bényász, Gábor
name: Badinka, Zoltán
Publisher: name: arXiv
Year: 2014
Subjects: subject: Software Engineering (cs.SE)
subject: FOS: Computer and information sciences

description: In this report we propose a solution to problem of the dependency on the experience of the software project quality assurance personnel by providing a transparent, objective and measurement based quality framework. The framework helps the quality assurance experts making objective and comparable decisions in software projects by defining and assessing measurable quality goals and thresholds, directly relating these to an escalation mechanism. First results of applying the proposed measurement based software quality framework in a real life case study are also addressed in this report.
description: 19 pages
Novel approaches to risk assessment and decision support
Creators: name: Ballesteros Riaza, Arantxa
name: Drobne, Damjana
name: Giese, Bernd
name: Hipfinger, Christina
name: Jemec Kokalj, Anita
name: Laforsch, Christian
name: Löder, Martin GJ
name: Peijnenburg, Willie
name: Pozuelo Rollón, Blanca María
name: Purker, Sebastian
name: Ramsperger, Anja FRM
name: Kühnel, Dana
Publisher: name: Zenodo
Year: 2022
Subjects: microplastics
nanoplastics
risk assessment
decision support
human health
environmental health
IATA Integrated Approach to Testing and Assessment

description: Poster describing novel approaches to risk assessment and decision support - Establishment of a risk assessment strategy for nano and microplastic (NMP) - Prospective multi criteria decision support (PMCDS) - Decision support system (DSS)
Venezuelan Equine Encephalitis Virus Replicon Particles Encoding Respiratory Syncytial Virus Surface Glycoproteins Induce Protective Mucosal Responses in Mice and Cotton Rats
Creators: name: Davis, N. L.
name: Mok, H.
name: Utley, T. J.
name: Crowe, J. E.
name: Lee, S.
name: Collier, M. L.
name: Johnston, R. E.
name: Shepherd, B. E.
name: Polosukhin, V. V.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Respiratory syncytial virus (RSV) is an important viral pathogen that causes severe lower respiratory tract infection in infants, the elderly, and immunocompromised individuals. There are no licensed RSV vaccines to date. To prevent RSV infection, immune responses in both the upper and lower respiratory tracts are required. Previously, immunization with Venezuelan equine encephalitis virus replicon particles (VRPs) demonstrated effectiveness in inducing mucosal protection against various pathogens. In this study, we developed VRPs encoding RSV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and efficacy of these vaccine candidates in mice and cotton rats. VRPs, when administered intranasally, induced surface glycoprotein-specific virus neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. In addition, fusion protein-encoding VRPs induced gamma interferon (IFN-γ)-secreting T cells in the lungs and spleen, as measured by reaction with an H-2Kd-restricted CD8+ T-cell epitope. In animals vaccinated with F protein VRPs, challenge virus replication was reduced below the level of detection in both the upper and lower respiratory tracts following intranasal RSV challenge, while in those vaccinated with G protein VRPs, challenge virus was detected in the upper but not the lower respiratory tract. Close examination of histopathology of the lungs of vaccinated animals following RSV challenge revealed no enhanced inflammation. Immunization with VRPs induced balanced Th1/Th2 immune responses, as measured by the cytokine profile in the lungs and antibody isotype of the humoral immune response. These results represent an important first step toward the use of VRPs encoding RSV proteins as a prophylactic vaccine for RSV.
X-Box-Binding Protein 1 Activates Lytic Epstein-Barr Virus Gene Expression in Combination with Protein Kinase D
Creators: name: Dickerson, S. J.
name: Sun, X.
name: Kenney, S. C.
name: Bhende, P. M.
name: Feng, W.-H.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Epstein-Barr virus (EBV) establishes a latent form of infection in memory B cells, while antibody-secreting plasma cells often harbor the lytic form of infection. The switch between latent and lytic EBV infection is mediated by the two viral immediate-early proteins BZLF1 (Z) and BRLF1 (R), which are not expressed in latently infected B cells. Here we demonstrate that a cellular transcription factor that plays an essential role in plasma cell differentiation, X-box-binding protein 1 (XBP-1), also activates the transcription of the two EBV immediate-early gene promoters. In reporter gene assays, XBP-1 alone was sufficient to activate the R promoter, whereas the combination of XBP-1 and protein kinase D (PKD) was required for efficient activation of the Z promoter. Most importantly, the expression of XBP-1 and activated PKD was sufficient to induce lytic viral gene expression in EBV-positive nasopharyngeal carcinoma cells and lymphoblastoid cells, while an XBP-1 small interfering RNA inhibited constitutive lytic EBV gene expression in lymphoblastoid cells. These results suggest that the plasma cell differentiation factor XBP-1, in combination with activated PKD, can mediate the reactivation of EBV, thereby allowing the viral life cycle to be intimately linked to plasma cell differentiation.
ZEB1 and c-Jun Levels Contribute to the Establishment of Highly Lytic Epstein-Barr Virus Infection in Gastric AGS Cells
Creators: name: Kenney, S. C.
name: Yu, X.
name: Mertz, J. E.
name: Dickerson, S. J.
name: Jones, R. J.
name: Kraus, R. J.
name: Feng, W.-h.
name: Lim, H. J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: The induction of lytic infection has been proposed as a therapeutic strategy for treating Epstein-Barr virus (EBV)-positive malignancies. To succeed, efficient methods are needed for activating the EBV immediate-early (IE) promoters, Zp and Rp. Here we compared factors which regulate Zp and Rp in AGS gastric carcinoma cells that support a remarkably high level of persistently lytic EBV infection with HeLa cervical cells that permit only tightly latent infection. We found that the level of Zp activity assayed by transient transfection assays with reporter plasmids was high in AGS cells but low in HeLa cells. The level of Rp activity was low in both cell types. Mutational analysis indicated that sequences within Zp located between −70 and +27 relative to the transcription initiation site were sufficient to confer a high level of Zp activity in AGS cells. The Zp CRE motif was necessary for this constitutive activity, while the ZIA and ZIB MEF2D motifs were not. Consistent with these findings, immunoblot analysis indicated that phosphorylated c-Jun, which activates Zp through the CRE motif, was expressed at a much higher level in EBV-infected AGS cells than in EBV-infected HeLa cells. In contrast, ZEB1, which represses Zp via the ZV motif located near the transcription initiation site, was abundant in HeLa cells, while it was absent from AGS cells. Exogenous addition of ZEB1 led to the repression of Zp in AGS cells. We conclude that the unusually high Zp activity level in AGS cells is due to the high abundance of positively acting transcription factors such as c-Jun combined with the low abundance of negatively acting factors such as ZEB1.
Black Phosphorus Radio-Frequency Transistors
Creators: name: Wang, Han
name: Wang, Xiaomu
name: Xia, Fengnian
name: Wang, Luhao
name: Jiang, Hao
name: Xia, Qiangfei
name: Chin, Matthew L.
name: Dubey, Madan
name: Han, Shu-jen
Publisher: name: arXiv
Year: 2014
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: Few-layer and thin film forms of layered black phosphorus (BP) have recently emerged as a promising material for applications in high performance nanoelectronics and infrared optoelectronics. Layered BP thin film offers a moderate bandgap of around 0.3 eV and high carrier mobility, leading to transistors with decent on-off ratio and high on-state current density. Here, we demonstrate the gigahertz frequency operation of black phosphorus field-effect transistors for the first time. The BP transistors demonstrated here show excellent current saturation with an on-off ratio exceeding 2000. We achieved a current density in excess of 270 mA/mm and DC transconductance above 180 mS/mm for hole conduction. Using standard high frequency characterization techniques, we measured a short-circuit current-gain cut-off frequency fT of 12 GHz and a maximum oscillation frequency fmax of 20 GHz in 300 nm channel length devices. BP devices may offer advantages over graphene transistors for high frequency electronics in terms of voltage and power gain due to the good current saturation properties arising from their finite bandgap, thus enabling the future ubiquitous transistor technology that can operate in the multi-GHz frequency range and beyond.
description: 15 pages, 4 figures, supporting information
A Novel Mutation in Murine Hepatitis Virus nsp5, the Viral 3C-Like Proteinase, Causes Temperature-Sensitive Defects in Viral Growth and Protein Processing
Creators: name: Sparks, J. S.
name: Baric, R. S.
name: Lu, X.
name: Donaldson, E. F.
name: Denison, M. R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: Sequencing and reversion analysis of murine hepatitis virus (MHV) temperature-sensitive (ts) viruses has identified putative ts mutations in the replicase nonstructural proteins (nsp's) of these coronaviruses. In this study, reverse transcriptase PCR sequencing of the RNA genome of an isolate of the MHV ts virus Alb ts6, referred to as Alb/ts/nsp5/V148A, identified a putative ts mutation in nsp5 (T10651C, Val148Ala), the viral 3C-like proteinase (3CLpro). The introduction of the T10651C mutation into the infectious MHV clone resulted in the recovery of a mutant virus, the nsp5/V148A virus, that demonstrated reduced growth and nsp5 proteinase activity identical to that of Alb/ts/nsp5/V148A at the nonpermissive temperature. Sequence analysis of 40°C revertants of Alb/ts/nsp5/V148A identified primary reversion to Ala148Val in nsp5, as well as two independent second-site mutations resulting in Ser133Asn and His134Tyr substitutions in nsp5. The introduction of the Ser133Asn or His134Tyr substitution into the cloned nsp5/V148A mutant virus background resulted in the recovery of viruses with increased growth fitness and the partial restoration of nsp5 activity at the nonpermissive temperature. Modeling of the nsp5 structure of Alb/ts/nsp5/V148A predicted that the Val148Ala mutation alters residue 148 interactions with residues of the substrate binding S1 subsite of the nsp5 active-site cavity. This study identifies novel residues in nsp5 that may be important for regulating substrate specificity and nsp5 proteinase activity.
Amino Acid Substitutions in the S2 Subunit of Mouse Hepatitis Virus Variant V51 Encode Determinants of Host Range Expansion
Creators: name: McRoy, W. C.
name: Baric, R. S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: We previously described mouse hepatitis virus (MHV) variant V51 derived from a persistent infection of murine DBT cells with an expanded host range (R. S. Baric, E. Sullivan, L. Hensley, B. Yount, and W. Chen, J. Virol. 73:638-649, 1999). Sequencing of the V51 spike gene, the mediator of virus entry, revealed 13 amino acid substitutions relative to the originating MHV A59 strain. Seven substitutions were located in the amino-terminal S1 cleavage subunit, and six were located in the carboxy-terminal S2 cleavage subunit. Using targeted RNA recombination, we constructed a panel of recombinant viruses to map the mediators of host range to the six substitutions in S2, with a subgroup of four changes of particular interest. This subgroup maps to two previously identified domains within S2, a putative fusion peptide and a heptad repeat, both conserved features of class I fusion proteins. In addition to an altered host range, V51 displayed altered utilization of CEACAM1a, the high-affinity receptor for A59. Interestingly, a recombinant with S1 from A59 and S2 from V51 was severely debilitated in its ability to productively infect cells via CEACAM1a, while the inverse recombinant was not. This result suggests that the S2 substitutions exert powerful effects on the fusion trigger that normally passes from S1 to S2. These novel findings play against the existing data that suggest that MHV host range determinants are located in the S1 subunit, which harbors the receptor binding domain, or involve coordinating changes in both S1 and S2. Mounting evidence also suggests that the class I fusion mechanism may possess some innate plasticity that regulates viral host range.
An Alphavirus Replicon-Based Human Metapneumovirus Vaccine Is Immunogenic and Protective in Mice and Cotton Rats
Creators: name: Shepherd, B. E.
name: Podsiad, A. B.
name: Crowe, J. E.
name: Polosukhin, V. V.
name: Mok, H.
name: Tollefson, S. J.
name: Johnston, R. E.
name: Williams, J. V.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that causes upper and lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. Here, we developed Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and protective efficacy of these vaccine candidates in mice and cotton rats. VRPs encoding hMPV F protein, when administered intranasally, induced F-specific virus-neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. Challenge virus replication was reduced significantly in both the upper and lower respiratory tracts following intranasal hMPV challenge in these animals. However, vaccination with hMPV G protein VRPs did not induce neutralizing antibodies or protect animals from hMPV challenge. Close examination of the histopathology of the lungs of VRP-MPV F-vaccinated animals following hMPV challenge revealed no enhancement of inflammation or mucus production. Aberrant cytokine gene expression was not detected in these animals. Together, these results represent an important first step toward the use of VRPs encoding hMPV F proteins as a prophylactic vaccine for hMPV.
"IMPROVING STRATEGIES FOR FOSTERING A COMMUNICATION CULTURE AMONG EMERGING DESIGNERS"
Creators: name: Djurayeva, Nilufar
Publisher: name: Zenodo
Year: 2025

description: This article is dedicated to improving the methodology for developing communication culture among design students. Effective communication is crucial for designers who frequently collaborate across various disciplines and interact with diverse stakeholders. This research aims to improve the methodology of developing a communication culture in future designers by enhancing their ability to communicate effectively across different platforms and environments. Using a mixed-methods approach, the study examined existing educational practices in design programs across ten leading institutions. It identified key gaps in digital, interdisciplinary, and cross-cultural communication skills. Based on the research findings, new methodological approaches, recommendations were made to integrate advanced digital tools, interdisciplinary project collaborations, and comprehensive cultural sensitivity training into design curricula. The proposed enhancements aim to equip future designers with the necessary skills to navigate complex global projects and foster a robust communication culture in professional settings.
Antibody Is Critical for the Clearance of Murine Norovirus Infection
Creators: name: Virgin, H. W.
name: Strong, D. W.
name: Baric, R. S.
name: Wobus, C. E.
name: Chachu, K. A.
name: LoBue, A. D.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: Human noroviruses cause more than 90% of epidemic nonbacterial gastroenteritis. However, the role of B cells and antibody in the immune response to noroviruses is unclear. Previous studies have demonstrated that human norovirus specific antibody levels increase upon infection, but they may not be protective against infection. In this report, we used murine norovirus (MNV), an enteric norovirus, as a model to determine the importance of norovirus specific B cells and immune antibody in clearance of norovirus infection. We show here that mice genetically deficient in B cells failed to clear primary MNV infection as effectively as wild-type mice. In addition, adoptively transferred immune splenocytes derived from B-cell-deficient mice or antibody production-deficient mice were unable to efficiently clear persistent MNV infection in RAG1−/− mice. Further, adoptive transfer of either polyclonal anti-MNV serum or neutralizing anti-MNV monoclonal antibodies was sufficient to reduce the level of MNV infection both systemically and in the intestine. Together, these data demonstrate that antibody plays an important role in the clearance of MNV and that immunoglobulin G anti-norovirus antibody can play an important role in clearing mucosal infection.
Biochemical Characterization of a Recombinant TRIM5  Protein That Restricts Human Immunodeficiency Virus Type 1 Replication
Creators: name: Alam, S. L.
name: Kar, A. K.
name: Sodroski, J. G.
name: Sundquist, W. I.
name: Eckert, D. M.
name: Chandrasekaran, V.
name: Christensen, D. E.
name: Aiken, C.
name: Sandrin, V.
name: Langelier, C. R.
name: Olsen, J. C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: The rhesus monkey intrinsic immunity factor TRIM5αrh recognizes incoming capsids from a variety of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV), and inhibits the accumulation of viral reverse transcripts. However, direct interactions between restricting TRIM5α proteins and retroviral capsids have not previously been demonstrated using pure recombinant proteins. To facilitate structural and mechanistic studies of retroviral restriction, we have developed methods for expressing and purifying an active chimeric TRIM5αrh protein containing the RING domain from the related human TRIM21 protein. This recombinant TRIM5-21R protein was expressed in SF-21 insect cells and purified through three chromatographic steps. Two distinct TRIM5-21R species were purified and shown to correspond to monomers and dimers, as analyzed by analytical ultracentrifugation. Chemically cross-linked recombinant TRIM5-21R dimers and mammalian-expressed TRIM5-21R and TRIM5α proteins exhibited similar sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobilities, indicating that mammalian TRIM5α proteins are predominantly dimeric. Purified TRIM5-21R had ubiquitin ligase activity and could autoubquitylate with different E2 ubiquitin conjugating enzymes in vitro. TRIM5-21R bound directly to synthetic capsids composed of recombinant HIV-1 CA-NC proteins and to authentic EIAV core particles. HIV-1 CA-NC assemblies bound dimeric TRIM5-21R better than either monomeric TRIM5-21R or TRIM5-21R constructs that lacked the SPRY domain or its V1 loop. Thus, our studies indicate that TRIM5α proteins are dimeric ubiquitin E3 ligases that recognize retroviral capsids through direct interactions mediated by the SPRY domain and demonstrate that these activities can be recapitulated in vitro using pure recombinant proteins.
Complement Receptor 3 Promotes Severe Ross River Virus-Induced Disease
Creators: name: Heise, M. T.
name: Morrison, T. E.
name: Simmons, J. D.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: Alphaviruses such as Ross River virus (RRV) and chikungunya virus are mosquito-transmitted viruses that cause explosive epidemics of debilitating arthritis and myositis affecting millions of humans worldwide. Previous studies using a mouse model of RRV-induced disease demonstrated that viral infection results in a severe inflammatory arthritis and myositis and that complement component 3 (C3) contributes to the destructive phase of the inflammatory disease but not the recruitment of cellular infiltrates to the sites of RRV-induced inflammation. Here, we demonstrate that mice deficient in complement receptor 3 (CR3) (CD11b−/−), a signaling receptor activated by multiple ligands including the C3 cleavage fragment iC3b, develop less-severe disease signs and decreased tissue destruction compared to RRV-infected wild-type mice. CR3 deficiency had no effect on viral replication, nor did it diminish the magnitude, kinetics, and composition of the cellular infiltrates at the sites of inflammation. However, the genetic absence of CR3 diminished the expression of specific proinflammatory and cytotoxic effectors, including S100A9/S100A8 and interleukin-6, within the inflamed tissues, suggesting that CR3-dependent signaling at the sites of inflammation contributes to tissue damage and severe disease.
Critical Role for Endocytosis in the Regulation of Signaling by the Kaposi's Sarcoma-Associated Herpesvirus K1 Protein
Creators: name: Damania, B.
name: Tomlinson, C. C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of the gammaherpesvirus family. KSHV is the etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The first open reading frame of the KSHV genome encodes a type 1 transmembrane glycoprotein named K1. K1 is structurally similar to the B-cell receptor (BCR), and its cytoplasmic tail contains an immunoreceptor tyrosine-based activation motif that can activate Syk kinase and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Recent evidence suggests that receptor signaling occurs not only at the cell membrane, but from intracellular compartments as well. We have found that K1 is internalized in a clathrin-dependent manner, and efficient internalization is coupled to its signaling function. Once internalized, K1 traffics from the early endosome to the recycling endosome. Interestingly, blocking K1's activation of Syk and PI3K prevents K1 from internalizing. We have also found that blocking clathrin-mediated endocytosis prevents downstream signaling by K1. These results strongly suggest that internalization of K1 is intimately associated with normal signaling. When K1 internalization was examined in B lymphocytes, we found that K1 cointernalized with the BCR. Altogether, these results suggest that K1's signaling function is tightly coupled to its internalization.
Universe in a black hole with spin and torsion
Creators: name: Poplawski, Nikodem J.
Publisher: name: arXiv
Year: 2014
Subjects: subject: General Relativity and Quantum Cosmology (gr-qc)
subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: High Energy Physics - Theory (hep-th)
subject: FOS: Physical sciences

description: The conservation law for the angular momentum in curved spacetime requires that the antisymmetric part of the affine connection (the torsion tensor) is a variable in the principle of least action. The coupling between spin and torsion generates gravitational repulsion in fermionic matter at extremely high densities and avoids the formation of singularities in black holes. We show that every black hole in the presence of torsion forms a nonsingular, closed, nearly flat, homogeneous, and isotropic universe on the other side of its event horizon. Quantum particle production in such a universe can generate a period of exponential expansion which creates an enormous amount of matter in that universe. Accordingly, our Universe may have originated from the interior of a black hole existing in another universe.
description: 10 pages