Role of erythroid Kruppel-like factor in human γ- to β-globin gene switching

Erythroid Kruppel-like factor (EKLF) is an erythroid-specific transcription factor that contains zinc finger domains similar to the Kruppel protein of Drosophila melanogaster. Previous studies demonstrated that EKLF binds to the CACCC box in the human β-globin gene promoter and activates transcription. CACCC box mutations that cause severe β-thalassemias in humans inhibit EKLF binding. Results described in this paper suggest that EKLF functions predominately in adult erythroid tissue. The EKLF gene is expressed at a 3-fold higher level in adult erythroid tissue than in fetal erythroid tissue, and the EKLF protein binds to the human β-globin promoter 8-fold more efficiently than to the human γ-globin promoter. Co-transfection experiments in the human fetal-like erythroleukemia cell line K562 demonstrate that over-expression of EKLF activates a β-globin reporter construct 1000-fold; a linked γ-globin reporter is activated only 3-fold. Mutation of the β-globin CACCC box severely inhibits activation. These results demonstrate that EKLF is a developmental stage-enriched protein that preferentially activates human β-globin gene expression. The data strongly suggest that EKLF is an important factor involved in human γ- to β-globin gene switching

Phase diagram for morphological transitions of wetting films on chemically structured substrates

Using an interface displacement model we calculate the shapes of thin liquidlike films adsorbed on flat substrates containing a chemical stripe. We determine the entire phase diagram of morphological phase transitions in these films as function of temperature, undersaturation, and stripe widthComment: 15 pages, RevTeX, 7 Figure

Wetting of Curved Surfaces

As a first step towards a microscopic understanding of the effective interaction between colloidal particles suspended in a solvent we study the wetting behavior of one-component fluids at spheres and fibers. We describe these phenomena within density functional theory which keeps track of the microscopic interaction potentials governing these systems. In particular we properly take into account the power-law decay of both the fluid-fluid interaction potentials and the substrate potentials. The thicknesses of the wetting films as a function of temperature and chemical potential as well as the wetting phase diagrams are determined by minimizing an effective interface potential which we obtain by applying a sharp-kink approximation to the density functional. We compare our results with previous approaches to this problem.Comment: 54 pages, 17 figures, accepted for publication in Physica

Shapes, contact angles, and line tensions of droplets on cylinders

Using an interface displacement model we calculate the shapes of nanometer-size liquid droplets on homogeneous cylindrical surfaces. We determine effective contact angles and line tensions, the latter defined as excess free energies per unit length associated with the two contact lines at the ends of the droplet. The dependences of these quantities on the cylinder radius and on the volume of the droplets are analyzed.Comment: 26 pages, RevTeX, 10 Figure

Critical adsorption on curved objects

A systematic fieldtheoretic description of critical adsorption on curved objects such as spherical or rodlike colloidal particles immersed in a fluid near criticality is presented. The temperature dependence of the corresponding order parameter profiles and of the excess adsorption are calculated explicitly. Critical adsorption on elongated rods is substantially more pronounced than on spherical particles. It turns out that, within the context of critical phenomena in confined geometries, critical adsorption on a microscopically thin `needle' represents a distinct universality class of its own. Under favorable conditions the results are relevant for the flocculation of colloidal particles.Comment: 52 pages, 10 figure

Biobank Oversight and Sanctions Under the General Data Protection Regulation

This contribution offers an insight into the function and problems of the oversight and sanctions mechanisms outlined in the General Data Protection Regulation as they relate to the biobanking context. These mechanisms might be considered as meta-mechanisms—mechanisms relating to, but not consisting of, substantive legal principles—functioning in tandem to ensure biobank compliance with data protection principles. Each of the mechanisms outlines, on paper at least, comprehensive and impressive compliance architecture—both expanding on their capacity in relation to Directive 95/46. Accordingly, each mechanism looks likely to have a significant and lasting impact on biobanks and biobanking. Despite this comprehensiveness, however, the mechanisms are not immune from critique. Problems appear regarding the standard of protection provided for research subject rights, regarding the disproportionate impact on legitimate interests tied up with the biobanking process—particularly genomic research interests—and regarding their practical implementability in biobanking

Hard-Sphere Fluids in Contact with Curved Substrates

The properties of a hard-sphere fluid in contact with hard spherical and cylindrical walls are studied. Rosenfeld's density functional theory (DFT) is applied to determine the density profile and surface tension $\gamma$ for wide ranges of radii of the curved walls and densities of the hard-sphere fluid. Particular attention is paid to investigate the curvature dependence and the possible existence of a contribution to $\gamma$ that is proportional to the logarithm of the radius of curvature. Moreover, by treating the curved wall as a second component at infinite dilution we provide an analytical expression for the surface tension of a hard-sphere fluid close to arbitrary hard convex walls. The agreement between the analytical expression and DFT is good. Our results show no signs for the existence of a logarithmic term in the curvature dependence of $\gamma$.Comment: 15 pages, 6 figure

Low Prevalence of Lactase Persistence in Bronze Age Europe Indicates Ongoing Strong Selection over the Last 3,000 Years

Lactase persistence (LP), the continued expression of lactase into adulthood, is the most strongly selected single gene trait over the last 10,000 years in multiple human populations. It has been posited that the primary allele causing LP among Eurasians, rs4988235-A [1], only rose to appreciable frequencies during the Bronze and Iron Ages [2, 3], long after humans started consuming milk from domesticated animals. This rapid rise has been attributed to an influx of people from the Pontic-Caspian steppe that began around 5,000 years ago [4, 5]. We investigate the spatiotemporal spread of LP through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany (∼3,200 before present, BP), the oldest large-scale conflict site north of the Alps. Genetic data indicate that these individuals represent a single unstructured Central/Northern European population. We complemented these data with genotypes of 18 individuals from the Bronze Age site Mokrin in Serbia (∼4,100 to ∼3,700 BP) and 37 individuals from Eastern Europe and the Pontic-Caspian Steppe region, predating both Bronze Age sites (∼5,980 to ∼3,980 BP). We infer low LP in all three regions, i.e., in northern Germany and South-eastern and Eastern Europe, suggesting that the surge of rs4988235 in Central and Northern Europe was unlikely caused by Steppe expansions. We estimate a selection coefficient of 0.06 and conclude that the selection was ongoing in various parts of Europe over the last 3,000 years