166 research outputs found
Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific
Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8(+) T cells are HIV specific in vivo
Spinning strings and integrable spin chains in the AdS/CFT correspondence
In this introductory review we discuss dynamical tests of the AdS_5 x S^5
string/N=4 super Yang-Mills duality. After a brief introduction to AdS/CFT we
argue that semiclassical string energies yield information on the quantum
spectrum of the string in the limit of large angular momenta on the S^5. The
energies of the folded and circular spinning string solutions rotating on a S^3
within the S^5 are derived, which yield all loop predictions for the dual gauge
theory scaling dimensions. These follow from the eigenvalues of the dilatation
operator of N=4 super Yang-Mills in a minimal SU(2) subsector and we display
its reformulation in terms of a Heisenberg s=1/2 spin chain along with the
coordinate Bethe ansatz for its explicit diagonalization. In order to make
contact to the spinning string energies we then study the thermodynamic limit
of the one-loop gauge theory Bethe equations and demonstrate the matching with
the folded and closed string result at this loop order. Finally the known gauge
theory results at higher-loop orders are reviewed and the associated long-range
spin chain Bethe ansatz is introduced, leading to an asymptotic all-loop
conjecture for the gauge theory Bethe equations. This uncovers discrepancies at
the three-loop order between gauge theory scaling dimensions and string theory
energies and the implications of this are discussed. Along the way we comment
on further developments and generalizations of the subject and point to the
relevant literature.Comment: 40 pages, invited contribution to Living Reviews in Relativity. v2:
improvements in the text and references adde
The Hilbert Series of the One Instanton Moduli Space
The moduli space of k G-instantons on R^4 for a classical gauge group G is
known to be given by the Higgs branch of a supersymmetric gauge theory that
lives on Dp branes probing D(p + 4) branes in Type II theories. For p = 3,
these (3 + 1) dimensional gauge theories have N = 2 supersymmetry and can be
represented by quiver diagrams. The F and D term equations coincide with the
ADHM construction. The Hilbert series of the moduli spaces of one instanton for
classical gauge groups is easy to compute and turns out to take a particularly
simple form which is previously unknown. This allows for a G invariant
character expansion and hence easily generalisable for exceptional gauge
groups, where an ADHM construction is not known. The conjectures for
exceptional groups are further checked using some new techniques like sewing
relations in Hilbert Series. This is applied to Argyres-Seiberg dualities.Comment: 43 pages, 22 figure
Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells
Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both “public” and “private” CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation
Non-minimal coupling of the Higgs boson to curvature in an inflationary universe
In the absence of new physics around 10^10 GeV, the electroweak vacuum is at best metastable. This represents a major challenge for high scale in ationary models as, during the early rapid expansion of the universe, it seems difficult to understand how the Higgs vacuum would not decay to the true lower vacuum of the theory with catas- trophic consequences if inflation took place at a scale above 10^10 GeV. In this paper we show that the non-minimal coupling of the Higgs boson to curvature could solve this problem by generating a direct coupling of the Higgs boson to the inflationary potential thereby stabilizing the electroweak vacuum. For specific values of the Higgs field initial condition and of its non-minimal coupling, inflation can drive the Higgs field to the electroweak vacuum quickly during inflation
Holographic c-theorems in arbitrary dimensions
We re-examine holographic versions of the c-theorem and entanglement entropy
in the context of higher curvature gravity and the AdS/CFT correspondence. We
select the gravity theories by tuning the gravitational couplings to eliminate
non-unitary operators in the boundary theory and demonstrate that all of these
theories obey a holographic c-theorem. In cases where the dual CFT is
even-dimensional, we show that the quantity that flows is the central charge
associated with the A-type trace anomaly. Here, unlike in conventional
holographic constructions with Einstein gravity, we are able to distinguish
this quantity from other central charges or the leading coefficient in the
entropy density of a thermal bath. In general, we are also able to identify
this quantity with the coefficient of a universal contribution to the
entanglement entropy in a particular construction. Our results suggest that
these coefficients appearing in entanglement entropy play the role of central
charges in odd-dimensional CFT's. We conjecture a new c-theorem on the space of
odd-dimensional field theories, which extends Cardy's proposal for even
dimensions. Beyond holography, we were able to show that for any
even-dimensional CFT, the universal coefficient appearing the entanglement
entropy which we calculate is precisely the A-type central charge.Comment: 62 pages, 4 figures, few typo's correcte
Unitarity and the Holographic S-Matrix
The bulk S-Matrix can be given a non-perturbative definition in terms of the
flat space limit of AdS/CFT. We show that the unitarity of the S-Matrix, ie the
optical theorem, can be derived by studying the behavior of the OPE and the
conformal block decomposition in the flat space limit. When applied to
perturbation theory in AdS, this gives a holographic derivation of the cutting
rules for Feynman diagrams.
To demonstrate these facts we introduce some new techniques for the analysis
of conformal field theories. Chief among these is a method for conglomerating
local primary operators to extract the contribution of an individual primary in
their OPE. This provides a method for isolating the contribution of specific
conformal blocks which we use to prove an important relation between certain
conformal block coefficients and anomalous dimensions. These techniques make
essential use of the simplifications that occur when CFT correlators are
expressed in terms of a Mellin amplitude.Comment: 33+12 pages, 6 figures; v2: typos corrected, some clarifications
adde
Skyrmions, Skyrme stars and black holes with Skyrme hair in five spacetime dimension
We consider a class of generalizations of the Skyrme model to five spacetime dimensions (d = 5), which is de fined in terms of an O (5) sigma model. A special ansatz for the Skyrme field allows angular momentum to be present and equations of motion with a radial dependence only. Using it, we obtain: 1) everywhere regular solutions describing localised energy lumps (Skyrmions); 2) Self-gravitating, asymptotically flat, everywhere non-singular solitonic solutions (Skyrme stars), upon minimally coupling the model to Einstein's gravity; 3) both static and spinning black holes with Skyrme hair, the latter with rotation in two orthogonal planes, with both angular momenta of equal magnitude. In the absence of gravity we present an analytic solution that satisfies a BPS-type bound and explore numerically some of the non-BPS solutions. In the presence of gravity, we contrast the solutions to this model with solutions to a complex scalar field model, namely boson stars and black holes with synchronised hair. Remarkably, even though the two models present key differences, and in particular the Skyrme model allows static hairy black holes, when introducing rotation, the synchronisation condition becomes mandatory, providing further evidence for its generality in obtaining rotating hairy black holes
Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report
Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA
Assessment of explanatory models of mental illness: effects of patient and interviewer characteristics
Background: Explanatory models (EMs) refer to patients’ causal attributions of illness and have been shown to affect treatment preference and outcome. Reliable and valid assessment of EMs may be hindered by interviewer and respondent disparities on certain demographic characteristics, such as ethnicity. The present study examined (a) whether ethnic minority patients reported different EMs to ethnically similar interviewers in comparison with those with a different ethnicity, and (b) whether this effect was related to respondents’ social desirability, the perceived rapport with the interviewer and level of uncertainty toward their EMs. Methods: A total of 55 patients of Turkish and Moroccan origins with mood and anxiety disorders were randomly assigned to ethnically similar or dissimilar interviewers. EMs were assessed, using a semi-structured interview, across 11 different categories of causes. Results: Participants who were interviewed by an ethnically similar interviewer perceived interpersonal, victimization and religious/mystical causes as more important, whereas interviews by ethnically dissimilar interviewers generated higher scores on medical causes. These effects were not mediated by the perceived rapport with the interviewer, and social desirability had a modest impact on the results. Higher uncertainty among participants toward medical and religious/mystical causes seemed to be associated with greater adjustment in the report of these EMs. Conclusion: The findings have significant implications for interviewer selection in epidemiological research and clinical practice
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