Genome reorganization in different cancer types: detection of cancer specific breakpoint regions

Background: Tumorigenesis is a multi-step process which is accompanied by substantial changes in genome organization. The development of these changes is not only a random process, but rather comprise specific DNA regions that are prone to the reorganization process. Results: We have analyzed previously published SNP arrays from three different cancer types (pancreatic adenocarcinoma, breast cancer and metastatic melanoma) and from non-malignant control samples. We calculated segmental copy number variations as well as breakpoint regions. Some of these regions were not randomly involved in genome reorganization since we detected fifteen of them in at least 20% of all tumor samples and one region on chromosome 9 where 43% of tumors have a breakpoint. Further, the top-15 breakpoint regions show an association to known fragile sites. The relevance of these common breakpoint regions was further confirmed by analyzing SNP arrays from 917 cancer cell lines. Conclusion: Our analyses suggest that genome reorganization is common in tumorigenesis and that some breakpoint regions can be found across all cancer types, while others exclusively occur in specific entities

Alpha suppression and connectivity modulations in left temporal and parietal cortices index partial awareness of words

The partial awareness hypothesis is a theoretical proposal that recently provided a reconciling solution to graded and dichotomous accounts of consciousness. It suggests that we can become conscious of distinct properties of an object independently, ranging from low-level features to complex forms of representation. We investigated this hypothesis using classic visual word masking adapted to a near-threshold paradigm. The masking intensity was adjusted to the individual perception threshold, at which individual alphabetical letters, but not words, could be perceived in approximately half of the trials. We confined perception to a pre-lexical stage of word processing that corresponded to a clear condition of partial awareness. At this level of representation, the stimulus properties began to emerge within consciousness, yet they did not escalate to full stimulus awareness. In other words, participants were able to perceive individual letters, while remaining unaware of the whole letter strings presented. Cortical activity measured with MEG was compared between physically identical trials that differed in perception (perceived, not perceived). We found that compared to no awareness, partial awareness of words was characterized by suppression of oscillatory alpha power in left temporal and parietal cortices. The analysis of functional connectivity with seeds based on the power effect in these two regions revealed sparse connections for the parietal seed, and strong connections between the temporal seed and other regions of the language network. We suggest that the engagement of language regions indexed by alpha power suppression is responsible for establishing and maintaining conscious representations of individual pre-lexical units

Stimulus-Driven Brain Oscillations in the Alpha Range: Entrainment of Intrinsic Rhythms or Frequency-Following Response?

First paragraph: Human brain activity is rich in rhythms of various characteristic frequencies. The last few decades have seen an increase in their use as an explanatory means, with a vast literature describing manifold correlations between dynamics of brain rhythms and behavioral performance in perceptual and cognitive tasks involving attention, memory, and language. More recently, the desire to study the causal role of neural rhythms in stimulus processing and corresponding performance has raised interest in externally entraining these rhythms

Not so different after all: The same oscillatory processes support different types of attention

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Variational Fluid Motion Estimation with Physical Priors

In this thesis, techniques for Particle Image Velocimetry (PIV) and Particle Tracking Velocimetry (PTV) are developed that are based on variational methods. The basic idea is not to estimate displacement vectors locally and individually, but to estimate vector fields as a whole by minimizing a suitable functional defined over the entire image domain (which may be 2D or 3D and may also include the temporal dimension). Such functionals typically comprise two terms: a data-term measuring how well two images of a sequence match as a function of the vector field to be estimated, and a regularization term that brings prior knowledge into the energy functional. Our starting point are methods that were originally developed in the field of computer vision and that we modify for the purpose of PIV. These methods are based on the so-called optical flow: Optical flow denotes the estimated velocity vector inferred by a relative motion of camera and image scene and is based on the assumption of gray value conservation (i.e. the total derivative of the image gray value over time is zero). A regularization term (that demands e.g. smoothness of the velocity field, or of its divergence and rotation) renders the system mathematically well-posed. Experimental evaluation shows that this type of variational approach is able to outperform standard cross-correlation methods. In order to develop a variational method for PTV, we replace the continuous data term of variational approaches to PIV with a discrete non-differentiable particle matching term. This raises the problem of minimizing such data terms together with continuous regularization terms. We accomplish this with an advanced mathematical method, which guarantees convergence to a local minimum of such a non-convex variational approach to PTV. With this novel variational approach (there has been no previous work on modeling PTV methods with global variational approaches), we achieve results for image pairs and sequences in two and three dimensions that outperform the relaxation methods that are traditionally used for particle tracking. The key advantage of our variational particle image velocimetry methods, is the chance to include prior knowledge in a natural way. In the fluid environments that we are considering in this thesis, it is especially attractive to use priors that can be motivated from a physical point of view. Firstly, we present a method that only allows flow fields that satisfy the Stokes equation. The latter equation includes control variables that allow to control the optical flow so as to fit the apparent velocities of particles in a given image pair. Secondly, we present a variational approach to motion estimation of instationary fluid flows. This approach extends the prior method along two directions: (i) The full incompressible Navier-Stokes equation is employed in order to obtain a physically consistent regularization which does not suppress turbulent flow variations. (ii) Regularization along the time-axis is employed as well, but formulated in a receding horizon manner contrary to previous approaches to spatio-temporal regularization. Ground-truth evaluations for simulated turbulent flows demonstrate that the accuracy of both types of physically plausible regularization compares favorably with advanced cross-correlation approaches. Furthermore, the direct estimation of, e.g., pressure or vorticity becomes possible

Systematische Literaturanalyse zur Therapie von chondralen und osteochondralen Knorpeldefekten am Kniegelenk durch osteochondrale Transplantation

Ziel und Gegenstand der Dissertation: Die osteochondrale Transplantation (OCT) ist eine einzeitige, autologe Therapieoption zur Behandlung von isolierten Knorpel-Knochenschäden des Kniegelenkes. Die vorliegende Arbeit analysiert alle publizierten Studien zur osteochondralen Transplantation, um auf der Basis patientenzentrierter subjektiver und funktionell objektiver sowie morphologischer Ergebnisse Empfehlungen zur Indikation abzuleiten und mögliche Einflussfaktoren des klinischen Ergebnisses herauszuarbeiten. Untersuchungsmethoden: Aus den Jahren 1997 bis 2016 wurde 45 Studien mit 3851 Patienten zur osteochondralen Transplantation am Kniegelenk beim Menschen analysiert. Bei 36 Studien mit 3641 Patienten handelte es sich um Fallserien zur OCT, 3 Studien mit dem höchsten Evidenzlevel verglichen die OCT mit der Mikrofrakturierung (110 Pat.) oder der autologen Chondrozytentransplantation (100 Pat.). 6 Studien waren dem Evidenzlevel 2 und 3 zuzuordnen. Die Defektgröße lag im Mittel bei 3,37 cm² (Min/Max 0,4-12,3). Das durchschnittliche Patientenalter lag bei 32,5 Jahren. Der mittlere Nachuntersuchungszeitraum betrug 60,7 Monaten, 82 % der Studien hatten einen Nachuntersuchungszeitraum von über 24 Monaten. Die Qualität der Studien wurde mit dem Coleman Methodology Score (CMS) evaluiert, um die Aussagekraft der Studien einzuordnen. In den 45 Studien wurde 20 verschiedene Bewertungssysteme verwendet, meistens basierend auf subjektiven Patientenangaben. Ergebnisse der Dissertation: Die Analyse der Studienqualität mittels CMS ergab 4 sehr gute Studien (CMS >80). Im Vergleich der Jahre 1997 bis 2016 zeigte sich kein Anstieg der Studienqualität. Das klinisch funktionelle Ergebnis stieg in fast allen Bewertungssystemen über die Nachuntersuchungszeiträume signifikant an und das Delta der Ergebnisevaluation lag über der klinisch relevanten minimalen Veränderung. Die Effektstärke konnte für 17 Studien berechnet werden, 15 Studien zeigten große Effekte, eine Studie kleine und eine negative Effekte. Positive Einflussfaktoren auf das Ergebnis nach OCT ist eine traumatische Ätiologie, eine Defektgröße bis 4cm², ein Patientenalter jünger als das 40. Lebensjahr und ein BMI <25kg/m². Defektlokalisation, Symptomdauer und das Geschlecht sind keine eindeutigen Prädiktoren. Die Komplikationsrate beim Verfahren der OCT lag bei 15,5%

Refraction Wiggles for Measuring Fluid Depth and Velocity from Video

We present principled algorithms for measuring the velocity and 3D location of refractive fluids, such as hot air or gas, from natural videos with textured backgrounds. Our main observation is that intensity variations related to movements of refractive fluid elements, as observed by one or more video cameras, are consistent over small space-time volumes. We call these intensity variations “refraction wiggles”, and use them as features for tracking and stereo fusion to recover the fluid motion and depth from video sequences. We give algorithms for 1) measuring the (2D, projected) motion of refractive fluids in monocular videos, and 2) recovering the 3D position of points on the fluid from stereo cameras. Unlike pixel intensities, wiggles can be extremely subtle and cannot be known with the same level of confidence for all pixels, depending on factors such as background texture and physical properties of the fluid. We thus carefully model uncertainty in our algorithms for robust estimation of fluid motion and depth. We show results on controlled sequences, synthetic simulations, and natural videos. Different from previous approaches for measuring refractive flow, our methods operate directly on videos captured with ordinary cameras, do not require auxiliary sensors, light sources or designed backgrounds, and can correctly detect the motion and location of refractive fluids even when they are invisible to the naked eye.Shell ResearchMotion Sensing Wi-Fi Sensor Networks Co. (Grant 6925133)National Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374)Microsoft Research (PhD Fellowship

Hand in Hand gegen Einsamkeit

HAND IN HAND GEGEN EINSAMKEIT Hand in Hand gegen Einsamkeit / Ruhnau, Franziska (Rights reserved) ( -