The presented thesis is devoted to the experimental and numerical analysis of concrete fracture under the mixed-mode I/II load. This phenomenon was analysed on various concrete grades and types which are used in the fabrication of precast concrete structural elements. Subsequently, the Brazilian disc test with central specimen was used in experimental and numerical parts. The numerical part employs both linear elastic fracture mechanics (LEFM) approach and non-linear material model to assess the concrete fracture and failure under the mixed mode I/II load. The LEFM part is dedicated to evaluation the geometry functions and higher order terms of the Williams’ expansion, while the non-linear analysis is dedicated to crack initiation and propagation throughout the specimen using the concrete damage plasticity model. The experimental part is dedicated to the analysis of the mixed mode-mode I/II fracture resistance by the generalised tangential stress (GMTS) criterion with focus set on the governing role of the critical distance rC. Furthermore, the experimental part validates the applicability of the Williams’ expansion on the concrete. For this, experimentally measured displacements by digital image correlation technique were used to calculate the Williams’s expansion terms. Lastly, the thesis deals with the influence of the aggressive environment on the material’s fracture toughness and on the fracture resistance under the mixed mode I/II has been studied.

Malaria, caused by the parasite Plasmodium falciparum, has a long history as a global health threat. The vector-borne disease causes millions of deaths yearly, especially in developing countries with tropical climates that facilitate transmission. Compounding the problem is the emergence of drug-resistant strains due to overuse of outdated treatments. New compounds with antiplasmodial activity are needed to be developed as effective drugs against malaria. The hypothesis for this project is that marine microorganisms have a high likelihood of yielding novel antiplasmodial chemotypes because of their high diversity, which has not yet been explored for antimalarial development. In this project, microbes harvested and fermented by the Harbor Branch Oceanographic Institute in Fort Pierce, Florida were explored as sources for antiplasmodial natural products. Using a SYBR Green I fluorescence-based assay, 1,000 microbial extracts were screened for inhibition of the multidrug-resistant Plasmodium falciparum strain Dd2. Dose-response analysis was performed on 46 fractions from isolates whose extracts demonstrated greater-than or equal to] 70% inhibition of Dd2 at 1 micro]g/mL. To evaluate cytotoxicity, the MTS cell viability assay was used to calculate IC50 of extracts from active isolates in NIH/3T3 embryonic mouse fibroblasts. Several extracts demonstrated low IC50 in Dd2 and high IC50 in 3T3, suggesting that they contain potential lead antimalarial compounds. Extracts with high selectivity indices (potent plasmodial inhibition with low mammalian toxicity) have been prioritized for dereplication, with the goal of identifying novel active components that can be developed as antimalarial drugs.

The PhD. thesis deals with the morphostructural evolution of the valley network of the Biala Lądecka river, (further refer as BL) during the Late Cenozoic. In this work, the selected methods as geomorphological research (morphostructural analysis, geomorphological mapping), structural-geological research (paleostres analysis) and geophysical survey on selected sites were used, to answer the questions of river basin development and its relationship with predicted tectonic activity within the area, as well as with anticipated or already known paleohydrographic changes. The BL basin is situated within the Rychlebské hory Mts. / Góry Złote (northern and eastern parts of the basin), Králický Sněžník (southern part) and the Krowiarki Mts. (western part) in Poland. The Marginal Sudetic fault zone, which represents one of the most important tectonic zones in the Central Europe, passes in vicinity of the study area as well as the regionally important Bělský fault, which passes directly through the BL basin. The results of the analysis indicate that the BL basin has undergone very complex development due to tectonic movements since Miocene up-to-day. Based on the results of the paleostress analysis, which was performed on the dated volcanites in Lutynia - Lądek Zdrój area, the parameters of the palaostress...

Little is known about the signaling pathways that contribute to treatment response in advanced stage head and neck tumors. Increased expression of epidermal growth factor receptor (EGFR) and downstream pathways such as nuclear factor kappa B (NFκB) are implicated in aggressive tumor phenotypes and limited response to therapy. This study explored the rationale for combining the proteasome inhibitor bortezomib with the EGFR inhibitor gefitinib in a subset of head and neck squamous cell carcinomas with high EGFR gene amplification. Drug responses of gefitinib and bortezomib as single agents and in combination within head and neck squamous cell carcinoma cell lines were analyzed using MTS assays. The effects of gefitinib on the activation of EGFR and itsthree major downstream pathways, Akt, STAT3 and MAPK were determined by western blotting. The activation status of NFκB and the effects of bortezomib on the canonical pathway were assessed by DNA binding assays. Resistance to lower doses of gefitinib was associated with elevated EGFR and activated Akt expression. Gefitinib was able to effectively inhibit activation of STAT3, Akt and MAPK in HNSCC to varying degrees depending on EGFR expression status. Bortezomib treatment inhibited TNFα –induced nuclear NFκB/RelA expression but demonstrated variability in levels of baseline nuclear NFκB/RelA expression between sensitive and resistant cell lines. Bortezomib effectively suppresses NFκB/RelA nuclear activation but demonstrates additional modes of cellular toxicity beyond the NFκB pathway in sensitive cell lines. Further understanding of tumor response to the targeted inhibitors gefitinib and bortezomib may provide novel approaches in managing HNSCCs.

No description available.

由績效觀點，品質(適質)與成本(適量)，在概念上是完全一致的。因此，績效的管理，應以品質與成本作為其目標達成與否的衡量標準。本研究以績效觀點來解決公司面臨到品質與成本的兩難的問題。隨著電子產品的功能多樣化，發熱問題卻接踵而來，發熱密度的不斷提昇，對於散熱設計的需求也越來越受到重視。本研究以電源轉換器為對象，其目前已設計完成且已通過美國UL安規認證，但因為其溫升及其變異很大，因此降低電源轉換器的溫升及其變異是一急需解決的問題，以期能找出穩健於不可控因子，使產品變異小且各零件溫升與損失均能降至最低的最適外部零件組合。透過了田口與實驗設計的方法規劃及進行實驗並收集數據。引用加權SN比(multi-response S/N ratio)的方法，分別透過(1)管制圖法及(2)資料包絡法的CCR保證領域法(指CCR-AR模型)來決定加權SN比的權數，以決定可控因子及其水準值。對矩陣實驗的數據利用MTS ( M a h a l o n o b I s － Taguchi System)來篩選研究問題中較重要的特性變數，再針對篩選結果中較重要的特性變數的數據分別利用(1)倒傳遞類神經網路結合資料包絡法及(2)資料包絡法結合主成份分析法兩種分析方法，得到外殼鑽孔形狀與矽膠片大小的最佳因子組合。由改善後的確認實驗結果得知，雖然平均溫升下降的程度不大，然而大部份量測點的溫升標準差都顯著變小了，因此本研究在降低該電源轉換器溫升變異的效果顯著。

Optical frequency standards are necessary tools for accurate measurement of time and length. In practice these standards are stabilised laser systems locked to a known frequency reference. These references are typically the resonant frequencies of the atoms of an absorption medium that have been theoretically calculated to a high degree of accuracy. This thesis describes a combination of experimental and theoretical research performed on modulation transfer spectroscopy (MTS)--a technique used to frequency stabilise a laser in order to produce an accurate frequency reference--with emphasis placed on developing techniques and procedures to overcome the limitations found in existing MTS stabilised laser systems. The focus of the thesis is to generate a highly accurate frequency reference by researching the system parameters that will increase the signal to noise ratio and improve the accuracy of the reference through refinement of the signal structure. The early theoretical interpretation of MTS was effectively a low absorption approximation that occurs at low pressures. This approximation ignores the depletion of beam energy through absorption and is a distinct limitation of the theoretical model in its ability to accurately predict the influence of a range of system parameters on signal strength and structure. To overcome this limitation a 3-D (or volumetric) analysis was developed and is presented here for the first time. This volumetric model is a measure of two depleted beams interacting collinearly in an absorbing medium of iodine and is described to accurately predict the signal maximum as a function of pressure for all wavelengths. This model was found to be more accurate in predicting the influence of system parameters on the signal strength and structure, including that of pump beam intensity, pressure, saturation parameter, cell length and modulation parameters. The volumetric model is a novel approach to MTS theory but is more complex computationally than the traditional low pressure model and therefore more difficult to implement in many situations. To overcome this problem a hybrid model was developed as a combination of the low pressure and volumetric models. The comparison between the rigorous volume model and the hybrid model indicate that there is a deviation in the signal strength at high pressures. However, the agreement was very good in the pressure regimes that are commonly used to realise actual frequency references. Comparison of the hybrid model to experimental data was performed over a range of different wavelengths (532 nm, 543.5 nm, 612 nm and 633 nm) and found to be in close agreement. This gives confidence in the model to accurately predict signal strength and structure in any situation. Three mechanisms have been identified that limit the accuracy of frequency references due to the creation of residual amplitude modulation (RAM) where it shifts the frequency of the reference. The influence of RAM is included in the hybrid model as a ratio of the amplitude modulated and frequency modulated components of the saturating beam. These RAM production mechanisms result from the modulation of the saturating beam, the overlap of the beams in the medium, and the differential absorption of the sidebands in the medium. While the first mechanism has been previously reported the latter two are discussed here in detail for the first time. RAM generated by the modulators used (acousto-optic or electro-optic modulators) was typically of the order of 10% to 12%, depending on the excursion of the created sidebands. RAM generated by an asymmetric beam overlap with the modulators used was found to be as large as 30%. A combination of these two independent mechanisms can be used to provide a "RAM-free" state of the system by using one to cancel the effects of the other. The third RAM generation process--medium induced RAM--is difficult to remove but through a careful combination of absorption related parameters--namely, pump intensity, cell length, pressure and detector phase--the effects of RAM can be removed, leading to a distortion free MTS signal. Further investigation into the predictions provided by the hybrid model shows that there is a complex relationship between cell length and the optimum pressure required for maximum signal strength, such that longer cell lengths will not necessarily improve the signal strength. This is contrary to conventional thinking and is important in the MTS design process to reduce unnecessary costs and improve the signal to noise ratio and frequency accuracy. Optimisation of frequency stabilised laser systems using MTS are generally performed using trial and error. Comparison of these optimum parameter values to those predicted by the hybrid model show that for popular wavelengths such as 532 nm they are similar. In addition, the hybrid model is able to predict the frequency shifts that arise within the system parameters used and has shown that existing systems being used at 532 nm, 633 nm and 778 nm could improve their signal to noise ratio and accuracy through a variation in the parameters. A methodology based on the hybrid model is presented that can be used to calculate the optimum parameters for maximum signal strength and a "RAM-free" state for any wavelength. This systematic approach can therefore be used to guide the design of actual frequency stabilised laser systems prior to and during the design process.

Made available in DSpace on 2016-06-02T19:46:08Z (GMT). No. of bitstreams: 1 2588.pdf: 959710 bytes, checksum: fe057f9dee825e64b6a9897674590534 (MD5) Previous issue date: 2009-03-27 / Financiadora de Estudos e Projetos / This study aimed to develop the procedure for study and analysis of the covert event and to verify verbal behavior emergency under covert stimulus control. Two children and two adolescents with intellectual disabilities, students at a specialized institution, were submitted to matching to sample tasks. Preliminarily, some preferred edibles were selected for each participant and then conditioned reinforcing value of tokens was taught to make it possible to use them as teaching consequences. There was an array of experimental procedures involving two stimulus sets: set A, composed by dictated words and set B, by pictures. There was also set A composed by participants spoken words. Sets A and B were composed by four stimuli. The experimental design consisted of (1) teaching relations AB and BA , (2) teaching arbitrary relations B3B1 and B4B2 and testing symmetry, and (3) testing relations A4A 2 and A3A 1. When systematic incorrect responses were observed during relations B3B1 and B4B2 teaching, blocked trial procedure was applied. Other additional teaching procedures consisted of withdrawing the S-, teaching symmetry (B1B3 and B2B4) and providing verbal cues. However, even after applying these additional procedures, performance were above criterion, characterized by instability and deterioration. The literature emphasizes the difficulties in teaching conditional discriminations with visual stimuli for participants with intellectual disabilities. The results lead to a discussion of the intervenient variables, such as: i. Difficulties found by persons with intellectual disabilities in the matching to sample procedure; ii. What type of instruction should be given by the experimenter to help them perform the task and have access to consequences; iii. The computer as a resource to present the tasks; iv. The modality of stimuli and stimulus relations; v. Different performances presented by the participants during the exposure to the same experimental condition; vi. The consequences of reinforcement; vii. The criterion of performance established for each experimental condition and for additional procedure and; viii. Interruption in data collection. We conclude that although the participants did not reach performance criterion in relations B3B1 and B4B2 teaching, this study provides contributions of procedure design, and raises methodological questions that advance the understanding of covert stimulus tact acquisition by persons with intellectual disabilities. Through the discussion on these possible intervenient variables, we may infer that participants errors may be a matter of procedure instead of being related to their learning disabilities. / Este estudo objetivou desenvolver um procedimento para estudo e análise do evento privado e, por meio deste, verificar a emergência de comportamento verbal sob controle de estímulos encobertos. Duas crianças e dois adolescentes com atraso no desenvolvimento intelectual, alunos de uma instituição especializada, foram submetidas a tarefas de escolha de acordo com o modelo. Preliminarmente foram selecionados itens de preferência comestíveis, dos participantes, e ensinado valor reforçador condicionado de fichas para que servissem como conseqüências ao ensino. Realizou-se um arranjo de procedimentos experimentais que envolveram dois conjuntos de estímulos: o conjunto A, composto por palavras ditadas; o conjunto B por figuras; e o conjunto A de respostas, constituídas por palavras correspondentes aos demais conjuntos, faladas pelos participantes. Cada um dos dois primeiros conjuntos era composto por quatro estímulos. O delineamento experimental constituiu-se de: ensino das relações AB e BA , ensino e, em seguida, teste de simetria das relações arbitrárias B3B1 e B4B2, e, teste das relações A4A 2 e A3A 1. Diante das sistemáticas respostas incorretas apresentadas durante o ensino das relações B3B1 e B4B2, aplicou-se o procedimento adicional de ensino de discriminação condicional com tentativas em bloco e estratégias de ensino de retirada de S-, simetria dos blocos 1 e 2 e dicas verbais. Mesmo com estas estratégias, as respostas incorretas se mantiveram, caracterizadas por instabilidade e deterioração de desempenhos. A literatura enfatiza as dificuldades em ensinar discriminações condicionais com estímulos visuais para pessoas com atraso no desenvolvimento intelectual. Algumas possíveis variáveis intervenientes são discutidas, como: i. Dificuldade encontrada por pessoas com atraso no desenvolvimento intelectual ao serem expostas a tarefas de escolha de acordo com o modelo; ii. A dificuldade de compreensão das instruções para executar a tarefa e para ter acesso às conseqüências reforçadoras; iii. A utilização do computador como recurso para apresentar as tarefas; iv. O tipo de estímulo e a relação de arbitrariedade entre os estímulos modelo e comparação; v. Diferentes desempenhos apresentados pelos participantes frente a exposição de uma mesma condição experimental; vi. As conseqüências de reforçamento; vii. O critério de desempenho estabelecido em cada condição experimental e no procedimento adicional e; viii. Interrupção na coleta de dados. Conclui-se que apesar de não ter sido possível alcançar critério de desempenho no ensino das relações B3B1 e B4B2, o presente estudo fornece contribuições de procedimento, e levanta questionamentos metodológicos, que avançam na compreensão do ensino de comportamentos verbais sob controle de estímulos encobertos, por pessoas com atraso no desenvolvimento intelectual. Depreende-se daí que os erros apresentados pelos participantes podem ser muito mais uma questão de procedimento do que função das dificuldades de aprendizagem.

The retention potential of landscapes, along with the water regime of spring areas, are important hydrological topics of research, particularly in the current context of increasing extreme drought frequencies. The present work is focused on monitoring the mountain peat bogs, which, due to their overall frequency of occurrence in the spring area of the Vydra river, represent a significant constituent of the rainfall-runoff process of the area of interest. The specific hydropedological features of the organogenous soils (Histosol type soil) provide the high retention potential of the area, however, the influence of these soils on the runoff process is determined by complex physicogeographical factors. The general opinion on the hydrological function of the peat bogs has changed in recent years and the most important factor in the runoff formation in the mountain area of the Šumava Mts. is now thought to be the actual saturation of the headwater, which is predominantly composed of hydromorphic and organogenous soils. The organogenous soils are significant water reservoirs and have an important impact on the landscape. However, they may also intensify the extreme values of the watercourses during extreme precipitation events. The fundamental part of this work focuses on detailed observations of the...

Exogenously supplied organoselenium compounds, capable of propagating a selenium redox cycle, were shown to supplement natural cellular defenses against oxidants generated during biological activity. Phenylaminoalkyl selenides were developed in our laboratory as novel substrate analogs for the enzyme dopamine beta-monooxygenase. Recently, phenylaminoalkyl selenides were found to protect plasmid DNA and Molecular beacons from oxoperoxynitrate – mediated damage by scavenging this oxidant and forming the corresponding selenoxides as the sole selenium – containing products. Rate constants were determined for the reactions of the phenylaminoalkyl selenoxides with GSH at physiological pH and 25 degrees C. The kinetic data obtained in current and previous research was subsequently used in a MatLab simulation, which showed the feasibility of selenium redox cycling by GSH in the presence of a cellular oxidant, oxoperoxynitrate. Loblolly pine (LP, Pinus taeda) is the primary commercial species in southern forests covering 11.7 million hectares. Somatic embryogenesis (SE) is an effective technique to implement production of high value genotypes of LP. SE is a multi-step process, which includes initiation of somatic embryo (SME) growth from tree tissue, maintenance and multiplication of early stage SMEs and the maturation / germination phase. In this work, we isolated a substance from stage 2 or 3 LP female gametophyte (FG) tissue that stimulates early stage SME growth, and characterized this substance as citric acid on the basis of 1H NMR and mass spectrometry. We then demonstrated that topical application of citric acid to SMEs stimulates embryo colony growth at p = 0.05 for 3 of the 5 genotypes tested. Phenylketonuria (PKU) is an autosomal recessive disorder caused by an impaired conversion of L-phenylalanine (L-Phe) to L-tyrosine (L-Tyr). A novel assay based on enzymatic - colorimetric methodology (ECA) was developed in order to detect elevated concentrations of L-Phe in undeproteinized plasma of PKU patients via continuous spectrophotometric detection. We report here that L-Phe concentrations in undeproteinized plasma measured using our ECA were comparable to those determined on an amino acid analyzer based on Pearson correlation coefficients and a Bland and Altman comparison.