ATP-dependent chromatosome remodeling

Chromatin serves to package, protect and organize the complex eukaryotic genomes to assure their stable inheritance over many cell generations. At the same time, chromatin must be dynamic to allow continued use of DNA during a cell's lifetime. One important principle that endows chromatin with flexibility involves ATP-dependent `remodeling' factors, which alter DNA-histone interactions to form, disrupt or move nucleosomes. Remodeling is well documented at the nucleosomal level, but little is known about the action of remodeling factors in a more physiological chromatin environment. Recent findings suggest that some remodeling machines can reorganize even folded chromatin fibers containing the linker histone H1, extending the potential scope of remodeling reactions to the bulk of euchromatin

Donor binding energy and thermally activated persistent photoconductivity in high mobility (001) AlAs quantum wells

A doping series of AlAs (001) quantum wells with Si delta-modulation doping on both sides reveals different dark and post-illumination saturation densities, as well as temperature dependent photoconductivity. The lower dark two-dimensional electron density saturation is explained assuming deep binding energy of Delta_DK = 65.2 meV for Si-donors in the dark. Persistent photoconductivity (PPC) is observed upon illumination, with higher saturation density indicating shallow post-illumination donor binding energy. The photoconductivity is thermally activated, with 4 K illumination requiring post-illumination annealing to T = 30 K to saturate the PPC. Dark and post-illumination doping efficiencies are reported.Comment: The values of binding energy changed from previous versions because of a better understanding for the dielectric permittivity. Also, the Gamma - X donor states are better explaine

Single-valley high-mobility (110) AlAs quantum wells with anisotropic mass

We studied a doping series of (110)-oriented AlAs quantum wells (QWs) and observed transport evidence of single anisotropic-mass valley occupancy for the electrons in a 150 \AA wide QW. Our calculations of strain and quantum confinement for these samples predict single anisotropic-mass valley occupancy for well widths $W$ greater than 53 \AA. Below this, double-valley occupation is predicted such that the longitudinal mass axes are collinear. We observed mobility anisotropy in the electronic transport along the crystallographic directions in the ratio of 2.8, attributed to the mass anisotropy as well as anisotropic scattering of the electrons in the X-valley of AlAs

Valley degeneracy in biaxially strained aluminum arsenide quantum wells

This paper details a complete formalism for calculating electron subband energy and degeneracy in strained multi-valley quantum wells grown along any orientation with explicit results for the AlAs quantum well case. A standardized rotation matrix is defined to transform from the conventional- cubic-cell basis to the quantum-well-transport basis whereby effective mass tensors, valley vectors, strain matrices, anisotropic strain ratios, and scattering vectors are all defined in their respective bases. The specific cases of (001)-, (110)-, and (111)-oriented aluminum arsenide (AlAs) quantum wells are examined, as is the unconventional (411) facet, which is of particular importance in AlAs literature. Calculations of electron confinement and strain in the (001), (110), and (411) facets determine the critical well width for crossover from double- to single-valley degeneracy in each system. The notation is generalized to include miscut angles, and can be adapted to other multi-valley systems. To help classify anisotropic inter-valley scattering events, a new primitive unit cell is defined in momentum space which allows one to distinguish purely in-plane inter-valley scattering events from those that requires an out-of-plane momentum scattering component.Comment: 17 pages, 4 figures, 2 table

Multiple-scattering effects on incoherent neutron scattering in glasses and viscous liquids

Incoherent neutron scattering experiments are simulated for simple dynamic models: a glass (with a smooth distribution of harmonic vibrations) and a viscous liquid (described by schematic mode-coupling equations). In most situations multiple scattering has little influence upon spectral distributions, but it completely distorts the wavenumber-dependent amplitudes. This explains an anomaly observed in recent experiments

Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients. Methods: In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 μg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy. Results: In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 μg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372-1.667); p < 0.001] and a higher HScore [OR 1.011 (95% CI 1.009-1.013); p < 0.001] were significantly associated with in-hospital mortality. Conclusions: An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients. Clinical trial registration: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016

Bringing Lived Lives to Swift’s Asylum: a psychiatric hospital perspective

Background: Few “interventions” around suicide and stigma have reached into psychiatric institutions. Lived Lives is a science-arts approach to addressing suicide and stigma, informed by a psychobiographical and visual arts autopsy. The resulting artworks and mediated exhibition (Lived Lives), with artist, scientist and the Lived Lives families, co-curated by communities, has facilitated dialogue, response and public action around stigma-reduction, consistent with a community intervention. Recent evidence from Lived Lives moved us to consider how it may situate within a psychiatric institution, where stigma is chronically apparent. Methods: Lived Lives manifested in St. Patrick’s University Hospital (Ireland’s oldest and largest psychiatric hospital) in November 2017. The mediated exhibition was open to the public for 4 days. Audiences included service users, policy makers, health professionals, senior hospital administrators and members of the public. Opinions and feelings were collected. The event was documented. Bereavement support was available. A Clinician and an artist provided independent evaluation. Results: 86 participants engaged with the exhibition. 62% of participants were suicide-bereaved; 46% had experienced a mental health difficulty, and 35% had been suicidal in the past. 91% thought Lived Lives could be of benefit in the aftermath of a suicide death. Half of participants thought Lived Lives could help reduce suicidal feelings, whereas 88% thought it could benefit those with Mental Health difficulties. The emotional response was of a visceral nature, including fear, anger, sadness, disgust and anxiety. Bereavement support was occasionally called upon in a supportive capacity. Conclusions: Lived Lives sits comfortably in discomfort, unafraid to call out the home-truths about stigma and its pervasive and pernicious impact, and with restoring identity at its core. Lived Lives can operate within a psychiatric hospital, as well as in community. The challenge is to move it forward for greater exposure and impacts in at-risk communities

Energy landscape - a key concept for the dynamics of glasses and liquids

There is a growing belief that the mode coupling theory is the proper microscopic theory for the dynamics of the undercooled liquid above a critical temperature T_c. In addition, there is some evidence that the system leaves the saddlepoints of the energy landscape to settle in the valleys at this critical temperature. Finally, there is a microscopic theory for the entropy at the calorimetric glass transition T_g by Mezard and Parisi, which allows to calculate the Kauzmann temperature from the atomic pair potentials. The dynamics of the frozen glass phase is at present limited to phenomenological models. In the spirit of the energy landscape concept, one considers an ensemble of independent asymmetric double-well potentials with a wide distribution of barrier heights and asymmetries (ADWP or Gilroy-Phillips model). The model gives an excellent description of the relaxation of glasses up to about T_g/4. Above this temperature, the interaction between different relaxation centers begins to play a role. One can show that the interaction reduces the number of relaxation centers needed to bring the shear modulus down to zero by a factor of three.Comment: Contribution to the III Workshop on Nonequilibrium Phenomena in Supercooled Fluids, Glasses and Amorphous Materials, 22-27 September 2002, Pisa; 14 pages, 3 figures; Version 3 takes criticque at Pisa into account; final version 4 will be published in J.Phys.: Condens.Matte

Pleniglacial dynamics in an oceanic central European loess landscape

Loess–palaeosol sequences (LPSs) of the oceanic-influenced European loess belt underwent frequent post-depositional processes induced by surface runoff or periglacial processes. The interpretation of such atypical LPSs is not straightforward, and they cannot be easily used for regional to continental correlations. Within the last few years, however, such sequences gained increased attention, as they are valuable archives for regional landscape dynamics. In this study, the Siersdorf LPS was analysed using a multi-proxy approach using sedimentological, geochemical, and spectrophotometric methods combined with luminescence dating and tentative malacological tests to unravel Pleniglacial dynamics of the Lower Rhine Embayment. A marshy wetland environment for the late Middle Pleniglacial to the early Upper Pleniglacial was shown by colour reflectance and grain size distribution. Age inversions from luminescence dating paired with geochemical and sedimentological data reveal long-lasting erosional processes during the early Upper Pleniglacial, which were constrained to a relatively small catchment with short transport ranges. The upper sequence shows typical marker horizons for the study area and indicate harsh, cold-arid conditions for the late Upper Pleniglacial. In comparison with other terrestrial archives, the Siersdorf LPS shows that the Lower Rhine Embayment was more diverse than previously assumed, regarding not only its geomorphological settings and related processes but also its ecosystems and environments.</p

Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells

Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in an concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog