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

Additional file 2: Table S2. of Transcriptional profiling of differentially vulnerable motor neurons at pre-symptomatic stage in the Smn 2b/- mouse model of spinal muscular atrophy

Table show a list of genes which are differentially expressed between SMAr and SMAv motor neurons when compared to their respective wild-types. (DOCX 113 kb

Additional file 1: Table S1. of Transcriptional profiling of differentially vulnerable motor neurons at pre-symptomatic stage in the Smn 2b/- mouse model of spinal muscular atrophy

Table shows a summary of the sequencing data obtained from the RNAseq analysis, as analysed using Tophat software. Table show the number of reads (reads), the percentage which mapped to a unique location (% unique), the percentage which mapped to a distinct location (% distinct), the number of mapped location (mapped locations), the number of mapped reads (mapped reads) and the percentage of 10.1186/s40478-015-0231-1 reads which were mapped (% mapped) for each of the 8 samples. (DOCX 53 kb

TSA administration decreases neuromuscular junction loss in <i>Smn^2B/-</i> mice.

<p>(<b>A</b>) Confocal micrographs show neuromuscular junctions (NMJs) labelled with antibodies against neurofilament (NF, red), synaptic vesicle protein 2 (SV2, red) and alpha-bungarotoxin (BTX, green). Note that whilst there is widespread NMJ pathology in vehicle treated mice, as evidence by full/partial denervation (white arrowhead/arrow respectively), NF accumulation (yellow arrow) and small, immature post-synaptic endplates, NMJs appear much more healthy in TSA treated mice, as evidenced by a decrease in denervation and NF accumulation, and an increase in post-synaptic size and maturity (scale bar = 50 µm). (<b>B, C</b>) Bar charts show an increase in the percentage of fully occupied endplates in both the transversus abdominis (TVA; <b>B</b>) and rectus abdominis (RA; <b>C</b>) muscles following TSA treatment. * P<0.05 by Mann Whitney test.</p

No alteration in the splicing pattern or levels of Smn mRNA in the brains of TSA-treated mice.

<p>(<b>A</b>) RT-PCR for <i>Smn</i> and a known target of TSA, <i>follistatin</i>, was conducted in total RNA extracted from brains of <i>Smn^2B/-</i> mice or littermate controls treated with TSA or DMSO vehicle. Ratio of full length <i>Smn</i> versus Δ7<i>Smn</i> transcripts remained similar after TSA treatment in <i>Smn^2B/-</i> or in control mice. Transcript level of <i>follistatin</i> is elevated in TSA-treated mice. Actin serves as a loading control. (<b>B</b>) Real-time quantitative RT-PCR analyses of RNA from spinal cord and brain. No significant change in the level of <i>Smn</i> transcripts (full length <i>Smn</i> plus Δ7<i>Smn</i>) was revealed after TSA treatment (n = 3). Fold increase normalized to reference gene <i>Gapdh</i>.</p

TSA treatment reduces motor neuron loss in the spinal cord and improves myofiber histology in <i>Smn^2B/-</i> mice.

<p>(<b>A</b>) Cross-sections through the L1 lumbar spinal cord from <i>Smn^2B/+</i> heterozygous control mice, and <i>Smn^2B/-</i> mice treated with vehicle (DMSO) or TSA were processed for haematoxylin/eosin staining. Scale bar = 200 µm. (<b>B</b>) Cross-sections through the tibialis anterior (TA) muscles from <i>Smn^2B/+</i> heterozygous control mice, and <i>Smn^2B/-</i> mice treated with DMSO or TSA were processed for haematoxylin/eosin staining. Scale bar = 200 µm. (<b>C</b>) Quantification of motor neuron cell body number in the spinal cord from TSA or vehicle treated mice. TSA treatment results in a significant increase in the number of motor neurons in the spinal cord of <i>Smn^2B/-</i> mice compared with DMSO treated <i>Smn^2B/-</i> mice. n = 3 (<i>Smn^2B/-</i> DMSO) and 4 (<i>Smn^2B/-</i> TSA).</p

TSA treatment does not increase Smn protein levels in mouse embryonic fibroblasts and myoblasts obtained from <i>Smn^2B/-</i> mice.

<p>Western blot analyses were performed with specific antibodies against acetylated histone H3 (<b>A</b>) or Smn (<b>B</b>) in protein extracts from TSA (100 nM) or DMSO vehicle treated MEFs obtained from <i>Smn^2B/-</i> mice. Total histone H3 or β-tubulin serves as a loading control, respectively. (<b>C </b><b>and </b><b>D</b>) A similar analysis was performed in TSA (100 nM) or DMSO vehicle treated myoblasts obtained from <i>Smn^2B/-</i> mice.</p

TSA treatment does not increase Smn protein levels.

<p>(<b>A</b>) Western blot analyses were performed with specific antibodies against Smn in protein extracts from brains, spinal cords, hind limb muscle, hearts, or livers of <i>Smn^2B/-</i> mice treated with either TSA or DMSO vehicle. Each lane represents one animal. β-tubulin or actin serve as a loading controls. (<b>B</b>) Quantification revealed no significant increase of Smn protein levels in brains, spinal cords, hind limb muscle, hearts, or livers of TSA-treated SMA mice (n = 3).</p

Genotype of <i>Smn^C-T-Neo</i> and <i>Smn^2B-Neo</i> intercross progeny.

<p>(+) denotes wild type, (−) denotes either C-T-Neo or 2B-Neo.</p

Smn induction in adults and embryos from a single injection of tamoxifen.

<p>(<b>A</b>) DNA analysis of adult mice i.p. injected with vehicle (corn oil) or TM (9 mg/40 g body weight) using the same 3-plex PCR reaction as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015887#pone-0015887-g004" target="_blank">Figures 4A and B</a>. Wild type mice (WT;Cre-) only amplified the wild type allele (lane 1). Doubly transgenic mice (<i>Smn^C-T-Neo/WT;Cre^Esr1</i>) in the absence of TM (-TM) displayed a low basal level of <i>pgk-neo</i> excision as has been previously reported for this <i>Cre</i> line <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015887#pone.0015887-Hayashi1" target="_blank">[37]</a>. In the absence of the <i>Cre^Esr1</i> transgene, <i>Smn^C-T-Neo/WT</i> mice injected with TM could not excise <i>pgk-neo</i> (lane 3), in all tissues analyzed, <i>pgk-neo</i> excision was only possible and efficient in the presence of <i>Cre^Esr1</i> and TM (lane 4). (<b>B</b>) PCR analysis of E18.5 embryos that received a single i.p. dose of TM (3 mg/40 g body weight) to the pregnant dam at E7.5 or E13.5 DNA was genotyped as above to differentiate <i>Smn^WT</i>, <i>Smn^C-T-Neo</i> and <i>Smn^C-T</i> alleles. Arrows identify the appropriate amplicons. (<b>C</b>) Photomicrograph of E18.5 embryos induced with TM at E7.5 or E13.5. Lines in photograph show where images were tiled together in Photoshop. (<b>D</b>) Western blot and semi-quantitative densitometry of protein extracted from brain tissue of induced and control E18.5 embryos. A small amount of protein was able to be extracted from severely deformed <i>Smn^{C-T-Neo/C-T-Neo}</i> embryos identified as “escapers” for comparison to induced <i>Smn^{C-T-Neo/C-T-Neo};Cre^Esr1</i> rescued embryos. Semi-quantitative densitometry was performed on a separate blot using the same samples shown and normalized to β-tubulin, without the uninduced mutant. Protein levels from induced homozygous embryos, <i>Smn^{C-T-Neo/C-T-Neo};Cre^ESR1</i>, (0.7±0.10) was greater than <i>Smn^WT/-</i> (0.5±0.2). Abbreviations: (WT) <i>Smn</i> wild type allele, (<i>Cre+</i> and <i>Cre-</i>) presence or absence of <i>Cre^Esr1</i>, (C-T-N/WT) <i>Smn^C-T-Neo/WT</i>, (C-T-N/C-T-N) <i>Smn^{C-T-Neo/C-T-Neo}</i>, (C-T) <i>Smn^C-T</i> allele, (C-T-Neo) <i>Smn^C-T-Neo</i> allele, (TM) tamoxifen.</p