cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Disulfiram Reactivates Latent HIV-1 in a Bcl-2-Transduced Primary CD4+ T Cell Model without Inducing Global T Cell Activation
Creators: name: Quinn, T. C.
name: Bhat, S.
name: Yang, H.-C.
name: Bullen, C. K.
name: Manucci, J. L.
name: Zhang, H.
name: Siliciano, R. F.
name: Siliciano, J. D.
name: Shroff, N. S.
name: Margolis, D. M.
name: Margolick, J. B.
name: Xing, S.
name: Shan, L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Highly active antiretroviral therapy (HAART) can reduce plasma HIV-1 levels to below the detection limit. However, due to the latent reservoir in resting CD4+ cells, HAART is not curative. Elimination of this reservoir is critical to curing HIV-1 infection. Agents that reactivate latent HIV-1 through nonspecific T cell activation are toxic. Here we demonstrate in a primary CD4+ T cell model that the FDA-approved drug disulfiram reactivates latent HIV-1 without global T cell activation. The extent to which disulfiram reactivates latent HIV-1 in patient cells is unclear, but the drug alone or in combination may be useful in future eradication strategies.
Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection
Creators: name: Overman, R. G.
name: Montefiori, D. C.
name: Freel, S. A.
name: Yates, N. L.
name: Ochsenbauer, C.
name: Perelson, A. S.
name: Haynes, B. F.
name: Vandergrift, N.
name: Kappes, J. C.
name: Cohen, M. S.
name: Chen, Y.
name: Liu, P.
name: Tomaras, G. D.
name: Gao, F.
name: Graw, F.
name: Alam, S. M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent transmission by neutralization of virus or mechanically prevent HIV-1 migration through mucosal layers. In this study, we quantified circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of AHI subjects, and compared the levels and antibody specificity to those in chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes) were in significantly lower levels relative to the viral load in acute infection than in chronic HIV-1 infection. The specificities of the antibodies in the immune complexes differed between acute and chronic infection (anti-gp41 Ab in acute infection and anti-gp120 in chronic infection), potentially suggesting different roles in immunopathogenesis for complexes arising at different stages of infection. We also determined the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that the composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection.
Enhanced Control of Pathogenic Simian Immunodeficiency Virus SIVmac239 Replication in Macaques Immunized with an Interleukin-12 Plasmid and a DNA Prime-Viral Vector Boost Vaccine Regimen
Creators: name: Kemelman, M.
name: Schultz, A.
name: Morrow, G.
name: Sardesai, N. Y.
name: Chiuchiolo, M. J.
name: Winstone, N.
name: McBride, D.
name: Lopez, M.
name: Parks, C. L.
name: Dean, H. J.
name: Narpala, S.
name: Ginsberg, A. A.
name: Boggiano, C.
name: King, C. R.
name: Coleman, J. W.
name: Wu, C.-D.
name: Felber, B. K.
name: Mullen, K.
name: Zamb, T. J.
name: Hudgens, M. G.
name: Cassamasa, H.
name: Pavlakis, G. N.
name: Ouellette, I.
name: Lin, F.
name: McDermott, A. B.
name: Wilson, A. J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent “blips” in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.
Quote di ricollocazione e meccanismi di solidarietà: le soluzioni troppo “flessibili” del Patto dell’Unione europea su migrazione e asilo
Creators: name: Russo, Teresa
Publisher: name: Universita' degli Studi di Salerno
Year: 2021
Subjects: Solidarity
Pact on Migration and Asylum
Relocation quotas
Migratory pressure and migratory crisis
Shared responsibility

description: Through the analysis of the critical issues that emerged during the implementation of the relocation quotas adopted as provisional measures by the Council to address the migration crisis of 2015, this contribution aims to provide a key to read the fallout from the related regulatory and judicial events on the principle of solidarity that should govern the European Union’s immigration and asylum policy. It also attempts, thanks to the analysis of the solutions announced in the 2020 Pact on Migration and Asylum and the solidarity mechanisms provided for therein, to check whether they are suitable of ensuring the fair sharing of solidarity-based responsibility between the Member States, regardless of the emergency and statecentric approaches which have so far characterised the measures taken and the proposals to amend the Dublin system.
Epigenetic Silencing of HIV-1 by the Histone H3 Lysine 27 Methyltransferase Enhancer of Zeste 2
Creators: name: Karn, J.
name: Archin, N. M.
name: Margolis, D. M.
name: Chu, C. K.
name: Friedman, J.
name: Cho, W.-K.
name: Keedy, K. S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Latent HIV proviruses are silenced as the result of deacetylation and methylation of histones located at the viral long terminal repeat (LTR). Inhibition of histone deacetylases (HDACs) leads to the reemergence of HIV-1 from latency, but the contribution of histone lysine methyltransferases (HKMTs) to maintaining HIV latency remains uncertain. Chromatin immunoprecipitation experiments using latently infected Jurkat T-cell lines demonstrated that the HKMT enhancer of Zeste 2 (EZH2) was present at high levels at the LTR of silenced HIV proviruses and was rapidly displaced following proviral reactivation. Knockdown of EZH2, a key component of the Polycomb repressive complex 2 (PRC2) silencing machinery, and the enzyme which is required for trimethyl histone lysine 27 (H3K27me3) synthesis induced up to 40% of the latent HIV proviruses. In contrast, there was less than 5% induction of latent proviruses following knockdown of SUV39H1, which is required for H3K9me3 synthesis. Knockdown of EZH2 also sensitized latent proviruses to external stimuli, such as T-cell receptor stimulation, and slowed the reversion of reactivated proviruses to latency. Similarly, cell populations that responded poorly to external stimuli carried HIV proviruses that were enriched in H3K27me3 and relatively depleted in H3K9me3. Treating latently infected cells with the HKMT inhibitor 3-deazaneplanocin A, which targets EZH2, led to the reactivation of silenced proviruses, whereas chaetocin and BIX01294 showed only minimal reactivation activities. These findings suggest that PRC2-mediated silencing is an important feature of HIV latency and that inhibitors of histone methylation may play a useful role in induction strategies designed to eradicate latent HIV pools.
Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) C-Terminal-Activating Region 3 Contributes to LMP1-Mediated Cellular Migration via Its Interaction with Ubc9
Creators: name: Pagano, J. S.
name: Whitehurst, C. B.
name: Bentz, G. L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), the principal viral oncoprotein and a member of the tumor necrosis factor receptor superfamily, is a constitutively active membrane signaling protein that regulates multiple signal transduction pathways via its C-terminal-activating region 1 (CTAR1) and CTAR2, and also the less-studied CTAR3. Because protein sumoylation among other posttranslational modifications may regulate many signaling pathways induced by LMP1, we investigated whether during EBV latency LMP1 regulates sumoylation processes that control cellular activation and cellular responses. By immunoprecipitation experiments, we show that LMP1 interacts with Ubc9, the single reported SUMO-conjugating enzyme. Requirements for LMP1-Ubc9 interactions include enzymatically active Ubc9: expression of inactive Ubc9 (Ubc9 C93S) inhibited the LMP1-Ubc9 interaction. LMP1 CTAR3, but not CTAR1 and CTAR2, participated in the LMP1-Ubc9 interaction, and amino acid sequences found in CTAR3, including the JAK-interacting motif, contributed to this interaction. Furthermore, LMP1 expression coincided with increased sumoylation of cellular proteins, and disruption of the Ubc9-LMP1 CTAR3 interaction almost completely abrogated LMP1-induced protein sumoylation, suggesting that this interaction promotes the sumoylation of downstream targets. Additional consequences of the disruption of the LMP1 CTAR3-Ubc9 interaction revealed effects on cellular migration, a hallmark of oncogenesis. Together, these data demonstrate that LMP1 CTAR3 does in fact function in intracellular signaling and leads to biological effects. We propose that LMP1, by interaction with Ubc9, modulates sumoylation processes, which regulate signal transduction pathways that affect phenotypic changes associated with oncogenesis.
Epstein-Barr Virus Latent Membrane Protein 1 Induces Cancer Stem/Progenitor-Like Cells in Nasopharyngeal Epithelial Cell Lines
Creators: name: Yoshizaki, T.
name: Endo, K.
name: Muramatsu, M.
name: Sugimoto, H.
name: Pagano, J. S.
name: Murono, S.
name: Yamaoka, S.
name: Zen, Y.
name: Kondo, S.
name: Wakisaka, N.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Recent studies suggest the existence of cancer stem cells (CSC) and cancer progenitor cells (CPC), although strict definitions of neither CSC nor CPC have been developed. We have produced evidence that the principal oncoprotein of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), which is associated with human malignancies, especially nasopharyngeal carcinoma (NPC), promotes tumor cell invasion and metastasis, as well as the epithelial-mesenchymal transition (EMT). However, whether LMP1 is involved in the development of CSC/CPC is still unclear. This study investigates whether the expression of EBV-LMP1 is related to the development of CSC/CPC. Analysis of cancer stem cell markers reveals that LMP1 induces the CD44high CD24low CSC/CPC-like phenotype as well as self-renewal abilities in LMP1-expressing epithelial cell lines. In addition, we show here that LMP1 induction in epithelial cells causes high tumorigenicity and rapid cellular proliferation. Furthermore, we found that LMP1 expression increased the expression of several CPC markers as well as producing increased levels of EMT markers. Our findings indicate that LMP1 can induce a CPC-like rather than a CSC-like phenotype in epithelial cells and suggest that LMP1-induced phenotypic changes contribute to the development of NPC.
Epstein-Barr Virus LMP1 Activates EGFR, STAT3, and ERK through Effects on PKC
Creators: name: Meckes, D. G.
name: Kung, C.-P.
name: Raab-Traub, N.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that infects more than 90% of the world's adult population and is linked to multiple malignancies, including Burkitt lymphoma, Hodgkin disease, and nasopharyngeal carcinoma (NPC). The EBV oncoprotein LMP1 induces transcription of the epidermal growth factor receptor (EGFR), which is expressed at high levels in NPC. EGFR transcription is induced by LMP1 through a p50 NFκB1-Bcl-3 complex, and Bcl-3 is induced by LMP1-mediated activation of STAT3. This study reveals that LMP1, through its carboxyl-terminal activation domain 1 (LMP1-CTAR1), activates both STAT3 and EGFR in a serum-independent manner with constitutive serine phosphorylation of STAT3. Upon treatment with EGF, the LMP1-CTAR1-induced EGFR was additionally phosphorylated and STAT3 became phosphorylated on tyrosine, concomitant with upregulation of a subset of STAT3 target genes. The kinase responsible for LMP1-CTAR1-mediated serine phosphorylation of STAT3 was identified to be PKCδ using specific RNAi, a dominant negative PKCδ, and the PKCδ inhibitor rottlerin. Interestingly, inhibition of PKCδ also inhibited constitutive phosphorylation of EGFR and LMP1-CTAR1-induced phosphorylation of ERK. Inhibition of PKCδ blocked LMP1-CTAR1-mediated transformation of Rat-1 cells, likely through the inhibition of ERK activation. These findings indicate that LMP1 activates multiple distinct signaling pathways and suggest that PKCδ functions as a master regulator of EGFR, STAT3, and ERK activation by LMP1-CTAR1.
Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model
Creators: name: Chau, J. Y.
name: Trott, K. A.
name: Hudgens, M. G.
name: Sullivan, J.
name: Mfalila, C. K.
name: Abel, K.
name: Tarara, R. P.
name: Collins, W. E.
name: Fine, J.
name: Luckhart, S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: In sub-Saharan Africa, HIV-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, Mycobacterium tuberculosis and malaria parasites. The consequences are often devastating, resulting in enhanced morbidity and mortality. Due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (SIV)-malaria coinfection. In sub-Saharan Africa, Plasmodium falciparum is the most common malaria parasite and is responsible for most malaria-induced deaths. The simian malaria parasite Plasmodium fragile can induce clinical symptoms, including cerebral malaria in rhesus macaques, that resemble those of P. falciparum infection in humans. Thus, based on the well-characterized rhesus macaque model of SIV infection, this study reports the development of a novel rhesus macaque SIV-P. fragile coinfection model to study human HIV-P. falciparum coinfection. Using this model, we show that coinfection is associated with an increased, although transient, risk of both HIV and malaria transmission. Specifically, SIV-P. fragile coinfected macaques experienced an increase in SIV viremia that was temporarily associated with an increase in potential SIV target cells and systemic immune activation during acute parasitemia. Conversely, primary parasitemia in SIV-P. fragile coinfected animals resulted in higher gametocytemia that subsequently translated into higher oocyst development in mosquitoes. To our knowledge, this is the first animal model able to recapitulate the increased transmission risk of both HIV and malaria in coinfected humans. Therefore, this model could serve as an essential tool to elucidate distinct immunological, virological, and/or parasitological parameters underlying disease exacerbation in HIV-malaria coinfected people.
Coronal magnetic reconnection driven by CME expansion -- the 2011 June 7 event
Creators: name: van Driel-Gesztelyi, L.
name: Baker, D.
name: Torok, T.
name: Pariat, E.
name: Green, L. M.
name: Williams, D. R.
name: Carlyle, J.
name: Valori, G.
name: Demoulin, P.
name: Kliem, B.
name: Long, D. M.
name: Matthews, S. A.
name: Malherbe, J. -M.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: Coronal mass ejections (CMEs) erupt and expand in a magnetically structured solar corona. Various indirect observational pieces of evidence have shown that the magnetic field of CMEs reconnects with surrounding magnetic fields, forming, e.g., dimming regions distant from the CME source regions. Analyzing Solar Dynamics Observatory (SDO) observations of the eruption from AR 11226 on 2011 June 7, we present the first direct evidence of coronal magnetic reconnection between the fields of two adjacent ARs during a CME. The observations are presented jointly with a data-constrained numerical simulation, demonstrating the formation/intensification of current sheets along a hyperbolic flux tube (HFT) at the interface between the CME and the neighbouring AR 11227. Reconnection resulted in the formation of new magnetic connections between the erupting magnetic structure from AR 11226 and the neighboring active region AR 11227 about 200 Mm from the eruption site. The onset of reconnection first becomes apparent in the SDO/AIA images when filament plasma, originally contained within the erupting flux rope, is re-directed towards remote areas in AR 11227, tracing the change of large-scale magnetic connectivity. The location of the coronal reconnection region becomes bright and directly observable at SDO/AIA wavelengths, owing to the presence of down-flowing cool, dense (10^{10} cm^{-3}) filament plasma in its vicinity. The high-density plasma around the reconnection region is heated to coronal temperatures, presumably by slow-mode shocks and Coulomb collisions. These results provide the first direct observational evidence that CMEs reconnect with surrounding magnetic structures, leading to a large-scale re-configuration of the coronal magnetic field.
description: 12 pages, 12 figures
Beyond 5G/6G KPI Measurements
Creators: name: Dieudonne, Michael
name: Wang, Hua
name: Mesogiti, Ioanna
name: Kosmatos, Evangelos
Publisher: name: Zenodo
Year: 2023

description: This white paper is the continuation of the 5G-PPP TMV Working Group white paper entitled «Beyond 5G/6G KPIs and Target Values». The latter provided an early analysis of possible Beyond 5G/6G KPIs based on current work and perspectives from ICT-52 projects, seeking to understand the level to which existing definitions in standard documents will apply to 6G and to identify, at early stages, gaps and new candidate KPIs for being standardized for 6G systems. The intention of this white paper is to provide an analysis of the nature of the beyond 5G/6G KPIs identified in the previous white paper, by further elaborating on the feasibility of these KPIs to be measured, on the methods and tools to be used for their evaluation, and on identifying challenges encountered, gaps identified and research steps to be followed on the measurement and evaluation methodologies to be used in the 6G era.
Equilibrium solutions of relativistic rotating stars with mixed poloidal and toroidal magnetic fields
Creators: name: Uryu, Koji
name: Gourgoulhon, Eric
name: Markakis, Charalampos
name: Fujisawa, Kotaro
name: Tsokaros, Antonios
name: Eriguchi, Yoshiharu
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: General Relativity and Quantum Cosmology (gr-qc)
subject: FOS: Physical sciences

description: Stationary and axisymmetric solutions of relativistic rotating stars with strong mixed poloidal and toroidal magnetic fields are obtained numerically. Because of the mixed components of the magnetic field, the underlying stationary and axisymmetric spacetimes are no longer circular. These configurations are computed from the full set of the Einstein-Maxwell equations, Maxwell's equations and from first integrals and integrability conditions of the magnetohydrodynamic equilibrium equations. After a brief introduction of the formulation of the problem, we present the first results for highly deformed magnetized rotating compact stars.
description: 7 pages, to appear in PRD rapid communication
Development of molecular models of interfaces using a multi-scale hybrid particle-field approach: application to composite materials and biomembranes
Creators: name: De Nicola, Antonio
Publisher: name: Universita degli studi di Salerno
Year: 2014
Subjects: subject: CHIM/04 CHIMICA INDUSTRIALE
subject: Dinamica molecolare

description: 2012-2013
description: The rule of the interface in systems including polymer composites and block-­‐ copolymer interacting with biomembrane has been investigated by computational approach. In particular, for the polymer composite investigation, a system composed of PMMA embedding a silica nanoparticle of 3 nm (diameter), and an analogue system made of MMA and silica nanoparticle have been simulated. The structuration of both, PMMA and MMA close to the surface of the nanoparticle have been evaluated and calculated. As main results we found a stronger structuration of PMMA close to the nanoparticle respect to the MMA bulk. Pluronics based formulations are among the most successful nanomedicines and block-­‐copolymer micelles including drugs are undergoing phase I/II studies as anticancer agents. Using coarse-­‐grained models, molecular dynamics simulations of large-­‐scale systems, modeling Pluronic micelles interacting with DPPC lipid bilayers, on the μs timescale have been performed. Simulations show, in agreement with experiments, a release of Pluronic chains from the micelle to the bilayer. This release changes the size of the micelle, moreover the presence of drug molecules inside the core of the micelle has a strong influence on this process. The picture emerging from the simulations is that the micelle stability is a result of an interplay between drug/micelle core and block-­‐copolymer/bilayer interactions. The equilibrium size of the drug vector shows a strong dependency on the hydrophobicity of the drug molecules embedded into the core of the micelle. In particular, the radius of the micelle shows an abrupt increase in a very narrow range of drug molecule hydrophobicity. [edited by Author]
Hepatitis C Virus Infection Causes Cell Cycle Arrest at the Level of Initiation of Mitosis
Creators: name: Evers, L. E.
name: Hensley, L. L.
name: Kannan, R. P.
name: Lemon, S. M.
name: McGivern, D. R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Chronic infection with the hepatitis C virus (HCV) is associated with increased risk for hepatocellular carcinoma (HCC). Chronic immune-mediated inflammation is likely to be an important factor in the development of HCV-associated HCC, but direct effects of HCV infection on the host cell cycle may also play a role. Although overexpression studies have revealed multiple interactions between HCV-encoded proteins and host cell cycle regulators and tumor suppressor proteins, the relevance of these observations to HCV-associated liver disease is not clear. We determined the net effect of these interactions on regulation of the cell cycle in the context of virus infection. Flow cytometry of HCV-infected carboxyfluorescein succinimidyl ester-labeled hepatoma cells indicated a slowdown in proliferation that correlated with abundance of viral antigen. A decrease in the proportions of infected cells in G1 and S phases with an accumulation of cells in G2/M phase was observed, compared to mock-infected controls. Dramatic decreases in markers of mitosis, such as phospho-histone H3, in infected cells suggested a block to mitotic entry. In common with findings described in the published literature, we observed caspase 3 activation, suggesting that cell cycle arrest is associated with apoptosis. Differences were observed in patterns of cell cycle disturbance and levels of apoptosis with different strains of HCV. However, the data suggest that cell cycle arrest at the interface of G2 and mitosis is a common feature of HCV infection.
Probing non-perturbative effects in M-theory
Creators: name: Hatsuda, Yasuyuki
name: Okuyama, Kazumi
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Physics - Theory (hep-th)
subject: FOS: Physical sciences

description: The AdS/CFT correspondence enables us to probe M-theory on various backgrounds from the corresponding dual gauge theories. Here we investigate in detail a three-dimensional U(N) N=4 super Yang-Mills theory coupled to one adjoint hypermultiplet and Nf fundamental hypermultiplets, which is large N dual to M-theory on AdS_4xS^7/Z_Nf. Using the localization and the Fermi-gas formulation, we explore non-perturbative corrections to the partition function. As in the ABJM theory, we find that there exists a non-trivial pole cancellation mechanism, which guarantees the theory to be well-defined, between worldsheet instantons and membrane instantons for all rational (in particular, physical or integral) values of Nf.
description: 34 pages
HIV-Specific Functional Antibody Responses in Breast Milk Mirror Those in Plasma and Are Primarily Mediated by IgG Antibodies
Creators: name: Pollara, J.
name: Montefiori, D. C.
name: Shaw, G. M.
name: Kang, H. H.
name: Tomaras, G. D.
name: Salazar-Gonzalez, J. F.
name: Fouda, G. G.
name: Haynes, B.
name: Letvin, N. L.
name: Shen, X.
name: Salazar, M. G.
name: Yates, N. L.
name: Wilks, A. B.
name: Overman, G. R.
name: Mahlokozera, T.
name: Kalilani, L.
name: Meshnick, S. R.
name: Denny, T. N.
name: Lovingood, R. V.
name: Hahn, B. H.
name: Ferrari, G.
name: Permar, S. R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies are present in the milk of HIV-infected mothers, but little is known about their virus-specific functions. In this study, HIV Env-specific antibody binding, autologous and heterologous virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001) in milk were directly correlated with that in the systemic compartment but were 2 log units lower in magnitude. Autologous neutralization was rarely detected in milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r = 0.17 and P = 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies against a tier 1 virus (r = 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG milk fractions had detectable neutralization. These results suggest that plasma-derived IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity in breast milk.
Nanoscale Topographical Replication of Graphene Architecture by Artificial DNA nanostructures
Creators: name: Moon, Y.
name: Shin, J.
name: Seo, S.
name: Park, J.
name: Dugasani, S. R.
name: Woo, S. H.
name: Park, T.
name: Park, S. H.
name: Ahn, J. R.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: Despite many studies on how geometry can be used to control the electronic properties of graphene, certain limitations to fabrication of designed graphene nanostructures exist. Here, we demonstrate controlled topographical replication of graphene by artificial deoxyribonucleic acid (DNA) nanostructures. Owing to the high degree of geometrical freedom of DNA nanostructures, we controlled the nanoscale topography of graphene. The topography of graphene replicated from DNA nanostructures showed enhanced thermal stability and revealed an interesting negative temperature coefficient of sheet resistivity when underlying DNA nanostructures were denatured at high temperatures.
description: 12 pages, 3 figures
Human Cytomegalovirus Induces the Activity and Expression of Acetyl-Coenzyme A Carboxylase, a Fatty Acid Biosynthetic Enzyme Whose Inhibition Attenuates Viral Replication
Creators: name: Spencer, C. M.
name: Schafer, X. L.
name: Moorman, N. J.
name: Munger, J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: We have previously reported that human cytomegalovirus (HCMV) infection induces large-scale changes to host cell glycolytic, nucleic acid, and phospholipid metabolism. Here we explore the viral mechanisms involved in fatty acid biosynthetic activation. Our results indicate that HCMV targets ACC1, the rate-limiting enzyme of fatty acid biosynthesis, through multiple mechanisms. HCMV infection was found to activate ACC1 expression, increasing the abundance of both ACC1 mRNA and protein. Viral gene expression but not viral DNA replication was found to be necessary for HCMV-mediated induction of ACC1 levels. HCMV infection was also found to increase the proteolytic processing of SREBP-2, a transcription factor whose proteolytic cleavage is known to activate a variety of phospholipid metabolic genes. Processing of SREBP-2 was found to be dependent on mTOR activity; pharmaceutical inhibition of mTOR blocked HCMV-induced SREBP-2 processing and prevented the induction of fatty acid biosynthesis and ACC1 expression. Independent of the increases in ACC1 expression, HCMV infection also induced ACC1's enzymatic activity. Inhibition of ACC1 through either RNA interference (RNAi) or inhibitor treatment was found to attenuate HCMV replication, and HCMV replication was sensitive to ACC1 inhibition even at the later stages of infection, suggesting a late role for fatty acid biosynthesis during HCMV replication. These findings indicate that HCMV infection actively modulates numerous functional aspects of a key metabolic regulatory enzyme that is important for high-titer viral replication.
Microvesicles and Viral Infection
Creators: name: Meckes, D. G.
name: Raab-Traub, N.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Cells secrete various membrane-enclosed microvesicles from their cell surface (shedding microvesicles) and from internal, endosome-derived membranes (exosomes). Intriguingly, these vesicles have many characteristics in common with enveloped viruses, including biophysical properties, biogenesis, and uptake by cells. Recent discoveries describing the microvesicle-mediated intercellular transfer of functional cellular proteins, RNAs, and mRNAs have revealed additional similarities between viruses and cellular microvesicles. Apparent differences include the complexity of viral entry, temporally regulated viral expression, and self-replication proceeding to infection of new cells. Interestingly, many virally infected cells secrete microvesicles that differ in content from their virion counterparts but may contain various viral proteins and RNAs. For the most part, these particles have not been analyzed for their content or functions during viral infection. However, early studies of microvesicles (L-particles) secreted from herpes simplex virus-infected cells provided the first evidence of microvesicle-mediated intercellular communication. In the case of Epstein-Barr virus, recent evidence suggests that this tumorigenic herpesvirus also utilizes exosomes as a mechanism of cell-to-cell communication through the transfer of signaling competent proteins and functional microRNAs to uninfected cells. This review focuses on aspects of the biology of microvesicles with an emphasis on their potential contributions to viral infection and pathogenesis.
Stable foliations and semi-flow Morse homology
Creators: name: Weber, Joa
Publisher: name: arXiv
Year: 2014
Subjects: subject: Differential Geometry (math.DG)
subject: Analysis of PDEs (math.AP)
subject: Algebraic Topology (math.AT)
subject: Dynamical Systems (math.DS)
subject: FOS: Mathematics
subject: 37L05 58J35 58E10 53C43

description: In case of the heat flow on the free loop space of a closed Riemannian manifold non-triviality of Morse homology for semi-flows is established by constructing a natural isomorphism to singular homology of the loop space. The construction is also new in finite dimensions. The main idea is to build a Morse filtration using Conley pairs and their pre-images under the time-$T$-map of the heat flow. A crucial step is to contract each Conley pair onto its part in the unstable manifold. To achieve this we construct stable foliations for Conley pairs using the recently found backward $λ$-Lemma [31]. These foliations are of independent interest [23].
description: 54 pages, 14 figures
A 52 hours VLT/FORS2 spectrum of a bright z~7 HUDF galaxy: no Ly-alpha emission
Creators: name: Vanzella, E.
name: Fontana, A.
name: Pentericci, L.
name: Castellano, M.
name: Grazian, A.
name: Giavalisco, M.
name: Nonino, M.
name: Cristiani, S.
name: Zamorani, G.
name: Vignali, C.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: FOS: Physical sciences

description: We aim to determine the redshift of GDS-1408, the most solid z~7 galaxy candidate lying in the Hubble Ultra Deep Field. We have used all the VLT spectra of GDS-1408 collected by us and two other groups with FORS2 at VLT in the last five years, for a total integration time of 52hr. The combined spectrum is the deepest ever obtained of a galaxy in the Reionization epoch. We do not detect any emission line or continuum over the whole wavelength range, up to 10100A. Based on an accurate set of simulations, we are able to put a stringent upper limit of f(Lya)<3x10^(-18) erg/s/cm2 at 3-9 sigma in the explored wavelength range, corresponding to a rest-frame equivalent width EW<9A. Combining this limit with the SED modelling we refine the redshift to be z=6.82+/- 0.1 (1-sigma). The same SED fitting indicates that GDS-1408 is relatively extinct (A1600~1) with a dust corrected star formation rate of ~ 20 Msol/yr. The comparison between the un-attenuated equivalent width predicted by the case-B recombination theory and the observed upper limit, provides a limit on the effective Lya escape fraction of f_(esc)^(eff)(Lya)<8%. Even though we cannot rule out a major contribution of the inter/circum galactic medium in damping the line, a plausible interpretation is that GDS-1408 is moderately evolved and contains sufficient gas and dust to attenuate the Lya emission, before it reaches the intergalactic medium. The redshift confirmation of even the best z~7 candidates is very hard to achieve (unless the Lya or unusually strong rest-UV nebular emission lines are present) with the current generation of 8-10m class telescopes. We show that both JWST and E-ELT will be necessary to make decisive progresses. Currently, the increased redshift accuracy obtained with this kind of analysis makes ALMA an interesting option for the redshift confirmation.
description: 8 pages, 5 figures; Accepted for publication in A&A
Neutralizing Monoclonal Antibodies against Hepatitis C Virus E2 Protein Bind Discontinuous Epitopes and Inhibit Infection at a Postattachment Step
Creators: name: Diamond, M. S.
name: Fremont, D. H.
name: Blight, K. J.
name: Evans, M. J.
name: Sabo, M. C.
name: Prentoe, J.
name: Bukh, J.
name: Lemon, S. M.
name: Hopcraft, S. E.
name: Ball, J. K.
name: Yi, M.
name: Luca, V. C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: The E2 glycoprotein of hepatitis C virus (HCV) mediates viral attachment and entry into target hepatocytes and elicits neutralizing antibodies in infected patients. To characterize the structural and functional basis of HCV neutralization, we generated a novel panel of 78 monoclonal antibodies (MAbs) against E2 proteins from genotype 1a and 2a HCV strains. Using high-throughput focus-forming reduction or luciferase-based neutralization assays with chimeric infectious HCV containing structural proteins from both genotypes, we defined eight MAbs that significantly inhibited infection of the homologous HCV strain in cell culture. Two of these bound E2 proteins from strains representative of HCV genotypes 1 to 6, and one of these MAbs, H77.39, neutralized infection of strains from five of these genotypes. The three most potent neutralizing MAbs in our panel, H77.16, H77.39, and J6.36, inhibited infection at an early postattachment step. Receptor binding studies demonstrated that H77.39 inhibited binding of soluble E2 protein to both CD81 and SR-B1, J6.36 blocked attachment to SR-B1 and modestly reduced binding to CD81, and H77.16 blocked attachment to SR-B1 only. Using yeast surface display, we localized epitopes for the neutralizing MAbs on the E2 protein. Two of the strongly inhibitory MAbs, H77.16 and J6.36, showed markedly reduced binding when amino acids within hypervariable region 1 (HVR1) and at sites ∼100 to 200 residues away were changed, suggesting binding to a discontinuous epitope. Collectively, these studies help to define the structural and functional complexity of antibodies against HCV E2 protein with neutralizing potential.
Norovirus GII.4 Strain Antigenic Variation
Creators: name: Lindesmith, L. C.
name: Baric, R. S.
name: Donaldson, E. F.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Noroviruses are the principal cause of epidemic gastroenteritis worldwide. Multiple reports have concluded that the major capsid proteins of GII.4 strains, which cause 80% of norovirus infections worldwide, are evolving rapidly, resulting in new epidemic strains. Surrogate neutralization assays using sera from outbreaks and from immunized mice suggest that, as with influenza virus, antigenic variation maintains GII.4 persistence in the face of human population herd immunity. To test this hypothesis, mice were hyperimmunized with virus-like particles (VLPs) representing an early (GII.4-1987) and a contemporary (GII.4-2006) GII.4 strain. Anti-GII.4-1987 IgG monoclonal antibodies (MAbs) strongly reacted with GII.4 VLPs derived between only 1987 and 2002. Ligand binding blockade was more efficient with GII.4-1987 and GII.4-1997 VLPs than with GII.4-2002. Anti-GII.4-2006 IgG MAbs recognized either a broad panel of GII.4 VLPs (1987 to 2006) or a subset of contemporary (2004 to 2006) VLPs. Most 2006 antibodies did not recognize or only poorly recognized GII.4 VLPs of 2007 or 2008, documenting rapid antigenic evolution of GII.4 capsids. Generally, 2006 MAbs blocked homotypic VLP-ligand binding but were unable to block VLPs representing strains primarily circulating during or earlier than 2002. These analyses demonstrate that both subtle and significant evolutionary change has occurred within antibody epitopes between epidemic strains, providing direct evidence that the GII.4 noroviruses are undergoing antigenic variation, likely in response to herd immunity. As with influenza virus, HIV, and hepatitis C virus, norovirus antigenic variation will significantly influence the design of efficacious vaccines and immunotherapeutics against these important human pathogens.
Nuclear Accumulation of the Papillomavirus E1 Helicase Blocks S-Phase Progression and Triggers an ATM-Dependent DNA Damage Response
Creators: name: Moody, C. A.
name: Lehoux, M.
name: Fradet-Turcotte, A.
name: Laimins, L. A.
name: Bergeron-Labrecque, F.
name: Archambault, J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Replication of the papillomavirus genome is initiated by the assembly of a complex between the viral E1 and E2 proteins at the origin. The E1 helicase is comprised of a C-terminal ATPase/helicase domain, a central domain that binds to the origin, and an N-terminal regulatory region that contains nuclear import and export signals mediating its nucleocytoplasmic shuttling. We previously reported that nuclear accumulation of E1 has a deleterious effect on cellular proliferation which can be prevented by its nuclear export. Here we have shown that nuclear accumulation of E1 from different papillomavirus types blocks cell cycle progression in early S phase and triggers the activation of a DNA damage response (DDR) and of the ATM pathway in a manner that requires both the origin-binding and ATPase activities of E1. Complex formation with E2 reduces the ability of E1 to induce a DDR but does not prevent cell cycle arrest. Transient viral DNA replication still occurs in S-phase-arrested cells but surprisingly is neither affected by nor dependent on induction of a DDR and of the ATM kinase. Finally, we provide evidence that a DDR is also induced in human papillomavirus type 31 (HPV31)-immortalized keratinocytes expressing a mutant E1 protein defective for nuclear export. We propose that nuclear export of E1 prevents cell cycle arrest and the induction of a DDR during the episomal maintenance phase of the viral life cycle and that complex formation with E2 further safeguards undifferentiated cells from undergoing a DDR when E1 is in the nucleus.
A hybrid neuro--wavelet predictor for QoS control and stability
Creators: name: Napoli, Christian
name: Pappalardo, Giuseppe
name: Tramontana, Emiliano
Publisher: name: arXiv
Year: 2014
Subjects: subject: Neural and Evolutionary Computing (cs.NE)
subject: Distributed, Parallel, and Cluster Computing (cs.DC)
subject: Networking and Internet Architecture (cs.NI)
subject: Performance (cs.PF)
subject: Systems and Control (eess.SY)
subject: FOS: Computer and information sciences
subject: FOS: Electrical engineering, electronic engineering, information engineering
subject: I.2.6; I.5.1; I.2.11
subject: 68T05

description: For distributed systems to properly react to peaks of requests, their adaptation activities would benefit from the estimation of the amount of requests. This paper proposes a solution to produce a short-term forecast based on data characterising user behaviour of online services. We use \emph{wavelet analysis}, providing compression and denoising on the observed time series of the amount of past user requests; and a \emph{recurrent neural network} trained with observed data and designed so as to provide well-timed estimations of future requests. The said ensemble has the ability to predict the amount of future user requests with a root mean squared error below 0.06\%. Thanks to prediction, advance resource provision can be performed for the duration of a request peak and for just the right amount of resources, hence avoiding over-provisioning and associated costs. Moreover, reliable provision lets users enjoy a level of availability of services unaffected by load variations.
One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates
Creators: name: Kwak, Y. T.
name: Krisko, J. F.
name: Appella, E.
name: Estes, J. D.
name: Zou, W.
name: Wahl, A.
name: Powell, D. A.
name: Martinez-Torres, F.
name: Othieno, F.
name: Garcia, J. V.
name: Gallay, P.
name: Lu, M.
name: Payne, D. A.
name: Fleming, E.
name: Zein, S.
name: Welch, B. D.
name: Denton, P. W.
name: Kay, M. S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Recent iPrEx clinical trial results provided evidence that systemic preexposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) can partially prevent rectal HIV transmission in humans. Similarly, we have previously demonstrated that systemic administration of the same FTC-TDF combination efficiently prevented rectal transmission in humanized bone marrow/liver/thymus (BLT) mice. The CAPRISA 004 trial recently demonstrated that topical application of the tenofovir could partially prevent vaginal HIV-1 transmission in humans. To further validate the usefulness of the BLT mouse model for testing HIV prevention strategies, we evaluated the topical administration of tenofovir as used in CAPRISA 004 to prevent vaginal HIV transmission in BLT mice. Our results demonstrate that vaginally administered 1% tenofovir significantly reduced HIV transmission in BLT mice (P = 0.002). Together with the results obtained after systemic antiretroviral PrEP, these topical inhibitor data serve to validate the use of humanized BLT mice to evaluate both systemic and topical inhibitors of HIV transmission. Based on these observations, we tested six additional microbicide candidates for their ability to prevent vaginal HIV transmission: a C-peptide fusion inhibitor (C52L), a membrane-disrupting amphipathic peptide inhibitor (C5A), a trimeric d-peptide fusion inhibitor (PIE12-Trimer), a combination of reverse transcriptase inhibitors (FTC-TDF), a thioester zinc finger inhibitor (TC247), and a small-molecule Rac inhibitor (NSC23766). No protection was seen with the Rac inhibitor NSC23766. The thioester compound TC247 offered partial protection. Significant protection was afforded by FTC-TDF, and complete protection was offered by three different peptide inhibitors tested. Our results demonstrate that these effective topical inhibitors have excellent potential to prevent vaginal HIV transmission in humans.