3,307 research outputs found
Kaluza-Klein Holography
We construct a holographic map between asymptotically AdS_5 x S^5 solutions
of 10d supergravity and vacuum expectation values of gauge invariant operators
of the dual QFT. The ingredients that enter in the construction are (i) gauge
invariant variables so that the KK reduction is independent of any choice of
gauge fixing; (ii) the non-linear KK reduction map from 10 to 5 dimensions
(constructed perturbatively in the number of fields); (iii) application of
holographic renormalization. A non-trivial role in the last step is played by
extremal couplings. This map allows one to reliably compute vevs of operators
dual to any KK fields. As an application we consider a Coulomb branch solution
and compute the first two non-trivial vevs, involving operators of dimension 2
and 4, and reproduce the field theory result, in agreement with
non-renormalization theorems. This constitutes the first quantitative test of
the gravity/gauge theory duality away from the conformal point involving a vev
of an operator dual to a KK field (which is not one of the gauged supergravity
fields).Comment: 47 pages, v2: minor improvements, version to appear in JHE
The Computational Power of Minkowski Spacetime
The Lorentzian length of a timelike curve connecting both endpoints of a
classical computation is a function of the path taken through Minkowski
spacetime. The associated runtime difference is due to time-dilation: the
phenomenon whereby an observer finds that another's physically identical ideal
clock has ticked at a different rate than their own clock. Using ideas
appearing in the framework of computational complexity theory, time-dilation is
quantified as an algorithmic resource by relating relativistic energy to an
th order polynomial time reduction at the completion of an observer's
journey. These results enable a comparison between the optimal quadratic
\emph{Grover speedup} from quantum computing and an speedup using
classical computers and relativistic effects. The goal is not to propose a
practical model of computation, but to probe the ultimate limits physics places
on computation.Comment: 6 pages, LaTeX, feedback welcom
Tissue-specific expression of a human Polymorphic Epithelial mucin (MUCI) in transgenic mice
The human MUC1 gene codes for the core protein of a mucin which is expressed by glandular epithelia and the carcinomas which develop from these tissues. The core protein is aberrantly glycosylated in cancers, and some antibodies show specificity in their reactions with the cancer-associated mucin, which also contains epitopes recognized by T-cells from breast and pancreatic cancer patients. For evaluating the potential use of mucin-reactive antibodies and mucin-based immunogens in cancer patients, a mouse model, expressing the MUC1 gene product PEM (polymorphic epithelial mucin) as a self antigen, would be extremely useful. To this end, we have developed transgenic mouse strains expressing the human MUC1 gene product in a tissue-specific manner. The TG4 mouse strain was established using a 40-kilobase fragment containing 4.5 kilobases of 5\u27 and 27 kilobases of 3\u27 flanking sequence. The TG18 strain was developed using a 10.6-kilobase SacII fragment from the 40-kilobase fragment; this fragment contained 1.6 kilobases of 5\u27 sequence and 1.9 kilobases of 3\u27 flanking sequence. Both strains showed tissue specificity of expression of the MUC1 gene, which was very similar to the profile of expression seen in human tissues. The antibody SM-3 is directed to a core protein epitope, which is selectively exposed in breast cancers and which shows a more restricted distribution on normal human tissues. It was established that the distribution of the SM-3 epitope of PEM in the tissues of the transgenic mice is similar to that seen in humans. The transgenic mouse strains described here should form the basis for the development of a preclinical model for the evaluation of PEM-based antigens and of antibodies directed to PEM in cancer therapy
Immunisation with ‘naïve' syngeneic dendritic cells protects mice from tumour challenge
Dendritic cells (DCs) ‘pulsed' with an appropriate antigen may elicit an antitumour immune response in mouse models. However, while attempting to develop a DC immunotherapy protocol for the treatment of breast cancer based on the tumour-associated MUC1 glycoforms, we found that unpulsed DCs can affect tumour growth. Protection from RMA-MUC1 tumour challenge was achieved in C57Bl/6 MUC1 transgenic mice by immunising with syngeneic DCs pulsed with a MUC1 peptide. However, unpulsed DCs gave a similar level of protection, making it impossible to evaluate the effect of immunisation of mice with DCs pulsed with the specific peptide. Balb/C mice could also be protected from tumour challenge by immunisation with unpulsed DCs prior to challenge with murine mammary tumour cells (410.4) or these cells transfected with MUC1 (E3). Protection was achieved with as few as three injections of 50 000 naïve DCs per mouse per week, was not dependent on injection route, and was not specific to cell lines expressing human MUC1. However, the use of Rag2-knockout mice demonstrated that the adaptive immune response was required for tumour rejection. Injection of unpulsed DCs into mice bearing the E3 tumour slowed tumour growth. In vitro, production of IFN-γ and IL-4 was increased in splenic cells isolated from mice immunised with DCs. Depleting CD4 T cells in vitro partially decreased cytokine production by splenocytes, but CD8 depletion had no effect. This paper shows that naïve syngeneic DCs may induce an antitumour immune response and has implications for DC immunotherapy preclinical and clinical trials
Efficient Immortalization of luminal Epithelial Cells from Human Mammary gland by introduction of Simian virus 40 large Tumor antigen with a Recombinant Retrovirus
When defined in terms of markers for normal cell lineages, most invasive breast cancer cells correspond to the phenotype of the common luminal epithelial cell found in the terminal ductal lobular units. Luminal epithelial cells cultured from milk, which have limited proliferative potential, have now been immortalized by introducing the gene encoding simian virus 40 large tumor (T) antigen. Infection with a recombinant retrovirus proved to be 50-100 times more efficient than calcium phosphate transfection, and of the 17 cell lines isolated, only 5 passed through a crisis period as characterized by cessation of growth. When characterized by immunohistochemical staining with monoclonal antibodies, 14 lines showed features of luminal epithelial cells and of these, 7 resembled the common luminal epithelial cell type in the profile of keratins expressed. These cells express keratins 7, 8, 18, and 19 homogeneously and do not express keratin 14 or vimentin; a polymorphic epithelial mucin produced in vivo by luminal cells is expressed heterogeneously and the pattern of fibronectin staining is punctate. Although the cell lines have a reduced requirement for added growth factors, they do not grow in agar or produce tumors in the nude mouse. When the v-Ha-ras oncogene was introduced into two of the cell lines by using a recombinant retrovirus, most of the selected clones senesced, but one entered crisis and emerged after 3 months as a tumorigenic cell line
Anatomy of bubbling solutions
We present a comprehensive analysis of holography for the bubbling solutions
of Lin-Lunin-Maldacena. These solutions are uniquely determined by a coloring
of a 2-plane, which was argued to correspond to the phase space of free
fermions. We show that in general this phase space distribution does not
determine fully the 1/2 BPS state of N=4 SYM that the gravitational solution is
dual to, but it does determine it enough so that vevs of all single trace 1/2
BPS operators in that state are uniquely determined to leading order in the
large N limit. These are precisely the vevs encoded in the asymptotics of the
LLM solutions. We extract these vevs for operators up to dimension 4 using
holographic renormalization and KK holography and show exact agreement with the
field theory expressions.Comment: 67 pages, 6 figures; v2: typos corrected, refs added; v3: expanded
explanations, more typos correcte
A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1
MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the luminal surface of glandular epithelium. It is highly expressed in an underglycosylated form on carcinomas and metastatic lesions and is, therefore, a potential target for immunotherapy of cancer. The monoclonal antibody HMFG1 binds the linear core protein sequence, PDTR, contained within the immunodominant domain of the tandem repeat of MUC1. The efficacy of murine and humanized HMFG1 (Ab1) used as an anti-idiotypic vaccine was examined in mice transgenic for human MUC1 (MUC1.Tg) challenged with murine epithelial tumour cells transfected with human MUC1. Humoral idiotypic cascade through Ab2 and Ab3 antibodies was observed in MUC1.Tg mice following multiple antibody inoculations in the presence of adjuvant. Impaired tumour growth at day 35 and highest Ab3 levels were found in mice that had received mHMFG1 with RAS adjuvant. However, comparison of Ab3 levels in individual mice with tumour size in all treatment groups did not show a correlation between smaller tumours and increased levels of anti-idiotype antibody. This suggests that the anti-tumour effects of anti-idiotype vaccination are not solely related to the induction of idiotypic antibody cascades and probably involve other mechanisms. © 2000 Cancer Research Campaig
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