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Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL. Chemokine and chemokine receptor expression were similar in primary ALCL and cHL cases apart from the known overexpression of the chemokines CCL17 and CCL22 in the Hodgkin and Reed-Sternberg (HRS) cells of cHL. Consistent with the overexpression of these chemokines, primary cHL cases encountered a significantly denser T cell microenvironment than ALCL. Additionally to differences in the interaction with their microenvironment, cHL cell lines presented a lower and less efficient intrinsic cell motility than ALCL cell lines, as assessed by time-lapse microscopy in a collagen gel and transwell migration assays. We thus propose that the combination of impaired basal cell motility and differences in the interaction with the microenvironment hamper the dissemination of HRS cells in cHL when compared with the tumor cells of ALCL.
Our recently developed LRSX Tool implements a technique to automatically prove the correctness of program transformations in higher-order program calculi which may permit recursive let-bindings as they occur in functional programming languages. A program transformation is correct if it preserves the observational semantics of programs- In our tool the so-called diagram method is automated by combining unification, matching, and reasoning on alpha-renamings on the higher-order metalanguage, and automating induction proofs via an encoding into termination problems of term rewrite systems. We explain the techniques, we illustrate the usage of the tool, and we report on experiments.
The focus of this paper are space-improvements of programs, which are transformations that do not worsen the space requirement during evaluations. A realistic theoretical treatment must take garbage collection method into account. We investigate space improvements under the assumption of an optimal garbage collector. Such a garbage collector is not implementable, but there is an advantage: The investigations are independent of potential changes in an implementable garbage collector and our results show that the evaluation and other similar transformations are space-improvements.
Human readers have the ability to infer knowledge from text, even if that particular information is not explicitly stated. In this thesis, we address the phenomena of text-level implicit information and outline novel automated methods for its recovery.
The main focus of this work is on two types of unexpressed content that arises between sentences (implicit discourse relations) and within sentences (implicit semantic roles).
Traditional approaches mostly rely on costly rich linguistic features, e.g., sentiment or frame-based lexicons, and require heuristics or manual feature engineering.
As an improvement, we propose a collection of generic resource-lean methods, implemented in the form of statistical background knowledge or by means of neural architectures.
Our models are largely language-independent and produce state-of-the-art performance, e.g., in the classification of Chinese implicit discourse relations, or the detection of locally covert predicative arguments in free texts.
In novel experiments, we quantitatively demonstrate that both types of implicit information are mutually dependent insofar as, for instance, some implicit roles directly correlate with implicit discourse relations of similar properties.
We show that implicit information processing further benefits downstream applications and demonstrate its applicability to the higher-level task of narrative story understanding.
In the conclusion of the dissertation, we argue for the need of implicit information processing in order to realize the goal of true natural language understanding.
The development of multimodal sensor-based applications designed to support learners with the improvement of their skills is expensive since most of these applications are tailor-made and built from scratch. In this paper, we show how the Presentation Trainer (PT), a multimodal sensor-based application designed to support the development of public speaking skills, can be modularly extended with a Virtual Reality real-time feedback module (VR module), which makes usage of the PT more immersive and comprehensive. The described study consists of a formative evaluation and has two main objectives. Firstly, a technical objective is concerned with the feasibility of extending the PT with an immersive VR Module. Secondly, a user experience objective focuses on the level of satisfaction of interacting with the VR extended PT. To study these objectives, we conducted user tests with 20 participants. Results from our test show the feasibility of modularly extending existing multimodal sensor-based applications, and in terms of learning and user experience, results indicate a positive attitude of the participants towards using the application (PT+VR module).
Programmable hardware in the form of FPGAs found its place in various high energy physics experiments over the past few decades. These devices provide highly parallel and fully configurable data transport, data formatting, and data processing capabilities with custom interfaces, even in rigid or constrained environments. Additionally, FPGA functionalities and the number of their logic resources have grown exponentially in the last few years, making FPGAs more and more suitable for complex data processing tasks. ALICE is one of the four main experiments at the LHC and specialized in the study of heavy-ion collisions. The readout chain of the ALICE detectors makes use of FPGAs at various places. The Read-Out Receiver Cards (RORCs) are one example of FPGA-based readout hardware, building the interface between the custom detector electronics and the commercial server nodes in the data processing clusters of the Data Acquisition (DAQ) system as well as the High Level Trigger (HLT). These boards are implemented as server plug-in cards with serial optical links towards the detectors. Experimental data is received via more than 500 optical links, already partly pre-processed in the FPGAs, and pushed towards the host machines. Computer clusters consisting of a few hundred nodes collect, aggregate, compress, reconstruct, and prepare the experimental data for permanent storage and later analysis. With the end of the first LHC run period in 2012 and the start of Run 2 in 2015, the DAQ and HLT systems were renewed and several detector components were upgraded for higher data rates and event rates. Increased detector link rates and obsolete host interfaces rendered it impossible to reuse the previous RORCs in Run 2.
This thesis describes the development, integration, and maintenance of the next generation of RORCs for ALICE in Run 2. A custom hardware platform, initially developed as a joint effort between the ALICE DAQ and HLT groups in the course of this work, found its place in the Run 2 readout systems of the ALICE and ATLAS experiments. The hardware fulfills all experiment requirements, matches its target performance, and has been running stable in the production systems since the start of Run 2. Firmware and software developments for the hardware evaluation, the design of the board, the mass production hardware tests, as well as the operation of the final board in the HLT, were carried out as part of this work. 74 boards were integrated into the HLT hardware and software infrastructure, with various firmware and software developments, to provide the main experimental data input and output interface of the HLT for Run 2. The hardware cluster finder, an FPGA-based data pre-processing core from the previous generation of RORCs, was ported to the new hardware. It has been improved and extended to meet the experimental requirements throughout Run 2. The throughput of this firmware component could be doubled and the algorithm extended, providing an improved noise rejection and an increased overall mean data compression ratio compared to its previous implementation. The hardware cluster finder forms a crucial component in the HLT data reconstruction and compression scheme with a processing performance of one board equivalent to around ten server nodes for comparable processing steps in software.
The work on the firmware development, especially on the hardware cluster finder, once more demonstrated that developing and maintaining data processing algorithms with the common low-level hardware description methods is tedious and time-consuming. Therefore, a high-level synthesis (HLS) hardware description method applying dataflow computing at an algorithmic level to FPGAs was evaluated in this context. The hardware cluster finder served as an example of a typical data processing algorithm in a high energy physics readout application. The existing and highly optimized low-level implementation provided a reference for comparisons in terms of throughput and resource usage. The cluster finder algorithm could be implemented in the dataflow description with comparably little effort, providing fast development cycles, compact code and at, the same time, simplified extension and maintenance options. The performance results in terms of throughput and resource usage are comparable to the manual implementation. The dataflow environment proved to be highly valuable for design space explorations. An integration of the dataflow description into the HLT firmware and software infrastructure could be demonstrated as a proof of concept. A high-level hardware description could ease both the design space exploration, the initial development, the maintenance, and the extension of hardware algorithms for high energy physics readout applications.
Background: Microarray analysis represents a powerful way to test scientific hypotheses on the functionality of cells. The measurements consider the whole genome, and the large number of generated data requires sophisticated analysis. To date, no gold-standard for the analysis of microarray images has been established. Due to the lack of a standard approach there is a strong need to identify new processing algorithms.
Methods: We propose a novel approach based on hyperbolic partial differential equations (PDEs) for unsupervised spot segmentation. Prior to segmentation, morphological operations were applied for the identification of co-localized groups of spots. A grid alignment was performed to determine the borderlines between rows and columns of spots. PDEs were applied to detect the inflection points within each column and row; vertical and horizontal luminance profiles were evolved respectively. The inflection points of the profiles determined borderlines that confined a spot within adapted rectangular areas. A subsequent k-means clustering determined the pixels of each individual spot and its local background.
Results: We evaluated the approach for a data set of microarray images taken from the Stanford Microarray Database (SMD). The data set is based on two studies on global gene expression profiles of Arabidopsis Thaliana. We computed values for spot intensity, regression ratio, and coefficient of determination. For spots with irregular contours and inner holes, we found intensity values that were significantly different from those determined by the GenePix Pro microarray analysis software. We determined the set of differentially expressed genes from our intensities and identified more activated genes than were predicted by the GenePix software.
Conclusions: Our method represents a worthwhile alternative and complement to standard approaches used in industry and academy. We highlight the importance of our spot segmentation approach, which identified supplementary important genes, to better explains the molecular mechanisms that are activated in a defense responses to virus and pathogen infection.
The production of K∗(892)0 and ϕ(1020) mesons has been measured in p–Pb collisions at √sNN = 5.02 TeV. K∗0 and ϕ are reconstructed via their decay into charged hadrons with the ALICE detector in the rapidity range - 0.5 < y < 0. The transverse momentum spectra, measured as a function of the multiplicity, have a pT range from 0 to 15 GeV/c for K∗0 and from 0.3 to 21 GeV/c for ϕ. Integrated yields, mean transverse momenta and particle ratios are reported and compared with results in pp collisions at √s = 7 TeV and Pb–Pb collisions at √sNN = 2.76 TeV. In Pb–Pb and p–Pb collisions, K∗0 and ϕ probe the hadronic phase of the system and contribute to the study of particle formation mechanisms by comparison with other identified hadrons. For this purpose, the mean transverse momenta and the differential proton-to-ϕ ratio are discussed as a function of the multiplicity of the event. The short-lived K∗0 is measured to investigate re-scattering effects, believed to be related to the size of the system and to the lifetime of the hadronic phase.
Heterologously expressed genes require adaptation to the host organism to ensure adequate levels of protein synthesis, which is typically approached by replacing codons by the target organism’s preferred codons. In view of frequently encountered suboptimal outcomes we introduce the codon-specific elongation model (COSEM) as an alternative concept. COSEM simulates ribosome dynamics during mRNA translation and informs about protein synthesis rates per mRNA in an organism- and context-dependent way. Protein synthesis rates from COSEM are integrated with further relevant covariates such as translation accuracy into a protein expression score that we use for codon optimization. The scoring algorithm further enables fine-tuning of protein expression including deoptimization and is implemented in the software OCTOPOS. The protein expression score produces competitive predictions on proteomic data from prokaryotic, eukaryotic, and human expression systems. In addition, we optimized and tested heterologous expression of manA and ova genes in Salmonella enterica serovar Typhimurium. Superiority over standard methodology was demonstrated by a threefold increase in protein yield compared to wildtype and commercially optimized sequences.