936 resultados para usage of the bandwidth in the future


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This study focuses on corporate social responsibility (or CSR)as the latest dimension to emerge in the corporate responsibility and sustainability agenda, which in the recent past has rapidly risen to the top of the list of concerns for civil societies worldwide. Despite the continuing debates and discussions about the scope, benefits, and impacts of CSR to business and community in various sectors, levels, and types of society, many companies have moved forward to confront the opportunities and challenges of CSR. Thus, this study is about those proactive companies with a focus on the importance of CSR and its management inside and outside the company. It is an exploration and learning from the experience of Finnish companies, as well as other actors interested or involved in shaping the course of CSR, locally and globally. It also looks closely at how national culture affects the views, thinking, and management of CSR in a welfare state. This dissertation primarily draws on the analyses of information collected from a series of qualitative interviews and the existing literature in the area. This is complemented by an analysis of written and published documents on CSR from various sources. The results of the study give insightful information and detailed descriptions of a roadmap useful in learning and understanding CSR in Finnish companies. Despite the varying conceptual connotations, essential roadmap indicators point to the importance of framing CSR within the corporate responsibility concept, Finnish development and the welfare state system, globalization, stakeholders, and the pursuit of sustainable development as the main drivers of CSR, the remarkable progress of CSR in companies, and identification of key management areas and practices relevant to CSR. Similarly,the study reveals the importance of culture as essential in understanding and learning CSR. Finnish culture has a positive influence on the views, thinking, and management practices of CSR issues. Such a positive influence of culture, therefore, makes it easy for business people to discuss and understand CSR, because those CSR issues are already considered common and taken-for-granted by Finns and are implicit in the welfare state provisions. The experience of Finnish companies in implementing CSR policies in the supply chain is a concrete proactive step in advancing the message of CSR, that is, to bring companies and suppliers together to work on improving and strengthening relationships towards socially responsible practices worldwide. Such a forward step to deal with CSR issues in the supply chain reflects the companies' commitments and belief that CSR can be managed with the suppliers and gain positive benefits. Despite the problems and complexities, particularly in the global supply chain, managing CSR for Finnish companies presents new opportunities and challenges that are expected to intensify in the near future. The focus on CSR policy implementation inthe supply chain points to the importance of companies taking initiatives and forging cooperation with suppliers with the aim of addressing and improving CSR questions in the supply chains. The proactive stance of Finnish companies toward CSR is complemented by the active supporting role of important societalactors such as the government and NGOs. These actors carry out various promotional efforts and campaigns, thus bringing CSR into the mainstream of Finnish companies and strengthening the synergistic learning about CSR within the Finnish business and civil circles. The efforts of the government and NGOs to promote CSR are indicative of the importance of multipartite involvement and the emergence of better civil regulations. Likewise, their drive to learn from each other, exchange experiences, and contribute in CSR debates facilitated the evolution of CSRnetworks in the country. The results of this study add to the mounting evidence that CSR, in general, has created a new dimension in managing corporate sustainability. This study provides compelling empirical evidence and some direct quotations about CSR in the Finnish context. This information can be used to learn and gain new useful insights, approaches, and concepts for managing CSR.

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In the European Union, the importance of mobile communications was realized early on. The process of mobile communications becoming ubiquitous has taken time, as the innovation of mobile communications diffused into the society. The aim of this study is to find out how the evolution and spatial patterns of the diffusion of mobile communications within the European Union could be taken into account in forecasting the diffusion process. There is relatively lot of research of innovation diffusion on the individual (micro) andthe country (macro) level, if compared to the territorial level. Territorial orspatial diffusion refers either to the intra-country or inter-country diffusionof an innovation. In both settings, the dif- fusion of a technological innovation has gained scarce attention. This study adds knowledge of the diffusion between countries, focusing especially on the role of location in this process. The main findings of the study are the following: The penetration rates of the European Union member countries have become more even in the period of observation, from the year 1981 to 2000. The common digital GSM system seems to have hastened this process. As to the role of location in the diffusion process, neighboring countries have had similar diffusion processes. They can be grouped into three, the Nordic countries, the central and southern European countries, and the remote southern European countries. The neighborhood effect is also domi- nating in thegravity model which is used for modeling the adoption timing of the countries. The subsequent diffusion within a country, measured by the logistic model in Finland, is af- fected positively by its economic situation, and it seems to level off at some 92 %. Considering the launch of future mobile communications systemsusing a common standard should implicate an equal development between the countries. The launching time should be carefully selected as the diffusion is probably delayed in economic downturns. The location of a country, measured by distance, can be used in forecasting the adoption and diffusion. Fi- nally, the result of penetration rates becoming more even implies that in a relatively homoge- nous set of countries, such as the European Union member countries, the estimated final pene- tration of a single country can be used for approximating the penetration of the others. The estimated eventual penetration of Finland, some 92 %, should thus also be the eventual level for all the European Union countries and for the European Union as a whole.

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Intrinsic resistance to the epidermal growth factor receptor (EGFR; HER1) tyrosine kinase inhibitor (TKI) gefitinib, and more generally to EGFR TKIs, is a common phenomenon in breast cancer. The availability of molecular criteria for predicting sensitivity to EGFR-TKIs is, therefore, the most relevant issue for their correct use and for planning future research. Though it appears that in non-small-cell lung cancer (NSCLC) response to gefitinib is directly related to the occurrence of specific mutations in the EGFR TK domain, breast cancer patients cannot be selected for treatment with gefitinib on the same basis as such EGFR mutations have beenreported neither in primary breast carcinomas nor in several breast cancer cell lines. Alternatively, there is a generalagreement on the hypothesis that the occurrence of molecular alterations that activate transduction pathways downstreamof EGFR (i.e., MEK1/MEK2 - ERK1/2 MAPK and PI-3'K - AKT growth/survival signaling cascades) significantly affect the response to EGFR TKIs in breast carcinomas. However,there are no studies so far addressing a role of EGF-related ligands as intrinsic breast cancer cell modulators of EGFR TKIefficacy. We recently monitored gene expression profiles andsub-cellular localization of HER-1/-2/-3/-4 related ligands (i.e., EGF, amphiregulin, transforming growth factor-α, ß-cellulin,epiregulin and neuregulins) prior to and after gefitinib treatment in a panel of human breast cancer cell lines. First, gefitinibinduced changes in the endogenous levels of EGF-related ligands correlated with the natural degree of breast cancer cellsensitivity to gefitinib. While breast cancer cells intrinsically resistant to gefitinib (IC50 ≥15 μM) markedly up-regulated(up to 600 times) the expression of genes codifying for HERspecific ligands, a significant down-regulation (up to 106 times)of HER ligand gene transcription was found in breast cancer cells intrinsically sensitive to gefitinib (IC50 ≤1 μM). Second,loss of HER1 function differentially regulated the nuclear trafficking of HER-related ligands. While gefitinib treatment induced an active import and nuclear accumulation of the HER ligand NRG in intrinsically gefitinib-resistant breastcancer cells, an active export and nuclear loss of NRG was observed in intrinsically gefitinib-sensitive breast cancer cells.In summary, through in vitro and pharmacodynamic studies we have learned that, besides mutations in the HER1 gene,oncogenic changes downstream of HER1 are the key players regulating gefitinib efficacy in breast cancer cells. It now appears that pharmacological inhibition of HER1 functionalso leads to striking changes in both the gene expression and the nucleo-cytoplasmic trafficking of HER-specific ligands,and that this response correlates with the intrinsic degree of breast cancer sensitivity to the EGFR TKI gefitinib. Therelevance of this previously unrecognized intracrine feedback to gefitinib warrants further studies as cancer cells could bypassthe antiproliferative effects of HER1-targeted therapeutics without a need for the overexpression and/or activation of other HER family members and/or the activation of HER-driven downstream signaling cascades

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Calcineurin is a key protein phosphatase required for hyphal growth and virulence in Aspergillus fumigatus, making it an attractive antifungal target. However, currently available calcineurin inhibitors, FK506 and cyclosporine A, are immunosuppressive, limiting usage in the treatment of patients with invasive aspergillosis. Therefore, the identification of endogenous inhibitors of calcineurin belonging to the calcipressin family is an important parallel strategy. We previously identified the gene cbpA as the A. fumigatus calcipressin member and showed its involvement in hyphal growth and calcium homeostasis. However, the mechanism of its activation/inhibition through phosphorylation and its interaction with calcineurin remains unknown. Here we show that A. fumigatus CbpA is phosphorylated at three distinct domains, including the conserved SP repeat motif (phosphorylated domain-I; PD-I), a filamentous fungal-specific domain (PD-II), and the C-terminal CIC motif (Calcipressin Inhibitor of Calcineurin; PD-III). While mutation of three phosphorylated residues (Ser208, Ser217, Ser223) in the PD-II did not affect CbpA function in vivo, mutation of the two phosphorylated serines (Ser156, Ser160) in the SP repeat motif caused reduced hyphal growth and sensitivity to oxidative stress. Mutational analysis in the key domains in calcineurin A (CnaA) and proteomic interaction studies confirmed the requirement of PxIxIT motif-binding residues (352-NIR-354) and the calcineurin B (CnaB)-binding helix residue (V371) for the binding of CbpA to CnaA. Additionally, while the calmodulin-binding residues (442-RVF-444) did not affect CbpA binding to CnaA, three mutations (T359P, H361L, and L365S) clustered between the CnaA catalytic and the CnaB-binding helix were also required for CbpA binding. This is the first study to analyze the phosphorylation status of calcipressin in filamentous fungi and identify the domains required for binding to calcineurin.

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BACKGROUND: Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. METHODS: A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. RESULTS: A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. CONCLUSION: The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST.

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To compare the cost and effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus combined oral contraception (COC) and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) in Spain. STUDY DESIGN: A cost-effectiveness and cost-utility analysis of LNG-IUS, COC and PROG was carried out using a Markov model based on clinical data from the literature and expert opinion. The population studied were women with a previous diagnosis of idiopathic heavy menstrual bleeding. The analysis was performed from the National Health System perspective, discounting both costs and future effects at 3%. In addition, a sensitivity analysis (univariate and probabilistic) was conducted. RESULTS: The results show that the greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time). Regarding costs, LNG-IUS produces savings of 174.2-309.95 and 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years. Apart from cost savings and gains in SFM, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1 and 2 QALM compared to COC and PROG. CONCLUSIONS: The results indicate that first-line use of the LNG-IUS is the dominant therapeutic option (less costly and more effective) in comparison with first-line use of COC or PROG for the treatment of DUB in Spain. LNG-IUS as first line is also the option that provides greatest health-related quality of life to patients.

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Työn tavoitteena oli selventää Elcoteqin Suomen ja Venäjän välisten yksiköiden logistista prosessia ja erityisesti siihen liittyviä ongelmia. Työ on tehty Elcoteqin Engineering Services yksikköön, jossa ei tyypillisesti ole ollut asiaan liittyvää tietoa. Pääasiallisena työmenetelmänä olivat haastattelut sekä tutustuminen logistiseen putkeen käytännössä. Myös kirjallisuudella oli oma osansa, sekä tullaukseen että asiaan liittyvien teorioiden osalta. Teorioita ja käytännön kokemuksia yhdistäen edettiin analysointiin ja vertailuun, jonka perusteella annettiin suosituksia tulevia projekteja silmällä pitäen. Myös tulevaisuuden odotuksia on käsitelty yleisellä tasolla, lähinnä liittyen erilaisten kehitysohjelmien tarjoamiin mahdollisuuksiin. Logistiikka Suomen ja Venäjän välillä on huomattavasti monimutkaisempaa kuin ensisilmäyksellä näyttää. Ongelmia on niin rajanylityksen, tullauksen kuin lisenssiprosessinkin kanssa. Asioiden kehittämiseksi on kuitenkin paljon tehtävissä, kehityspotentiaali on valtava. Vahvaa panostusta liiketoiminnan kehittämiseksi Venäjällä on jatkettava, vaikka siihen liittyvät ongelmat välillä tuntuvatkin ylivoimaisen suurilta. Erityisen turhauttavia ovat asiat, joihin ei pystytä vaikuttamaan. Työn edetessä tuli kuitenkin esiin uusia näkökulmia, joita ei aiemmin ole otettu huomioon. Tuotteiden valintaan on jatkossa kiinnitettävä enemmän huomiota. Silti myös kuljetuksen ja rajanylityksen nopeuttamisen tutkimista on edelleen jatkettava.

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Abstract Purpose: Several well-known managerial accounting performance measurement models rely on causal assumptions. Whilst users of the models express satisfaction and link them with improved organizational performance, academic research, of the realworld applications, shows few reliable statistical associations. This paper provides a discussion on the"problematic" of causality in a performance measurement setting. Design/methodology/approach: This is a conceptual study based on an analysis and synthesis of the literature from managerial accounting, organizational theory, strategic management and social scientific causal modelling. Findings: The analysis indicates that dynamic, complex and uncertain environments may challenge any reliance upon valid causal models. Due to cognitive limitations and judgmental biases, managers may fail to trace correct cause-and-effect understanding of the value creation in their organizations. However, even lacking this validity, causal models can support strategic learning and perform as organizational guides if they are able to mobilize managerial action. Research limitations/implications: Future research should highlight the characteristics necessary for elaboration of convincing and appealing causal models and the social process of their construction. Practical implications: Managers of organizations using causal models should be clear on the purposes of their particular models and their limitations. In particular, difficulties are observed in specifying detailed cause and effect relations and their potential for communicating and directing attention. They should therefore construct their models to suit the particular purpose envisaged. Originality/value: This paper provides an interdisciplinary and holistic view on the issue of causality in managerial accounting models.

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Sähkönkulutuksen lyhyen aikavälin ennustamista on tutkittu jo pitkään. Pohjoismaisien sähkömarkkinoiden vapautuminen on vaikuttanut sähkönkulutuksen ennustamiseen. Aluksi työssä perehdyttiin aiheeseen liittyvään kirjallisuuteen. Sähkönkulutuksen käyttäytymistä tutkittiin eri aikoina. Lämpötila tilastojen käyttökelpoisuutta arvioitiin sähkönkulutusennustetta ajatellen. Kulutus ennusteet tehtiin tunneittain ja ennustejaksona käytettiin yhtä viikkoa. Työssä tutkittiin sähkönkulutuksen- ja lämpötiladatan saatavuutta ja laatua Nord Poolin markkina-alueelta. Syötettävien tietojen ominaisuudet vaikuttavat tunnittaiseen sähkönkulutuksen ennustamiseen. Sähkönkulutuksen ennustamista varten mallinnettiin kaksi lähestymistapaa. Testattavina malleina käytettiin regressiomallia ja autoregressiivistä mallia (autoregressive model, ARX). Mallien parametrit estimoitiin pienimmän neliösumman menetelmällä. Tulokset osoittavat että kulutus- ja lämpötiladata on tarkastettava jälkikäteen koska reaaliaikaisen syötetietojen laatu on huonoa. Lämpötila vaikuttaa kulutukseen talvella, mutta se voidaan jättää huomiotta kesäkaudella. Regressiomalli on vakaampi kuin ARX malli. Regressiomallin virhetermi voidaan mallintaa aikasarjamallia hyväksikäyttäen.

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Biologic agents (also termed biologicals or biologics) are therapeutics that are synthesized by living organisms and directed against a specific determinant, for example, a cytokine or receptor. In inflammatory and autoimmune diseases, biologicals have revolutionized the treatment of several immune-mediated disorders. Biologicals have also been tested in allergic disorders. These include agents targeting IgE; T helper 2 (Th2)-type and Th2-promoting cytokines, including interleukin-4 (IL-4), IL-5, IL-9, IL-13, IL-31, and thymic stromal lymphopoietin (TSLP); pro-inflammatory cytokines, such as IL-1β, IL-12, IL-17A, IL-17F, IL-23, and tumor necrosis factor (TNF); chemokine receptor CCR4; and lymphocyte surface and adhesion molecules, including CD2, CD11a, CD20, CD25, CD52, and OX40 ligand. In this task force paper of the Interest Group on Biologicals of the European Academy of Allergy and Clinical Immunology, we review biologicals that are currently available or tested for the use in various allergic and urticarial pathologies, by providing an overview on their state of development, area of use, adverse events, and future research directions.

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Tutkimuksen tavoitteena oli selvittää miten Bluetooth-teknologia voi vaikuttaa ICT-alan arvoverkkoon ja alan toimijoiden rooleihin. Tutkimuksessa käytettiin kvalitatiivisia menetelmiä ja siinä oli piirteitä tulevaisuuden tutkimuksesta, koska myös eksploratiivisia menetelmiä käytettiin. Tutkimus perustui laajalti kirjallisuuteen ja artikkeleihin, joiden perusteella muodostettiin skenaarioita ICT-alan tulevaisuuden arvoverkosta. Tutkimus sisälsi myös empiirisen osion, jossa järjestettiin kaksi ryhmäkeskustelua, joissa alan toimijat keskustelivat muodostetuista skenaarioista sekä yleisemmin Bluetoothin vaikutuksista arvoverkkoon. Tutkimuksen mukaan ICT-alan arvoverkko tulevaisuudessa on rakenteeltaan strateginen arvoverkko, jota johtaa eri toimija erilaisissa markkinatilanteissa. Verkon strateginen keskus voi muuttua ajan kuluessa kun Bluetoothin sovelluskohteet lisääntyvät ja se voi vaihdella markkina-alueesta toiseen. Bluetooth luo uuden kommunikaatiokanavan nykyisten rinnalle ja se voi paikallisesti korvata nykyisten kanavien käytön tiedon siirrossa. Bluetooth voi synnyttää lukuisia uusia liiketoimintamahdollisuuksia ja sen avulla voidaan tuottaa lisäarvopalveluita. Suurimpien muutosten voidaan olettaa koskevan teleoperaattoreiden ja sisällöntuottajien liiketoimintaa.

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The purpose of this thesis was to investigate Job Definition Format (JDF) and how it could be used in printing house's systems. JDF is a very new information exchange standard, and it gives a lot of opportunities to the printing industry. JDF is the first standard, that has an ability to carry a print job from genesis through completion. Besides, JDF has an ability to bridge the communication gap between production and management information services. In the study of JDF we focused on examining how JDF will effect on printing industry .The thesis also examines printing houses's systems ability to work with JDF standard. The result of the study is a comprehensive picture, what is JDF. We also researched the system developers' visions, how JDF will effect on their products in the future.

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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.

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The EpiNet project has been established to facilitate investigator-initiated clinical research in epilepsy, to undertake epidemiological studies, and to simultaneously improve the care of patients who have records created within the EpiNet database. The EpiNet database has recently been adapted to collect detailed information regarding status epilepticus. An incidence study is now underway in Auckland, New Zealand in which the incidence of status epilepticus in the greater Auckland area (population: 1.5 million) will be calculated. The form that has been developed for this study can be used in the future to collect information for randomized controlled trials in status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".

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The untargeted integration of foreign DNA into the mammalian cell genome, extensively used in gene therapy and biotechnology, remains an incompletely understood process. It is believed to be based on cellular DNA double strand break (DSB) repair machinery and to involve two major steps: i) the formation of long gene arrays (concatemers), and ii) recombination of the resulting concatemer with the genome. The main DSB repair pathways in eukaryotes include non-homologous end-joining (NHEJ), homologous recombination (HR), and microhomology-mediated end-joining (MMEJ). However, it is still not clear, which of these pathways are responsible for transgene integration. Here, we show that NHEJ is not the primary pathway used by mammalian cells in the transgene integration process, while the components of the HR pathway seem to be important for genomic integration but not concatemerization. Instead, concatemer formation appears to be mediated by a subset of the MMEJ pathway, termed synthesis-dependent MMEJ (SD-MMEJ). This mechanism also seems to be preferentially used for plasmid integration into the genome, as confirmed by the analysis of plasmid-to-genome junction sequences, which were found to display an SD-MMEJ pattern. Therefore, we propose the existence of two distinct SD-MMEJ subpathways, relying on different subsets of enzymes. One of these mechanisms appears to be responsible for concatemerization, while the other mechanism, partially dependent in HR enzymes, seems to mediate recombination with the genome. Previous studies performed by our group suggested that matrix attachment regions (MARs), which are epigenetic regulatory DNA elements that participate in the formation of chromatin boundaries and augment transcription, may mediate increased plasmid integration into the genome of CHO cells by stimulating DNA recombination. In the present work, we demonstrate that MAR-mediated plasmid integration results from the enhanced SD-MMEJ pathway. Analysis of transgene integration loci and junction DNA sequences validated the prevalent use of this pathway by the MAR elements to target plasmid DNA into gene-rich areas of the CHO genome. We propose that this finding should in the future help to engineer cells for improved recombinant protein production. In addition to investigating the process of transgene integration, we designed recombination assays to better characterize the components of the MMEJ and SD-MMEJ pathways. We also used CHO cells expressing cycle-sensitive reporter genes to demonstrate a potential role of HR proteins in the cell cycle regulation.