Analysis of 83mKr prompt scintillation signals in the PIXeY detector

Prompt scintillation signals from 83mKr calibration sources are a useful metric to calibrate the spatial variation of light collection efficiency and electric field magnitude of a two phase liquid-gas xenon time projection chamber. Because 83mKr decays in two steps, there are two prompt scintillation pulses for each calibration event, denoted S1a and S1b. We study the ratio of S1b to S1a signal sizes in the Particle Identification in Xenon at Yale (PIXeY) experiment and its dependence on the time separation between the two signals (Δ t), notably its increase at low Δ t. In PIXeY data, the Δ t dependence of S1b/S1a is observed to exhibit two exponential components: one with a time constant of 0.05 ± 0.02 μ s, which can be attributed to processing effects and pulse overlap and one with a time constant of 10.2 ± 2.2 μs that increases in amplitude with electric drift field, the origin of which is not yet understood

The CMB and the measure of the multiverse

In the context of eternal inflation, cosmological predictions depend on the choice of measure to regulate the diverging spacetime volume. The spectrum of inflationary perturbations is no exception, as we demonstrate by comparing the predictions of the fat geodesic and causal patch measures. To highlight the effect of the measure---as opposed to any effects related to a possible landscape of vacua---we take the cosmological model, including the model of inflation, to be fixed. We also condition on the average CMB temperature accompanying the measurement. Both measures predict a 1-point expectation value for the gauge-invariant Newtonian potential, which takes the form of a (scale-dependent) monopole, in addition to a related contribution to the 3-point correlation function, with the detailed form of these quantities differing between the measures. However, for both measures both effects are well within cosmic variance. Our results make clear the theoretical relevance of the measure, and at the same time validate the standard inflationary predictions in the context of eternal inflation.Comment: 28 pages; v2: reference added, some clarification

Tubulohelical membrane arrays: From the initial observation to the elucidation of nanophysical properties and cellular function

Lipids undergo self-assembly to form ordered nonlamellar, nanoperiodic arrays both in vitro and in vivo. While engineering of such membrane arrays for technical devices is envisaged, we know little about their cellular function. Do they represent building blocks of an inherent cellular nanotechnology? Prospects for answering this question could be improved if the nanophysical properties of the membrane arrays could be studied in the context of specific cellular functions. Therefore, we draw attention to exceptional complex membrane arrays found in the renal epithelial cell line PtK2 that could provide perfect conditions for both biophysical and cell functional studies. The so-called tubulohelical membrane arrays (TUHMAs) combine nanoperiodicity of lipid membranes with that of helix-like proteinaceous core structures. Strikingly, they show several characteristics of dynamic, microtubule-associated single organelles. Our initial data indicate that TUHMA formation occurs in the depth of the cytoplasm under participation of cytoplasmic nucleoporins. Once matured, they may fuse with the nuclear membrane in polarized positions, either perpendicularly or in parallel to the nucleus. As a starting point for the initiation of functional studies we found a connection between TUHMAs and primary cilia, indicated by immunolabeling patterns of detyrosynated tubulin and cytoplasmic nucleoporins. We discuss these observations in the context of the ciliary cycle and of the specific requirement of ciliated renal epithelial cells for oriented cell division. Finally, we raise the question of whether putative nanooptical properties of TUHMAs could serve for communicating orientation between dividing cells

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

An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer

<p>Abstract</p> <p>Background</p> <p>Patients diagnosed with lung adenocarcinoma (AD) and squamous cell carcinoma (SCC), two major histologic subtypes of lung cancer, currently receive similar standard treatments, but resistance to adjuvant chemotherapy is prevalent. Identification of differentially expressed genes marking AD and SCC may prove to be of diagnostic value and help unravel molecular basis of their histogenesis and biologies, and deliver more effective and specific systemic therapy.</p> <p>Methods</p> <p>MiRNA target genes were predicted by union of miRanda, TargetScan, and PicTar, followed by screening for matched gene symbols in NCBI human sequences and Gene Ontology (GO) terms using the PANTHER database that was also used for analyzing the significance of biological processes and pathways within each ontology term. Microarray data were extracted from Gene Expression Omnibus repository, and tumor subtype prediction by gene expression used Prediction Analysis of Microarrays.</p> <p>Results</p> <p>Computationally predicted target genes of three microRNAs, miR-34b/34c/449, that were detected in human lung, testis, and fallopian tubes but not in other normal tissues, were filtered by representation of GO terms and their ability to classify lung cancer subtypes, followed by a meta-analysis of microarray data to classify AD and SCC. Expression of a minimal set of 17 predicted miR-34b/34c/449 target genes derived from the developmental process GO category was identified from a training set to classify 41 AD and 17 SCC, and correctly predicted in average 87% of 354 AD and 82% of 282 SCC specimens from total 9 independent published datasets. The accuracy of prediction still remains comparable when classifying 103 AD and 79 SCC samples from another 4 published datasets that have only 14 to 16 of the 17 genes available for prediction (84% and 85% for AD and SCC, respectively). Expression of this signature in two published datasets of epithelial cells obtained at bronchoscopy from cigarette smokers, if combined with cytopathology of the cells, yielded 89–90% sensitivity of lung cancer detection and 87–90% negative predictive value to non-cancer patients.</p> <p>Conclusion</p> <p>This study focuses on predicted targets of three lung-enriched miRNAs, compares their expression patterns in lung cancer by their GO terms, and identifies a minimal set of genes differentially expressed in AD and SCC, followed by validating this gene signature in multiple published datasets. Expression of this gene signature in bronchial epithelial cells of cigarette smokers also has a great sensitivity to predict the patients having lung cancer if combined with cytopathology of the cells.</p

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Evaluation of the proliferation markers Ki-67/MIB-1, mitosin, survivin, pHH3, and DNA topoisomerase IIα in human anaplastic astrocytomas - an immunohistochemical study

<p>Abstract</p> <p>Background</p> <p>Histological malignancy grading of astrocytomas can be challenging despite criteria given by the World Health Organisation (WHO). Grading is fundamental for optimal prognostication and treatment, and additional biomarkers are needed to support the histopathological diagnosis. Estimation of proliferative activity has gained much enthusiasm, and the present study was designed to evaluate and compare novel immunohistochemical proliferative markers in human anaplastic astrocytomas.</p> <p>Methods</p> <p>Proliferative activity was determined in twenty-seven cases with antibodies reactive against the Ki-67 antigen, mitosin, survivin, pHH3, and DNA topoisomerase IIα, and they were mutually compared as well as related to mitotic activity.</p> <p>Results</p> <p>The markers correlated well with each other, but poorly with mitoses, probably because of small and squeezed tumour samples, in which identification of mitoses can be difficult. Positive association to overall survival was observed as well.</p> <p>Conclusions</p> <p>Our data show that these markers may assist significantly in the evaluation of proliferative activity in anaplastic astrocytomas and even have prognostic value.</p

Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue

Aims/hypothesis Increasing the expression of the brown adipose tissue-specific gene uncoupling protein-1 (Ucp1) is a potential target for treating obesity. We investigated the role of DNA methylation and histone modification in Ucp1 expression in adipose cell lines and ex vivo murine adipose tissues. Methods Methylation state of the Ucp1 enhancer was studied using bisulphite mapping in murine adipose cell lines, and tissue taken from cold-stressed mice, coupled with functional assays of the effects of methylation and demethylation of the Ucp1 promoter on gene expression and nuclear protein binding. Results We show that demethylation of the Ucp1 promoter by 5-aza-deoxycytidine increases Ucp1 expression while methylation of Ucp1 promoter–reporter constructs decreases expression. Brown adipose tissue-specific Ucp1 expression is associated with decreased CpG dinucleotide methylation of the Ucp1 enhancer. The lowest CpG dinucleotide methylation state was found in two cyclic AMP response elements (CRE3, CRE2) in the Ucp1 promoter and methylation of the CpG in CRE2, but not CRE3 decreased nuclear protein binding. Chromatin immunoprecipitation assays revealed the presence of the silencing DiMethH3K9 modification on the Ucp1 enhancer in white adipose tissue and the appearance of the active TriMethH3K4 mark at the Ucp1 promoter in brown adipose tissue in response to a cold environment. Conclusions/interpretation The results demonstrate that CpG dinucleotide methylation of the Ucp1 enhancer exhibits tissue-specific patterns in murine tissue and cell lines and suggest that adipose tissue-specific Ucp1 expression involves demethylation of CpG dinucleotides found in regulatory CREs in the Ucp1 enhancer, as well as modification of histone tails