Asiakkuudenhallinnan kehittäminen tietojärjestelmiä tuottavassa ohjelmistoyrityksessä

Työssä on tutkittu asiakkuudenhallintaan liittyvää kirjallisuutta tarkoituksena löytää tekijöitä, joilla tietojärjestelmiä tuottavan ohjelmistoyrityksen asiakkuudenhallintaa voidaan kehittää. Samalla työn tarkoitus on nostaa esille tekijöitä, joihin työn kohteena olevassa yrityksessä tulisi keskittyä asiakkuudenhallinnan näkökulmasta tulevaisuuden toimintaa suunniteltaessa. Kirjallisuusosassa käsitellään asiakaslähtöistä toimintaa, asiakkuuden elinkaaren vaiheita, asiakkuuden arvoa yritykselle ja teoreettisia malleja asiakaskannan analysointiin. Tutkimuksen soveltavassa osassa käydään läpi kohdeyritystä ja sen toimintaa, sekä analysoidaan yrityksen asiakkaat ja muodostetaan analysoinnin perusteella asiakassalkkuja, jotka muodostavat kohdeyrityksen asiakasportfolion. Muodostettuja asiakasryhmiä käytetään hyväksi, kun muodostetaan uusia asiakastrategioita tuotekehitykseen, asiakaspalveluun ja myyntiin sekä markkinointiin.

Metal dealing at the origin of the Chordata phylum: The metallothionein system and metal overload response in Amphioxus.

Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins), the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (BfMT1 and BfMT2) have been identified in a contiguous region of the genome, as well as several ARE (antioxidant response element) and MRE (metal response element) located upstream the transcribed region. Their corresponding cDNAs exhibit identical sequence in the two lancelet species (B. floridae and B. lanceolatum), BfMT2 cDNA resulting from an alternative splicing event. BfMT1 is a polyvalent metal binding peptide that coordinates any of the studied metal ions (Zn, Cd or Cu) rendering complexes stable enough to last in physiological environments, which is fully concordant with the constitutive expression of its gene, and therefore, with a metal homeostasis housekeeping role. On the contrary, BfMT2 exhibits a clear ability to coordinate Cd(II) ions, while it is absolutely unable to fold into stable Cu (I) complexes, even as mixed species. This identifies it as an essential detoxification agent, which is consequently only induced in emergency situations. The cephalochordate MTs are not directly related to vertebrate MTs, neither by gene structure, protein similarity nor metal-binding behavior of the encoded peptides. The closest relative is the echinoderm MT, which confirm proposed phylogenetic relationships between these two groups. The current findings support the existence in most organisms of two types of MTs as for their metal binding preferences, devoted to different biological functions: multivalent MTs for housekeeping roles, and specialized MTs that evolve either as Cd-thioneins or Cu-thioneins, according to the ecophysiological needs of each kind of organisms.

Characterization of the chemical composition of the essential oils from Annona emarginata (Schltdl.) H. Rainer 'terra-fria' and Annona squamosa L.

The objective of this study was to characterize the chemical composition of the essential oil from the leaves of Annona emarginata (Schltdl.) H. Rainer 'terra-fria' and Annona squamosa L. The species were grown in a greenhouse for 18 months, which nutrient solution was applied weekly; the plants were then harvested and the leaves dried to extract the essential oil. The essential oil was analyzed by gas chromatography and mass spectrometry to study its chemical profiles. Eleven substances were found in the essential oil of A. emarginata, primarily (E)-caryophyllene (29.29%), (Z)-caryophyllene (16.86%), γ-muurolene (7.54%), α-pinene (13.86%), and tricyclene (10.04%). Ten substances were detected in the oil from A. squamosa, primarily (E)-caryophyllene (28.71%), (Z)-caryophyllene (14.46%), α-humulene (4.41%), camphene (18.10%), α-pinene (7.37%), β-pinene (8.71%), and longifolene (5.64%). Six substances were common to both species: (E)-caryophyllene, (Z)-caryophyllene, α-humulene, camphene, α-pinene, and β-pinene.

Molecular Analysis of NOTCH2 in Patients with Primary Open-Angle Glaucoma.

BACKGROUND AND PURPOSE: Transgenic mice overexpressing Notch2 in the uvea exhibit a hyperplastic ciliary body leading to increased IOP and glaucoma. The aim of this study was to investigate the possible presence of NOTCH2 variants in patients with primary open-angle glaucoma (POAG). METHODS: We screened DNA samples from 130 patients with POAG for NOTCH2 variants by denaturing high-performance liquid chromatography after PCR amplification and validated our data by direct Sanger sequencing. RESULTS: No mutations were observed in the coding regions of NOTCH2 or in the splice sites. 19 known SNPs (single nucleotide polymorphisms) were detected. An SNP located in intron 24, c.[4005+45A>G], was seen in 28.5% of the patients (37/130 patients). As this SNP is reported to have a minor allele frequency of 7% in the 1000 genomes database, it could be associated with POAG. However, we evaluated its frequency in an ethnic-matched control group of 96 subjects unaffected by POAG and observed a frequency of 29%, indicating that it was not related to POAG. CONCLUSION: NOTCH2 seemed to be a good candidate for POAG as it is expressed in the anterior segment in the human eye. However, mutational analysis did not show any causative mutation. This study also shows that proper ethnic-matched control groups are essential in association studies and that values given in databases are sometimes misleading.

Cannabis Users Identifying Themselves as Non-Cigarette Smokers : Who Are They?

Introduction and Aims. About 20% of cannabis consumers report not smoking cigarettes. Studies that have compared cannabis and cigarette smokers, cigarette smokers, and cannabis users who do not smoke cigarettes (CNSs) have shown that CNSs have better outcomes across a range of indicators compared to the others. Therefore, we conducted a qualitative study to determine why CNSs did not smoke cigarettes and how they managed to resist cigarette smoking in order to better inform prevention efforts. Design and Methods. We conducted five focus groups (FG) with a total of 19 CNSs between ages 16 and 25. A narrative analysis of FGs was conducted using qualitative analysis software. Results. CNSs' non-smoking choice was rooted in a negative opinion of cigarettes and a harm-reduction strategy. They were unique cases within their peer groups, but there were no CNSs groups. All participants were confronted to the mulling paradox. Discussion and Conclusions. While tobacco-use prevention seems to have been successful, CNSs need to be informed of harmful consequences of chronic cannabis use. Given their habit of adding tobacco to cannabis, CNSs need to be alerted that they may be nicotine dependent even though they do not smoke tobacco on its own. This exploratory study brings essential insight concerning this specific population of cannabis consumers which future research should continue to develop.

Ship Leases under IAS 17, case Fortum Shipping

International accounting standards will be applied from the1st of January 2005 in accounting of member states of the EU with a view of harmonizing the accounting practices in Europe, and on the long term even more widely. The purpose of adopting IAS accounting standards is to make the financial statements and financial information received from companies more comparable and more transparent for investors and other interest groups. IAS 17 introduces the treatment of a lease agreement in the light of the new accounting standards. Finnish companies have used finance leases widely as an alternative, off-balance sheet form of financing capital investments consistently with Finnish GAAP. Along with the appliance of IAS 17 the off-balance-sheet financing possibility of leases classified as finance leases will no longer exist. IAS 17 states that finance leases are going to be recognized in the balance sheet as both assets, in form of fixed assets, and loans in liabilities classified as long and short term loans. IAS 17 will make two major changes to the income statement. Firstly, the lease payments formerly treated as variable costs are moved below the operating profit level to finance costs. Secondly, the depreciations from the leased assets are also introduced. The effects to the case company's, Fortum Shipping's, income statement and balance sheet are remarkable. Along with the appliance of IAS Fortum Shipping's net assets are somewhat going to be doubled, the amount of liabilities increases significantly and the earnings before interests and taxes increases moderately. The preceding factors have a big effect on the case company's financial key figures. So, the IAS originated effects on balance sheet and income statement have essential impacts on a company's key financial indicators. Most significant changes can be found in key ratios measuring profitability, capital structure, and efficiency. This means that when comparing the IAS calculated profits of companies with the profits calculated prior with Finnish GAAP, the analysis should be made with prudence because the figures are not comparable on straight-forward basis.

ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines

In this study we demonstrate that accumulation of reactive oxygen species (ROS) is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT) induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell cycle activator.

Tilintarkastajan palkkiot osana riippumattomuussääntelyä

Tutkimuksen tavoitteena on selvittää, millä eri tavoin tilintarkastajan palkkiot voivat vaarantaa tilintarkastajan riippumattomuuden sekä minkälaisen uhan eri tilanteet riippumattomuudelle aiheuttavat. Tavoitteisiin pyritään teoriaosuuden käsiteanalyyttisen tutkimusmetodologian sekä rahoituslaitosten yritystutkijoille suunnatun empiirisen kyselytutkimuksen avulla. Sidosryhmien odotukset eivät aina vastaa säännöksiä tai tilintarkastuskäytäntöä. Palkkioriippuvuutta yhdestä asiakkaasta sekä palkkion riippumista työn tuloksista pidetään uhkina riippumattomuudelle. Tilanneharkintaa on käytettävä, kun tarjotaan muita palveluja tarkastusasiakkaille. Sisäistä tarkastusta sekä konsultointia pidetään usein uhkina riippumattomuudelle. Epätavallisista eduista ja lahjoista tulee kieltäytyä, kun ne liittyvät tilintarkastukseen. Tilintarkastajan oma vakavaraisuus on riippumattomuden kannalta olennaista. Tilintarkastajan valitsevat usein samat henkilöt, joita tarkastetaan. Tätä pidetään riippumattomuuden kannalta hankalana. Tilintarkastajan omaa moraalia ja etiikkaa sekä tilintarkastajiin kohdistuvaa valvontaa pidetään tehokkaimpina keinoina riippumattomuuden turvaamiseksi.

Critical Success Factors in the Implementation of the Balanced Scorecard

Tutkielman tavoitteena on tunnistaa kriittiset menestystekijät balanced scorecardin käyttöönotossa. Tutkimus on luonteeltaan selittävä tapaustutkimus. Tutkimuksen haastatteluaineisto on kerätty suomalaisyrityksistä, jotka ovat ottaneet onnistuneesti balanced scorecardin käyttöön organisaatiossa. Yksi tapauksista osoittautui kuitenkin epäonnistuneeksi. Balanced scorecardin onnistuneeseen käyttöönottoon vaikuttaa usea eri tekijä. Tutkielmassa käyttöönottoon vaikuttavat menestystekijät on jaettu neljään eri ryhmään, jotka ovat tekijät liittyen organisaatioon, resursseihin, käyttöönottoprosessiin ja itse balanced scorecardiin. Viitekehys havainnollistaa kriittisten menestystekijöiden keskinäisiä suhteita. Johdon sitoutuminen, ajankäyttö sekä avoin kommunikaatio ovat eräitä keskeisiä menestystekijöitä balanced scorecardin käyttöönottoprosessissa. Lisäksi balanced scorecardin onnistuneeseen käyttöönottoon on kaksi perusedellytystä: organisaation strategian selkeys sekä ympäristön tuki prosessille.

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

BACKGROUND: Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR). METHODS: We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT). RESULTS: SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype. CONCLUSION: In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

Optical trapping: a review of essential concepts

Optical tweezers are an innovative technique for the non-contact, all-optical manipulation of small material samples, which has extraordinarily expanded and evolved since its inception in the mid-80s of the last century. Nowadays, the potential of optical tweezers has been clearly proven and a wide range of applications both from the physical and biological sciences have solidly emerged, turning the early ideas and techniques into a powerful paradigm for experimentation in the micro- and nanoworld. This review aims at highlighting the fundamental concepts that are essential for a thorough understanding of optical trapping, making emphasis on both its manipulation and measurement capabilities, as well as on the vast array of important biological applications appeared in the last years.

Microtubule Associated Protein 1b (MAP1B) Is a Marker of the Microtubular Cytoskeleton in Podocytes but Is Not Essential for the Function of the Kidney Filtration Barrier in Mice.

Podocytes are essential for the function of the kidney glomerular filter. A highly differentiated cytoskeleton is requisite for their integrity. Although much knowledge has been gained on the organization of cortical actin networks in podocyte's foot processes, less is known about the molecular organization of the microtubular cytoskeleton in primary processes and the cell body. To gain an insight into the organization of the microtubular cytoskeleton of the podocyte, we systematically analyzed the expression of microtubule associated proteins (Maps), a family of microtubules interacting proteins with known functions as regulator, scaffold and guidance proteins. We identified microtubule associated protein 1b (MAP1B) to be specifically enriched in podocytes in human and rodent kidney. Using immunogold labeling in electron microscopy, we were able to demonstrate an enrichment of MAP1B in primary processes. A similar association of MAP1B with the microtubule cytoskeleton was detected in cultured podocytes. Subcellular distribution of MAP1B HC and LC1 was analyzed using a double fluorescent reporter MAP1B fusion protein. Subsequently we analyzed mice constitutively depleted of MAP1B. Interestingly, MAP1B KO was not associated with any functional or structural alterations pointing towards a redundancy of MAP proteins in podocytes. In summary, we established MAP1B as a specific marker protein of the podocyte microtubular cytoskeleton.