bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virological Outcome after Structured Interruption of Antiretroviral Therapy for Human Immunodeficiency Virus Infection Is Associated with the Functional Profile of Virus-Specific CD8+T Cells
Authors: Daucher Marybeth , Price David A. , Brenchley Jason M. , Lamoreaux Laurie , Metcalf Julia A. , Rehm Catherine , Nies-Kraske Elizabeth , Urban Elizabeth , Yoder Christian , Rock Diane , Gumkowski Julie , Betts Michael R. , Dybul Mark R. , Douek Daniel C. 
Published: January 2008

ABSTRACTA clear understanding of the antiviral effects of CD8+T cells in the context of chronic human immunodeficiency virus (HIV) infection is critical for the development of prophylactic vaccines and therapeutics designed to support T-cell-mediated immunity. However, defining the potential correlates of effective CD8+T-cell immunity has proven difficult; notably, comprehensive analyses have demonstrated that the size and shape of the CD8+T-cell response are not necessarily indicative of efficacy determined by measures of plasma viral load. Here, we conducted a detailed quantitative and qualitative analysis of CD8+T-cell responses to autologous virus in a cohort of six HIV-infected individuals with a history of structured interruption of antiretroviral therapy (ART) (SIT). The magnitude and breadth of the HIV-specific response did not, by themselves, explain the changes observed in plasma virus levels after the cessation of ART. Furthermore, mutational escape from targeted epitopes could not account for the differential virological outcomes in this cohort. However, the functionality of HIV-specific CD8+T-cell populations upon antigen encounter, determined by the simultaneous and independent measurement of five CD8+T-cell functions (degranulation and gamma interferon, macrophage inflammatory protein 1β, tumor necrosis factor alpha, and interleukin-2 levels) reflected the emergent level of plasma virus, with multiple functions being elicited in those individuals with lower levels of viremia after SIT. These data show that the quality of the HIV-specific CD8+T-cell response, rather than the quantity, is associated with the dynamics of viral replication in the absence of ART and suggest that the effects of SIT can be assessed by measuring the functional profile of HIV-specific CD8+T cells.
Systematic Mutagenesis of the Murine Gammaherpesvirus 68 M2 Protein Identifies Domains Important for Chronic Infection
Authors: Herskowitz Jeremy H. , Siegel Andrea M. , Jacoby Meagan A. , Speck Samuel H. 
Published: January 2008

ABSTRACT
Murine gammaherpesvirus 68 (MHV68) infection of inbred mice represents a genetically tractable small-animal model for assessing the requirements for the establishment of latency, as well as reactivation from latency, within the lymphoid compartment. By day 16 postinfection, MHV68 latency in the spleen is found in B cells, dendritic cells, and macrophages. However, as with Epstein-Barr virus, by 3 months postinfection MHV68 latency is predominantly found in isotype-switched memory B cells. The MHV68 M2 gene product is a latency-associated antigen with no discernible homology to any known cellular or viral proteins. However, depending on experimental conditions, the M2 protein has been shown to play a critical role in both the efficient establishment of latency in splenic B cells and reactivation from latently infected splenic B cells. Inspection of the sequence of the M2 protein reveals several hallmarks of a signaling molecule, including multiple PXXP motifs and two potential tyrosine phosphorylation sites. Here, we report the generation of a panel of recombinant MHV68 viruses harboring mutations in the M2 gene that disrupt putative functional motifs. Subsequent analyses of the panel of M2 mutant viruses revealed a functionally important cluster of PXXP motifs in the C-terminal region of M2, which have previously been implicated in binding Vav proteins (P. A. Madureira, P. Matos, I. Soeiro, L. K. Dixon, J. P. Simas, and E. W. Lam, J. Biol. Chem. 280:37310-37318, 2005; L. Rodrigues, M. Pires de Miranda, M. J. Caloca, X. R. Bustelo, and J. P. Simas, J. Virol. 80:6123-6135, 2006). Further characterization of two adjacent PXXP motifs in the C terminus of the M2 protein revealed differences in the functions of these domains in M2-driven expansion of primary murine B cells in culture. Finally, we show that tyrosine residues 120 and 129 play a critical role in both the establishment of splenic latency and reactivation from latency upon explant of splenocytes into tissue culture. Taken together, these analyses will aide future studies for identifying M2 interacting partners and B-cell signaling pathways that are manipulated by the M2 protein.
Expansion and Exhaustion of T-Cell Responses during Mutational Escape from Long-Term Viral Control in Two DNA/Modified Vaccinia Virus Ankara-Vaccinated and Simian-Human Immunodeficiency Virus SHIV-89.6P-Challenged Macaques
Authors: Sadagopal Shanmugalakshmi , Amara Rama Rao , Kannanganat Sunil , Sharma Sunita , Chennareddi Lakshmi , Robinson Harriet L. 
Published: January 2008

ABSTRACT
In this study, we monitored the temporal breadths, frequencies, and functions of antiviral CD4 and CD8 T cells in 2 of 22 DNA/modified vaccinia virus Ankara-vaccinated macaques that lost control of a simian-human immunodeficiency virus 89.6P challenge by 196 weeks postchallenge. Our results show that both mutation and exhaustion contributed to escape. With the reappearance of viremia, responding CD8 and CD4 T cells underwent an initial increase and then loss of breadth and frequency. Antiviral gamma interferon (IFN-γ)- and interleukin 2-coproducing cells were lost before IFN-γ-producing cells and CD4 cells before CD8 cells. At euthanasia, all CD8, but no CD4, Gag epitopes detected during long-term control contained mutations.
Human HLA-DR Transgenes Protect Mice from Fatal Virus-Induced Encephalomyelitis and Chronic Demyelination
Authors: Rodriguez Moses , Zoecklein Laurie , Kerkvliet Jason G. , Pavelko Kevin D. , Papke Louisa , Howe Charles L. , Pease Larry R. , David Chella 
Published: January 2008

ABSTRACTWe evaluated the participatory role of human HLA-DR molecules in control of virus from the central nervous system and in the development of subsequent spinal cord demyelination. The experiments utilized intracranial infection with Theiler's murine encephalomyelitis virus (TMEV), a picornavirus that, in some strains of mice, results in primary demyelination. We studied DR2 and DR3 transgenic mice that were bred onto a combined class I-deficient mouse (beta-2 microglobulin deficient; β2m0) and class II-deficient mouse (Aβ0) of theH-2bbackground. Aβ0.β2m0mice infected with TMEV died within 18 days of infection. These mice showed severe encephalomyelitis due to rapid replication of virus genome. In contrast, transgenic mice with insertion of a single human class II major histocompatibility complex (MHC) gene (DR2 or DR3) survived the acute infection. DR2 and DR3 mice controlled virus infection by 45 days and did not develop spinal cord demyelination. Levels of virus RNA were reduced in HLA-DR transgenic mice compared to Aβ0.β2m0mice. Virus-neutralizing antibody responses did not explain why DR mice survived the infection and controlled virus replication. However, DR mice showed an increase in gamma interferon and interleukin-2 transcripts in the brain, which were associated with protection. The findings support the hypothesis that the expression of a single human class II MHC molecule can, by itself, influence the control of an intracerebral pathogen in a host without a competent class I MHC immune response. The mechanism of protection appears to be the result of cytokines released by CD4+T cells.
Redundancy and Plasticity of Neutralizing Antibody Responses Are Cornerstone Attributes of the Human Immune Response to the Smallpox Vaccine
Authors: Benhnia Mohammed Rafii-El-Idrissi , McCausland Megan M. , Su Hua-Poo , Singh Kavita , Hoffmann Julia , Davies D. Huw , Felgner Philip L. , Head Steven , Sette Alessandro , Garboczi David N. , Crotty Shane 
Published: January 2008

ABSTRACT
The smallpox vaccine is widely considered the gold standard for human vaccines, yet the key antibody targets in humans remain unclear. We endeavored to identify a stereotypic, dominant, mature virion (MV) neutralizing antibody target in humans which could be used as a diagnostic serological marker of protective humoral immunity induced by the smallpox vaccine (vaccinia virus [VACV]). We have instead found that diversity is a defining characteristic of the human antibody response to the smallpox vaccine. We show that H3 is the most immunodominant VACV neutralizing antibody target, as determined by correlation analysis of immunoglobulin G (IgG) specificities to MV neutralizing antibody titers. It was determined that purified human anti-H3 IgG is sufficient for neutralization of VACV; however, depletion or blockade of anti-H3 antibodies revealed no significant reduction in neutralization activity, showing anti-H3 IgG is not required in vaccinated humans (or mice) for neutralization of MV. Comparable results were obtained for human (and mouse) anti-L1 IgG and even for anti-H3 and anti-L1 IgG in combination. In addition to H3 and L1, human antibody responses to D8, A27, D13, and A14 exhibited statistically significant correlations with virus neutralization. Altogether, these data indicate the smallpox vaccine succeeds in generating strong neutralizing antibody responses not by eliciting a stereotypic response to a single key antigen but instead by driving development of neutralizing antibodies to multiple viral proteins, resulting in a “safety net” of highly redundant neutralizing antibody responses, the specificities of which can vary from individual to individual. We propose that this is a fundamental attribute of the smallpox vaccine.
The VP7 Genes of Two G9 Rotaviruses Isolated in 1980 from Diarrheal Stool Samples Collected in Washington, DC, Are Unique Molecularly and Serotypically
Authors: Cao Dianjun , Santos Norma , Jones Ronald W. , Tatsumi Masatoshi , Gentsch Jon R. , Hoshino Yasutaka 
Published: January 2008

ABSTRACT
In a retrospective study of archival diarrheal stool samples collected from 1974 to 1991 at Children's Hospital National Medical Center, Washington, DC, we detected three genotype G9P[8] viruses in specimens collected in 1980, which represented the earliest human G9 viruses ever isolated. The VP7 genes of two culture-adapted 1980 G9 viruses were phylogenetically related closely to the lineage 2 G9 virus VP7 gene. Unexpectedly, however, the VP7s of the 1980 G9 viruses were more closely related serotypically to lineage 3 VP7s than to lineage 2 VP7, which may be supported by amino acid sequence analyses of the VP7 proteins.
Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain
Authors: Kong Qingzhong , Zheng Mengjie , Casalone Cristina , Qing Liuting , Huang Shenghai , Chakraborty Bikram , Wang Ping , Chen Fusong , Cali Ignazio , Corona Cristiano , Martucci Francesca , Iulini Barbara , Acutis Pierluigi , Wang Lan , Liang Jingjing , Wang Meiling , Li Xinyi , Monaco Salvatore , Zanusso Gianluigi , Zou Wen-Quan , Caramelli Maria , Gambetti Pierluigi 
Published: January 2008

ABSTRACT
Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to be caused by only one strain, BSE-C. BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE strains by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE strain-infected cattle. Sixty percent of the inoculated Tg mice became infected after 20 to 22 months of incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE strain-infected Tg mice, but none of the Tg mice infected with prions causing a sporadic human prion disease, showed the presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE strain-infected humanized Tg mouse brains are different from those from the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation times are observed for the BASE strain-infected Tg mice. These results suggest that in humans, the BASE strain is a more virulent BSE strain and likely lymphotropic.
Single-Dose Protection againstPlasmodium bergheiby a Simian Adenovirus Vector Using a Human Cytomegalovirus Promoter Containing Intron A
Authors: Sridhar S. , Reyes-Sandoval A. , Draper S. J. , Moore A. C. , Gilbert S. C. , Gao G. P. , Wilson J. M. , Hill A. V. S. 
Published: February 2008

ABSTRACTHuman adenovirus serotype 5 (AdH5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. We designed AdH5 vectors expressing antigen under the control of a human cytomegalovirus (HCMV) immediate-early promoter containing its intron A sequence. The transcriptional levels of antigen and immune responses to antigen for vectors with the HCMV promoter with the intron A sequence (LP) were greater than those for AdH5 vectors using the HCMV promoter sequence without intron A (SP). We compared an E1E3-deleted AdH5 adenoviral vector, which affords more space for insertion of foreign sequences, and showed it to be as immunogenic as an E1-deleted AdH5 vector. Neutralizing antibodies to AdH5 limit the efficacy of vaccines based on the AdH5 serotype, and simian adenoviral vectors offer an attractive option to overcome this problem. We constructed E1E3-deleted human and simian adenoviral vectors encoding the pre-erythrocytic-stage malarial antigenPlasmodium bergheicircumsporozoite protein. We compared the immunogenicity and efficacy of AdC6, a recombinant simian adenovirus serotype 6 vector, in a murine malaria model to those of AdH5 and the poxviral vectors MVA and FP9. AdC6 induced sterile protection from a single dose in 90% of mice, in contrast to AdH5 (25%) and poxviral vectors MVA and FP9 (0%). Adenoviral vectors maintained potent CD8+T-cell responses for a longer period after immunization than did poxviral vectors and mainly induced an effector memory phenotype of cells. Significantly, AdC6 was able to maintain protection in the presence of preexisting immunity to AdH5.
4-(OCTYLOXY)-N-(4-HEXYLPHENYL)-2-HYDROXYBENZALIMINE THERMOTROPIC COMPOUND: MORPHOLOGIC, MESOMORPHIC, THERMOTROPIC, THERMOOPTICAL AND THERMODYNAMICAL PROPERTIES
Authors: NESRULLAJEV ARIF , ERAN BELKIZ BILGIN , YÖRÜR ÇIDEM 
Published: January 2008

In this work, the mesomorphic, morphologic, thermotropic, thermooptical, and thermodynamical properties of 4-(octyloxy)-N-(4-hexylphenyl)-2-hydroxybenzalimine thermotropic liquid crystalline compound, which was synthesized by our group, have been studied in detail. This compound displays smectic C and nematic mesophases. These mesophases are enantiotropic and exhibit specific confocal and schlieren textures, respectively.Thermotropic, thermooptical, and thermodynamical properties of the compound at direct and reverse phase transitions between smectic C and nematic mesophases and also between nematic mesophase and isotropic liquid have been investigated. The peculiarities of the bistable heterophase regions of these phase transitions have been studied.
SPIN INTERFERENCE IN RASHBA 2DEG SYSTEMS
Authors: NITTA JUNSAKU 
Published: January 2008

The gate controllable SOI provides useful information about spin interference.1 Spin interference effects are studied in two different interference loop structures. It is known that sample specific conductance fluctuations affect the conductance in the interference loop. By using array of many interference loops, we carefully pick up TRS Altshuler-Aronov-Spivak (AAS)-type oscillation which is not sample specific and depends on the spin phase. The experimentally obtained gate voltage dependence of AAS oscillations indicates that the spin precession angle can be controlled by the gate voltage.2 We demonstrate the time reversal Aharonov-Casher (AC) effect in small arrays of mesoscopic rings.3 By using an electrostatic gate we can control the spin precession angle rate and follow the AC phase over several interference periods. We also see the second harmonic of the AC interference, oscillating with half the period. The spin interference is still visible after more than 20π precession angle. We have proposed a Stern-Gerlach type spin filter based on the Rashba SOI.4 A spatial gradient of effective magnetic field due to the nonuniform SOI separates spin up and down electrons. This spin filter works even without any external magnetic fields and ferromagnetic contacts. We show the semiconductor/ferromagnet hybrid structure is an effective way to detect magnetization process of submicron magnets. The problem of the spin injection from ferromagnetic contact into 2DEG is also disicussed. Note from Publisher: This article contains the abstract only.
GENERATING and MANIPULATING SPINS IN SEMICONDUCTORS
Authors: AWSCHALOM DAVID D. 
Published: January 2008

Spin-orbit coupling in semiconductors relates the spin of an electron to its momentum, and provides a pathway for electrically initializing and manipulating electron spins for applications in spintronics and spin-based quantum information processing. This coupling can be regulated with strain in bulk semiconductors and quantum confinement in semiconductor heterostructures. We will provide an overview of optical studies exploring spin dynamics in conventional and magnetic semiconductors, followed by recent experiments probing all-electrical generation and manipulation of spins. Using Faraday and Kerr rotation magneto-optical spectroscopies with temporal and spatial resolution, current-induced spin polarization1 and the spin Hall effect2 have been observed using both spatially-resolved and temporally-resolved techniques in bulk semiconductors. More recently, we have investigated the spin Hall effect and current-induced spin polarization in two-dimensional electron gases confined in (110) AlGaAs quantum wells using Kerr rotation microscopy.3 In marked contrast to previous measurements in three dimensional systems, the spin Hall profile in two dimensions shows a surprisingly complex structure and the current-induced spin polarization is out-of-plane. The experiments map the strong dependence of the current-induced spin polarization to the crystal axis along which the electric field is applied, reflecting the anisotropy of the spin-orbit interaction. The effect of reducing feature sizes in electrical spintronic devices is relevant for future technological applications. To this end, we discuss related measurements probing electron spin dynamics in narrow two-dimensional InGaAs quantum well wires with widths ranging from the micron to the submicron scale.4 The data reveal a surprising slowing of the electron spin relaxation in reduced geometries. These results reveal opportunities for tuning a spin source using quantum confinement, strain and device engineering in non-magnetic materials. This work was supported by the ARO, DARPA, NSF and ONR. Note from Publisher: This article contains the abstract only.
MAGNETIC RACE-TRACK — A NOVEL STORAGE CLASS SPINTRONIC MEMORY
Authors: PARKIN STUART 
Published: January 2008

A proposal for a novel storage-class memory is described in which magnetic domains are used to store information in a "magnetic race-track".1 The magnetic race-track shift register storage memory promises a solid state memory with storage capacities and cost rivaling that of magnetic disk drives but with much improved performance and reliability. The magnetic race track is comprised of tall columns of magnetic material arranged perpendicularly to the surface of a silicon wafer. The domains are moved up and down the race-track by nanosecond long current pulses using the phenomenon of spin momentum transfer. The domain walls in the magnetic race-track are read using magnetic tunnel junction magnetoresistive sensing devices arranged in the silicon substrate. Recent progress in developing magnetic tunnel junction devices with giant tunneling magnetoresistance exceeding 350% at room temperature will be mentioned.2 Experiments exploring the current induced motion and depinning of domain walls in magnetic nano-wires with artificial pinning sites will be discussed. The domain wall structure, whether vortex or transverse, and the magnitude of the pinning potential is shown to have surprisingly little effect on the current driven dynamics of the domain wall motion.3 By contrast the motion of DWs under nanosecond long current pulses is surprisingly sensitive to their length.4 In particular, we find that the probability of dislodging a DW, confined to a pinning site in a permalloy nanowire, oscillates with the length of the current pulse, with a period of just a few nanoseconds. Using an analytical model and micromagnetic simulations we show that this behaviour is connected to a current induced oscillatory motion of the DW. The period is determined by the DW mass and the curvature of the confining potential. When the current is turned off during phases of the DW motion when the DW has enough momentum, there is a boomerang effect that can drive the DW out of the confining potential in the opposite direction to the flow of spin angular momentum. Note from Publisher: This article contains the abstract only.
ANOMALOUS TRANSPORT IN METALS AND SEMICONDUCTORS
Authors: MACDONALD A. H. 
Published: January 2008

According to the Kubo formula, the static uniform electric fields in a metal or semiconductor can induce coherence between band states far from the Fermi energy. This interband coherence response appears to be at odds with the normal view that transport is a Fermi-energy property, and is relatively unfamiliar since it makes a negligibly small contribution to the most commonly studied transport coefficients such as the longitudinal conductivity. It has recently been argued that interband coherence response can dominate the anomalous Hall conductivity of ferromagnetic metals and semiconductors and the spin-Hall conductivity of paramagnetic materials. I will review recent theoretical ideas related to the charge Hall conductivity of ferromagnetic materials and the spin Hall conductivity of paramagnetic materials and their relation to recent and future experiments. Note from Publisher: This article contains the abstract only.