Cohesion decay: quantitative analysis of partial sister chromatid cohesion

Cell division is a highly dynamic process where sister chromatids remain associated with each other from the moment of DNA replication until the later stages of mitosis, giving rise to two daughter cells with equal genomes. The “molecular glue” that links sister DNA molecules is called cohesin, a tripartite ring-like protein complex composed of two Structural Maintenance of Chromosome proteins (Smc1 and Smc3) bridged by a kleisin subunit Rad21/Scc1, that together prevent precocious sister chromatid separation. Accumulating evidence has suggested that cohesion decay may be the cause of segregation errors that underlie certain human pathologies. However it remains to be determined how much cohesin loss abolishes functional sister chromatid cohesion. To answer these questions, we have developed different experimental conditions aiming to titrate the levels of cohesin on mitotic chromosomes in a precise manner. Using these tools, we will determine the minimal amount of cohesin needed to confer functional cohesion. The approaches described here take advantage of a system in Drosophila melanogaster where the Tobacco Etch Virus (TEV) protease can cleave the Rad21 subunit of cohesin leading to precocious sister chromatid separation. Firstly, we tried to express different levels of TEV protease to obtain partial loss of cohesion. However, this approach has failed to produce systematic different levels of sister chromatid separation. Most of the work was therefore focused on a second strategy, for which we established strains with different levels of cohesin sensitive/cohesin resistant to TEV protease. Strains containing different amounts of functional cohesin (TEV resistant) were tested by in vitro cleavage and by in vivo injections in embryos for their ability to promote sister chromatid cohesion. Our results reveal that removal of half of the cohesin complexes does not impair chromosome segregation, implying that chromosome cohesion is less sensitive to cohesin amounts than previously anticipated.

Design of a low-voltage CMOS RF receiver for energy harvesting sensor node

In this thesis a CMOS low-power and low-voltage RF receiver front-end is presented. The main objective is to design this RF receiver so that it can be powered by a piezoelectric energy harvesting power source, included in a Wireless Sensor Node application. For this type of applications the major requirements are: the low-power and low-voltage operation, the reduced area and cost and the simplicity of the architecture. The system key blocks are the LNA and the mixer, which are studied and optimized with greater detail, achieving a good linearity, a wideband operation and a reduced introduction of noise. A wideband balun LNA with noise and distortion cancelling is designed to work at a 0.6 V supply voltage, in conjunction with a double-balanced passive mixer and subsequent TIA block. The passive mixer operates in current mode, allowing a minimal introduction of voltage noise and a good linearity. The receiver analog front-end has a total voltage conversion gain of 31.5 dB, a 0.1 - 4.3 GHz bandwidth, an IIP3 value of -1.35 dBm, and a noise figure lower than 9 dB. The total power consumption is 1.9 mW and the die area is 305x134.5 m2, using a standard 130 nm CMOS technology.

Technical optimization of the synthesis of flavours

The goal of this thesis is the investigation and optimization of the synthesis of potential fragrances. This work is projected as collaboration between the University of Applied Sciences in Merseburg and the company Miltitz Aromatics GmbH in Bitterfeld‐Wolfen (Germany). Flavoured compounds can be synthesized in different ways and by various methods. In this work, methods like the phase transfer catalysis and the Cope‐rearrangement were investigated and applied, for getting a high yield and quantity of the desired substances and without any by‐products or side reactions. This involved the study of syntheses with different process parameters such as temperature, solvent, pressure and reaction time. The main focus was on Cope‐rearrangement, which is a common method in the synthesis of new potential fragrance compounds. The substances synthesized in this work have a hepta‐1,5‐diene‐structure and that is why they can easily undergo this [3,3]‐sigma tropic rearrangement. The lead compound of all research was 2,5‐dimethyl‐2‐vinyl‐4‐hexenenitrile (Neronil). Neronil is synthesized by an alkylation of 2‐methyl‐3‐butenenitrile with prenylchloride under basic conditions in a phase‐transfer system. In this work the yield of isolated Neronil is improved from about 35% to 46% by according to the execution conditions of the reaction. Additionally the amount of side product was decreased. This synthesized hexenenitrile involved not only the aforementioned 1,5‐diene‐structure, but also a cyano group, that makes this structure a suitable base for the synthesis of new potential fragrance compounds. It was observed that Neronil can be transferred into 2,5‐dimethyl‐2‐vinyl‐4‐hexenoic acid by a hydrolysis under basic conditions. After five hours the acid can be obtained with a yield of 96%. The following esterification is realized with isobutanol to produce 2,5‐dimethyl‐2‐vinyl‐4‐hexenoic acid isobutyl ester with quantitative conversion. It was observed that the Neronil and the corresponding ester can be converted into the corresponding Cope‐product, with a conversion of 30 % and 80%. Implementing the Cope‐rearrangement, the acid was heated and an unexpected decarboxylated product is formed. To achieve the best verification of reaction development and structure, scrupulous analyses were done using GC‐MS, 1H‐NMR and 13C‐ NMR.

Reflux esophagitis and gastroesophageal reflux disease: a cross-sectional study of gastroesophageal reflux disease patients by age group

The purpose of this study was to explore the relationship between the intensity of acid reflux and severity of esophageal tissue damage in a cross-sectional study of patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with were selected in accordance with the strict 24-hour ambulatory esophageal pHmetry (24h-pHM) criteria and distributed into three age groups: Group A: 14 - 24 years of age. Group B: 25 - 54; and Group C: 55 - 64. The 24h-pHM was carried out in accordance with DeMeester standardization, and the Savary-Miller classification for the diagnosis of reflux esophagitis was used. The groups were similar in 24h-pHM parameters (p > 0.05), having above normal values. For the study group as a whole, there was no correlation between age group and intensity of acid reflux, and there was no correlation between intensity of acid reflux and severity of esophageal tissue damage. However, when the same patients were sub-grouped in accordance with the depth of their epithelial injury and then distributed into age groups, there was a significant difference in esophagitis without epithelial discontinuity. Younger patients had less epithelial damage than older patients. Additionally, although there was a significant progression from the least severe to the moderate stages of epithelial damage among the age groups, there was no apparent difference among the age groups in the distribution between the moderate stages and most severe stages. The findings support the conclusion that the protective response of individuals to acid reflux varies widely. Continued aggression by acid reflux appears to lead to the exhaustion of individual mechanisms of epithelial protection in some patients, but not others, regardless of age or duration of the disease. Therefore, the diagnosis and follow-up of GERD should include both measurements of the quantity of refluxed acid and an assessment of the damage to the esophageal epithelium.

Assessing the production of jet mix columns using alkali activated waste based on mechanical and financial performance and CO2 (eq) emissions

Recent research has proved the potential of alkaline activated fly-ash for soil stabilisation. However, such studies have not focused on the link between financial, mechanical and environmental aspects of this solution, but only on their absolute mechanical properties. The present paper characterises the mechanical behaviour of a large spectrum of activator-ash-soil combinations used to build jet mixing columns, analysing also the cost and CO2 (eq) emissions. The concern with these two vectors forced a decrease in the quantity of stabilising agent added to the soil, relatively to previous research, and the effects of such low quantities have not yet been published. However, the results clearly showed a significant improve in strength, still well above the average values expected when improving the stressstrain behaviour of a weak soil. Uniaxial compressive strength tests were used to assess the effects of the fly-ash percentage, the alkalieash ratio and the water content. The carbon calculator recently developed by the European Federation of Foundation Contractors and the Deep Foundations Institute was used to quantify the CO2 (eq) emissions associated with this technique. The financial cost was estimated based on the experience of a major Portuguese contractor. For comparison purposes, soil cement mixtures were also analysed, using similar conditions and tools used for the soil-ash analysis. Results showed that the cement and ash solutions are very similar in terms of overall performance, with some advantage of the former regarding financial cost, and a significant advantage of the latter regarding the CO2 (eq) emissions. This new grout, although it is in an embryonic stage, it has the potential for broader developments in the field.

Summary of the searches for squarks and gluinos using root s=8 TeV pp collisions with the ATLAS experiment at the LHC

A summary is presented of ATLAS searches for gluinos and first- and second-generation squarks in final states containing jets and missing transverse momentum, with or without leptons or b-jets, in the s√=8 TeV data set collected at the Large Hadron Collider in 2012. This paper reports the results of new interpretations and statistical combinations of previously published analyses, as well as a new analysis. Since no significant excess of events over the Standard Model expectation is observed, the data are used to set limits in a variety of models. In all the considered simplified models that assume R-parity conservation, the limit on the gluino mass exceeds 1150 GeV at 95% confidence level, for an LSP mass smaller than 100 GeV. Furthermore, exclusion limits are set for left-handed squarks in a phenomenological MSSM model, a minimal Supergravity/Constrained MSSM model, R-parity-violation scenarios, a minimal gauge-mediated supersymmetry breaking model, a natural gauge mediation model, a non-universal Higgs mass model with gaugino mediation and a minimal model of universal extra dimensions.

Cognitive functioning and efficacy of cognitive intervention in Multiple Sclerosis

Tese de Doutoramento em Psicologia Clínica / Psicologia

Development of sandwich panels of customized functionalities for the rehabilitation of the built patrimony

Dissertação de International Master in Sustainable Built Environment

Terapéutica racional, mediante indicadores de eficacia antimicrobiana, de la mastitis caprina utilizando marbofloxacina y cefquinoma. Rational therapeutics, indicators of antimicrobial efficiency in the mastitis goats using marbofloxacine and cefquinome

La producción de leche de cabra es considerada en nuestro país, y en la provincia de Córdoba, una alternativa productiva para el desarrollo sustentable y socio – económico de la población. Por otra parte, existe una mayor demanda del mercado nacional e internacional de esta leche, por lo que los productores deben garantizar la seguridad y calidad de la misma de acuerdo a las normas vigentes. Es por ello que el control y tratamiento de las diferentes enfermedades es de vital importancia tanto para maximizar la producción del hato como para cumplir con los cánones de seguridad exigidos. En este contexto la mastitis caprina es una de las enfermedades que afecta la productividad del sector, y para controlarla una de las medidas a emplear es la terapéutica con antimicrobianos. Se trabajará en este proyecto con marbofloxacina y cefquinoma, estableciendo pautas racionales (eficaces y seguras) para su empleo en la afección a nivel regional. Los indicadores de eficacia estarán fijados de acuerdo a los parámetros integrados de farmacocinética (FC) y farmacodinamia (FD). Estos últimos (FD) serán calculados a través de la determinación concentraciones inhibitorias mínimas de cepas bacterianas aisladas de mastitis caprinas en Córdoba. Se establecerán los parámetros farmacocinéticos a dosis únicas y múltiples para la marbofloxacina (5 mg/kg IV, IM) y cefquinoma (2 mg/kg IV, IM e IMM) a partir de muestras de suero y leche de cabras Anglo Nubian (n = 6 por antimicrobiano; diseño cruzado en función de la ruta de administración). Se determinarán sus concentraciones en dichos fluidos, por cromatografía líquida de alta precisión. Los resultados FC/FD para ambos medicamentos se compararán con parámetros recomendados por expertos para cada tipo de antimicrobiano y se utilizarán como medida para recomendar una terapéutica racional, fundamental para optimizar la posología, garantizar la eficacia clínica, y reducir al mínimo la selección y propagación de cepas resistentes de agentes patógenos. The production of milk of goat is considered the province of Cordoba, a productive alternative for the sustainable development and partner - economically of the population. There is a major demand of the domestic and international market of this milk, for what the producers must guarantee the safety and quality of the same one of agreement to the in force procedure. It is for it that the control and treatment of the different diseases performs vital importance so much to maximize the production of the herd as to expire with the safety demanded. In this context the mastitis goat is one of the diseases that affect the productivity of the sector, and to control her one of the measures to using is the therapeutics with antimicrobial. One will be employed at this project with marbofloxacine and cefquinome, establishing rational guidelines (effective and sure) for his employment in the affection to regional level. The indicators of efficiency will be fixed in agreement to the integrated parameters of pharmacokinetics (PK) and pharmacodinamics (PD). The latter (PK) will be calculated across the determination inhibitory minimal concentrations of bacterial strains isolated of mastitis goat in Córdoba. The parameters will be established pharmacokinetics to the only and multiple doses for the marbofloxacine (5 mg/kg the IV, IM) and cefquinome (2 mg/kg the IVth, IM and IMM), From samples of whey and milk of goats Anglo Nubian (n = 6 for antimicrobial; design crossed depending on the route of administration). Its concentrations will decide in the above mentioned fluids, for liquid chromatography of high precision. The results PK/PD for both antimicrobial will be compared with parameters recommended by experts for every type of antimicrobial and will be in use as measure for recommending a rational, fundamental therapeutics for optimizing the dosage, for guaranteeing the clinical efficiency, and to reduce to the minimum the selection and spread of resistant of pathogenic agents.

The appraisal of mesophilic anaerobic digestion and thermophilic aerobic digestion in the treatment of municipal sludge in Ireland

It has been well documented that the optimum feedstock for anaerobic digesters consists of readily biodegradable compounds, as found in primary sludge or even a mixed substrate of primary and excess activated sludge. Due to the requirements of the Urban Wastewater Treatment Plant Directive of 1991, the quantities of secondary sludge generated is set to increase substantially. A pilot scale study was undertaken to evaluate the performance of both Mesophilic Anaerobic Digestion and Thermophilic Aerobic digestion in the treatment of secondary sludge. The results indicated that the anaerobic pilot scale digester achieved a greater solids destruction than the aerobic pilot plant averaging at 28% T.S. removal verses 20% for the aerobic digester, despite the fact that secondary sludge is the optimum feedstock for aerobic digestion. This can, however, be attributed to the greater biomass yield experienced with aerobic systems, and to the absence of Autothermal conditions. At present, the traditional technique of Mesophilic Anaerobic Digestion is in widespread application throughout Ireland, for the stabilisation of sewage sludge. There is only one Autothermal Thermophilic Aerobic Digester at present situated in Killarney, Co. Kerry. A further objectives of the study was to compare full-scale applications of Mesophilic Anaerobic Digestion to ATAD. Two Sludge Treatment plants, situated in Co. Kerry, were used for this purpose, and were assessed mainly under the following headings; process stability, solids reduction on average, the ATAD plant in Killarney has the advantage of producing a “Class A” Biosolid in terms of pathogen reduction, and can effectively treat double the quantity of sludge. In addition, economically the ATAD plant is cheaper to run, costing €190 / t.d.s verses €211 / t.d.s. for the anaerobic digester in Tralee. An overview of additional operational Anaerobic Digestion Plants throughout Ireland is also presented.

An analysis of the use of photogrammetric sorting to audit construction and demolition waste production on site

This study analyses the area of construction and demolition waste (C & D W) auditing. The production of C&DW has grown year after year since the Environmental Protection Agency (EPA) first published a report in 1996 which provided data for C&D W quantities for 1995 (EPA, 1996a). The most recent report produced by the EPA is based on data for 2005 (EPA, 2006). This report estimated that the quantity of C&DW produced for that period to be 14 931 486 tonnes. However, this is a ‘data update’ report containing an update on certain waste statistics so any total provided would not be a true reflection of the waste produced for that period. This illustrates that a more construction site-specific form of data is required. The Department of Building and Civil Engineering in the Galway-Mayo Institute of Technology have carried out two recent research projects (Grimes, 2005; Kelly, 2006) in this area, which have produced waste production indicators based on site-specific data. This involved the design and testing of an original auditing tool based on visual characterisation and the application of conversion factors. One of the main recommendations of these studies was to compare this visual characterisation approach with a photogrammetric sorting methodology. This study investigates the application of photogrammetric sorting on a residential construction site in the Galway region. A visual characterisation study is also carried out on the same project to compare the two methodologies and assess the practical application in a construction site environment. Data collected from the waste management contractor on site was also used to provide further evaluation. From this, a set of waste production indicators for new residential construction was produced: □ 50.8 kg/m2 for new residential construction using data provided by the visual characterisation method and the Landfill Levy conversion factors. □ 43 kg/m2 for new residential construction using data provided by the photogrammetric sorting method and the Landfill Levy conversion factors. □ 23.8 kg/m2 for new residential construction using data provided by Waste Management Contractor (WMC). The acquisition of the data from the waste management contractor was a key element for testing of the information produced by the visual characterisation and photogrammetric sorting methods. The actual weight provided by the waste management contractor shows a significant difference between the quantities provided.

Bromeliad-associated mosquitoes from Atlantic forest in Santa Catarina Island, southern Brazil (Diptera, Culicidae), with new records for the State of Santa Catarina

Bromeliad-associated mosquitoes (Diptera: Culicidae) in Atlantic Forest in Florianópolis, Santa Catarina, southern Brazil, were studied, examining plants of Vriesea philippocoburgi Wawra and Aechmea lindenii (E. Morren) Baker var. lindenii at secondary Atlantic rain forest, and A. lindenii and Vriesea friburgensis Mez var. paludosa (L. B. Smith) at "restinga" per month, during 12 months. No immature forms of mosquitoes were collected from A. lindenii in the secondary forest. Collections obtained 368 immature mosquitoes, none of them from A. lindenii from rain forest. Culex (Microculex) spp. constituted 79.8% of the total, Wyeomyia (Phoniomyia) spp. 17.93%, and Anopheles (Kerteszia) cruzii (Dyar & Knab, 1908) only 1.36%. The study shows the great predominance of species of medical importance not yet proved, and the small number of immature stages of anopheline mosquitoes. The rainfall, but not the mean temperatures, significantly influenced the quantity of mosquitoes from V. philippocoburgi. Significant differences between the quantities of immature forms of all the bromeliad species were found, and the shape of the plants could be important to the abundance of mosquitoes. All six species of Cx. (Microculex) found are recorded for the first time in the State of Santa Catarina, and all six species of Wyeomyia (Phoniomyia) are recorded for the first time in bromeliads in this state.

Diversity and structure of microcrustacean assemblages (Cladocera and Copepoda) and limnological variability in perennial and intermittent pools in a semi-arid region, Bahia, Brazil

Temporary wetlands undergo recurrent drought due to the scarcity of water, which disrupts the hydrological connectivity with adjacent aquatic systems. However, some environments retain water for longer periods, allowing greater persistence of the community. The current study evaluated differences in the microcrustacean assemblages and limnological variability between perennial and intermittent pools in a semi-arid region of Brazil. The abiotic features (water temperature, pH, total alkalinity, electrical conductivity and depth) of intermittent pools were affected more than perennial pools due to loss of water volume. This may have contributed to a higher average richness and diversity index in some intermittent pools and differences in the structure of the assemblages. The lowest species richness and diversity were recorded where physical factors, such as a large quantity of suspended solids and variability in the electrical conductivity of the water and pH, make the environment unsuitable for these organisms. These results suggest that community development in intermittent pools is interrupted by the dry season; when the water returns, due to rainfall or rising groundwater, each pond undergoes a different process of colonization. In these circumstances, the biological importance of temporary aquatic environments is clear, since such pools provide shelters and have an important role in the maintenance of the regional diversity of aquatic environments.

Myeloid Metaplasia of Spleen in Hookworm Disease

We investigated, in the liver and the spleen of ten pures cases of ankylostomiasis haemocytopoietic elements. We verified the weight of spleen in 23 cases of individuals from 3 to 60 years old. In no case did we meet with haemopoietic cells in liver. In seven cases we found in spleen elements of the red series at an advanced evolutional stage (orthochromatic erythroblasts with pyknotic nucleus). In some of these cases we observed megakaryocytes and numerous eosinophilous myelocytes.The three cases which did not show any myeloid metaplasia in spleen were from individuals of over 50 years. Nevertheless, in another case of an individual 59 years old this metaplasia was verified. In individuals of over 20 years, the average weight of spleen in nine cases appeared to be equal to the normal weight. In 14 other cases, between 3 and 14 years of age, the weight of this organ was always sensibly higher than in normal individuals of the corresponding age. These results suggest the possibility of the myeloid metaplasia being the fact responsible for the weight increase of spleen in young individuals victimatized by hookworm anaemia. The remarkable proliferation of orthochromatic erythroblasts shows that the degree and quickness of blood regeneration after iron administration are due, essentially, to the great quantity of haemoglobin previously formed in the spleen and bone marrow of ankylostomized organisms.

Combinatorial and metric properties of Thompson's group T

We discuss metric and combinatorial properties of Thompson's group T, such as the normal forms for elements and uniqueness of tree pair diagrams. We relate these properties to those of Thompson's group F when possible, and highlight combinatorial differences between the two groups. We define a set of unique normal forms for elements of T arising from minimal factorizations of elements into convenient pieces. We show that the number of carets in a reduced representative of T estimates the word length, that F is undistorted in T, and that cyclic subgroups of T are undistorted. We show that every element of T has a power which is conjugate to an element of F and describe how to recognize torsion elements in T.