Failure analysis and assessment of flat jointless concrete structures with soil-structure interaction effect

Import 15/01/2013Předmětem předložené diplomové práce je zpracování analýzy poruch a posouzení monolitické železobetonové ochranné protipovodňové stěny silově zatížené zemními tlaky, hydrostatickým tlakem vody a zatížením od dopravy na přilehlé komunikaci a deformačně zatížené smršťováním a teplotními vlivy prostředí. Součástí práce je návrh konstrukčního řešení s respektováním zavedených Eurokódů.The aim of submitted master’s thesis is to make a failure analysis and assessment of reinforced concrete flood wall loaded by force action of the soil pressure, fluid pressure of water and traffic and also loaded by the deformation action of the shrinkage and temperature variation arround. The next is to design a structural solution of this wall following established Eurocode’s standards.Prezenční221 - Katedra konstrukcívýborn

Control over imidazoquinoline immune stimulation by pH-degradable poly(norbornene) nanogels

The reactivation of the innate immune system by toll-like receptor (TLR) agonists holds promise for anticancer immunotherapy. Severe side effects caused by unspecific and systemic activation of the immune system upon intravenous injection prevent the use of small-molecule TLR agonists for such purposes. However, a covalent attachment of small-molecule imidazoquinoline (IMDQ) TLR7/8 agonists to pH-degradable polymeric nanogels could be shown to drastically reduce the systemic inflammation but retain the activity to tumoral tissues and their draining lymph nodes. Here, we introduce the synthesis of poly(norbornene)-based, acid-degradable nanogels for the covalent ligation of IMDQs. While the intact nanogels trigger sufficient TLR7/8 receptor stimulation, their degraded version of soluble, IMDQ-conjugated poly(norbornene) chains hardly activates TLR7/8. This renders their clinical safety profile, as degradation products are obtained, which would not only circumvent nanoparticle accumulation in the body but also provide nonactive, polymer-bound IMDQ species. Their immunologically silent behavior guarantees both spatial and temporal control over immune activity and, thus, holds promise for improved clinical applications

Electrical resistivity and ultrasonic measurements during sequential fracture test of cementitious composite

Cracks in cover of reinforced and pre-stressed concrete structures significantly influence the ingress of deleterious species causing decrease in durability of these structures. The paper is focused on the effect of fracture process on two selected physical parameters of concrete – the electrical resistivity and the ultrasonic pulse passing time – which might be employed as the quality indicator of concrete cover within (nondestructive) procedure(s) of assessment of the structural durability. The concrete electrical resistivity and ultrasonic passing time were investigated here with respect to two variants of treatment of the test specimens’ surface (the pre-dried surface and the wet surface). Test configuration of three-point bending of notched beam was utilized to control the crack propagation; the fracture process passed through several loading–unloading sequences between which the electrical resistivity and ultrasonic passing time readings over the fractured region were performed. Equivalent elastic crack model was used for estimation of the fracture advance (described via the effective crack length) at the loading stages corresponding to the resistivity and ultrasonic measurements. Relationships between changes of both the concrete resistivity and ultrasonic pulse passing time and the effective crack length is determined and discussed

Preliminary study on Se-enriched Lentinula edodes mycelium as a proposal of new feed additive in selenium deficiency

The presence of selenium in European soil is low and this causes its deficiency in livestock and, in consequence, in humans. This study aimed to obtain Lentinula (L.) edodes mycelium with the maximum content of selenium. This species was used for experiment based on its documented medicinal properties. Calves were fed with selenium-enriched L. edodes mycelium, and serum selenium concentration, average daily weight gains and selected immune parameters were estimated. The selenium-enriched mushroom was found to be safe based on cytotoxicity tests (MTT and LDH tests) and for this reason it was used for further experiments. The mean quantity of selenium in the serum of calves fed with selenium-enriched L. edodes mycelium was significantly higher than that of control calves. Additionally, the calves fed with selenium-enriched L. edodes mycelium had higher body weight gains than those of control calves. White blood cell counts and subpopulations of lymphocytes in the experimental and control calves were within the reference range. The administration of L. edodes enriched with selenium had a beneficial effect on state of health of the calves

Urinary hepcidin levels in iron-deficient and iron-supplemented piglets correlate with hepcidin hepatic mRNA and serum levels and with body iron status

Among livestock, domestic pig (Sus scrofa) is a species, in which iron metabolism has been most intensively examined during last decade. The obvious reason for studying the regulation of iron homeostasis especially in young pigs is neonatal iron deficiency anemia commonly occurring in these animals. Moreover, supplementation of essentially all commercially reared piglets with iron entails a need for monitoring the efficacy of this routine practice followed in the swine industry for several decades. Since the discovery of hepcidin many studies confirmed its role as key regulator of iron metabolism and pointed out the assessment of its concentrations in biological fluids as diagnostic tool for iron-related disorder. Here we demonstrate that urine hepcidin-25 levels measured by a combination of weak cation exchange chromatography and time-of-flight mass spectrometry (WCX-TOF MS) are highly correlated with mRNA hepcidin expression in the liver and plasma hepcidin-25 concentrations in anemic and iron-supplemented 28-day old piglets. We also found a high correlation between urine hepcidin level and hepatic non-heme iron content. Our results show that similarly to previously described transgenic mouse models of iron disorders, young pigs constitute a convenient animal model to explore accuracy and relationship between indicators for assessing systemic iron status

Controlled Supramolecular Assembly of Peptides via Chemical Reactions

Peptide assembly is an emerging tool for designing novel biomaterials with extraordinary properties. Biocompatibility and biodegradability are key requirements for application in biomedicine and can often be achieved by utilizing peptide-based materials. Furthermore, the simplicity of peptide synthesis and the ease of chemical modification as well as the cost- and time efficiency and monodispersity of peptides contribute to the popularity of these compounds in recent years. The diversity of oligopeptides that form various nanostructures offers new opportunities to tailor material properties in order to accomplish many different tasks. Additionally, introducing stimuli responsive moieties can lead to greater control by using internal and external triggers in vivo, yielding in assembly, disassembly, degradation or rearrangement of peptide nanostructures. While some amino acids intrinsically can respond to ambient factors such as pH and redox environment, introducing non-natural amino acids and other chemical modifications expands the palette of stimulus-responsive properties of peptide assemblies. Within this thesis, the controlled assembly and disassembly of peptides was investigated using multiple biologically relevant triggers such as pH and oxidative stress. Peptides from different classes of pro-assembling compounds were synthesized incorporating different stimulus-responsive chemical modifications or amino acids and the compounds were subsequently examined for the controlled formation of nanostructures. In the first chapter, the self-assembly of an amphiphilic peptide KIKISQINM is prevented upon introduction of a kink into the primary sequence by replacing one amide bond in the amino acid chain with a carboxylic ester in the side chain of serine, giving a so-called depsipeptide. After hydrolytic removal of a protecting group from the N-terminus, a physiological pH induced O,N-acyl shift within the amino acid sequence leads to self-assembly into fibrillar architectures. Oxidation of methionine into methionine sulfoxide by naturally abundant hydrogen peroxide causes an imbalance between hydrophobic and hydrophilic amino acid side chains and electrostatic repulsion between peptides, which leads to partial destruction of β-sheets and subsequent disassembly of peptide fibers. This study shows how simple chemical tools can be exploited for orthogonal, controlled peptide assembly and disassembly and lays foundation for following studies on responsive peptide materials. Subsequently, in the second project using the depsipeptide approach, assembly of short aromatic peptides is prevented by a boronic acid secured kink in the primary sequence. The boronic acid enables dynamic covalent conjugation with a salicylhydroxamate functionalized cell-penetrating peptide, which leads to uptake of two pro-assembling peptide sequences by A549 cancer cells. Depsipeptides are released into the cytosol by pH triggered hydrolytic removal of the delivery vehicle. The boronic acid caging group is removed by endogenous hydrogen peroxide which leads to an O,N-acyl shift unleashing the assembling peptide sequences. Co-assembly of the peptides inside cancer cells leads to formation of fluorescent fibres that have a detrimental effect on cell morphology and viability, which opens the pathway for potential applications in high oxidative stress related diseases. Finally, the assembly of complementary peptide strands utilizing pH-responsive boronic acid-catechol chemistry is presented. Here, various numbers of L-3,4-dihydroxyphenylalanine and L-boronophenylalanine were incorporated into peptide sequences in order to elucidate the influence of multivalency and order of amino acids in the primary sequence on binding affinity. Peptides with the possibility of divalent and trivalent binding showed significantly enhanced affinities towards each other, while no binding occurred using mismatched peptide sequences. Furthermore, trivalent binding exhibited similar affinity as binding of eight base pair long DNA strands. The enhanced binding affinity, higher backbone stability, ease of further chemical modification and molecular recognition of these sequences could be beneficial for use as synthetic DNA mimics and could further be utilized for programming macromolecular assemblies, which was shown within this study by dynamic covalent conjugation of polymers to proteins. In summary, this thesis presents multiple approaches for controlled peptide assembly processes including disassembly using various peptide types and triggers. Here, dynamic covalent and immolation chemistry of boronic acids was utilized to assemble and disassemble peptides on demand using the biologically relevant triggers pH, salt concentration and hydrogen peroxide. The utility of such compounds for application in biomedicine was shown by intracellular assembly as well as by creating dynamic covalently bound conjugates between peptides or between proteins and polymers with biological relevance