Annotation of genomics data using bidirectional hidden Markov models unveils variations in Pol II transcription cycle

DNA replication, transcription and repair involve the recruitment of protein complexes that change their composition as they progress along the genome in a directed or strand-specific manner. Chromatin immunoprecipitation in conjunction with hidden Markov models (HMMs) has been instrumental in understanding these processes, as they segment the genome into discrete states that can be related to DNA-associated protein complexes. However, current HMM-based approaches are not able to assign forward or reverse direction to states or properly integrate strand-specific (e.g.,RNA expression) with non-strand-specific (e.g.,ChIP) data, which is indispensable to accurately characterize directed processes. To overcome these limitations, we introduce bidirectional HMMs which infer directed genomic states from occupancy profiles de novo. Application to RNA polymerase II-associated factors in yeast and chromatin modifications in human T cells recovers the majority of transcribed loci, reveals gene-specific variations in the yeast transcription cycle and indicates the existence of directed chromatin state patterns at transcribed, but not at repressed, regions in the human genome. In yeast, we identify 32 new transcribed loci, a regulated initiation-elongation transition, the absence of elongation factors Ctk1 and Paf1 from a class of genes, a distinct transcription mechanism for highly expressed genes and novel DNA sequence motifs associated with transcription termination. We anticipate bidirectional HMMs to significantly improve the analyses of genome-associated directed processes

Kassiopeia: A Modern, Extensible C++ Particle Tracking Package

The Kassiopeia particle tracking framework is an object-oriented software package using modern C++ techniques, written originally to meet the needs of the KATRIN collaboration. Kassiopeia features a new algorithmic paradigm for particle tracking simulations which targets experiments containing complex geometries and electromagnetic fields, with high priority put on calculation efficiency, customizability, extensibility, and ease of use for novice programmers. To solve Kassiopeia's target physics problem the software is capable of simulating particle trajectories governed by arbitrarily complex differential equations of motion, continuous physics processes that may in part be modeled as terms perturbing that equation of motion, stochastic processes that occur in flight such as bulk scattering and decay, and stochastic surface processes occuring at interfaces, including transmission and reflection effects. This entire set of computations takes place against the backdrop of a rich geometry package which serves a variety of roles, including initialization of electromagnetic field simulations and the support of state-dependent algorithm-swapping and behavioral changes as a particle's state evolves. Thanks to the very general approach taken by Kassiopeia it can be used by other experiments facing similar challenges when calculating particle trajectories in electromagnetic fields. It is publicly available at https://github.com/KATRIN-Experiment/Kassiopei

Multicentre analysis of current strategies and outcomes in open aortic arch surgery: heterogeneity is still an issue

Abstract OBJECTIVES: The study was conducted to evaluate, on the basis of a multicentre analysis, current results of elective open aortic arch surgery performed during the last decade. METHODS: Data of 1232 consecutive patients who underwent aortic arch repair with reimplantation of at least one supra-aortic artery between 2004 and 2013 were collected from 11 European cardiovascular centres, and retrospective statistical examination was performed using uni-and multi-variable analyses to identify predictors for 30-day mortality. Acute aortic dissections and arch surgeries not involving the supra-aortic arteries were not included. RESULTS: Arch repair involving all 3 arch arteries (total), 2 arch arteries (subtotal) or 1 arch artery ( partial) was performed in 956 (77.6%), 155 (12.6%) and 121 (9.8%) patients, respectively. The patients' characteristics as well as the surgical techniques, including the method of cannulation, perfusion and protection, varied considerably between the clinics participating in the study. The in-hospital and 30-day mortality rates were 11.4 and 8.8% for the entire cohort, respectively, ranging between 1.7 and 19.0% in the surgical centres. Multivariable logistic regression analysis identified surgical centre, patient's age, number of previous surgeries with sternotomy and concomitant surgeries as independent risk factors of 30-day mortality. The follow-up of the study group was 96.5% complete with an overall follow-up duration of 3.3 ± 2.9 years, resulting in 4020 patient-years. After hospital discharge, 176 (14.3%) patients died, yielding an overall mortality rate of 25.6%. The actuarial survival after 5 and 8 years was 72.0 ± 1.5% and 64.0 ± 2.0, respectively. CONCLUSIONS: The surgical risk in elective aortic arch surgery has remained high during the last decade despite the advance in surgical techniques. However, the patients' characteristics, numbers of surgeries, the techniques and the results varied considerably among the centres. The incompleteness of data gathered retrospectively was not effective enough to determine advantages of particular cannulation, perfusion, protection or surgical techniques; and therefore, we strongly recommend further prospective multicentre studies, preferably registries, in which all relevant data have to be clearly defined and collected

Integration eines optischen 3D-Sensors in ein Koordinatenmessgerät für die Digitalisierung komplexer Oberflächen

The aim of this dissertation was the integration of a fringe projection system in a coordinate measuring machine. As a result large and complex workpieces can be digitalized fast, flexible and accurate. By digitalization of complex or large workpieces with the fringe projection system it is not possible to get the measuring data of the complete surface in one view. So it is necessary to merge sub-measuring fields respectively the point-clouds. In this dissertation workpiece surfaces are considered large or complex, if the workpiece that has to be digitalized is larger than the measuring field of the fringe projection system. If workpieces cannot be digitalized in one view because of reflection or shadowing effects, they are also considered large or complex. The registration (merging) of the sub-measuring fields results from the defined sensor position to the measuring object in the coordinate measuring machine. For this procedure it is necessary to know the relative position of the sensor coordinate system and the coordinate system of the CMM to each other. This is warranted by a special, that was developed in this dissertation, calibration procedure of the fringe projection system referring to the coordinate measuring machine. The digitalization of complex shaped workpieces demands a high flexibility in the positioning of the sensor to the measuring object. In this way all surface areas can be touched with the sensor in an optimal way. Therefore, the calibration procedure is realized in five degrees of freedom: three translatory degrees of freedom to implement the linear movement of the fringe projection system in three orthogonal directions inside the measuring volume of the CMM as well as two rotational degrees of freedom. On the one hand the rotational degrees of freedom allow the possibility of rotation of a clamped measuring object. On the other hand the rotation of the fringe projection system around the measuring object can be realized. The calibration procedure is afflicted with an uncertainty, which has an effect on the precision of the registration process. The resulting residual error in the total point-clouds results in height offsets between the partial point-clouds. Based on the residual error of the registered point-clouds, the concept of roughly-registered point-clouds was introduced in the framework of this dissertation. The minimization of the existing residual error in the roughly-registered point clouds was reached with an additional fine registration on basis of an iterative-closest-point algorithm. In particular different minimization methods based on simulated annealing, simplex procedure or conjugate-gradient method were examined regarding attainable precision. The fine registration was realised sucessfully both for norm-geometries like spheres or planes and for free form surfaces and was successfully implemented in the registration software. The present work makes a contribution to the multi-sensor application of coordinate measuring machines. For integration of the optical 3D-sensor a multi-sensor-coordinate measuring machine of the company "Werth Messtechnik" was used. Factory-made it consists of a tactile sensing device, an image processing unit and a video autofocus sensor. By the integration of the fringe projection system it could be expanded the functionality of the multi-sensor coordinate measuring machine with the objective of the flexible and exact three-dimensional surface digitalization