Fast simulation of new coins from old

Let S\subset (0,1). Given a known function f:S\to (0,1), we consider the problem of using independent tosses of a coin with probability of heads p (where p\in S is unknown) to simulate a coin with probability of heads f(p). We prove that if S is a closed interval and f is real analytic on S, then f has a fast simulation on S (the number of p-coin tosses needed has exponential tails). Conversely, if a function f has a fast simulation on an open set, then it is real analytic on that set.Comment: Published at http://dx.doi.org/10.1214/105051604000000549 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Random soups, carpets and fractal dimensions

We study some properties of a class of random connected planar fractal sets induced by a Poissonian scale-invariant and translation-invariant point process. Using the second-moment method, we show that their Hausdorff dimensions are deterministic and equal to their expectation dimension. We also estimate their low-intensity limiting behavior. This applies in particular to the "conformal loop ensembles" defined via Poissonian clouds of Brownian loops for which the expectation dimension has been computed by Schramm, Sheffield and Wilson.Comment: To appear in J. London Math. So

Channel Uncertainty in Ultra Wideband Communication Systems

Wide band systems operating over multipath channels may spread their power over bandwidth if they use duty cycle. Channel uncertainty limits the achievable data rates of power constrained wide band systems; Duty cycle transmission reduces the channel uncertainty because the receiver has to estimate the channel only when transmission takes place. The optimal choice of the fraction of time used for transmission depends on the spectral efficiency of the signal modulation. The general principle is demonstrated by comparing the channel conditions that allow different modulations to achieve the capacity in the limit. Direct sequence spread spectrum and pulse position modulation systems with duty cycle achieve the channel capacity, if the increase of the number of channel paths with the bandwidth is not too rapid. The higher spectral efficiency of the spread spectrum modulation lets it achieve the channel capacity in the limit, in environments where pulse position modulation with non-vanishing symbol time cannot be used because of the large number of channel paths

Down-Regulation of the Interferon Signaling Pathway in T Lymphocytes from Patients with Metastatic Melanoma

BACKGROUND: Dysfunction of the immune system has been documented in many types of cancers. The precise nature and molecular basis of immune dysfunction in the cancer state are not well defined. METHODS AND FINDINGS: To gain insights into the molecular mechanisms of immune dysfunction in cancer, gene expression profiles of pure sorted peripheral blood lymphocytes from 12 patients with melanoma were compared to 12 healthy controls. Of 25 significantly altered genes in T cells and B cells from melanoma patients, 17 are interferon (IFN)-stimulated genes. These microarray findings were further confirmed by quantitative PCR and functional responses to IFNs. The median percentage of lymphocytes that phosphorylate STAT1 in response to interferon-α was significantly reduced (Δ = 16.8%; 95% confidence interval, 0.98% to 33.35%) in melanoma patients (n = 9) compared to healthy controls (n = 9) in Phosflow analysis. The Phosflow results also identified two subgroups of patients with melanoma: IFN-responsive (33%) and low-IFN-response (66%). The defect in IFN signaling in the melanoma patient group as a whole was partially overcome at the level of expression of IFN-stimulated genes by prolonged stimulation with the high concentration of IFN-α that is achievable only in IFN therapy used in melanoma. The lowest responders to IFN-α in the Phosflow assay also showed the lowest gene expression in response to IFN-α. Finally, T cells from low-IFN-response patients exhibited functional abnormalities, including decreased expression of activation markers CD69, CD25, and CD71; T(H)1 cytokines interleukin-2, IFN-γ, and tumor necrosis factor α, and reduced survival following stimulation with anti-CD3/CD28 antibodies compared to controls. CONCLUSIONS: Defects in interferon signaling represent novel, dominant mechanisms of immune dysfunction in cancer. These findings may be used to design therapies to counteract immune dysfunction in melanoma and to improve cancer immunotherapy

Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

<p>Abstract</p> <p>Background</p> <p>Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome.</p> <p>Methods</p> <p>We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays.</p> <p>Results</p> <p>Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%.</p> <p>We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the <it>SLC45A3-ELK4 </it>e4-e2 TIC to <it>ERG</it>-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines.</p> <p>Conclusions</p> <p>Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as <it>MSMB-NCOA4</it>, may play functional roles in cancer.</p

Random soups, carpets and fractal dimensions

To appear in J. London Math. Soc.We study some properties of a class of random connected planar fractal sets induced by a Poissonian scale-invariant and translation-invariant point process. Using the second-moment method, we show that their Hausdorff dimensions are deterministic and equal to their expectation dimension. We also estimate their low-intensity limiting behavior. This applies in particular to the “conformal loop ensembles” defined via Poissonian clouds of Brownian loops for which the expectation dimension has been computed by Schramm, Sheffield and Wilson