Challenges of Post-acquisition Integration

Työ käsittelee suomalaisen kemianalan yrityksen Yhdysvalloissa tekemää yritysostoa. Tarkastelun kohteena on yritysoston jälkeinen integraatio erityisesti kulttuurin näkökulmasta. Ongelma on jaettu kahteen suurempaan osakokonaisuuteen: kulttuurierojen analysointiin sekä mahdollisten muiden ongelma-alueiden kartoittamiseen. Kulttuuri on jaettu työssä neljään tasoon. Koska kyseessä on kansainvälinen liiketoiminta, laajimmasta tasosta, kansallisesta kulttuurista on erotettu omaksi käsitteekseen liiketoimintatavat tietyssä maassa. Lisäksi tarkastellaan teollisuudenalan kulttuuria ja yrityskulttuuria. Näitä kulttuurin eri dimensioita on lähestytty empiirisessä osassa lähinnä haastattelujen avulla. Kultuurierojen lisäksi muita huomioitavia seikkoja Yhdysvalloissa tehtävien yritysostojen integraatiossa ovat mm. riittävä ja selkeä kommunikonti, etukäteissuunnitelmat ja –tutkimukset, päätöksenteon ja organisaatiorakenteen erilaisuus sekä asianajajien merkittävä asema amerikkalaisessa yhteiskunnassa. Tulokset analysoitiin kyselystä, joka lähetettiin niille suomalaisille yrityksille, jotka vuoden 1990 jälkeen olivat tehneet yritysostoja Yhdysvalloissa.

Kernel-PCA data integration with enhanced interpretability

Background Nowadays, combining the different sources of information to improve the biological knowledge available is a challenge in bioinformatics. One of the most powerful methods for integrating heterogeneous data types are kernel-based methods. Kernel-based data integration approaches consist of two basic steps: firstly the right kernel is chosen for each data set; secondly the kernels from the different data sources are combined to give a complete representation of the available data for a given statistical task. Results We analyze the integration of data from several sources of information using kernel PCA, from the point of view of reducing dimensionality. Moreover, we improve the interpretability of kernel PCA by adding to the plot the representation of the input variables that belong to any dataset. In particular, for each input variable or linear combination of input variables, we can represent the direction of maximum growth locally, which allows us to identify those samples with higher/lower values of the variables analyzed. Conclusions The integration of different datasets and the simultaneous representation of samples and variables together give us a better understanding of biological knowledge.

Robust Estimates of the Negative Binomial Model

We consider robust parametric procedures for univariate discrete distributions, focusing on the negative binomial model. The procedures are based on three steps: ?First, a very robust, but possibly inefficient, estimate of the model parameters is computed. ?Second, this initial model is used to identify outliers, which are then removed from the sample. ?Third, a corrected maximum likelihood estimator is computed with the remaining observations. The final estimate inherits the breakdown point (bdp) of the initial one and its efficiency can be significantly higher. Analogous procedures were proposed in [1], [2], [5] for the continuous case. A comparison of the asymptotic bias of various estimates under point contamination points out the minimum Neyman's chi-squared disparity estimate as a good choice for the initial step. Various minimum disparity estimators were explored by Lindsay [4], who showed that the minimum Neyman's chi-squared estimate has a 50% bdp under point contamination; in addition, it is asymptotically fully efficient at the model. However, the finite sample efficiency of this estimate under the uncontaminated negative binomial model is usually much lower than 100% and the bias can be strong. We show that its performance can then be greatly improved using the three step procedure outlined above. In addition, we compare the final estimate with the procedure described in

Financial integration, capital misallocation and global imbalances

This paper shows that in a stylized model with two countries, characterized by different levels of financial development, the following facts can be replicated: 1) persistent current account surpluses and 2) high TFP growth in China. Under autarky, entrepreneurs in the emerging country overinvest in short-term projects and underinvest in long-term projects because short-term assets help them secure long-term investments in the presence of credit constraints. This creates an aggregate misallocation of capital. When financial markets integrate, entrepreneurs with long-term projects can have access to cheaper short-term assets abroad, which leaves them more resources to invest in their projects. This both reduces capital misallocations and generates capital outflows.

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.

Cryptococcus neoformans meningitis with negative cryptococcal antigen: Evaluation of a new immunochromatographic detection assay.

Detection of cryptococcal antigen in serum or cerebrospinal fluid allows cryptococcal meningitis diagnosis within few hours with >90% sensitivity. In an HIV-positive patient with Cryptococcus neoformans meningitis, initial antigen detection by immunoagglutination was negative. We thus evaluated a new immunochromatographic detection assay that exhibited a higher sensitivity.

Opettajan monikulttuurinen työ

Teacher's multicultural work The purpose of the present study is to explore teachers’ conceptions of their work as teachers of multicultural students. Teachers’ experiences of multicultural work and conceptions derived from them are part of the teacher’s multicultural competence which is seen as a key component of the teacher’s multicultural teachership. The teacher’s multicultural competence consists of the teacher’s cultural knowledge, pedagogical skills and experiences and attitudes related to multiculturalism. The teacher’s multicultural competence constitutes the basis on which the teacher implements multicultural education. The foundation for the teacher’s work is laid by laws and decrees, curricula, regulations issued by authorities in charge of the education of immigrant students, resources available and other demands and expectations set by the ambient society. The study was conducted in the city of Turku, Finland. The sample consisted of class teachers who taught both immigrant and majority students. Main objects of study in the theoretical part are the multicultural and pluralistic school and the multicultural teachership. The basic assumption is that the multicultural and pluralistic school forms the frame of activity in which the teacher implements multicultural teaching. The research strategy is based on methodological triangulation. The quantitative part of the study was carried out using a questionnaire typical of survey methods. The questionnaire was returned by 71 teachers. The qualitative part was conducted using theme-based interviews typical of phenomenological philosophical research. Of the total of teachers who returned the questionnaire, twelve (12) teachers were selected for interviews. According to the results, the participating teachers enjoyed their work regardless of the ample extra work caused by the students with immigrant backgrounds. The teachers experienced their work as teachers of multicultural student groups as strenuous, yet challenging. Students with immigrant backgrounds had caused many changes in the teacher’s work. The teachers regarded their multicultural skills as inadequate in relation to the demands of the work. They had not received education related to teaching students with immigrant backgrounds, but they were ready for in-service education. The teachers’ previous attitudes concerning immigrant students had been enforced. Teaching experiences strengthened the earlier, both positive and negative, attitudes. The central problems related to multiculturalism in the teacher’s work were caused by the deficient Finnish skills of the students with immigrant background. This was apparent in both teaching and learning as well as in contacts with parents. The teachers reported on relatively few inclusions of multicultural angles in their teaching. However, they believed that they could aid students with different cultural backgrounds in their integration process. At the same time they felt that their own chances to enhance the students’ cultural identities were slim. On the basis of the interviews conducted in connection with the teacher’s multicultural competence, the teachers were divided into three groups: assimilative, indeterminate and integrating multicultural teachers. The present study provides a strong indication that teachers tend to interpret multiculturalism in narrow terms. School activities, such as Finnish as a second language, first language and religious instruction, which were targeted exclusively at immigrant students were in most cases considered adequate. A holistic, cross-disciplinary, all-inclusive multicultural education that would permeate all school activities remains largely unimplemented.

Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration.

The cellular DNA repair hRAD51 protein has been shown to restrict HIV-1 integration both in vitro and in vivo. To investigate its regulatory functions, we performed a pharmacological analysis of the retroviral integration modulation by hRAD51. We found that, in vitro, chemical activation of hRAD51 stimulates its integration inhibitory properties, whereas inhibition of hRAD51 decreases the integration restriction, indicating that the modulation of HIV-1 integration depends on the hRAD51 recombinase activity. Cellular analyses demonstrated that cells exhibiting high hRAD51 levels prior to de novo infection are more resistant to integration. On the other hand, when hRAD51 was activated during integration, cells were more permissive. Altogether, these data establish the functional link between hRAD51 activity and HIV-1 integration. Our results highlight the multiple and opposite effects of the recombinase during integration and provide new insights into the cellular regulation of HIV-1 replication.

Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype.

Mantle cell lymphoma is a mature lymphoid neoplasm characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. SOX11 is a transcription factor commonly overexpressed in these tumors but absent in most other mature B-cell lymphomas whose function is not well understood. Experimental studies have shown that silencing of SOX11 in mantle cell lymphoma cells promotes the shift from a mature B cell into an early plasmacytic differentiation phenotype, suggesting that SOX11 may contribute to tumor development by blocking the B-cell differentiation program. The relationship between SOX11 expression and terminal B-cell differentiation in primary mantle cell lymphoma and its relationship to the plasmacytic differentiation observed in occasional cases is not known. In this study we have investigated the terminal B-cell differentiation phenotype in 60 mantle cell lymphomas, 41 SOX11-positive and 19 SOX11-negative. Monotypic plasma cells and lymphoid cells with plasmacytic differentiation expressing cyclin D1 were observed in 7 (37%) SOX11-negative but in none of 41 SOX11-positive mantle cell lymphomas (P<0.001). Intense cytoplasmic expression of a restricted immunoglobulin light chain was significantly more frequent in SOX11-negative than -positive tumors (58 vs 13%) (P=0.001). Similarly, BLIMP1 and XBP1 expression was also significantly more frequent in SOX11-negative than in -positive cases (83 vs 34% and 75 vs 11%, respectively) (P=0.001). However, no differences in the expression of IRF4/MUM1 were observed among these subtypes of mantle cell lymphoma. In conclusion, these results indicate that SOX11-negative mantle cell lymphoma may be a particular subtype of this tumor characterized by more frequent morphological and immunophenotypic terminal B-cell differentiation features that may be facilitated by the absence of SOX11 transcription factor.

MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.

Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and #NCT00135499.

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group.

PURPOSE: Pediatric rhabdomyosarcoma (RMS) has two common histologic subtypes: embryonal (ERMS) and alveolar (ARMS). PAX-FOXO1 fusion gene status is a more reliable prognostic marker than alveolar histology, whereas fusion gene-negative (FN) ARMS patients are clinically similar to ERMS patients. A five-gene expression signature (MG5) previously identified two diverse risk groups within the fusion gene-negative RMS (FN-RMS) patients, but this has not been independently validated. The goal of this study was to test whether expression of the MG5 metagene, measured using a technical platform that can be applied to routine pathology material, would correlate with outcome in a new cohort of patients with FN-RMS. EXPERIMENTAL DESIGN: Cases were taken from the Children's Oncology Group (COG) D9803 study of children with intermediate-risk RMS, and gene expression profiling for the MG5 genes was performed using the nCounter assay. The MG5 score was correlated with clinical and pathologic characteristics as well as overall and event-free survival. RESULTS: MG5 standardized score showed no significant association with any of the available clinicopathologic variables. The MG5 signature score showed a significant correlation with overall (N = 57; HR, 7.3; 95% CI, 1.9-27.0; P = 0.003) and failure-free survival (N = 57; HR, 6.1; 95% CI, 1.9-19.7; P = 0.002). CONCLUSIONS: This represents the first, validated molecular prognostic signature for children with FN-RMS who otherwise have intermediate-risk disease. The capacity to measure the expression of a small number of genes in routine pathology material and apply a simple mathematical formula to calculate the MG5 metagene score provides a clear path toward better risk stratification in future prospective clinical trials. Clin Cancer Res; 21(20); 4733-9. ©2015 AACR.

Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes.

Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons.