Second-order electronic correlation effects in a one-dimensional metal

The Pariser-Parr-Pople (PPP) model of a single-band one-dimensional (1D) metal is studied at the Hartree-Fock level, and by using the second-order perturbation theory of the electronic correlation. The PPP model provides an extension of the Hubbard model by properly accounting for the long-range character of the electron-electron repulsion. Both finite and infinite version of the 1D-metal model are considered within the PPP and Hubbard approximations. Calculated are the second-order electronic-correlation corrections to the total energy, and to the electronic-energy bands. Our results for the PPP model of 1D metal show qualitative similarity to the coupled-cluster results for the 3D electron-gas model. The picture of the 1D-metal model that emerges from the present study provides a support for the hypothesis that the normal metallic state of the 1D metal is different from the ground state.Comment: 21 pages, 16 figures; v2: small correction in title, added 3 references, extended and reformulated a few paragraphs (detailed information at the end of .tex file); added color to figure

Scalable in vitro production of defined mouse erythroblasts

Mouse embryonic stem cells (mESCs) can be manipulated in vitro to recapitulate the process of erythropoiesis, during which multipotent cells undergo lineage specification, differentiation and maturation to produce erythroid cells. Although useful for identifying specific progenitors and precursors, this system has not been fully exploited as a source of cells to analyse erythropoiesis. Here, we establish a protocol in which characterised erythroblasts can be isolated in a scalable manner from differentiated embryoid bodies (EBs). Using transcriptional and epigenetic analysis, we demonstrate that this system faithfully recapitulates normal primitive erythropoiesis and fully reproduces the effects of natural and engineered mutations seen in primary cells obtained from mouse models. We anticipate this system to be of great value in reducing the time and costs of generating and maintaining mouse lines in a number of research scenarios

Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development

The transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and is frequently disrupted in leukemia. Runx1 is a large, complex gene that is expressed from two alternative promoters under the spatiotemporal control of multiple hematopoietic enhancers. To dissect the dynamic regulation of Runx1 in hematopoietic development, we analyzed its three-dimensional chromatin conformation in mouse embryonic stem cell (ESC) differentiation cultures. Runx1 resides in a 1.1 Mb topologically associating domain (TAD) demarcated by convergent CTCF motifs. As ESCs differentiate to mesoderm, chromatin accessibility, Runx1 enhancer-promoter (E-P) interactions, and CTCF-CTCF interactions increase in the TAD, along with initiation of Runx1 expression from the P2 promoter. Differentiation to hematopoietic progenitor cells is associated with the formation of tissue-specific sub-TADs over Runx1, a shift in E-P interactions, P1 promoter demethylation, and robust expression from both Runx1 promoters. Deletion of promoter-proximal CTCF sites at the sub-TAD boundaries has no obvious effects on E-P interactions but leads to partial loss of domain structure, mildly affects gene expression, and delays hematopoietic development. Together, our analysis of gene regulation at a large multi-promoter developmental gene reveals that dynamic sub-TAD chromatin boundaries play a role in establishing TAD structure and coordinated gene expression

Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy

OBJECTIVE—Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD)

The helium trimer with soft-core potentials

The helium trimer is studied using two- and three-body soft-core potentials. Realistic helium-helium potentials present an extremely strong short-range repulsion and support a single, very shallow, bound state. The description of systems with more than two helium atoms is difficult due to the very large cancellation between kinetic and potential energy. We analyze the possibility of describing the three helium system in the ultracold regime using a gaussian representation of a widely used realistic potential, the LM2M2 interaction. However, in order to describe correctly the trimer ground state a three-body force has to be added to the gaussian interaction. With this potential model the two bound states of the trimer and the low energy scattering helium-dimer phase shifts obtained with the LM2M2 potential are well reproduced.Comment: 15 pages, 3 figures, submitted to Few-Body System

On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation

Determining the mechanisms by which genes are switched on and off during development is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using an on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in transcriptional activity whereas at the peak of gene expression, in early erythroblasts, transcription is relatively stable. Later during differentiation as α-globin expression declines, we again observe more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of active transcriptional compartments as gene expression is regulated during differentiation

Formation and dynamics of van der Waals molecules in buffer-gas traps

We show that weakly bound He-containing van der Waals molecules can be produced and magnetically trapped in buffer-gas cooling experiments, and provide a general model for the formation and dynamics of these molecules. Our analysis shows that, at typical experimental parameters, thermodynamics favors the formation of van der Waals complexes composed of a helium atom bound to most open-shell atoms and molecules, and that complex formation occurs quickly enough to ensure chemical equilibrium. For molecular pairs composed of a He atom and an S-state atom, the molecular spin is stable during formation, dissociation, and collisions, and thus these molecules can be magnetically trapped. Collisional spin relaxations are too slow to affect trap lifetimes. However, helium-3-containing complexes can change spin due to adiabatic crossings between trapped and untrapped Zeeman states, mediated by the anisotropic hyperfine interaction, causing trap loss. We provide a detailed model for Ag3He molecules, using ab initio calculation of Ag-He interaction potentials and spin interactions, quantum scattering theory, and direct Monte Carlo simulations to describe formation and spin relaxation in this system. The calculated rate of spin-change agrees quantitatively with experimental observations, providing indirect evidence for molecular formation in buffer-gas-cooled magnetic traps.Comment: 20 pages, 13 figure

The ^4He trimer as an Efimov system

We review the results obtained in the last four decades which demonstrate the Efimov nature of the $^4$He three-atomic system.Comment: Review article for a special issue of the Few-Body Systems journal devoted to Efimov physic

Reactivation of a developmentally silenced embryonic globin gene

The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues