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The issue of the thesis fall under the department of non destructive testing of wood. The thesis description is an experiment, which includes the measurement by application of a new semi destructive device on wooden beams commonly used in historical constructions in the Czech Republic. This measurement was monitored by DIC technology at the same time. The part of the results of work is also the treatise about the influence of different factors like the wood density, moisture content and others. This final thesis also discusses about the accuracy and appropriateness the measurement by a new diagnostic device for in-situ determination of strength and modulus of deformability in compression of wood parallel to fibers.

Cryogenic detectors are an advanced technology for both dark matter and neutrinoless double beta decay searches, having the key advantage of a range of possible absorber materials that can be used for the detectors. Neutron transmutation doped germanium sensors are highly sensitive thermometers ideal for use at milli kelvin temperatures, with a simple repeatable resistance temperature relation. To discriminate between candidate events and background events simultaneous measurements can be made of the energy deposited in the detector as phonons and the energy emitted by the absorber crystal as scintillation light. Phonon detectors with a calcium tungstate or calcium molybdate crystal as the target and an NTD sensor as a thermometer were made in Oxford, along with a light detector with a light-absorbing silicon layer on a sapphire crystal, also with an NTD thermometer. A system of electronics was designed and tested in Oxford to bias and readout the NTD thermometers, while the setup inside the cryostat was developed to provide a thermally and mechanically stable shielded environment for the detectors. As part of this, prototype semi-rigid kapton cabling for use in the EDELWEISS experiment was installed and tested in the cryostat. Three different NTD germanium sensor types were characterized and calibrated in the cryostat and two of these selected for use on the phonon and light detectors. The detectors were operated at temperatures as low as 9 mK and tested with radioactive sources to produce energy spectra. Baseline resolutions of 1.7 keV and 2.5 keV, respectively, were achieved for the calcium molybdate and calcium tungstate phonon detectors. A working scintillation light detector was demonstrated as part of a phonon-scintillation detector module with a suggested application in double-beta decay searches.

Cette thèse se situe à l’interface entre la biologie et la biophysique. Les méthodologies utilisées recouvrent principalement la résonance magnétique nucléaire (RMN), la diffusion des rayons X aux petits angles (SAXS), le dichroïsme circulaire (CD) et la spectroscopie de fluorescence. Une première partie vise à étudier le domaine de liaison à l’ADN (DBD) du récepteur des androgènes (AR) et les déterminants de l’interaction avec l’ADN. Une mutation faux-sens dans le DBD altère la spécificité de reconnaissance de l’ADN du récepteur bien que la structure tridimensionnelle soit identique au DBD sauvage. Les résultats montrent un changement dans la dynamique du récepteur mutant entrainant une déstabilisation de l’homo-dimère.La seconde partie de ma thèse consiste à établir un lien séquence/fonction au niveau du domaine N terminal (NTD) de AR. D’après la littérature, cette région joue un rôle important pour l’activité du récepteur, et elle est également décrite comme étant intrinsèquement désordonnée. Les résultats révèlent que cette région établit des contacts transitoires avec le DBD. Ceci suggère l’existence d'un couplage allostérique entre le DBD et les résidus adjacents sur le NTD.Ce couplage modifie l'ensemble conformationnel accessible au NTD en favorisant une conformation en hélice-α. / My PhD project is at the boundary between biology and biophysic. Methods used include nuclear magnetic resonance (NMR), small ange X-ray scattering (SAXS), circular dichroïsm (CD) and fluorescence spectroscopy. The androgen receptor (AR) DNA binding domain (DBD) and its interaction with DNA was studied in a first part. A mutation in the DBD leads to a modified DNA recognition by the mutant compared to the wild-type. Our results indicate changes in dynamic of the mutant receptor that leads to the homodimer destabilisation.The second part of my project aim to establish a link between sequence and function of the AR N terminal domain (NTD).As described in literature, this region is involved in the activity of the receptor and is also an intrinsically disordered protein (IDP). The results obtained during my thesis indicate that this region is involved in transient contact with the DBD. This suggest an allosteric coupling between the DBD and the neighboring residues on the NTD.This coupling modifies the conformational ensemble accessible to the NTD by stabilizing a α-helix conformation.

NtdB is an enzyme encoded within the ntd operon in Bacillus subtilis. This operon is reported to contain a complete set of genes necessary for the biosynthesis of 3,3'-neotrehalosadiamine (NTD), a compound composed of two kanosamine subunits linked together by a 1,1'-(α,β)-linkage. Both NTD and kanosamine have reported antibiotic properties. The function of NtdB has been a matter of speculation, but has never been investigated in vitro. Using a phosphate assay and an array of substrates, NtdB was determined to be a phosphatase, specific to kanosamine-6-phosphate (K6P) (kcat = 32 ± 1 s-1, Km = 93 ± 7 µM). Site-directed mutagenesis of amino acid residues in the core and the cap domains of the enzyme identified residues important for the catalytic reaction and substrate specificity. These mutations confirmed the presence of four motifs, characteristic of members of the haloacid dehalogenase (HAD) superfamily, and allowed identification of the substrate binding site of the enzyme. KabB, a homologue of NtdB from Bacillus cereus, showed notably lower activity with K6P than NtdB. This research defines the role of NtdB as a specific K6P phosphatase and challenges the previously reported NTD biosynthesis pathway by demonstrating a novel pathway for the production of the antibiotic kanosamine.

Neural tube defects (NTDs) are malformations affecting about 2.6/1000 births worldwide, and 1/1000 in the United States. Their etiology remains unknown, and is likely due to interaction of genetic susceptibility factors with environmental exposure. Of the many environmental agents considered to potentially contribute to NTD risk, arsenic is one that is surrounded in controversy. We have developed a model system utilizing maternal intraperitoneal (I.P.) exposure on E7.5 and E8.5 to As 9.6 mg/kg (as sodium arsenate) in a normal inbred mouse strain, LM/Bc/Fnn, that is sensitive to arsenate-induced exencephaly. We investigated arsenate induced gene expression changes using DNA microarrays of embryonic anterior neural tube tissue, as well as monitoring of metabolic function in conjunction with the administration of select compounds to rescue the normal phenotype. Finally, to address questions concerning the importance of route of administration and potential maternal toxicity, a teratology study was performed using three arsenate doses administered orally. Regarding the gene expression study, we identified several candidate genes and ontology groups that may be responsible for arsenate’s teratogenicity. Genes include: engrailed 1 (En-1), platelet derived growth factor receptor alpha (Pdgfrα) and ephrinA7 (EphA7). Gene ontology groups identified include oxidative phosphorylation, redox response, and regulation of I-kappaB kinase/NF-kappaB cascade. Acute arsenate exposure induced disruption of mitochondrial function and dependent glucose homeostasis: subsequent hyperglycemia was teratogenic. Maternal treatment with insulin or n-acetyl cysteine, an antioxidant and precursor of glutathione synthesis, proved highly successful in rescuing both the normal phenotype, and to differing degree, the maternal hyperglycemia. Maternal oral arsenate administration also resulted in exencephaly, with exposed embryos exhibiting a positive linear trend with arsenate dosage. There were also linear trends in the relationships between arsenate dose and anomalies involving several components of the axial skeleton: the vertebrae and calvarium. There was no evidence of maternal toxicity as shown by lack of differences in maternal body weight gain, liver, and kidney weights. In conclusion, maternal arsenate exposure (regardless of exposure route) was teratogenic in our model, primarily causing NTDs. Responsible mechanisms may involve disruption of redox and glucose homeostasis as well as expression of established NTD candidate genes.

Neural tube defects (NTDs) are malformations affecting about 2.6/1000 births worldwide, and 1/1000 in the United States. Their etiology remains unknown, and is likely due to interaction of genetic susceptibility factors with environmental exposure. Of the many environmental agents considered to potentially contribute to NTD risk, arsenic is one that is surrounded in controversy. We have developed a model system utilizing maternal intraperitoneal (I.P.) exposure on E7.5 and E8.5 to As 9.6 mg/kg (as sodium arsenate) in a normal inbred mouse strain, LM/Bc/Fnn, that is sensitive to arsenate-induced exencephaly. We investigated arsenate induced gene expression changes using DNA microarrays of embryonic anterior neural tube tissue, as well as monitoring of metabolic function in conjunction with the administration of select compounds to rescue the normal phenotype. Finally, to address questions concerning the importance of route of administration and potential maternal toxicity, a teratology study was performed using three arsenate doses administered orally. Regarding the gene expression study, we identified several candidate genes and ontology groups that may be responsible for arsenate’s teratogenicity. Genes include: engrailed 1 (En-1), platelet derived growth factor receptor alpha (Pdgfrα) and ephrinA7 (EphA7). Gene ontology groups identified include oxidative phosphorylation, redox response, and regulation of I-kappaB kinase/NF-kappaB cascade. Acute arsenate exposure induced disruption of mitochondrial function and dependent glucose homeostasis: subsequent hyperglycemia was teratogenic. Maternal treatment with insulin or n-acetyl cysteine, an antioxidant and precursor of glutathione synthesis, proved highly successful in rescuing both the normal phenotype, and to differing degree, the maternal hyperglycemia. Maternal oral arsenate administration also resulted in exencephaly, with exposed embryos exhibiting a positive linear trend with arsenate dosage. There were also linear trends in the relationships between arsenate dose and anomalies involving several components of the axial skeleton: the vertebrae and calvarium. There was no evidence of maternal toxicity as shown by lack of differences in maternal body weight gain, liver, and kidney weights. In conclusion, maternal arsenate exposure (regardless of exposure route) was teratogenic in our model, primarily causing NTDs. Responsible mechanisms may involve disruption of redox and glucose homeostasis as well as expression of established NTD candidate genes.

Aim: The aim of this paper is to provide a deeper understanding of the spread of NTDs but to also determine what is missing in the health interventions that are conducted in the countries affected by NTD. Method and theory: The method used in this paper is the theory testing approach which is the Social Cognitive Theory. Development in the 1970s by A. Badura, it’s based on the concept of interaction between personal, environmental and social factors. Results: The results showed that both the previous research and today’s health interventions lack the understanding of the roll social and personal factors play in the spread of NTD. They mainly target the environmental factors and medical. Therefore, the NTDs are still endemic despite the effort during many years.

Study questions: Does the proportion of neural tube defects (NTDs) in which there are co-occurring anomalies of other systems vary by geographical area and time in Europe between 1980 and 2015? Which group of factors, e.g., sex, age, family history, condition at discovery, and prenatal screening during pregnancy that potentially affect ascertainment of isolated NTD cases and co-occurring anomalies, are associated with the presence of these anomalies? Methods: Data on fetuses or births with NTDs recorded in 28 European Surveillance of Congenital Anomalies (EUROCAT) registries operating throughout or during a part of the period 1980-2015, were obtained and analysed. Information on the corresponding denominators of total births for each registry were compiled, comprising approximately 15.7 million births. We developed algorithms to classify NTDs that occurred as part of certain recognized genetic and unknown etiology syndromes, isolated NTD cases (either with no other anomaly reported or only an anomaly considered to be secondary to the NTD), and NTDs not occurring as part of recognized syndromes but with one or more co-occurring anomalies. We assessed factors that could impact ascertainment of isolated NTD cases and NTD cases with co-occurring anomalies. We also conducted a sensitivity analysis to evaluate the effect of family history and consanguinity on NTD outcomes. Lastly, we reported on the prevalence of NTDs across Eastern, Western, Northern, and Southern Europe as defined by the World Bank. Results: A total of 14,703 fetuses or births with NTDs were recorded in the EUROCAT registries. The total number of births (live and stillbirths) that occurred during the periods when the EUROCAT registries were operating was 15.7 million. The overall prevalence at birth of NTDs in Eastern Europe was 11.6 per 10,000 births, in Western Europe 11.0 per 10,000 births, in Northern Europe 10.5 cases per 10,000 births and in Southern Europe 6.7 per 10,000 births. The most prevalent genetic syndromes were chromosomal anomalies, particularly trisomy 18. The most common secondary anomaly was Arnold-Chiari syndrome which occurred mostly with spina bifida. The most prevalent associated anomalies were limb defects, followed by congenital heart defects, abdominal wall, and urinary system defects. We found anencephaly to be most prevalent in isolated NTD cases without secondary anomalies and spina bifida in secondary anomalies and most of the co-occurring anomalies. For factors that could affect ascertainment, we found that birth type, birth weight, family history, maternal and paternal age (≥30 years) were risk factors for isolated NTD cases and for co-occurring anomalies. Lastly, approximately 48% of NTDs occurred in Northern Europe, followed 29% in Western Europe, 16% in Southern Europe, and 7.6% in Eastern Europe. Conclusion: In the absence of folate fortification, isolated NTD cases showed higher prevalence than NTDs with co-occurring anomalies over the past 35 years across Europe. This research suggests that Europe should develop and implement policies and guidelines for folate fortification to help prevent simpler NTD cases. Further research and data are needed for newer EUROCAT registries to predict trends and prevalence of NTDs. Contribution and involvement: This project was done in collaboration with the experts from the School of Epidemiology and Public Health (SEPH) and dysmorphologists that provided support with regards to NTD classification. AB spearheaded the development of the research protocol and thesis manuscript with funding and support from JL and TR. Evaluation of the output of cases from the algorithm was provided to AB by JL, TR, JE, FB, AN, EB, ML, and the EUROCAT Joint Research Centre.

5 Abstract The final thesis addresses certain aspects of current topic of online intermediaries' liability for user-generated content ("UGC"). Under Act No. 480/2004 Coll., on certain information society services ("2004 Act on ISS"), which transposes e- Commerce Directive 2000/31/EC, online intermediaries in the Czech Republic benefit from "safe harbours". Essentially, it means that online intermediaries can be held liable for UGC only if they had actual or constructive knowledge of illegality of the content. This rule implicitly creates the so called "Notice and Take Down" procedure ("NTD"). Online intermediary upon receiving a notice, and thereby learning about the illegality of the content, is obliged to expeditiously take down the illegal content in order to preserve his immunity. However, NTD is neither expressly regulated within the ECD nor within the 2004 Act on ISS. Therefore, the purpose of the thesis is to illuminate NTD procedure and provide guidelines for it successful application within the Czech Republic. The thesis should be helpful not only to online intermediaries, but also to aggrieved parties serving notices. For this purpose the thesis looks not only at the ECD and its transpositions in various Member States, but also at American Digital Millennium Copyright Act 1998 that has been the...