Adaptive Computation of the Swap-Insert Correction Distance

The Swap-Insert Correction distance from a string $S$ of length $n$ to another string $L$ of length $m\geq n$ on the alphabet $[1..d]$ is the minimum number of insertions, and swaps of pairs of adjacent symbols, converting $S$ into $L$. Contrarily to other correction distances, computing it is NP-Hard in the size $d$ of the alphabet. We describe an algorithm computing this distance in time within $O(d^2 nm g^{d-1})$, where there are $n_\alpha$ occurrences of $\alpha$ in $S$, $m_\alpha$ occurrences of $\alpha$ in $L$, and where $g=\max_{\alpha\in[1..d]} \min\{n_\alpha,m_\alpha-n_\alpha\}$ measures the difficulty of the instance. The difficulty $g$ is bounded by above by various terms, such as the length of the shortest string $S$, and by the maximum number of occurrences of a single character in $S$. Those results illustrate how, in many cases, the correction distance between two strings can be easier to compute than in the worst case scenario.Comment: 16 pages, no figures, long version of the extended abstract accepted to SPIRE 201

An Outdoor Stereo Camera System for the Generation of Real-World Benchmark Datasets with Ground Truth

In this report we describe a high-performance stereo camera system to capture image sequences with high temporal and spatial resolution for the evaluation of various image processing tasks. The system was primarily designed for complex outdoor and traffic scenes which frequently occur in the automotive industry, but is also suited for other applications. For this task the system is equipped with a very accurate inertial measurement unit and global positioning system, which provides exact camera movement and position data. The system is already in active use and has produced several terabyte of challenging image sequences which are available for download

Methods for fast construction of bounding volume hierarchies

katedra počítačové grafiky a interakc

3DPolyS-LE: an accessible simulation framework to model the interplay between chromatin and loop extrusion.

SUMMARY Recent studies suggest that the loop extrusion activity of Structural Maintenance of Chromosomes complexes is central to proper organization of genomes in vivo. Polymer physics-based modeling of chromosome structure has been instrumental to assess which structures such extrusion can create. Only few laboratories however have the technical and computational expertise to create in silico models combining dynamic features of chromatin and loop extruders. Here we present 3DPolyS-LE, a self-contained, easy to use modeling and simulation framework allowing non-specialists to ask how specific properties of loop extruders and boundary elements impact on 3D chromosome structure. 3DPolyS-LE also provides algorithms to compare predictions with experimental Hi-C data. AVAILABILITY Software available at https://gitlab.com/togop/3DPolyS-LE; implemented in Python and Fortran 2003 and supported on any Unix-based operating system (Linux, Mac OS). SUPPLEMENTARY INFORMATION Supplementary information are available at Bioinformatics online

Unnatural Amino Acids Improve Affinity and Modulate Immunogenicity: Developing Peptides to Treat MHC Type II Autoimmune Disorders

Many autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), and celiac disease (CD), arise from improper immune system recognition of self or benign peptides as threats. No autoimmune disease currently has a cure. Many treatments suppress the entire immune system to decrease symptom severity. The core molecular interaction underlying these diseases involves specific alleles of the human leukocyte antigen (HLA) receptor hosting the immunodominant peptides associated with the disease (i.e. myelin basic protein, Type II collagen, or α-gliadin) in their binding groove. Once bound, circulating T-cells can recognize the HLA-antigen complex and initiate the complex cascade that forms an adaptive immune response. This initial HLA-antigen interaction is a promising target for therapeutic intervention. Two general strategies have been pursued: altered peptide ligands (APLs) that attempt to recruit a different class of T-cell to induce an anti-inflammatory response to balance the pro-inflammatory response associated with the antigen; and HLA blockers (HLABs), peptides that, due to a much higher affinity for the HLA receptor, quantitatively displace the antigen, inhibiting the immune response. Both approaches would benefit from improved HLA-drug binding, but as the HLA receptors are highly promiscuous, the binding sites are not specific for any natural amino acid. Unnatural amino acids, either designed or screened through high-throughput assays, may provide a solution. This review summarizes the nascent field of using non-canonical residues to treat MS, RA and CD, focusing on the importance of specific molecular interactions, and provides some examples of the synthesis of these unnatural residues

Die intertextuelle Dimension der Darstellung der Gegner Jesu im Matthäusevangelium. Mit besonderer Berücksichtigung des Propheten Jeremia

Zu den Eigenheiten des Matthäusevangeliums gehört, dass es sich sehr intensiv mit der Schrift (dem Alten Testament) auseinandersetzt. Davon zeugen in besonderer Weise die zehn Erfüllungszitate, darüber hinaus gibt es aber noch viele weitere Schriftzitate und Anspielungen. Der Bezug auf die Schrift im Matthäusevangelium dient in erster Linie der theologischen Profilierung Jesu. Allerdings nicht nur: Die Geschichte Jesu ist nämlich im Matthäusevangelium über weite Strecken als Konfliktgeschichte zwischen Jesus und den jüdischen Autoritäten dargestellt. Die vorliegende Untersuchung fragt, inwiefern auch die jüdischen Autoritäten als Gegner Jesu im Lichte der Schrift verstanden und dargestellt werden. Dabei wird eine intertextuelle Methodik angewandt. Ausgangspunkt sind zwei Erfüllungszitate, die auf die Gegner Jesu angewendet werden: Mt 2,17f (die Klage Rahels aus Jer 31,15 wird auf den Kindermord des Herodes bezogen) und Mt 27,9f (Sach 11,13 – obwohl als Jeremia-Zitat angekündigt – wird auf die Hohenpriester angewandt). Diese beiden Zitate zeigen beispielhaft, dass der Prophet Jeremia für Matthäus besonders wichtig ist. Matthäus ist der einzige Evangelist (der einzige Autor des Neuen Testament überhaupt), der Jeremia namentlich erwähnt. Unter diesen Voraussetzungen wird versucht, die matthäische Gesamtkonfiguration der Gegner durch die Schrift darzustellen und so einen Beitrag zur Frage nach der Eigenart der matthäischen und frühchristlichen Schriftrezeption zu leisten

Cultivation of CHO Cells in Thomson Optimum Growth™ Shake Flasks and Scale-up

In biotechnology, the usage of shaking flasks in upstream processing is widely common due to the easy handling. Frequent applications are process screening and optimization. Thereby, the focus lies mostly on a homogeneous and fast distribution of substrates and gases whilst power consumption and shearing force are meant to be kept low, which ideally results in high biomass concentrations and product titers. For characterization purposes, the mixing time and the oxygen mass transfer coefficient (kLa) were measured in 5 L and 500 mL Thomson Optimal Growth™ shaking flasks, using the de-colorization or the dynamic gassing-out method, respectively. Those geometrical optimized bioreactors are promising higher space-time yields compared to the predominant Erlenmeyer-shake flask design. According to the results of the procedural experiments, CHO (Chinese hamster ovary) cells were cultivated at selected, auspicious parameter combinations. The effectiveness of the predetermined parameters was evaluated and a scale-up method elaborated. The results can be summarized as follows: The key parameter for all experimental setups is the shaking rate. In contrast, the filling volume showed to have a more ambiguous role. Modeling results in the 500 mL flasks showed no significant influence of the filling volume to the maximal cell density, in contrast to the 5L flask (both shaken at 50 mm throw). The highest viable cell density (up to 4.8∙10⁶ cells mL⁻¹) was reached using the 500 mL flask with high shaking rates at 50 mm shaking diameter. Thereby, a µmax of 0.038 h-1 was achieved that correlates with a td of less than 19 h. All in all, the highest µmax of 0.055 h⁻¹ was reached during the scale-up process, whereby higher viable cell densities were reached compared to the batch cultivations using the same parameter settings. In addition to the experiments performed to date, simulations with computational fluid dynamics and experimental determination of specific power consumption rates are already in progress, increasing the range of applicability and the validity of the proposed model correlations

Synthesis of Selective CDK2/SPY1 Inhibitors employing Stereochemical Control - An invaluable tool in an Organic Chemist’s belt

The cell cycle of a healthy eukaryotic cell depends on the efficiency of cyclin-dependent kinase (CDKs) checkmarks, to ensure normal cell proliferation. CDK2 is responsible for progression of cells into the S and M phases, and it is critical to the abnormal growth processes of cancer cells. Examination of different kinds of human cancers, for their vulnerability to CDK2 inhibition, has revealed CDK2 as a good therapeutic target. In the past two decades, various CDK2 inhibitors have been designed but have stumbled on the roadblock of selectivity issue, since CDK2 shares 74 and 68% sequence identity and active sites with its family members’ CDK3 and CDK1, respectively. Moreover, it’s not CDK2 alone that needs to be targeted but the activated complex it forms with Spy1, a protein that can activate CDK2 in the same way as cyclin but is highly upregulated in cancer cells. After extensive computational studies, we found some unique yet challenging CDK2/SPY1 inhibitors. In this presentation, I will discuss the importance of stereochemical control in the design and synthesis of novel and selective CDK2/SPY1 inhibitors. The synthesis ensures that the inhibitors are stereochemically pure, and thus the biological activity can be accurately evaluated. These results can then be used to refine our computational models to further improve the selectivity of our drug candidates