Differentiation vs. low cost strategies in Romania

The theoretical analysis dealing with the possibilities of supporting certain generic strategies is useful in order to guide the efforts needed to gain a competitive advantage at national level. Subsequently, the problem of this advantage can be taken into account at an international level. In parallel with the theoretical approach, it's important to make an evaluation of the existing situation from the point of view related to the preference for a certain type of strategy, and of the relation between the type of strategy and the level of profitability. An explicit modeling of the effort to define a certain strategy will be guided by the corroborated results of these analyses. The study aims at being a referential framework for an ampler discussion on the theme related to the sustainability of the generic strategies with an extreme positioning on the scale of competitive advantages provided by the cost and differentiation.differentiation strategy, generic strategies, low cost strategy.

USING STRATEGIC MANAGEMENT STUDY CASES IN ROMANIA

The paper discuss the use of study case in the teaching of strategic management and the translation of the method from United States to Romania. Some technical aspects of American experience in strategic management case researching are underlined, with a focalised approach on financial analysis and their informational context. The basic weaknesses of the method are also analysed in order to understand the practical problems in Romanian educational environment. The general value as a tool in achieving participation and in developing communication is magnified with a specific Romanian one: gathering direct information.case study, strategic management, qualitative data, financial analysis, firm classification

OBJECTIVES, PERFORMANCES, RESULTS – VIEWS ON THEIR USE IN THE PUBLIC ORGANIZATIONS FROM ROMANIA

The pre sent paper focuses on the management associated with relatively common concepts: objective, result and performance (ORP). The study is important because in the Romania of the year 2011, a “state reform” is being planned, which will substantiate into the reorganization of public institutions, as the improvement of their activity is set forth by utilizing the set of tools associated with the aforementioned concepts. The study represents an analysis related to the use of the set of management tools associated with the aforementioned concepts within the Romanian public organizations. The study is concerned with a qualitative estimation involving the translation of the existing theory into the practice of the present moment. The review of the specialized literature is aimed at selecting the most common theoretical milestones, in order to increase the probability to retrieve them from the practice of the organizations. The works of Drucker represent the first theoretical system of reference. The way the ORP concepts have been utilized within the American organizations generate the guiding elements of the present study. The research presents a longitudinal segmentation, the frontier between the two parts being the present moment. The current state of facts is studied by means of an inductive approach. The hypothesis related to the ORP management in the near future is actually built on the grounds provided by the estimation of this state of facts. Its deductive approach starts from evaluating the pragmatic premises, involving the support of the process that will utilize the ORP in the near future, according to the theoretical percepts. The analysis is qualitative in nature. The identification of the cases that represented “the exception” was taken into account. The analysis focused on public institutions considered a priori as more transparent: the university, the hospital and the town hall. Even if in the case of the university there are regulations that facilitate the strategic planning, the utilization of objectives according to the MBO precepts is absent. The same situation is to be found in the case of hospitals and town halls. The use of primary and secondary information sources prove that the ORP has not been utilized. It was ascertained that the premises for utilizing the ORP are the same for the near future, a fact that implies the same results. The main implication is associated with the “myth or reality?” question. The result has a demystifying impact, showing that a reliable estimation on the ORP basis related to the activities of or people working in these organizations cannot be developed nowadays - in 2011. The present study aims at a realistic analysis related to the discrepancy between words and facts within the management of the Romanian public organizations. The fact that the aforementioned organizations represent the object of the “management of shallow labels content” is signaled and demonstrated.objectives, MBO, results, performance, public organization

10 ANI DE "MANAGEMENT STRATEGIC" LA BRASOV

The paper presents the story of a new course – Strategic Management, adopted by Faculty of Economic Sciences of “Transilvania” University of Brasov. After 1990 the context was favorable for new courses, despite the lack of experience or Romanian textbooks. The publication of the first textbook and some supplemental material provided a dynamic learning environment. The instructor spent more time to discuss and the students to create. A new challenging approach is coined by the course, seminar and home work. The form of each is explained and motivated. The final evaluation represents a mixed mark based on the course, seminar and home work. Finally, I discussed the results of the course.teaching strategic management, competence building

Association Testing Strategy for Data from Dense Marker Panels

Genome wide association studies have been usually analyzed in a univariate manner. The commonly used univariate tests have one degree of freedom and assume an additive mode of inheritance. The experiment-wise significance of these univariate statistics is obtained by adjusting for multiple testing. Next generation sequencing studies, which assay 10-20 million variants, are beginning to come online. For these studies, the strategy of additive univariate testing and multiple testing adjustment is likely to result in a loss of power due to (1) the substantial multiple testing burden and (2) the possibility of a non-additive causal mode of inheritance. To reduce the power loss we propose: a new method (1) to summarize in a single statistic the strength of the association signals coming from all not-very-rare variants in a linkage disequilibrium block and (2) to incorporate, in any linkage disequilibrium block statistic, the strength of the association signals under multiple modes of inheritance. The proposed linkage disequilibrium block test consists of the sum of squares of nominally significant univariate statistics. We compare the performance of this method to the performance of existing linkage disequilibrium block/gene-based methods. Simulations show that (1) extending methods to combine testing for multiple modes of inheritance leads to substantial power gains, especially for a recessive mode of inheritance, and (2) the proposed method has a good overall performance. Based on simulation results, we provide practical advice on choosing suitable methods for applied analyses

RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia

Background While genome-wide association studies identified some promising candidates for schizophrenia, the majority of risk genes remained unknown. We were interested in testing whether integration gene expression and other functional information could facilitate the identification of susceptibility genes and related biological pathways. Results We conducted high throughput sequencing analyses to evaluate mRNA expression in blood samples isolated from 3 schizophrenia patients and 3 healthy controls. We also conducted pooled sequencing of 10 schizophrenic patients and matched controls. Differentially expressed genes were identified by t-test. In the individually sequenced dataset, we identified 198 genes differentially expressed between cases and controls, of them 19 had been verified by the pooled sequencing dataset and 21 reached nominal significance in gene-based association analyses of a genome wide association dataset. Pathway analysis of these differentially expressed genes revealed that they were highly enriched in the immune related pathways. Two genes, S100A8 and TYROBP, had consistent changes in expression in both individual and pooled sequencing datasets and were nominally significant in gene-based association analysis. Conclusions Integration of gene expression and pathway analyses with genome-wide association may be an efficient approach to identify risk genes for schizophrenia

The cellular thermal shift assay (CETSA) for elucidating drug mechanism of action and resistance in cancer

A complete understanding over drug mechanism of action (MoA) is important when attempting to predict treatment outcome or the presence of resistance in patients. Despite decades of scientific efforts, the MoAs of even some of the oldest and most utilized drugs in cancer therapy today remain only partially understood, while resistance continues to be a frequent and often unpredictable occurrence. The absence of a protein-focused systems-wide characterization of drug-induced changes in cellular states contributes to these gaps in knowledge, as proteins are difficult to study yet they are key players in nearly all cellular processes and the targets for most drugs. The cellular thermal shift assay (CETSA) is a recently introduced method that can directly monitor drug target engagement and drug-induced cellular changes at proteome level in intact living cells. The research presented in this thesis focuses on the protein-centric CETSA approach to charting drug MoA and resistance development by evaluating the drug-induced changes in protein thermal stability for several important cancer drugs utilized in the clinic e.g. pyrimidine analogues, taxanes, or apoptosis-blockade releasing compounds in intact living cells or tissues. We report on an extensive set of CETSA responses that reflect on drug-target engagement or other MoA-revealing alterations in cellular processes that are either compound-specific or overlapping between some of the studied drugs. Several of the highlighted proteins or ensembles of proteins show promise for further evaluation as candidate biomarkers for drug efficacy with potential future applications in a clinical setting

DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts

Motivation: To increase the signal resolution for large-scale meta-analyses of genome-wide association studies, genotypes at unmeasured single nucleotide polymorphisms (SNPs) are commonly imputed using large multi-ethnic reference panels. However, the ever increasing size and ethnic diversity of both reference panels and cohorts makes genotype imputation computationally challenging for moderately sized computer clusters. Moreover, genotype imputation requires subject-level genetic data, which unlike summary statistics provided by virtually all studies, is not publicly available. While there are much less demanding methods which avoid the genotype imputation step by directly imputing SNP statistics, e.g. Directly Imputing summary STatistics (DIST) proposed by our group, their implicit assumptions make them applicable only to ethnically homogeneous cohorts. Results: To decrease computational and access requirements for the analysis of cosmopolitan cohorts, we propose DISTMIX, which extends DIST capabilities to the analysis of mixed ethnicity cohorts. The method uses a relevant reference panel to directly impute unmeasured SNP statistics based only on statistics at measured SNPs and estimated/user-specified ethnic proportions. Simulations show that the proposed method adequately controls the Type I error rates. The 1000 Genomes panel imputation of summary statistics from the ethnically diverse Psychiatric Genetic Consortium Schizophrenia Phase 2 suggests that, when compared to genotype imputation methods, DISTMIX offers comparable imputation accuracy for only a fraction of computational resources

Sharing extended summary data from contemporary genetics studies is unlikely to threaten subject privacy

Background Starting from a forensic problem, Homer et al. showed that it was possible to detect if an individual contributes only 0.5% of the DNA in a pool. The finding was extended to prove the possibility of detecting whether a subject participated in a small homogeneous GWAS. We denote this as the detection of a subject belonging to a certain cohort (SBCC). Subsequently, Visscher and Hill showed that the power to detect SBCC signal for an ethnically homogeneous cohort depends roughly on the ratio of the number of independent markers and total sample size. However, it is not clear if the same holds for more ethnically diverse cohorts. Later, Masca et al. propose running as SBCC test a regression of departure from assumed population frequency of i) subject genotype on ii) cohort of interest frequency. They use simulations to show that the approach has better SBCC detection power than the original Homer method but is impeded by population stratification. Approach To investigate the possibility of SBCC detection in multi-ethnic cohorts, we generalize the Masca et al. approach by theoretically deriving the correlation between a subject genotype and the cohort reference allele frequencies (RAFs) for stratified cohorts. Based on the derived formula, we theoretically show that, due to background stratification noise, SBCC detection is unlikely even for mildly stratified cohorts of size greater than around a thousand subjects. Thus, for the vast majority of contemporary cohorts, the fear of compromising privacy via SBCC detection is unfounded

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing