Conditioned spin and charge dynamics of a single electron quantum dot

In this article we describe the incoherent and coherent spin and charge dynamics of a single electron quantum dot. We use a stochastic master equation to model the state of the system, as inferred by an observer with access to only the measurement signal. Measurements obtained during an interval of time contribute, by a past quantum state analysis, to our knowledge about the system at any time $t$ within that interval. Such analysis permits precise estimation of physical parameters, and we propose and test a modification of the classical Baum-Welch parameter re-estimation method to systems driven by both coherent and incoherent processes.Comment: 9 pages, 9 figure

Role of MBNL1 and RBFOX1 in splicing regulation.

<p>(<b>A–C</b>) <b>A.</b> Venn diagram representing the overlap of hits obtained by knocking down MBNL1 and RBFOX1 in the HFN embryonic muscle cell line. In panels <b>B</b> and <b>C</b>, Venn diagrams are presented to illustrate events coregulated by MBNL1 and RBFOX1 that are mis-spliced in embryonic DM1 lines or and DM1 adult samples. The number and identity of the ASEs in each category are indicated. Gene names in bold indicate that the splicing shift for those ASEs occur in the reverse direction to the DM1 mis-splice.</p

Alternative splicing events co-regulated by MBNL1 and RBFOX1.

<p>Genes in bold are mis-spliced in DM1 tissues.</p><p>Alternative splicing events co-regulated by MBNL1 and RBFOX1.</p

Splicing defects in a mouse strain expressing CUG repeats.

<p>Total RNA from muscle tissues of transgenic C57BL6 mice expressing 600 and 1200 CUG-repeats were screened for alternative splicing defects. We interrogated 172 ASEs in genes reported to be susceptible to changes in HSA^LR and MBNL knockout mice <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107324#pone.0107324-Du1" target="_blank">[14]</a>. Using a false discovery rate threshold (<i>q-</i>value) of 0.05 and |ΔΨ| greater than 5 percentage points, we identified 24 ASEs in CUG1200 (black bars) that are significantly different from WT (white bars). Changes that were also significant in CUG600 (grey bars) are indicated with an asterisk. Results are presented in histograms by order of significance based on <i>q</i>-values.</p

Splicing defects in DM1 patient tissues.

<p>(<b>A–B</b>) <b>A.</b> Ψ values for ten misspliced ASEs are represented as histograms for 4 adult controls (white bars) and 5 DM1 patients (black bars). Error bars represent standard deviations for each ASE. Hits were defined as changes displaying <i>q</i> values <0.05 and |ΔΨ| >5%. <b>B.</b> Sample UCSC Genome Browser (<a href="http://genome.ucsc.edu" target="_blank">http://genome.ucsc.edu</a>) adaptation showing the chromosome 19 region harboring human insulin receptor, INSR. Top image shows reported full-length RefSeq transcripts, the targeted ASE is boxed and shown in detail in the bottom image. The positions and names of the primers used for mRNA amplification by RT-PCR are shown above the transcripts. Links to transcript maps and primer positions for all human ASEs studied here can be found at <a href="http://palace.lgfus.ca/data/related/2073/odgene_/" target="_blank">http://palace.lgfus.ca/data/related/2073/odgene_/</a>.</p

Differences in alternative splicing events (ASEs) when normal adult muscle cell lines are compared to normal embryonic muscle cell lines.

<p>(<b>A–C</b>) <b>A.</b> Histograms representing the four ASEs (<i>ABCB8</i>, <i>C10orf58</i>, <i>ACTN1</i>, <i>ENO3</i>) that are differentially spliced when normal embryonic cell lines (white bars) are compared to normal adult cell lines (black bars). <b>B.</b> Venn diagram representing hits when the three embryonic cell line categories (ST-750, ST-1200, and ST-3500) were compared to normal fetal cell lines. <b>C.</b> Histograms representing Ψ values in the normal fetal (white bars), ST-750 (light grey bars), ST-1200 (dark grey bars) and ST-3500 cells (black bars). Only the top 27 of the 50 splicing alterations seen in ST-3500 (<i>q</i> ≤ 0.05) are shown which also include all ST-750 (†) and ST-1200 (*) hits (respective <i>q</i>≤0.05) relative to normal fetal cells.</p

Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas

<div><p>Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein–Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS.</p></div

Involvement of EBNA1 in alternative splicing.

<p><b>(A)</b> Immunoblotting analysis using anti-HA antibody for the detection of EBNA1-HA-FLAG protein in cell lysates from a stable HEK293T cell line expressing EBNA1. Control HEK293T cells (T(-)) were also used in this assay. <b>(B)</b> List of ASEs common to EBVaGC and EBNA1-expressing cells. <b>(C)</b> Example of a modified ASE following the expression of EBNA1. Overview of the two isoforms encoded by <i>OSBPL9</i> gene. Exons are represented in red and the intervening introns are displayed as thin black lines (not to scale). The primers used to detect the isoforms by RT-PCR assays are presented in gray and the sizes of the expected amplicons are also specified (top panel). RT-PCR reactions were performed on control cells (T(-)) and cells expressing EBNA1 using specific primers to detect both isoforms of the transcripts encoded by the <i>OSBPL9</i> gene. Capillary electrophoresis assays were performed and an image of the detected reaction products is presented (lower panel). The positions of the expected amplicons are shown by arrows. <b>(D)</b> Mass spectrometry analysis of nuclear proteins interacting with EBNA1. The average ratios (MS/MS counts) of the EBNA1 affinity purification-mass spectrometry experiments were plotted versus the total intensities. <b>(E)</b> Validation of the interaction between EBNA1 and splicing factor hnRNP H1. Nuclear extracts were immunoprecipitated with anti-HA. The extracts (input) and immunoprecipitates (IP-EBNA1) were analyzed by immunoblotting and probed with the indicated antibodies.</p

Validation of ASEs dysregulated in gastric cancer.

<p><b>(A)</b> Overview of the two isoforms encoded by <i>PTBP2</i> and <i>TPM1</i> genes. The exons are represented in red and the intervening introns are displayed as thin black lines (not to scale). The primers used to detect the isoforms by RT-PCR are presented in gray and the sizes of the expected amplicons are also presented. <b>(B)</b> The cDNAs acquired from gastric tissues were analyzed by PCR using specific primers to detect both isoforms of the transcripts encoded by the <i>PTBP2</i> and <i>TPM1</i> genes. Capillary electrophoregrams of the PCR reactions are presented. The positions and the amplitude of the detected amplicons are emphasized by red boxes. The positions of the internal markers are also indicated. <b>(C)</b> Correlation between PSI values obtained from RNA-Seq and RT-PCR data. The analysis was performed on seven selected ASEs (CAPN14, PLA2G4F, PTBP2, S100A1, SLC52A1, SOGA2, and TPM1). In all cases, the changes in AS levels detected by RT-PCR and the ones revealed through transcriptome sequencing displayed high levels of correlation (R = 0.93).</p

Global profiling of alternative splicing event modifications in EBVaGC.

<p>Hierarchical cluster and heatmap representation of alternative splicing events modified in EBVaGC tissues. The row at the top shows the clustering information in the form of a dendogram and the similarity relationships among the alternative splicing events and patients. The column at the left of the heatmap shows the different clusters associated with the PSI values. The heatmap shows PSI values for EBVaGC tissues (TEBV, Tumors with EBV, <i>in red</i>) compared with normal tissues (NNoV, Normal tissues, no virus, <i>in green</i>).</p