1,318 research outputs found

    Holographic Anyons in the ABJM Theory

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    We consider the holographic anyons in the ABJM theory from three different aspects of AdS/CFT correspondence. First, we identify the holographic anyons by using the field equations of supergravity, including the Chern-Simons terms of the probe branes. We find that the composite of Dp-branes wrapped over CP3 with the worldvolume magnetic fields can be the anyons. Next, we discuss the possible candidates of the dual anyonic operators on the CFT side, and find the agreement of their anyonic phases with the supergravity analysis. Finally, we try to construct the brane profile for the holographic anyons by solving the equations of motion and Killing spinor equations for the embedding profile of the wrapped branes. As a by product, we find a BPS spiky brane for the dual baryons in the ABJM theory.Comment: 1+33 pages, 3 figures; v2 discussion for D4-D6 case added, references added; v3 comments adde

    Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

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    Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

    Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

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    BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p

    Structure and mechanism of human DNA polymerase η

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    The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

    More on the Nambu-Poisson M5-brane Theory: Scaling limit, background independence and an all order solution to the Seiberg-Witten map

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    We continue our investigation on the Nambu-Poisson description of M5-brane in a large constant C-field background (NP M5-brane theory) constructed in Refs.[1, 2]. In this paper, the low energy limit where the NP M5-brane theory is applicable is clarified. The background independence of the NP M5-brane theory is made manifest using the variables in the BLG model of multiple M2-branes. An all order solution to the Seiberg-Witten map is also constructed.Comment: expanded explanations, minor corrections and typos correcte

    To respond or not to respond - a personal perspective of intestinal tolerance

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    For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

    A simple statistical model for prediction of acute coronary syndrome in chest pain patients in the emergency department

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    BACKGROUND: Several models for prediction of acute coronary syndrome (ACS) among chest pain patients in the emergency department (ED) have been presented, but many models predict only the likelihood of acute myocardial infarction, or include a large number of variables, which make them less than optimal for implementation at a busy ED. We report here a simple statistical model for ACS prediction that could be used in routine care at a busy ED. METHODS: Multivariable analysis and logistic regression were used on data from 634 ED visits for chest pain. Only data immediately available at patient presentation were used. To make ACS prediction stable and the model useful for personnel inexperienced in electrocardiogram (ECG) reading, simple ECG data suitable for computerized reading were included. RESULTS: Besides ECG, eight variables were found to be important for ACS prediction, and included in the model: age, chest discomfort at presentation, symptom duration and previous hypertension, angina pectoris, AMI, congestive heart failure or PCI/CABG. At an ACS prevalence of 21% and a set sensitivity of 95%, the negative predictive value of the model was 96%. CONCLUSION: The present prediction model, combined with the clinical judgment of ED personnel, could be useful for the early discharge of chest pain patients in populations with a low prevalence of ACS

    Heterochronic faecal transplantation boosts gut germinal centres in aged mice

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    Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system, however it is not clear if there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli

    Search for the standard model Higgs boson at LEP

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