From the Resource-Base to Firm Boundaries in the Electricity Network Business - Case Lappeenrannan Energia Oy

Tutkielman tavoitteena oli selvittääcase -yrityksen resurssi- ja kyvykkyyspohjaa resurssiperustaisen näkemyksen mukaan, sekä yrityksen rajoja transaktiokustannusteorian mukaan. Tutkimusongelmia lähestyttiin kirjallisuuskatsauksella, puoli-strukturoiduilla teemahaastatteluilla, sekä kyselylomakkeilla. Tutkielman päätuloksiksi voidaan Tukea löydetty resurssikuilu, resurssien ja kyvykkyyksien tutkinta, sekä kyselylomakkeiden rakentaminen ja käyttö. Tutkielman paljastamasta kuilusta voidaan erottaa kolme päähaastetta; ikääntyvät sähköverkot, ikääntyvä henkilökunta ja liiketoimintaosaamisen puute. Lisäksi resurssien ja kyvykkyyksien tutkinta nosti esille organisaation rutiineja ja prosesseja, ja kyselylomakkeet osoittautuivat varsin toimiviksi tutkimuksen kontekstissa. Yhteenvetona voidaan todeta, että sähköverkkoliiketoiminta ja case yritys ovat suuren rakennemuutoksen alla, joka tuo mukanaan suuria haasteita myös lähitulevaisuudessa.

Correcting for the bias due to expression specificity improves the estimation of constrained evolution of expression between mouse and human.

MOTIVATION: Comparative analyses of gene expression data from different species have become an important component of the study of molecular evolution. Thus methods are needed to estimate evolutionary distances between expression profiles, as well as a neutral reference to estimate selective pressure. Divergence between expression profiles of homologous genes is often calculated with Pearson's or Euclidean distance. Neutral divergence is usually inferred from randomized data. Despite being widely used, neither of these two steps has been well studied. Here, we analyze these methods formally and on real data, highlight their limitations and propose improvements. RESULTS: It has been demonstrated that Pearson's distance, in contrast to Euclidean distance, leads to underestimation of the expression similarity between homologous genes with a conserved uniform pattern of expression. Here, we first extend this study to genes with conserved, but specific pattern of expression. Surprisingly, we find that both Pearson's and Euclidean distances used as a measure of expression similarity between genes depend on the expression specificity of those genes. We also show that the Euclidean distance depends strongly on data normalization. Next, we show that the randomization procedure that is widely used to estimate the rate of neutral evolution is biased when broadly expressed genes are abundant in the data. To overcome this problem, we propose a novel randomization procedure that is unbiased with respect to expression profiles present in the datasets. Applying our method to the mouse and human gene expression data suggests significant gene expression conservation between these species. CONTACT: marc.robinson-rechavi@unil.ch; sven.bergmann@unil.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Using the optical flow to implement a relative virtual mouse controlled by head movements

The following paper introduces the work conducted to create a relative virtual mouse based on the interpretation of head movements and face gesture through a low cost camera and the optical flow of the images. This virtual device is designed specifically as an alternative non-contact pointer for people with mobility impairments in the upper extremities and reduced head control. The proposed virtual device was compared with a conventional mouse, a touchpad and a digital joystick. Validation results show performances close to a digital joystick but far away from a conventional mouse.

Targeting the tumor vasculature to enhance T cell activity.

T cells play a critical role in tumor immune surveillance as evidenced by extensive mouse-tumor model studies as well as encouraging patient responses to adoptive T cell therapies and dendritic cell vaccines. It is well established that the interplay of tumor cells with their local cellular environment can trigger events that are immunoinhibitory to T cells. More recently it is emerging that the tumor vasculature itself constitutes an important barrier to T cells. Endothelial cells lining the vessels can suppress T cell activity, target them for destruction, and block them from gaining entry into the tumor in the first place through the deregulation of adhesion molecules. Here we review approaches to break this tumor endothelial barrier and enhance T cell activity.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.

Aquaporin 3 (AQP3) participates in the cytotoxic response to nucleoside-derived drugs

Background: Nucleoside analogs used in the chemotherapy of solid tumors, such as the capecitabine catabolite50-deoxy-5-fluorouridine (50-DFUR) trigger a transcriptomic response that involves the aquaglyceroporin aquaporin 3 along with other p53-dependent genes. Here, we examined whether up-regulation of aquaporin 3 (AQP3) mRNA incancer cells treated with 50-DFUR represents a collateral transcriptomic effect of the drug, or conversely, AQP3participates in the activity of genotoxic agents. Methods: The role of AQP3 in cell volume increase, cytotoxicity and cell cycle arrest was analyzed using loss-of-function approaches. Results: 50-DFUR and gemcitabine, but not cisplatin, stimulated AQP3 expression and cell volume, which was partially and significantly blocked by knockdown of AQP3. Moreover, AQP3 siRNA significantly blocked other effects of nucleoside analogs, including G1/S cell cycle arrest, p21 and FAS up-regulation, and cell growth inhibition. Short incubations with 5-fluorouracil (5-FU) also induced AQP3 expression and increased cell volume, and the inhibition of AQP3 expression significantly blocked growth inhibition triggered by this drug. To further establish whether AQP3 induction is related to cell cycle arrest and apoptosis, cells were exposed to long incubations with escalating doses of 5-FU. AQP3 was highly up-regulated at doses associated with cell cycle arrest, whereas at doses promoting apoptosis induction of AQP3 mRNA expression was reduced. Conclusions: Based on the results, we propose that the aquaglyceroporin AQP3 is required for cytotoxic activity of 5’-DFUR and gemcitabine in the breast cancer cell line MCF7 and the colon adenocarcinoma cell line HT29, and is implicated in cell volume increase and cell cycle arrest.

Aquaporin 3 (AQP3) participates in the cytotoxic response to nucleoside-derived drugs

Background: Nucleoside analogs used in the chemotherapy of solid tumors, such as the capecitabine catabolite50-deoxy-5-fluorouridine (50-DFUR) trigger a transcriptomic response that involves the aquaglyceroporin aquaporin 3 along with other p53-dependent genes. Here, we examined whether up-regulation of aquaporin 3 (AQP3) mRNA incancer cells treated with 50-DFUR represents a collateral transcriptomic effect of the drug, or conversely, AQP3participates in the activity of genotoxic agents. Methods: The role of AQP3 in cell volume increase, cytotoxicity and cell cycle arrest was analyzed using loss-of-function approaches. Results: 50-DFUR and gemcitabine, but not cisplatin, stimulated AQP3 expression and cell volume, which was partially and significantly blocked by knockdown of AQP3. Moreover, AQP3 siRNA significantly blocked other effects of nucleoside analogs, including G1/S cell cycle arrest, p21 and FAS up-regulation, and cell growth inhibition. Short incubations with 5-fluorouracil (5-FU) also induced AQP3 expression and increased cell volume, and the inhibition of AQP3 expression significantly blocked growth inhibition triggered by this drug. To further establish whether AQP3 induction is related to cell cycle arrest and apoptosis, cells were exposed to long incubations with escalating doses of 5-FU. AQP3 was highly up-regulated at doses associated with cell cycle arrest, whereas at doses promoting apoptosis induction of AQP3 mRNA expression was reduced. Conclusions: Based on the results, we propose that the aquaglyceroporin AQP3 is required for cytotoxic activity of 5’-DFUR and gemcitabine in the breast cancer cell line MCF7 and the colon adenocarcinoma cell line HT29, and is implicated in cell volume increase and cell cycle arrest.

Validity of the FACIT-Sp to assess spiritual well-being in elderly patients

Among instruments measuring spiritual well-being, the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp-12) is the most widely used instrument in research. It has been validated in patients suffering from cancer or HIV/AIDS, but has rarely been used in elderly patients. The objectives of this study were to determine the psychometric properties and suitability of the FACIT-Spto assess spiritual well-being in hospitalized elderly patients. This cross-sectional study uses a mixed method approach. Subjects were patients (N = 208), aged 65 years and older, consecutively admitted in post-acute rehabilitation. Psychometric properties of the FACITSp were investigated. The internal structure of the FACIT-Sp (factor structure and internal consistency) was assessed. Convergent validity of the FACIT-Sp was assessed using the Spiritual Distress Assessment Tool (SDAT), the question "Are you at peace?" and the Geriatric Depression Scale (GDS). Predictive validity was assessed using length of stay (LOS) and discharge destination. Understanding and interpretation of FACIT-Sp items were consecutively assessed in a sub-sample of 135 patients. Results show that FACIT-Sp scores ranged from 7 to 46 (mean 29.6 ± 7.8); 23.1% of the patients had high spiritual well-being. Cronbach's α was g ood ( 0.85). Item-to-total correlations were all significant (0.34 to 0.73). Principal component analyses performed with 2 or 3 factors were only moderately consistent with previous work. FACIT-Sp correlated with SDAT, "Are you at peace?" and GDS (Rho = −0.45, P < 0.001; 0.51, P < 0.001 and −0.38, P < 0.001). No association was found with LOS or discharge destination. Spontaneous comments about one or more FACIT-Sp items were made by 97/135 (71.9%). Specifically, items that address purpose and meaning in life were frequently found difficult to answer. Analyses suggest that the FACIT-Sp may underestimate spiritual well-being in older patients. In conclusion, despite having acceptable psychometric properties, the FACIT-Sp presents limitations for measurement of spiritual well-being in hospitalized elderly patients.