Population Variation and Genetic Control of Modular Chromatin Architecture in Humans.

Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.

A Generic Framework Architecture for Portal Front End

A modem software development requires quick results and excellent quality, which leads to high demand for reusability in design and implementation of software components. The purpose of this thesis was to design and implement a reusable framework for portal front ends, including common portal features, such as authentication and authorization. The aim was also to evaluate frameworks as components of reuse and compare them to other reuse techniques. As the result of this thesis, a goo'd picture of framework's life cycle, problem domain and the actual implementation process of the framework, was obtained. It was also found out that frameworks fit well to solve recurrent and similar problems in a restricted problem domain. The outcome of this thesis was a prototype of a generic framework and an example application built on it. The implemented framework offered an abstract base for the portal front ends, using object-oriented methods and wellknown design patterns. The example application demonstrated the speed and ease of the application development based on the application frameworks.

Problems of the architecture design in the system integration

This thesis studies the problems and their reasons a software architect faces in his work. The purpose of the study is to search and identify potential factors causing problens in system integration and software engineering. Under a special interest are non-technical factors causing different kinds of problems. Thesis was executed by interviewing professionals that took part in e-commerce project in some corporation. Interviewed professionals consisted of architects from technical implementation projects, corporation's architect team leader, different kind of project managers and CRM manager. A specific theme list was used as an guidance of the interviews. Recorded interviews were transcribed and then classified using ATLAS.ti software. Basics of e-commerce, software engineering and system integration is described too. Differences between e-commerce and e-business as well as traditional business are represented as are basic types of e-commerce. Software's life span, general problems of software engineering and software design are covered concerning software engineering. In addition, general problems of the system integration and the special requirements set by e-commerce are described in the thesis. In the ending there is a part where the problems founded in study are described and some areas of software engineering where some development could be done so that same kind of problems could be avoided in the future.

Marked increase in incidence for bloodstream infections due to Escherichia coli, a side effect of previous antibiotic therapy in the elderly.

We conducted a survey including 3334 bloodstream infections (BSIs) due to E. coli diagnosed in 2005-2014 at a stable cohort of hospitals. Marked increases in incidence were observed for community-acquired (CA) BSIs in patients aged >75 years, CA-BSIs of digestive origin in patients aged 60-74 years, healthcare-associated BSIs, and BSIs associated with ESBL (extended-spectrum B-lactamase)-producing E. coli (ESBLEc). Using MLST, we studied the genetic diversity of 412 BSI isolates recovered during the 2014 survey: 7 major sequence type complexes (STCs) were revealed in phylogenetic group B2, 3 in group A/B1 and 2 in group D. Among the 31 ESBLEc isolates, 1/3 belonged to STC 131. We searched for possible associations between clonal groups, clinical determinants and characteristics of BSIs: isolates from groups B2 (except STC 131) and D were susceptible to antibiotics and associated with BSIs of urinary origin in patients <60 years. STC 131 and group A/B1 isolates were multi-drug resistant and associated with CA-BSIs of digestive origin in patients aged 60-74 with a recent history of antibiotic treatment. STC 131 isolates were associated with HCA-BSIs in patients with recent/present hospitalization in a long-stay unit. We provide a unique population-based picture of the epidemiology of E. coli BSI. The aging nature of the population led to an increase in the number of cases caused by the B2 and D isolates generally implicated in BSIs. In addition, the association of a trend toward increasing rates of gut colonization with multi drug-resistant isolates revealed by the rise in the incidence of BSIs of digestive origin caused by STC 131 and A/B1 (STCs 10, 23, and 155) isolates, and a significant increase in the frequency of BSIs in elderly patients with recent antibiotic treatment suggested that antibiotic use may have contributed to the growing incidence of BSI.

Operational Reliability Analysis of a Three-Tiered Thin-Client ERP-system in an International Corporate Environment

Internationalization and the following rapid growth have created the need to concentrate the IT systems of many small-to-medium-sized production companies. Enterprise Resource Planning systems are a common solution for such companies. Deployment of these ERP systems consists of many steps, one of which is the implementation of the same shared system at all international subsidiaries. This is also one of the most important steps in the internationalization strategy of the company from the IT point of view. The mechanical process of creating the required connections for the off-shore sites is the easiest and most well-documented step along the way, but the actual value of the system, once operational, is perceived in its operational reliability. The operational reliability of an ERP system is a combination of many factors. These factors vary from hardware- and connectivity-related issues to administrative tasks and communication between decentralized administrative units and sites. To accurately analyze the operational reliability of such system, one must take into consideration the full functionality of the system. This includes not only the mechanical and systematic processes but also the users and their administration. All operational reliability in an international environment relies heavily on hardware and telecommunication adequacy so it is imperative to have resources dimensioned with regard to planned usage. Still with poorly maintained communication/administration schemes no amount of bandwidth or memory will be enough to maintain a productive level of reliability. This thesis work analyzes the implementation of a shared ERP system to an international subsidiary of a Finnish production company. The system is Microsoft Dynamics Ax, currently being introduced to a Slovakian facility, a subsidiary of Peikko Finland Oy. The primary task is to create a feasible base of analysis against which the operational reliability of the system can be evaluated precisely. With a solid analysis the aim is to give recommendations on how future implementations are to be managed.

Benefits and Limitations of Service Oriented Architecture

In this thesis I examine Service Oriented Architecture (SOA) considering both its positive and negative qualities for business organizations and IT. In SOA, services are loosely coupled and invoked through standard interfaces to enable business process independence from the underlying technology. As an architecture, SOA brings the key benefit of service reuse that may mean anything from simple application reuse to taking advantage of entire business processes across enterprises. SOA also promises interoperability especially by the Web services standards that enable platform independency. Cost efficiency is mainly a result of the savings in IT maintenance and reduced development costs. The most severe limitations of SOA are performance implications and security issues, but the applicability of SOA is also limited. Additional disadvantages of a service oriented approach include problems in data management and complexity questions, and the lack of agreement about SOA and its twofold nature as a business as well as technology approach leads to problematic interpretation of the available information. In this thesis I find the benefits and limitations of SOA for the purpose described above and propose that companies need to consider the decision to implement SOA carefully to determine whether the benefits will outdo the costs in the individual case.

Radiothérapie « flash » à très haut débit de dose : un moyen d'augmenter l'indice thérapeutique par minimisation des dommages aux tissus sains [Ultrahigh dose-rate, "flash" irradiation minimizes the side-effects of radiotherapy].

PURPOSE: Pencil beam scanning and filter free techniques may involve dose-rates considerably higher than those used in conventional external-beam radiotherapy. Our purpose was to investigate normal tissue and tumour responses in vivo to short pulses of radiation. MATERIAL AND METHODS: C57BL/6J mice were exposed to bilateral thorax irradiation using pulsed (at least 40Gy/s, flash) or conventional dose-rate irradiation (0.03Gy/s or less) in single dose. Immunohistochemical and histological methods were used to compare early radio-induced apoptosis and the development of lung fibrosis in the two situations. The response of two human (HBCx-12A, HEp-2) tumour xenografts in nude mice and one syngeneic, orthotopic lung carcinoma in C57BL/6J mice (TC-1 Luc+), was monitored in both radiation modes. RESULTS: A 17Gy conventional irradiation induced pulmonary fibrosis and activation of the TGF-beta cascade in 100% of the animals 24-36 weeks post-treatment, as expected, whereas no animal developed complications below 23Gy flash irradiation, and a 30Gy flash irradiation was required to induce the same extent of fibrosis as 17Gy conventional irradiation. Cutaneous lesions were also reduced in severity. Flash irradiation protected vascular and bronchial smooth muscle cells as well as epithelial cells of bronchi against acute apoptosis as shown by analysis of caspase-3 activation and TUNEL staining. In contrast, the antitumour effectiveness of flash irradiation was maintained and not different from that of conventional irradiation. CONCLUSION: Flash irradiation shifted by a large factor the threshold dose required to initiate lung fibrosis without loss of the antitumour efficiency, suggesting that the method might be used to advantage to minimize the complications of radiotherapy.

Brief report : Academic amotivation in light of the dark side of identity formation

The study intended to determine motivational profiles of first-year undergraduates and aimed their characterization in terms of identity processes. First, a cluster analysis revealed five motivational profiles: combined (i.e., high quantity of motivation, low amotivation); intrinsic (i.e., high intrinsic, low introjected and external regulation, low amotivation); "demotivated" (i.e., very low quantity of motivation and amotivation); extrinsic (i.e., high extrinsic and identified regulation and low intrinsic and amotivation); and "amotivated" (i.e., low intrinsic and identified, very high amotivation). Second, using Lebart's (2000) methodology, the most characteristic identity processes were listed for each motivational cluster. Demotivated and amotivated profiles were refined in terms of adaptive and maladaptive forms of exploration. Notably, exploration in breadth and in depth were underrepresented in demotivated students compared to the total sample; commitment and ruminative exploration were under and overrepresented respectively in amotivated students. Educational and clinical implications are proposedand future research is suggested.