Machine tool coolant concentration and pH data.

The project deals with the testing of SRAM memories using method MBIST with the utilisation of sofware tool Tessent Memory BIST. The main purpose is to get familiar with memory testing and to create a design for testing on a specific chip which after its implementation on the chip will retain the original features and functions. Subsequently, the tool is evaluated on its usability.

This thesis deals with automatic bacteria genotyping by rep-PCR method. Its theoretical part presents various methods of DNA typing, basic information on electrophoresis and modern electrophoretic approaches, including their problems, misleading data distortion. In order to automate typing, there has been introduced a program for phylogenetic sample classification from rep-PCR, also applicable for data from chip capillary electrophoresis. The program consists of three main parts: digitization, bandmatching and clustering apparatus to bacterial type classification. The result of the algorithm is a phylogenetic tree, which indicates the cluster of sapmles according to bacterial type. The program has a graphical user interface for possible use in the Children's Hospital. Finally, the program is tested with data from the Children´s Hospital.

Three-dimensional spheroid arrays represent in vivo activity better than conventional 2D cell culturing. A high-throughput microfluidic chip may be capable of depositing cells into spheroid arrays, but it is difficult to regulate the path of individual cells for deposition. Droplets that encapsulate cells may aid in facilitating cell delivery and deposition in the return bend of a microfluidic chip. In this study, a low-cost method for fabricating polymer-cast microfluidic chips has been developed for rapid device prototyping. Computational fluid dynamic (CFD) simulations were conducted to quantify how a change in geometry or fluid properties affects the dynamics of a droplet. These simulations have shown that the deformation, velocity, and trajectory of a droplet are altered when varying the geometry and fluid properties of a multiphase microfluidic system. This quantitative data will be beneficial for the future design of a microfluidic chip for cell deposition into 3D spheroid arrays.

A biosensor is an analytical device integrating a biological element and a physicochemical transducer that convert a biological response into a measurable signal. The advantages of biosensors include low cost, small size, quick, sensitivity and selectivity greater than the conventional instruments. Biosensors have a wide range of applications ranging from clinical diagnostics through to environmental monitoring, agriculture industry, et al. The different types of biosensors are classified based on the sensor device as well as the biological material. Biosensors can be broadly classified into (piezoelectric, etc.), electrochemical biosensors (potentiometric, amperometric, etc.), and optical types of biosensors (fiber optics, etc.). Here, we introduce a novel microfluidics-integrated biosensor platform system that can be flexibly adapted to form individual biosensors for different applications. In this dissertation, we present five examples of different emerging areas with this biosensor system including anti-cancer drug screening, glucose monitoring, heavy metal elements measurement, obesity healthcare, and waterborne pathogen DNA detection. These micro-biosensors have great potential to be further developed to emerging portable sensing devices especially for the uses in the developing and undeveloped world. At the last chapter, Raman spectroscopy applied to assess gestational status and the potential for pregnancy complications is presented and discussed. This technique could significantly benefit animal reproduction.

Sex differences in mammalian gene expression result from differences in genotypic sex as well as in hormonal regulators between males and females. In rat, mouse and human liver, ~1000 genes are expressed in a sex-dependent manner, and contribute to sex differences in metabolism of drugs, steroids and lipids, and in liver and cardiovascular disease risk. In rats and mice, sex-biased liver gene expression is primarily dictated by the sexually dimorphic pattern of pituitary growth hormone (GH) release and its STAT5-dependent transcriptional activities. Studies presented in this thesis include the following. (1) A computational approach based on DNA sequence and phylogenetic conservation was developed and used to identify novel functional STAT5 binding sites - both consensus and non-consensus STAT5 sequences - near prototypic GH-responsive genes. (2) Global gene expression analysis of livers from pituitary-ablated male and female mice identified four major classes of sex-biased genes differing in their profiles of GH dependence. (3) Sex-differences in DNase-hypersensitive sites (DHS, corresponding to open chromatin regions) were identified genome-wide in mouse liver. These sex-differential DHSs were enriched for association with sex-biased genes, but a majority was distant from sex-biased genes. Furthermore, many were responsive to GH treatment, demonstrating that GH-mediated regulation involves chromatin remodeling. Analysis of sequence motifs enriched at sex-biased DHSs implicated STAT5 and novel transcription factors such as PBX1 and TAL1 in sex-biased gene regulation. (4) Genome-wide mapping of histone modifications revealed distinct mechanisms of sex-biased gene regulation in male and female liver: sex-dependent K27me3-mediated repression is an important mechanism of repression of female-biased, but not of male-biased, genes, and a sex-dependent K4me1 distribution, suggesting nucleosome repositioning by pioneer factors, is observed at male-biased, but not female-biased, regulatory sites. STAT5-mediated activation was most strongly associated with sex-biased chromatin modifications, while BCL6-mediated repression primarily occurs in association with sex-independent chromatin modifications, both at binding sites and at target genes. The relationships between sex-dependent chromatin accessibility, chromatin modifications and transcription-factor binding uncovered by these studies help elucidate the molecular mechanisms governing sex-differential gene expression, and underscore the utility of functional genomic and epigenetic studies as tools for elucidating transcriptional regulation in complex mammalian systems.

Heterogeneous System-on-Chip (SoC) architectures combine general-purpose processors with many accelerators, which are application-specific computing engines. By having their hardware optimized to perform specific tasks, accelerators deliver massive speedups and energy savings compared to corresponding software executions on a processor. Heterogeneity and hardware specialization complicate accelerator design and integration, reducing regularity and reusability across platforms. The many system-level architectural aspects to consider make it hard to explore the design space and arrive to optimal solutions. Furthermore, integrating accelerators affects the programmability of the applications and the security of the entire SoC. In this dissertation, I present design methodologies and architectural contributions that use multi-functional interfaces to simplify many of the tasks that designers perform when designing and integrating accelerators in heterogeneous SoCs. The accelerator interfaces exploit latency-insensitive design to effectively explore the design space when multiple accelerators are integrated and to speed up the verification of accelerators. This improves their reusability across SoC platforms, while ensuring correctness when the accelerators are integrated with the various components of the SoC. In addition, the accelerator interfaces improve the integration with software by making it transparent and by establishing a strong layer of protection between accelerators and applications.The interfaces aim at securing the accelerators and the applications without requiring modifications to the accelerator implementations and without degrading their performance and energy efficiency.

Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-D-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.

Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-D-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.

The overall goal of this series is to detail the paradigm shift that proteomics will bring to the practice of pediatric medicine and research. Proteomics is the global study of proteins in a biological system, tissue or bodily fluid. This first review will provide a brief overview of proteomics and describe its niche in the other "omics" of system biology. The underlying technology and methodology will be outlined as well as the obstacles that must be surmounted before pediatric proteomics is optimally useful for clinicians. The potential of proteomics in the area of personalized pediatric medicine will also be discussed since this is of particular clinical relevance. The second article in this series will focus on the application of proteomics to neonatology with particular emphasis on diseases where oxidative stress plays a key pathophysiological role.