Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment

During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation

Trends in Mathematical Imaging and Surface Processing

Motivated both by industrial applications and the challenge of new problems, one observes an increasing interest in the field of image and surface processing over the last years. It has become clear that even though the applications areas differ significantly the methodological overlap is enormous. Even if contributions to the field come from almost any discipline in mathematics, a major role is played by partial differential equations and in particular by geometric and variational modeling and by their numerical counterparts. The aim of the workshop was to gather a group of leading experts coming from mathematics, engineering and computer graphics to cover the main developments

Applications of DNA origami encoded nanoscale patterns

It was almost four decades ago when the recognition of DNA’s potential use as a programmable, self-assembling building material for nanostructures led to the birth and rapid expansion of the field of DNA nanotechnology, but it was two decades later when the development of the DNA origami technique initiated the widespread use of DNA based nanoconstructs through the simplification of the design process and the reduction of the required control over the quality and stoichiometry of the assembly components by using a single-stranded “scaffold” DNA and a set of “staple” oligonucleotides that “fold” the mentioned scaffold DNA into a predesigned shape by binding different regions of the scaffold strand together. This robust approach not only permitted the construction of intricate two- and three-dimensional structures, but it also allowed the design and fabrication of molecular patterns with unprecedented accuracy as each functionalizible component’s relative position in the DNA origami structure is known to nanometer precision. In this thesis we utilize the DNA origami technology’s before mentioned patterning capability to create research tools for a diverse set of biomedical and biophysical applications. In paper I we studied the effect of different receptor ligand distributions in the ephrin/Eph signaling pathway by following the receptor activation in cancer cells stimulated with DNA origami probes displaying different, rationally designed Eph receptor ligand patterns. We found that incubation of cells with receptor ligands at shorter distance relative to each other led to significantly higher receptor activation and lower invasiveness of these cells. In paper II we used DNA origami to create reference samples for measuring the imaging accuracy of two of the most commonly used super resolution techniques, STED and STORM. We demonstrated that accuracy is a less biased metric for imaging faithfulness than precision and that DNA origami can be used to create a highly conserved and uniform pattern of fluorophores to measure and compare this metric for STED and STORM. In paper III we developed a DNA origami platform to study the photophysical behavior of two reversibly switchable fluorescent protein (rsFP) tags commonly used in microscopy in a quantitative, controlled fashion. With this system we were able to show that rsFPs at low numbers exhibit similar behavior to what was seen for them in bulk measurements, we could optimize imaging parameters more precisely and we could measure the achievable resolution using these samples. We were also able to show that some of the measured parameters scaled linearly with the amount of rsFPs making this DNA origami system a valuable calibration tool for quantitative imaging. In paper IV we developed a DNA origami-based optical tagging system detectable by next generation sequencing and super resolution microscopy to be used for introducing high resolution spatial information into RNA sequencing data. Using a combinatorial enzymatic approach, we were able to create a highly complex barcode library with which we successfully tagged cells and which we made compatible with one of the commonly used single cell RNA sequencing sample preparation techniques

Partial differential equations for self-organization in cellular and developmental biology

Understanding the mechanisms governing and regulating the emergence of structure and heterogeneity within cellular systems, such as the developing embryo, represents a multiscale challenge typifying current integrative biology research, namely, explaining the macroscale behaviour of a system from microscale dynamics. This review will focus upon modelling how cell-based dynamics orchestrate the emergence of higher level structure. After surveying representative biological examples and the models used to describe them, we will assess how developments at the scale of molecular biology have impacted on current theoretical frameworks, and the new modelling opportunities that are emerging as a result. We shall restrict our survey of mathematical approaches to partial differential equations and the tools required for their analysis. We will discuss the gap between the modelling abstraction and biological reality, the challenges this presents and highlight some open problems in the field

Copy move forgery detection using key point localized super pixel based on texture features

The most important barrier in the image forensic is to ensue a forgery detection method such can detect the copied region which sustains rotation, scaling reflection, compressing or all. Traditional SIFT method is not good enough to yield good result. Matching accuracy is not good. In order to improve the accuracy in copy move forgery detection, this paper suggests a forgery detection method especially for copy move attack using Key Point Localized Super Pixel (KLSP). The proposed approach harmonizes both Super Pixel Segmentation using Lazy Random Walk (LRW) and Scale Invariant Feature Transform (SIFT) based key point extraction. The experimental result indicates the proposed KLSP approach achieves better performance than the previous well known approaches