Quantum-Dot Assisted Spectroscopy of Degeneracy-Lifted Landau Levels in Graphene

Energy spectroscopy of strongly interacting phases requires probes which minimize screening while retaining spectral resolution and local sensitivity. Here we demonstrate that such probes can be realized using atomic sized quantum dots bound to defects in hexagonal Boron Nitride tunnel barriers, placed at nanometric distance from graphene. With dot energies capacitively tuned by a planar graphite electrode, dot-assisted tunneling becomes highly sensitive to the graphene excitation spectrum. The spectra track the onset of degeneracy lifting with magnetic field at the ground state, and at unoccupied exited states, revealing symmetry-broken gaps which develop steeply with magnetic field - corresponding to Land\'e $g$ factors as high as 160. Measured up to $B = 33$ T, spectra exhibit a primary energy split between spin-polarized excited states, and a secondary spin-dependent valley-split. Our results show that defect dots probe the spectra while minimizing local screening, and are thus exceptionally sensitive to interacting states

Intraoperative pain during caesarean delivery: Incidence, risk factors and physician perception

Background: Intraoperative pain is a possible complication of neuraxial anaesthesia for caesarean delivery. There is little information available about its incidence, risk factors and physician perception. Methods: Parturients undergoing spinal anaesthesia for elective caesarean delivery were enrolled. Before surgery, parturients were asked about preoperative anxiety on a verbal numerical scale (VNS), anticipated analgesic requirement, postoperative pain levels, Spielberger STATE-TRAIT inventory index, Pain Catastrophizing Scale. After surgery, parturients were asked to answer questions (intraoperative VNS pain). The anaesthesiologist and obstetrician were asked to fill out a questionnaire asking about perceived intraoperative pain. Influence of preoperative anxiety on intraoperative pain (yes/no) was assessed using logistic regression. Mc Fadden's R2 was calculated. The agreement in physician perception of intraoperative pain with reported pain by the parturient was examined by calculating Cohen's kappa and 95% Confidence Intervals (CI). Results: We included 193 parturients in our analysis. Incidence of intraoperative pain was 11.9%. Median intraoperative VNS pain of parturients with pain was 4.0 (1st quartile 4.0; 3rd quartile 9.0). Preoperative anxiety was not a good predictor of intraoperative pain (p-value of β-coefficient = 0.43, Mc Fadden's R2 = 0.01). Including further preoperative variables did not result in a good prediction model. Cohen's kappa between reported pain by parturient and by the obstetrician was 0.21 (95% CI: 0.01, 0.41) and by the anaesthesiologist was 0.3 (95% CI: 0.12, 0.48). Conclusions: We found a substantial incidence (11.9%) of intraoperative pain during caesarean delivery. Preoperative anxiety did not predict intraoperative pain. Physicians did not accurately identify parturients' intraoperative pain. Significance: Intraoperative pain occurred in 11.9% and severe intraoperative pain occurred in 1.11% of parturients undergoing elective caesarean delivery under spinal anaesthesia. We did not find any preoperative variables that could reliably predict intraoperative pain. Obstetricians and anaesthesiologists underestimated the incidence of intraoperative pain in our cohort and thus, more attention must be put to parturients' pain

Many-body dispersions in interacting ballistic quantum wires

We have measured the collective excitation spectrum of interacting electrons in one-dimension. The experiment consists of controlling the energy and momentum of electrons tunneling between two clean and closely situated, parallel quantum wires in a GaAs/AlGaAs heterostructure while measuring the resulting conductance. We measure excitation spectra that clearly deviate from the non-interacting spectrum, attesting to the importance of Coulomb interactions. Notable is an observed 30% enhancement of the velocity of the main excitation branch relative to non-interacting electrons with the same density. In short wires, finite size effects resulting from broken translational invariance are observed. Spin - charge separation is manifested through moire patterns, reflecting different spin and charge excitation velocities.Comment: 14 pages, 6 eps figures. To be published in NANOWIRE, a special issue of Solid State Communication

Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution

Actively maintained close appositions, or contact sites, between organelle membranes, enable the efficient transfer of biomolecules between the various cellular compartments. Several such sites have been described together with their tethering machinery. Despite these advances we are still far from a comprehensive understanding of the function and regulation of most contact sites. To systematically characterize the proteome of contact sites and support the discovery of new tethers and functional molecules, we established a high throughput screening approach in Saccharomyces cerevisiae based on co-localization imaging. We imaged split fluorescence reporters for six different contact sites, two of which have never been studied before, on the background of 1165 strains expressing a mCherry-tagged yeast protein that have a cellular punctate distribution (a hallmark of contact sites). By scoring both co-localization events and effects on reporter size and abundance, we discovered over 100 new potential contact site residents and effectors in yeast. Focusing on several of the newly identified residents, we identified one set of hits as previously unrecognized homologs to Vps13 and Atg2. These proteins share their lipid transport domain, thus expanding this family of lipid transporters. Analysis of another candidate, Ypr097w, which we now call Lec1 (Lipid-droplet Ergosterol Cortex 1), revealed that this previously uncharacterized protein dynamically shifts between lipid droplets and the cell cortex, and plays a role in regulation of ergosterol distribution in the cell

Increased Risk of Genetic and Epigenetic Instability in Human Embryonic Stem Cells Associated with Specific Culture Conditions

The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them a promising source of material for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a combinatorial study on both hESCs and hiPSCs to compare the effects of enzymatic vs. mechanical passaging, and feeder-free vs. mouse embryonic fibroblast feeder substrate, on the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. In extensive experiments involving over 100 continuous passages, we observed that both enzymatic passaging and feeder-free culture were associated with genetic instability, higher rates of cell proliferation, and persistence of OCT4/POU5F1-positive cells in teratomas, with enzymatic passaging having the stronger effect. In all combinations of culture conditions except for mechanical passaging on feeder layers, we noted recurrent deletions in the genomic region containing the tumor suppressor gene TP53, which was associated with decreased mRNA expression of TP53, as well as alterations in the expression of several downstream genes consistent with a decrease in the activity of the TP53 pathway. Among the hESC cultures, we also observed culture-associated variations in global gene expression and DNA methylation. The effects of enzymatic passaging and feeder-free conditions were also observed in hiPSC cultures. Our results highlight the need for careful assessment of the effects of culture conditions on cells intended for clinical therapies

Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution

Actively maintained close appositions between organelle membranes, also known as contact sites, enable the efficient transfer of biomolecules between cellular compartments. Several such sites have been described as well as their tethering machineries. Despite these advances we are still far from a comprehensive understanding of the function and regulation of most contact sites. To systematically characterize contact site proteomes, we established a high-throughput screening approach in Saccharomyces cerevisiae based on co-localization imaging. We imaged split fluorescence reporters for six different contact sites, several of which are poorly characterized, on the background of 1165 strains expressing a mCherry-tagged yeast protein that has a cellular punctate distribution (a hallmark of contact sites), under regulation of the strong TEF2 promoter. By scoring both co-localization events and effects on reporter size and abundance, we discovered over 100 new potential contact site residents and effectors in yeast. Focusing on several of the newly identified residents, we identified three homologs of Vps13 and Atg2 that are residents of multiple contact sites. These proteins share their lipid transport domain, thus expanding this family of lipid transporters. Analysis of another candidate, Ypr097w, which we now call Lec1 (Lipid-droplet Ergosterol Cortex 1), revealed that this previously uncharacterized protein dynamically shifts between lipid droplets and the cell cortex, and plays a role in regulation of ergosterol distribution in the cell. Overall, our analysis expands the universe of contact site residents and effectors and creates a rich database to mine for new functions, tethers, and regulators

Coordinations between gene modules control the operation of plant amino acid metabolic networks

<p>Abstract</p> <p>Background</p> <p>Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results.</p> <p>Results</p> <p>Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes.</p> <p>Conclusion</p> <p>Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.</p

Charge Fractionalization in nonchiral Luttinger systems

One-dimensional metals, such as quantum wires or carbon nanotubes, can carry charge in arbitrary units, smaller or larger than a single electron charge. However, according to Luttinger theory, which describes the low-energy excitations of such systems, when a single electron is injected by tunneling into the middle of such a wire, it will tend to break up into separate charge pulses, moving in opposite directions, which carry definite fractions $f$ and $(1-f)$ of the electron charge, determined by a parameter $g$ that measures the strength of charge interactions in the wire. (The injected electron will also produce a spin excitation, which will travel at a different velocity than the charge excitations.) Observing charge fractionalization physics in an experiment is a challenge in those (nonchiral) low-dimensional systems which are adiabatically coupled to Fermi liquid leads. We theoretically discuss a first important step towards the observation of charge fractionalization in quantum wires based on momentum-resolved tunneling and multi-terminal geometries, and explain the recent experimental results of H. Steinberg {\it et al.}, Nature Physics {\bf 4}, 116 (2008).Comment: 31 pages, final version to appear in Annals of Physic

DNA Methylation

<p><b>A</b>. X Chromosome DNA Methylation and XIST Expression. Methylation levels of genes in the X-chromosome (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118307#pone.0118307.s009" target="_blank">S6A Table</a>) are shown on the heatmap. Hierarchical clustering was performed on the samples, as indicated by the dendrogram. The genes are ordered according to their location (from the beginning to the end of the chromosome). Samples that show loss of DNA methylation for the “Enz” cluster are highlighted in blue, those that show DNA methylation for the “Ecm” cluster are highlighted in pink, and for both clusters in mauve. Genes located in the regions of loss of DNA methylation are listed to the right of the heatmap. XIST expression is shown on the line graph, with the detection limit for the microarray indicated by the red line. <b>B</b>. DNA methylation at imprinted loci. Methylation levels for imprinted probes (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118307#pone.0118307.s009" target="_blank">S6B Table</a>) are shown on the heatmap. Hierarchical clustering was performed on the samples, as indicated by the dendrogram. The genes are ordered according to chromosome location; genes are listed to the left. The inset at the right shows a detail of the NESP/GNAS complex locus, indicating the positions of the CpG sites that were hypermethylated (red triangle) vs. hypomethylated (green triangle) in the late passage samples relative to the NESP/GNAS and NESPAS exons. <b>C, D, E</b>. Heatmaps showing differential DNA methylation genes for early vs. late passage <b>(C)</b>, mechanical vs. enzymatic passage <b>(D)</b>, and Mef vs. Ecm substrate <b>(E)</b>. In heatmap <b>(C)</b>, the black boxes indicate genes for which the DNA methylation levels in the late passage MefMech (P103) samples was more similar to those in the early passage samples. Probes were selected by multivariate regression. Functional enrichments identified by GREAT analysis are shown to the right of the heatmaps, visualized using REVIGO [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118307#pone.0118307.ref013" target="_blank">13</a>]. Samples were arranged according to passage and culture method, and hierarchical clustering was performed on the genes only. In the functional enrichment results, the size of the node indicated the number of contributing GO terms, and color of the nodes indicates the FDR (darker color for lower FDR), and the edge length indicates the similarity between GO terms (shorter edge for more similar terms).</p

Effectiveness of third-class biologic treatment in Crohn's disease : a multi-center retrospective cohort study

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