Applied Aspects of Modern Metrology

In the modern era of scientific and technological development, the role of measurements and metrology in scientific research is becoming more and more important due to the increase in the testing of various products. Moreover, requirements for the accuracy and reliability of measurement results are increasing significantly and their ranges are expanding. Improving measurement accuracy allows us to identify the shortcomings of certain technological processes and either eliminate them or reduce their influence. This leads to better-quality products and contributes to saving energy and other resources, as well as raw materials and materials. This book discusses relevant aspects of practical metrological activity to establish traceability of measurements while increasing their accuracy and reliability. It also presents procedures for the calibration and testing of measuring instruments

Intermediate Filament Mechanics Across Scales – From Single Filaments to Single Interactions and Networks in Cells

The mechanical properties of cells are largely determined by the cytoskeleton. The cytoskeleton is an intricate and complex structure formed by protein filaments, motor proteins, and crosslinkers. The three main types of protein filaments are microtubules, actin filaments, and intermediate filaments ( IFs ). Whereas the proteins that form microtubules and actin filaments are exceptionally conserved throughout cell types and organisms, the family of IFs is diverse. For example, the IF protein vimentin is expressed in relatively motile fibroblasts, and keratin IFs are found in epithelial cells. This variety of IF proteins might therefore be linked to the various mechanical properties of different cell types. In the scope of this thesis, I combine studies of IF mechanics on different time scales and in systems of increasing complexity, from single filaments to networks in cells. This multiscale approach allows for the simplification necessary to interpret observations while adding increasing physiological context in subsequent experiments. We especially focus on the tunability of the IF mechanics by environmental cues in these increasingly complex systems. In a series of experiments, including single filament elongation studies, single filament stretching measurements with optical tweezers, filament-filament interaction measurements with four optical tweezers, microrheology, and isotropic cell stretching, we characterize how electrostatic (pH and ion concentration) and hydrophobic interactions (detergent) provide various mechanisms by which the mechanics of the IF cytoskeleton can be tuned. These studies reveal how small changes, such as charge shifts, influence IF mechanics on multiple scales. In combination with simulations, we determine the mechanisms by which charge shifts alter single vimentin filament mechanics and we extract energy landscapes for interactions between single filaments. Such insights will provide a deeper understanding of the mechanisms by which cells can maintain their integrity and adapt to the mechanical requirements set by their environment

Particle Physics Reference Library

This third open access volume of the handbook series deals with accelerator physics, design, technology and operations, as well as with beam optics, dynamics and diagnostics. A joint CERN-Springer initiative, the “Particle Physics Reference Library” provides revised and updated contributions based on previously published material in the well-known Landolt-Boernstein series on particle physics, accelerators and detectors (volumes 21A,B1,B2,C), which took stock of the field approximately one decade ago. Central to this new initiative is publication under full open acces

Concatenative speech synthesis: a Framework for Reducing Perceived Distortion when using the TD-PSOLA Algorithm

This thesis presents the design and evaluation of an approach to concatenative speech synthesis using the Titne-Domain Pitch-Synchronous OverLap-Add (I'D-PSOLA) signal processing algorithm. Concatenative synthesis systems make use of pre-recorded speech segments stored in a speech corpus. At synthesis time, the `best' segments available to synthesise the new utterances are chosen from the corpus using a process known as unit selection. During the synthesis process, the pitch and duration of these segments may be modified to generate the desired prosody. The TD-PSOLA algorithm provides an efficient and essentially successful solution to perform these modifications, although some perceptible distortion, in the form of `buzzyness', may be introduced into the speech signal. Despite the popularity of the TD-PSOLA algorithm, little formal research has been undertaken to address this recognised problem of distortion. The approach in the thesis has been developed towards reducing the perceived distortion that is introduced when TD-PSOLA is applied to speech. To investigate the occurrence of this distortion, a psychoacoustic evaluation of the effect of pitch modification using the TD-PSOLA algorithm is presented. Subjective experiments in the form of a set of listening tests were undertaken using word-level stimuli that had been manipulated using TD-PSOLA. The data collected from these experiments were analysed for patterns of co- occurrence or correlations to investigate where this distortion may occur. From this, parameters were identified which may have contributed to increased distortion. These parameters were concerned with the relationship between the spectral content of individual phonemes, the extent of pitch manipulation, and aspects of the original recordings. Based on these results, a framework was designed for use in conjunction with TD-PSOLA to minimise the possible causes of distortion. The framework consisted of a novel speech corpus design, a signal processing distortion measure, and a selection process for especially problematic phonemes. Rather than phonetically balanced, the corpus is balanced to the needs of the signal processing algorithm, containing more of the adversely affected phonemes. The aim is to reduce the potential extent of pitch modification of such segments, and hence produce synthetic speech with less perceptible distortion. The signal processingdistortion measure was developed to allow the prediction of perceptible distortion in pitch-modified speech. Different weightings were estimated for individual phonemes,trained using the experimental data collected during the listening tests.The potential benefit of such a measure for existing unit selection processes in a corpus-based system using TD-PSOLA is illustrated. Finally, the special-case selection process was developed for highly problematic voiced fricative phonemes to minimise the occurrence of perceived distortion in these segments. The success of the framework, in terms of generating synthetic speech with reduced distortion, was evaluated. A listening test showed that the TD-PSOLA balanced speech corpus may be capable of generating pitch-modified synthetic sentences with significantly less distortion than those generated using a typical phonetically balanced corpus. The voiced fricative selection process was also shown to produce pitch-modified versions of these phonemes with less perceived distortion than a standard selection process. The listening test then indicated that the signal processing distortion measure was able to predict the resulting amount of distortion at the sentence-level after the application of TD-PSOLA, suggesting that it may be beneficial to include such a measure in existing unit selection processes. The framework was found to be capable of producing speech with reduced perceptible distortion in certain situations, although the effects seen at the sentence-level were less than those seen in the previous investigative experiments that made use of word-level stimuli. This suggeststhat the effect of the TD-PSOLA algorithm cannot always be easily anticipated due to the highly dynamic nature of speech, and that the reduction of perceptible distortion in TD-PSOLA-modified speech remains a challenge to the speech community

Standard Model Theory for the FCC-ee Tera-Z stage

The future 100-km circular collider FCC at CERN is planned to operate in one of its modes as an electron-positron FCC-ee machine. We give an overview comparing the theoretical status to the experimental demands of one of four foreseen FCC-ee operating stages, Z-boson resonance energy physics, called the FCC-ee Tera-Z stage for short. The FCC-ee Tera-Z will deliver the highest integrated luminosities as well as very small systematic errors for a study of the Standard Model (SM) with unprecedented precision. In fact, the FCC-ee Tera-Z will allow the study of at least one more perturbative order in quantum field theory compared to the LEP/SLC precision. The real problem is that the present precision of theoretical calculations of the various SM observables does not match that of the anticipated experimental measurements. The bottle-necks to overcoming this situation are identified. In particular, the issues of precise QED unfolding and the correct calculation of SM pseudo-observables are critically reviewed. In an Executive Summary, we specify which basic theoretical calculations are needed to meet the strong experimental expectations at the FCC-ee Tera-Z. Several methods, techniques and tools needed for higher-order multi-loop calculations are presented. By inspection of the Z-boson partial and total decay width analyses, it is argued that at the beginning of operation of the FCC-ee Tera-Z, the theory predictions may be tuned to be precise enough not to limit the physics interpretation of the measurements. This statement is based on anticipated progress in analytical and numerical calculations of multi-loop and multi-scale Feynman integrals and on the completion of two-loop electroweak radiative corrections to the SM pseudo-observables this year. However, the above statement is conditional as the theoretical issues demand a very dedicated and focused investment by the community.Comment: Published versio

Concatenative speech synthesis : a framework for reducing perceived distortion when using the TD-PSOLA algorithm

This thesis presents the design and evaluation of an approach to concatenative speech synthesis using the Titne-Domain Pitch-Synchronous OverLap-Add (I'D-PSOLA) signal processing algorithm. Concatenative synthesis systems make use of pre-recorded speech segments stored in a speech corpus. At synthesis time, the `best' segments available to synthesise the new utterances are chosen from the corpus using a process known as unit selection. During the synthesis process, the pitch and duration of these segments may be modified to generate the desired prosody. The TD-PSOLA algorithm provides an efficient and essentially successful solution to perform these modifications, although some perceptible distortion, in the form of `buzzyness', may be introduced into the speech signal. Despite the popularity of the TD-PSOLA algorithm, little formal research has been undertaken to address this recognised problem of distortion. The approach in the thesis has been developed towards reducing the perceived distortion that is introduced when TD-PSOLA is applied to speech. To investigate the occurrence of this distortion, a psychoacoustic evaluation of the effect of pitch modification using the TD-PSOLA algorithm is presented. Subjective experiments in the form of a set of listening tests were undertaken using word-level stimuli that had been manipulated using TD-PSOLA. The data collected from these experiments were analysed for patterns of co- occurrence or correlations to investigate where this distortion may occur. From this, parameters were identified which may have contributed to increased distortion. These parameters were concerned with the relationship between the spectral content of individual phonemes, the extent of pitch manipulation, and aspects of the original recordings. Based on these results, a framework was designed for use in conjunction with TD-PSOLA to minimise the possible causes of distortion. The framework consisted of a novel speech corpus design, a signal processing distortion measure, and a selection process for especially problematic phonemes. Rather than phonetically balanced, the corpus is balanced to the needs of the signal processing algorithm, containing more of the adversely affected phonemes. The aim is to reduce the potential extent of pitch modification of such segments, and hence produce synthetic speech with less perceptible distortion. The signal processingdistortion measure was developed to allow the prediction of perceptible distortion in pitch-modified speech. Different weightings were estimated for individual phonemes,trained using the experimental data collected during the listening tests.The potential benefit of such a measure for existing unit selection processes in a corpus-based system using TD-PSOLA is illustrated. Finally, the special-case selection process was developed for highly problematic voiced fricative phonemes to minimise the occurrence of perceived distortion in these segments. The success of the framework, in terms of generating synthetic speech with reduced distortion, was evaluated. A listening test showed that the TD-PSOLA balanced speech corpus may be capable of generating pitch-modified synthetic sentences with significantly less distortion than those generated using a typical phonetically balanced corpus. The voiced fricative selection process was also shown to produce pitch-modified versions of these phonemes with less perceived distortion than a standard selection process. The listening test then indicated that the signal processing distortion measure was able to predict the resulting amount of distortion at the sentence-level after the application of TD-PSOLA, suggesting that it may be beneficial to include such a measure in existing unit selection processes. The framework was found to be capable of producing speech with reduced perceptible distortion in certain situations, although the effects seen at the sentence-level were less than those seen in the previous investigative experiments that made use of word-level stimuli. This suggeststhat the effect of the TD-PSOLA algorithm cannot always be easily anticipated due to the highly dynamic nature of speech, and that the reduction of perceptible distortion in TD-PSOLA-modified speech remains a challenge to the speech community.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Metastatic Progression and Tumour Heterogeneity

Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors