Distribution profile of zwitterions and hydrolysis of esters derived from N-benzylpiperazine

Résumé Les esters sont des agents thérapeutiques largement utilisés comme médicaments et prodrogues. Leurs dégradation est chimique et enzymatique. Le Chapitre IV de cette thèse a comme objet l'hydrolyse chimique de plusieurs dérivés esters du 2,3-dimethoxyphenol. Des composés modèles ont été synthétisés dans le but de déterminer leur mécanismes de dégradation. Les profils d'ionisation et d'hydrolyse de ces composés ont permis d'identifier la présence d'une catalyse intramoléculaire basique par un atome d'azote non-protoné. Les effets électroniques exercés par les groupes phenylethenyle et phenylcyclopropyle influencent également la vitesse d'hydrolyse des esters. La résolution des problèmes liés à l'adsorption et la perméation est devenue à nos jours l'étape limitante dans la conception de nouveaux médicaments car de trop nombreux candidats prometteurs ont échoué à cause d'une mauvaise biodisponibilité. La lipophilie décrit le partage d'un médicament entre une membrane lipidique et son environnement physiologique aqueux, et de ce fait elle influence sa pharmacocinétique. Des études récents ont mis en évidence l'importance de la détermination de la lipophilie des espèces ionisées vu leur considérable impact biologique. Le Chapitre V de cette thèse est centré sur une classe particulière de composés ionisables, les zwitterions. Plusieurs methoxybenzylpiperazines de nature zwitterionique ont été étudiées. Leurs profils d'ionisation ont montré que dans un large intervalle de pH, l'espèce prédominante est le zwitterion. Les profils de lipophilie ont montré que leur lipophilie est plus élevée que celles des zwitterions courants. Une interaction électrostatique entre l'oxygène du carboxylate et l'azote protoné est responsable de ce profil et rend la plupart des zwitterions non-donneurs de liaison hydrogène. Ces deux aspects peuvent favoriser le passage de la barrière hémato-éncephalique. Les données biologiques ont par la suite confirmé cette hypothèse pour un certain nombre de composés. Résumé large public Les esters sont des composés souvent rencontrés en chimie thérapeutique. Ils sont dégradés en milieu aqueux par une réaction d'hydrolyse, avec ou sans la participation d'enzymes. Dans ce travail de thèse, une série d'esters ont été étudiés dans le but d'établir une relation entre leur structure et les mécanismes responsables de leur dégradation chimique. Il a été prouvé que la dégradation est accélérée par un atome d'azote non-protoné. D'autres mécanismes peuvent intervenir en fonction du pH du milieu. La présence d'une liaison simple ou double ou d'un groupe phenylcyclopropyle peut également influencer la vitesse de dégradation. Il est essentiel, dans la conception de nouveaux médicaments, d'optimiser les étapes qui influencent leur distribution dans le corps. Ce dernier peut être visualisé comme une série infinie de compartiments aqueux séparés par des membranes lipidiques. La lipophilie est une propriété moléculaire importante qui décrit le passage des barrières rencontrées par les médicaments. Des études récentes ont mis en évidence l'importance de déterminer la lipophilie des espèces ionisées vu leur considérable impact biologique. Dans ce travail de thèse a été étudiée une série particulière de composés ionisables , les zwitterions. Une relation a été établie entre leur structure et leur proprietés physico-chimiques. Une lipophilie plus élevée par rapport à celle des zwitterions courants a été trouvée. Une interaction entre les groupes chargés des zwitterions étudiés est responsable de ce comportement inattendu et rend la plupart d'entre eux non-donneurs de liaison hydrogène. Ces deux facteurs peuvent favoriser la pénétration cérébrale. Les données biologiques ont confirmé cette hypothèse pour un certain nombre de composés. Summary Esters are often encountered in medicinal chemistry. Their hydrolysis may be chemical as well as enzymatic. Chapter IV of this manuscript provides a mechanistic insight into the chemical hydrolysis of a particular series of basic esters derived from 2,3-dimethoxyphenol. Their ionization and pH-rate profiles allowed to identify the presence of an intramolecular base catalysis by a non-protonated nitrogen atom. Electronic effects exerted by the phenylethenyl and phenylcyclopropyl groups that are present in the structure of the esters also influenced their rate of hydrolysis. Numerous works in the literature witness of the importance of lipophilicity in determining the fate of a drug. Most published partition coefficients are those of neutral species. In contrast, no exhaustive treatment of the lipophilicity of charged molecules is available at present, and a lack of information characterizes in particular zwitterions. Chapter V of this manuscript provides an insight into the physicochemical parameters of a series of zwitterionic methoxybenzylpiperazines. Their ionization profiles showed that they exist predominantly in the zwitterionic form in a broad pH-range. An electrostatic interaction between the oxygen of the carboxylate and the protonated nitrogen atom is increases the lipophilicity of the investigated zwitterions, and prevents the majority of them to express their hydrogen-bonding capacity. These two aspects may favor the crossing of the blood-brain barrier. The available ratios PSt/PSf measured in vitro have confirmed this point for a number of compounds.

Role of habitat in the distribution and abundance of marsh birds, 1965

This is Special Report no. 43 that studies habitat changes and the affects on marsh birds. It covers the history of vegetation and birds of two marshes, Little Wall and Goose Lake, in Iowa for a 5-year period beginning in 1958 at the culmination of a series of drought years in central Iowa.

Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe.

BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS: Of 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI}, 0.24-0.53]), whereas patients positive for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4, respectively. A greater HCV RNA level was associated with a greater chance of being infected with HCV genotype 1 (aOR, 1.60 per 1 log higher [95% CI, 1.36-1.88]). CONCLUSIONS: More than three-quarters of the HIV- and HCV Ab-positive patients in EuroSIDA showed active HCV replication. Viremia was more frequent in IDUs and, conversely, was less common in HBsAg-positive patients. Of the patients with HCV viremia analyzed, 53% were found to carry HCV genotype 1, and this genotype was associated with greater serum HCV RNA levels.

Different concentrations of Mg++ ions affect nuclear matrix protein distribution during thermal stabilization of isolated nuclei.

The nuclear matrix, a proteinaceous network believed to be a scaffolding structure determining higher-order organization of chromatin, is usually prepared from intact nuclei by a series of extraction steps. In most cell types investigated the nuclear matrix does not spontaneously resist these treatments but must be stabilized before the application of extracting agents. Incubation of isolated nuclei at 37C or 42C in buffers containing Mg++ has been widely employed as stabilizing agent. We have previously demonstrated that heat treatment induces changes in the distribution of three nuclear scaffold proteins in nuclei prepared in the absence of Mg++ ions. We studied whether different concentrations of Mg++ (2.0-5 mM) affect the spatial distribution of nuclear matrix proteins in nuclei isolated from K562 erythroleukemia cells and stabilized by heat at either 37C or 42C. Five proteins were studied, two of which were RNA metabolism-related proteins (a 105-kD component of splicing complexes and an RNP component), one a 126-kD constituent of a class of nuclear bodies, and two were components of the inner matrix network. The localization of proteins was determined by immunofluorescent staining and confocal scanning laser microscope. Mg++ induced significant changes of antigen distribution even at the lowest concentration employed, and these modifications were enhanced in parallel with increase in the concentration of the divalent cation. The different sensitivity to heat stabilization and Mg++ of these nuclear proteins might reflect a different degree of association with the nuclear scaffold and can be closely related to their functional or structural role.

Distribution systems of the food sector in Russia: the perspective of Finnish food industry

Finnish food producers' trade with Russia has experienced profound changes since the collapse of the Soviet Union. Simultaneously, the distribution systems of foodstuffs have changed remarkably. This study sheds some light into these changes and analyses the current situation in distribution systems of foodstuffs in Russia. In addition, the study discusses the possibilities of Finnish food producers to get more of their products to the shelves of Russian food retail stores. Before the 1998 financial crisis, the import of foreign foodstuffs was booming in Russia due to the overvalued rouble. As a result of the financial crisis, food import collapsed. The export of Finnish foodstuffs to Russia has been slowly recovering during the past few years, but in the most important product categories the pre-crisis levels have so far not been reached and maybe will not be reached. In certain product categories the growth has been only marginal. It seems that starting localproduction will become increasingly important in the future. This is further encouraged by the fact that Russian consumers favour domestic food products. Russian consumers are very price conscious and demand quality in food products. The perceived price-quality ratio is an important criterion in the purchase decision.The majority of foodstuff retail is still conducted via unorganised forms of trade (e.g. kiosks and marketplaces) but modern retail chains are developing at a fast pace in Russia. They are also expected to dominate the retail trade in foodstuffs over the unorganised forms of trade in the future. This will change the distribution systems as well. The retail chains are trying to shorten the distribution chain, similarly to what has been seen in the Western countries. This together with the strengthening of retail chains is likely to shrink the role of wholesalers, as the chains increasingly want to work directly with the producers. Many large retail chains are acquiring or have already acquired a distribution centre or centres in order to boost efficiency and control the flow of products. The strengthening of the retail chains also gives them power in negotiations, which the producers and distributors have to adjust to. For example store entry fees and retail chains' own private label products pose challenges to the food producers. In the food production sector the competition is fierce, as large Russianand foreign producers want to ensure their piece of the market. The largest producers utilise their size: they invest in big marketing campaigns and are willing to pay high entry fees to retail chains in order to secure a place on the store shelves and to build a strong brand in Russia. This complicates the situation from the viewpoint of small producers. Currently, the most popular type of distribution system among the interviewed Finnish food producers is based on a network of local distributors. There is, however, a strong consensus on the importanceof starting local production in order to be a serious actor in Russia in the future. Factors that hinder the starting of local production include the lack of local infrastructure and qualified staff, and the low risk tolerance of Finnish firms. Major barriers for entry in Russia are the actions of authorities, fierce competition, fragmented market and Finnish producers' heavy production costs. The suggested strategies for increasing the market share include focusing geographically or segment-wise, introducing new products, starting local production, andcooperation between Finnish producers. Smallness was one reason why Finnish producers had to cut down their operations in Russia due to the 1998 crisis. Smaller producers had fewer resources to tolerate losses during the period of crisis. Smallness is reflected also on trade negotiations with retail chains and distributors. It makes it harder to cope with the store entry fees and to differentiatefrom the mass of products propped up by expensive advertising. Finally, it makes it harder for Finnish producers to start or expand local production, as it is more difficult for a small producer to get financing and to tolerate the increased risks. Compensating for the smallness might become the crucial factor determining the future success of Finnish food producers in the Russian market.

Comparison between land suitability and actual crop distribution in an irrigation district of the Ebro valley (Spain)

El objetivo de la presente investigación fue analizar la correspondencia entre los resultados de una evaluación de tierras con la distribución real de los cultivos. Para ello la aptitud biofísica de las tierras se comparó con diferentes tipologías de frecuencia de ocurrencia de los cultivos y rotaciones derivadas de mapas de cultivos multitemporales. La investigación fue llevada a cabo en el distrito de riego de Flumen (33.000 ha), localizado en el valle del Ebro (NE España). La evaluación de tierras se basó en una cartografía de suelos 1:100.000, según el esquema FAO, para los principales cultivos presentes en el área de estudio (alfalfa, cereales de invierno, maíz, arroz y girasol). Se utilizaron tres mapas de frecuencia de cultivos y un mapa de rotaciones, derivado de una serie temporal de imágenes Landsat TM y ETM+ del periodo 1993-2000, y se compararon con los mapas de aptitud de tierras para los diferentes cultivos. Se analizó estadísticamente (Pearson χ2, Cramer V, Gamma y Somers D) la relación entre los dos tipos de variables. Los resultados muestran la existencia de una relación significativa (P=0,001) entre la localización de los cultivos y la idoneidad de las tierras, excepto de cultivos oportunistas como el girasol, muy influenciado por las subvenciones en el periodo estudiado. Las rotaciones basadas en la alfalfa muestran los mayores porcentajes (52%) de ocupación en las tierras más aptas para la agricultura en el área de estudio. El presente enfoque multitemporal de análisis de la información ofrece una visión más real que la comparación entre un mapa de evaluación de tierras y un mapa de cultivos de una fecha determinada, cuando se valora el grado de acuerdo entre las recomendaciones sobre la aptitud de las tierras y los cultivos realmente cultivados por los agricultores.

Variabilidad espacial del arroz como cultivo indicador de salinidad en regadíos del valle del Ebro a partir de series temporales en imágenes Landsat TM

El presente trabajo pretende la caracterización de la distribución espacial típica del cultivo de arroz en regadíos del valle del Ebro, donde la presencia del cultivo está ligada a la existencia de suelos salino-sódicos. Esta caracterización ha de permitir identificar las áreas donde es típica la presencia del cultivo año tras año y las áreas donde es frecuente su fluctuación debido tanto a condiciones variables de salinidad del suelo como a variabilidad en las condiciones de mercado. Para ello se ha recurrido al análisis de una serie temporal de mapas de cultivos (7 años) derivados de la clasificación supervisada de imágenes Landsat TM. La determinación de las áreas típicas y de fluctuación del cultivo de arroz se hace entonces a partir del análisis estadístico de clases, y mediante superposición espacial de coberturas en un entorno SIG-Raster.

Trolley R&D project for a small portal log yard crane

This master’s thesis was done for Andritz Inc. Atlanta Georgia. The purpose of the thesis was to develop a new trolley for a small portal log yard crane. In the beginning of the thesis the basic principles of the systematic design processes have been described, along which the design work of the trolley has proceeded. The second literature part consists of the design and dimensioning of the welded steel structures under fatigue loading. The design work of the trolley consists of the engineering and the selection of the mechanical components and the design of the load carrying structure for the trolley. The realization of the steel structure of the trolley is based on the fatigue and static dimensioning. The fatigue dimensioning is grounded in the life expectations estimated for the trolley and the static dimensioning is based on the CMAA guidelines. The computer aided element method was utilized in the design of the steel structure. The effective notch method and the hot spot method were used in the fatigue calculations. The trolley structure was carried out by using the sheet metal parts in order to manufacture the structure as effective and low cost way as possible. The corner stone of the dimensioning of the trolley structure was the utilization of the open profiles made of welded or cold formed sheet metals, which provide better weldability, weld inspection, access for repairs and corrosion protection. As a last part of the thesis a new trolley traveling system was developed. The distribution of the wheel loads of the trolley bogies on the main girder was also studied, which led to an innovative suspension arrangement between the trolley leg and the bogie. The new bogie solution increases the service life of the main girder of the crane and improves the stability of the bogies. The outcome of the thesis is an excellent trolley structure from the weight and the service life point of view.

Potential impact of the global climate changes on the spatial distribution of areas of risk for the occurrence of eucalyptus rust in Brazil

Rust, caused by Puccinia psidii, is one of the most important diseases affecting eucalyptus in Brazil. This pathogen causes disease in mini-clonal garden and in young plants in the field, especially in leaves and juvenile shoots. Favorable climate conditions for infection by this pathogen in eucalyptus include temperature between 18 and 25 ºC, together with at least 6-hour leaf wetness periods, for 5 to 7 consecutive days. Considering the interaction between the environment and the pathogen, this study aimed to evaluate the potential impact of global climate changes on the spatial distribution of areas of risk for the occurrence of eucalyptus rust in Brazil. Thus, monthly maps of the areas of risk for the occurrence of this disease were elaborated, considering the current climate conditions, based on a historic series between 1961 and 1990, and the future scenarios A2 and B2, predicted by IPCC. The climate conditions were classified into three categories, according to the potential risk for the disease occurrence, considering temperature (T) and air relative humidity (RH): i) high risk (18 < T < 25 ºC and RH > 90%); ii) medium risk (18 < T < 25 ºC and RH < 90%; T< 18 or T > 25 ºC and RH > 90%); and iii) low risk (T < 18 or T > 25 ºC and RH < 90%). Data about the future climate scenarios were supplied by GCM Change Fields. In this study, the simulation model Hadley Centers for Climate Prediction and Research (HadCm3) was adopted, using the software Idrisi 32. The obtained results led to the conclusion that there will be a reduction in the area favorable to eucalyptus rust occurrence, and such a reduction will be gradual for the decades of 2020, 2050 and 2080 but more marked in scenario A2 than in B2. However, it is important to point out that extensive areas will still be favorable to the disease development, especially in the coldest months of the year, i.e., June and July. Therefore, the zoning of areas and periods of higher occurrence risk, considering the global climate changes, becomes important knowledge for the elaboration of predicting models and an alert for the integrated management of this disease.

Probabilistic structure of an annual extreme rainfall series of a coastal area of the State of São Paulo, Brazil

This study aimed to describe the probabilistic structure of the annual series of extreme daily rainfall (Preabs), available from the weather station of Ubatuba, State of São Paulo, Brazil (1935-2009), by using the general distribution of extreme value (GEV). The autocorrelation function, the Mann-Kendall test, and the wavelet analysis were used in order to evaluate the presence of serial correlations, trends, and periodical components. Considering the results obtained using these three statistical methods, it was possible to assume the hypothesis that this temporal series is free from persistence, trends, and periodicals components. Based on quantitative and qualitative adhesion tests, it was found that the GEV may be used in order to quantify the probabilities of the Preabs data. The best results of GEV were obtained when the parameters of this function were estimated using the method of maximum likelihood. The method of L-moments has also shown satisfactory results.

Distribution of HCV genotypes among different exposure categories in Brazil

Hepatitis C virus (HCV) infection is widespread and responsible for more than 60% of chronic hepatitis cases. HCV presents a genetic variability which has led to viral classification into at least 6 genotypes and a series of subtypes. These variants present characteristic geographical distribution, but their association with different responses to treatment with interferon and severity of disease still remains controversial. The aim of this study was to investigate the patterns of distribution of HCV genotypes among different exposure categories in Brazil. Two hundred and fifty anti-HCV positive samples were submitted to HCV-RNA detection by RT-PCR and their genotype was determined by restriction fragment length polymorphism (RFLP) analysis. In addition, the genotype/subtype of 60 samples was also determined by a reverse hybridization assay. HCV 1 was the most prevalent (72.0%), followed by type 3 (25.3%), HCV 2 (2.0%) and HCV 4 (0.7%). The HCV genotype distribution varied among the different exposure categories, with HCV 1 being more frequent among blood donors, hemophiliacs and hemodialysis patients. A high frequency of HCV 3 was observed in cirrhotic patients, blood donors from the South of Brazil and injecting drug users (IDUs). The general distribution of the HCV genotype in Brazil is similar to that in other regions of the world.

Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

Water and electrolyte content and distribution in tissues of thermally-acclimated rainbow trout, Salmo gairdneri

The primary objective of this investigation was that of providing a comprehensive tissue-by-tissue assessment of water-electrolyte status in thermally-acclimated rainbow trout, Salmo gairdneri. To this end levels of water and the major ions, sodium, chloride and potassium were evaluated in the plasma, at three skeletal muscle sites, and in cardiac muscle, liver, spleen, gut and brain of animals acclimated to 2°, 10° and 18°C. The occurrence of possible seasonal variations in water-electrolyte balance was evaluated by sampling sununer and late fall-early winter populations of trout. On the basis of values for water and electrolyte content, estimates of extracellular and cellular phase volumes, cellular electrolyte concentrations and Nernst equilibrium potentials were made. Since accurate assessment of the extracellular phase volume is critical in the estimation of cellular electrolyte concentrations and parameters based on assumed cellular ion levels, [14 C]-polyethylene glycol-4000, which is assumed to be confined to the extracellular space, was employed to provide comparisons with various ion-defined spaces (H20~~s, H20~~/K and H20~~s). Subsequently, the ion-defined space yielding the most realistic estimate of extracellular phase volume for each tissue was used in cellular electrolyte calculations. Water and electrolyte content and distribution varied with temperature. Tissues, such as liver, spleen and brain appeared to be the most thermosensitive, whereas skeletal and cardiac muscle and gut tissue were less influenced. 'Summer' series trout appeared to be more capable of maintaining their water- electrolyte balance than the ~fall-winter' series animals. i The data are discussed in terms of their possible effect on maintenance of appropriate cellular metabolic and electrophysiological functions.

Asymptotic Distribution of a Simple Linear Estimator for VARMA Models in Echelon Form

In this paper, we study the asymptotic distribution of a simple two-stage (Hannan-Rissanen-type) linear estimator for stationary invertible vector autoregressive moving average (VARMA) models in the echelon form representation. General conditions for consistency and asymptotic normality are given. A consistent estimator of the asymptotic covariance matrix of the estimator is also provided, so that tests and confidence intervals can easily be constructed.

Irrégularités dans la distribution des nombres premiers et des suites plus générales dans les progressions arithmétiques

Le sujet principal de cette thèse est la distribution des nombres premiers dans les progressions arithmétiques, c'est-à-dire des nombres premiers de la forme $qn+a$, avec $a$ et $q$ des entiers fixés et $n=1,2,3,\dots$ La thèse porte aussi sur la comparaison de différentes suites arithmétiques par rapport à leur comportement dans les progressions arithmétiques. Elle est divisée en quatre chapitres et contient trois articles. Le premier chapitre est une invitation à la théorie analytique des nombres, suivie d'une revue des outils qui seront utilisés plus tard. Cette introduction comporte aussi certains résultats de recherche, que nous avons cru bon d'inclure au fil du texte. Le deuxième chapitre contient l'article \emph{Inequities in the Shanks-Rényi prime number race: an asymptotic formula for the densities}, qui est le fruit de recherche conjointe avec le professeur Greg Martin. Le but de cet article est d'étudier un phénomène appelé le <>, qui s'observe dans les <>. Chebyshev a observé qu'il semble y avoir plus de premiers de la forme $4n+3$ que de la forme $4n+1$. De manière plus générale, Rubinstein et Sarnak ont montré l'existence d'une quantité $\delta(q;a,b)$, qui désigne la probabilité d'avoir plus de premiers de la forme $qn+a$ que de la forme $qn+b$. Dans cet article nous prouvons une formule asymptotique pour $\delta(q;a,b)$ qui peut être d'un ordre de précision arbitraire (en terme de puissance négative de $q$). Nous présentons aussi des résultats numériques qui supportent nos formules. Le troisième chapitre contient l'article \emph{Residue classes containing an unexpected number of primes}. Le but est de fixer un entier $a\neq 0$ et ensuite d'étudier la répartition des premiers de la forme $qn+a$, en moyenne sur $q$. Nous montrons que l'entier $a$ fixé au départ a une grande influence sur cette répartition, et qu'il existe en fait certaines progressions arithmétiques contenant moins de premiers que d'autres. Ce phénomène est plutôt surprenant, compte tenu du théorème des premiers dans les progressions arithmétiques qui stipule que les premiers sont équidistribués dans les classes d'équivalence $\bmod q$. Le quatrième chapitre contient l'article \emph{The influence of the first term of an arithmetic progression}. Dans cet article on s'intéresse à des irrégularités similaires à celles observées au troisième chapitre, mais pour des suites arithmétiques plus générales. En effet, nous étudions des suites telles que les entiers s'exprimant comme la somme de deux carrés, les valeurs d'une forme quadratique binaire, les $k$-tuplets de premiers et les entiers sans petit facteur premier. Nous démontrons que dans chacun de ces exemples, ainsi que dans une grande classe de suites arithmétiques, il existe des irrégularités dans les progressions arithmétiques $a\bmod q$, avec $a$ fixé et en moyenne sur $q$.