Correlation function of null polygonal Wilson loops with local operators

We consider the correlator of a light-like polygonal Wilson loop with n cusps with a local operator (like the dilaton or the chiral primary scalar) in planar N =4 super Yang-Mills theory. As a consequence of conformal symmetry, the main part of such correlator is a function F of 3n-11 conformal ratios. The first non-trivial case is n=4 when F depends on just one conformal ratio \zeta. This makes the corresponding correlator one of the simplest non-trivial observables that one would like to compute for generic values of the `t Hooft coupling \lambda. We compute F(\zeta,\lambda) at leading order in both the strong coupling regime (using semiclassical AdS5 x S5 string theory) and the weak coupling regime (using perturbative gauge theory). Some results are also obtained for polygonal Wilson loops with more than four edges. Furthermore, we also discuss a connection to the relation between a correlator of local operators at null-separated positions and cusped Wilson loop suggested in arXiv:1007.3243.Comment: 36 pages, 2 figure

On semiclassical approximation for correlators of closed string vertex operators in AdS/CFT

We consider the 2-point function of string vertex operators representing string state with large spin in AdS_5. We compute this correlator in the semiclassical approximation and show that it has the expected (on the basis of state-operator correspondence) form of the strong-coupling limit of the 2-point function of single trace minimal twist operators in gauge theory. The semiclassical solution representing the stationary point of the path integral with two vertex operator insertions is found to be related to the large spin limit of the folded spinning string solution by a euclidean continuation, transformation to Poincare coordinates and conformal map from cylinder to complex plane. The role of the source terms coming from the vertex operator insertions is to specify the parameters of the solution in terms of quantum numbers (dimension and spin) of the corresponding string state. Understanding further how similar semiclassical methods may work for 3-point functions may shed light on strong-coupling limit of the corresponding correlators in gauge theory as was recently suggested by Janik et al in arXiv:1002.4613.Comment: 19 pages, 1 figure; minor corrections, references added, footnote below eq. (4.5) adde

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Correlators of Vertex Operators for Circular Strings with Winding Numbers in AdS5xS5

We compute semiclassically the two-point correlator of the marginal vertex operators describing the rigid circular spinning string state with one large spin and one windining number in AdS_5 and three large spins and three winding numbers in S^5. The marginality condition and the conformal invariant expression for the two-point correlator obtained by using an appropriate vertex operator are shown to be associated with the diagonal and off-diagonal Virasoro constraints respectively. We evaluate semiclassically the three-point correlator of two heavy circular string vertex operators and one zero-momentum dilaton vertex operator and discuss its relation with the derivative of the dimension of the heavy circular string state with respect to the string tension.Comment: 16 pages, LaTeX, no figure

GCA in 2d

We make a detailed study of the infinite dimensional Galilean Conformal Algebra (GCA) in the case of two spacetime dimensions. Classically, this algebra is precisely obtained from a contraction of the generators of the relativistic conformal symmetry in 2d. Here we find quantum mechanical realisations of the (centrally extended) GCA by considering scaling limits of certain 2d CFTs. These parent CFTs are non-unitary and have their left and right central charges become large in magnitude and opposite in sign. We therefore develop, in parallel to the usual machinery for 2d CFT, many of the tools for the analysis of the quantum mechanical GCA. These include the representation theory based on GCA primaries, Ward identities for their correlation functions and a nonrelativistic Kac table. In particular, the null vectors of the GCA lead to differential equations for the four point function. The solution to these equations in the simplest case is explicitly obtained and checked to be consistent with various requirements.Comment: 45 pages; v2: 47 pages. Restructured introduction, minor corrections, added references. Journal versio

Feedback between p21 and reactive oxygen production is necessary for cell senescence

The sustained activation of CDKN1A (p21/Waf1/Cip1) by a DNA damage response induces mitochondrial dysfunction and reactive oxygen species (ROS) production via signalling through CDKN1A-GADD45A-MAPK14- GRB2-TGFBR2-TGFbeta in senescing primary human and mouse cells in vitro and in vivo.Enhanced ROS production in senescing cells generates additional DNA damage. Although this damage is repairable and transient, it elevates the average levels of DNA damage response permanently, thus forming a positive feedback loop.This loop is necessary and sufficient to maintain the stability of growth arrest until a ‘point of no return' is reached during establishment of senescence

A nested case–control study of the association of Helicobacter pylori infection with gastric adenocarcinoma in Korea

In a nested case–control study of 86 cases of gastric adenocarcinoma in relation to Helicobactor pylori infection in the Korean Multi-center Cancer Cohort, the H. pylori IgG seropositivity was 83.7% and that of the 344 matched controls was 80.8%, with a matched odds ratio for H. pylori infection of 1.06 (95% CI, 0.80–1.40)

Novel enzyme-linked immunosorbent assay for bivalent ZnT8 autoantibodies

Autoantibodies to zinc transporter 8 (ZnT8A) are a powerful diagnostic or predictive marker in type 1 diabetes. However, the widely used current ZnT8A radioligand binding assay (RBA) has proved to be difficult for many laboratories to implement. The aim of this study was the development and characterization of the performance of a novel fluid-phase ZnT8A enzyme-linked immunosorbent assay (ELISA) in relation to standard RBA in type 1 diabetes. Sera from 114 patients with type 1 diabetes and 140 blinded Islet Autoantibody Standardization Program (IASP2012) samples were studied. The sensitivity of ELISA-ZnT8A is equivalent to or slightly higher than that of conventional RBA with similar specificity. Furthermore, the median SD score using this ELISA was significantly higher than that obtained with RBA (P < 0.0001). Multiple logistic regression analysis revealed that ELISA-ZnT8A positivity was associated with younger age of onset (?20 years; OR 15.91, P = 0.0002), acute-onset form of type 1 diabetes (OR 3.38, P = 0.019), and the presence of IA-2 autoantibodies (OR 3.75, P = 0.014). Furthermore, the levels of ELISA-ZnT8A were associated with the reactivity to ZnT8-325Arg, but not ZnT8-325Trp. We conclude that this nonradioactive bivalent ZnT8A assay has high performance and should facilitate large-scale autoantibody screening. Moreover, these results suggest that the humoral autoimmunity against ZnT8 is related to a high risk of faster development of type 1 diabetes and the ZnT8A levels are associated with the known aa325 variants

Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study

INTRODUCTION: We compared levels of protein and mRNA expression of three members of the claudin (CLDN) family in malignant breast tumours and benign lesions. METHODS: Altogether, 56 sections from 52 surgically resected breast specimens were analyzed for CLDN1, CLDN3 and CLDN4 expression by immunohistochemistry. mRNA was also analyzed using real-time PCR in 17 of the 52 cases. RESULTS: CLDNs were rarely observed exclusively at tight junction structures. CLDN1 was present in the membrane of normal duct cells and in some of the cell membranes from ductal carcinoma in situ, and was frequently observed in eight out of nine areas of apocrine metaplasia, whereas invasive tumours were negative for CLDN1 or it was present in a scattered distribution among such tumour cells (in 36/39 malignant tumours). CLDN3 was present in 49 of the 56 sections and CLDN4 was present in all 56 tissue sections. However, CLDN4 was highly positive in normal epithelial cells and was decreased or absent in 17 out of 21 ductal carcinoma grade 1, in special types of breast carcinoma (mucinous, papillary, tubular) and in areas of apocrine metaplasia. CLDN1 mRNA was downregulated by 12-fold in the sample (tumour) group as compared with the control group using GAPDH as the reference gene. CLDN3 and CLDN4 mRNA exhibited no difference in expression between invasive tumours and surrounding tissue. CONCLUSIONS: The significant loss of CLDN1 protein in breast cancer cells suggests that CLDN1 may play a role in invasion and metastasis. The loss of CLDN4 expression in areas of apocrine metaplasia and in the majority of grade 1 invasive carcinomas also suggests a particular role for this protein in mammary glandular cell differentiation and carcinogenesis

Differentially expressed alternatively spliced genes in Malignant Pleural Mesothelioma identified using massively parallel transcriptome sequencing

<p>Abstract</p> <p>Background</p> <p>Analyses of Expressed Sequence Tags (ESTs) databases suggest that most human genes have multiple alternative splice variants. The alternative splicing of pre-mRNA is tightly regulated during development and in different tissue types. Changes in splicing patterns have been described in disease states. Recently, we used whole-transcriptome shotgun pryrosequencing to characterize 4 malignant pleural mesothelioma (MPM) tumors, 1 lung adenocarcinoma and 1 normal lung. We hypothesized that alternative splicing profiles might be detected in the sequencing data for the expressed genes in these samples.</p> <p>Methods</p> <p>We developed a software pipeline to map the transcriptome read sequences of the 4 MPM samples and 1 normal lung sample onto known exon junction sequences in the comprehensive AceView database of expressed sequences and to count how many reads map to each junction. 13,274,187 transcriptome reads generated by the Roche/454 sequencing platform for 5 samples were compared with 151,486 exon junctions from the AceView database. The exon junction expression index (EJEI) was calculated for each exon junction in each sample to measure the differential expression of alternative splicing events. Top ten exon junctions with the largest EJEI difference between the 4 mesothelioma and the normal lung sample were then examined for differential expression using Quantitative Real Time PCR (qRT-PCR) in the 5 sequenced samples. Two of the differentially expressed exon junctions (ACTG2.aAug05 and CDK4.aAug05) were further examined with qRT-PCR in additional 18 MPM and 18 normal lung specimens.</p> <p>Results</p> <p>We found 70,953 exon junctions covered by at least one sequence read in at least one of the 5 samples. All 10 identified most differentially expressed exon junctions were validated as present by RT-PCR, and 8 were differentially expressed exactly as predicted by the sequence analysis. The differential expression of the AceView exon junctions for the ACTG2 and CDK4 genes were also observed to be statistically significant in an additional 18 MPM and 18 normal lung samples examined using qRT-PCR. The differential expression of these two junctions was shown to successfully classify these mesothelioma and normal lung specimens with high sensitivity (89% and 78%, respectively).</p> <p>Conclusion</p> <p>Whole-transcriptome shotgun sequencing, combined with a downstream bioinformatics pipeline, provides powerful tools for the identification of differentially expressed exon junctions resulting from alternative splice variants. The alternatively spliced genes discovered in the study could serve as useful diagnostic markers as well as potential therapeutic targets for MPM.</p