Rethinking ERP-Outsourcing Decisions for Leveraging Technological and Preserving Business Knowledge

During the selection, implementation and stabilization phases, as well as the operations and optimization phase of an ERP system (ERP-lifecycle), numerous companies consider to utilize the support of an external service provider. This paper analyses how different categories of knowledge influence the sourcing decision of crucial tasks within the ERP lifecycle. Based on a review of the IS outsourcing literature, essential knowledge-related determinants for the IS outsourcing decision are presented and aggregated in a structural model. It will be hypothesized that internal deficits in technological knowledge in comparison to external vendors as well as the specificity of the synthesis of special technological and specific business knowledge have a profound impact on the outsourcing decision. Then, a classification framework will be developed which facilitates the assignment of various tasks within the ERP lifecycle to their respective knowledge categories and knowledge carriers which might be internal or external stakeholders. The configuaration task will be used as an example to illustrate how the structural model and the classification framework may be applied to evaluate the outsourcing of tasks within the ERP lifecycle.

Benzo(a)pyrene Metabolism and EROD and GST Biotransformation Activity in the Liver of Red- and White-Blooded Antarctic Fish.

Climate change and anthropogenic pollution are of increasing concern in remote areas such as Antarctica. The evolutionary adaptation of Antarctic notothenioid fish to the cold and stable Southern Ocean led to a low plasticity of their physiological functions, what may limit their capacity to deal with altered temperature regimes and pollution in the Antarctic environment. Using a biochemical approach, we aimed to assess the hepatic biotransformation capacities of Antarctic fish species by determining (i) the activities of ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST), and (ii) the metabolic clearance of benzo(a)pyrene by hepatic S9 supernatants. In addition, we determined the thermal sensitivity of the xenobiotic biotransformation enzymes. We investigated the xenobiotic metabolism of the red-blooded Gobionotothen gibberifrons and Notothenia rossii, the hemoglobin-less Chaenocephalus aceratus and Champsocephalus gunnari, and the rainbow trout Oncorhynchus mykiss as a reference. Our results revealed similar metabolic enzyme activities and metabolic clearance rates between red- and white-blooded Antarctic fish, but significantly lower rates in comparison to rainbow trout. Therefore, bioaccumulation factors for metabolizable lipophilic contaminants may be higher in Antarctic than in temperate fish. Likewise, the thermal adaptive capacities and flexibilities of the EROD and GST activities in Antarctic fish were significantly lower than in rainbow trout. As a consequence, increasing water temperatures in the Southern Ocean will additionally compromise the already low detoxification capacities of Antarctic fish.

[The abdominal catastrophe]

Patients with an abdominal catastrophe are in urgent need of early, interdisciplinary medical help. The treatment plan should be based on medical priorities and clear leadership. First priority should be given to achieve optimal oxygenation of blood and stabilization of circulation during all treatment-phases. The sicker the patient, the less invasive the (surgical) treatment should to be, which means "damage control only". This short article describes 7 important, pragmatic rules that will help to increase the survival of a patient with an abdominal catastrophe. Preexisting morbidity and risk factors must be included in the overall risk-evaluation for every therapeutic intervention. The challenge in patients with an abdominal catastrophe is to carefully balance the therapeutic stress and the existing resistance of the individual patient. The best way to avoid abdominal disaster, however, is its prevention.

Zurich Fabry study - prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA

BACKGROUND AND PURPOSE: The etiology of stroke in young patients remains undetermined in up to half of the cases. Data on prevalence of Fabry disease (FD) in young people with cryptogenic ischaemic stroke are limited and controversial. We aimed to evaluate the frequency of unrecognized FD in a cohort of stroke patients at a tertiary stroke center. METHODS: Patients suffering from first cryptogenic ischaemic stroke or transient ischaemic attack (TIA) at the age of 18-55 years were screened for the presence of FD. We measured the serum activity of α-galactosidase (α-GAL) in all patients. In addition, sequencing of α-GAL gene was performed in men with low enzyme activity and in all women. RESULTS: Between January, 2006, and October, 2009, we recruited 150 patients (102 men, 48 women) with a mean age of 43 ± 9 years at symptom onset (135 ischaemic stroke, 15 TIA). The α-GAL activity was low in nine patients (6%; six men and three women). Genetic sequencing in six men with low enzyme activity and all 48 women detected no α-GAL gene mutation. CONCLUSION: Our study suggests that the yield of screening for FD in patients with first cryptogenic ischaemic stroke or TIA is very low. Further large-scale studies are needed to investigate the importance of FD amongst patients with recurrent cryptogenic strokes.

Hypoxia-induced gene activity in disused oxidative muscle

Hypoxia is an important modulator of the skeletal muscle's oxidative phenotype. However, little is known regarding the molecular circuitry underlying the muscular hypoxia response and the interaction of hypoxia with other stimuli of muscle oxidative capacity. We hypothesized that exposure of mice to severe hypoxia would promote the expression of genes involved in capillary morphogenesis and glucose over fatty acid metabolism in active or disused soleus muscle of mice. Specifically, we tested whether the hypoxic response depends on oxygen sensing via the alpha-subunit of hypoxia-inducible factor-1 (HIF-1 alpha). Spontaneously active wildtype and HIF-1 alpha heterozygous deficient adult female C57B1/6 mice were subjected to hypoxia (PiO2 70 mmHg). In addition, animals were subjected to hypoxia after 7 days of muscle disuse provoked by hindlimb suspension. Soleus muscles were rapidly isolated and analyzed for transcript level alterations with custom-designed AtlasTM cDNA expression arrays (BD Biosciences) and cluster analysis of differentially expressed mRNAs. Multiple mRNA elevations of factors involved in dissolution and stabilization of blood vessels, glycolysis, and mitochondrial respiration were evident after 24 hours of hypoxia in soleus muscle. In parallel transcripts of fat metabolism were reduced. A comparable hypoxia-induced expression pattern involving complex alterations of the IGF-I axis was observed in reloaded muscle after disuse. This hypoxia response in spontaneously active animals was blunted in the HIF-1 alpha heterozygous deficient mice demonstrating 35% lower HIF-1 alpha mRNA levels. Our molecular observations support the concept that severe hypoxia provides HIF-1-dependent signals for remodeling of existing blood vessels, a shift towards glycolytic metabolism and altered myogenic regulation in oxidative mouse muscle and which is amplified by enhanced muscle use. These findings further imply differential mitochondrial turnover and a negative role of HIF-1 alpha for control of fatty acid oxidation in skeletal muscle exposed to one day of severe hypoxia.

[Microalbuminuria--a new cardiovascular risk factor?]

Microalbuminuria is an established risk factor for renal disease, especially in the diabetic population. Recent studies have shown that microalbuminuria has also a highly relevant predictive value for cardiovascular morbidity and mortality. From normal to overt proteinuria levels, albuminuria shows a continuous marked increase in cardiovascular risk. This association is independent of other "classical" cardiovascular risk factors such as hypertension, hyperlipidemia or smoking. Furthermore it has a predictive value not only for patients with diabetic or renal disease, but also for hypertensive individuals or the general population. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to display not only reno--but also cardioprotective effects. Their unique ability to lower albuminuria by 40% is related to a significant risk reduction in cardiovascular mortality. New clinical trials are needed to define "normal" albuminuria levels and how low we should go.

Infantile hypophosphatasia due to a new compound heterozygous TNSALP mutation - functional evidence for a hydrophobic side-chain?

BACKGROUND: Infantile hypophosphatasia (IH) is an inherited disorder characterized by defective bone mineralization and a deficiency of alkaline phosphatase activity. OBJECTIVE/DESIGN: The aim of the study was to evaluate a new compound heterozygous TNSALP mutation for its residual enzyme activity and localization of the comprised amino acid residues in a 3D-modeling. PATIENT: We report on a 4-week old girl with craniotabes, severe defects of ossification, and failure to thrive. Typical clinical features as low serum alkaline phosphatase, high serum calcium concentration, increased urinary calcium excretion, and nephrocalcinosis were observed. Vitamin D was withdrawn and the patient was started on calcitonin and hydrochlorothiazide. Nonetheless, the girl died at the age of 5 months from respiratory failure. RESULTS: Sequence analysis of the patient's TNSALP gene revealed two heterozygous mutations [c.653T>C (I201T), c.1171C>T (R374C)]. Transfection studies of the unique I201T variant in COS-7 cells yielded a mutant TNSALP protein with only a residual enzyme activity (3.7%) compared with wild-type, whereas the R374C variant was previously shown to reduce normal activity to 10.3%. 3D-modeling of the mutated enzyme showed that I201T resides in a region that does not belong to any known functional site. CONCLUSION: We note that I201, which has been conserved during evolution, is buried in a hydrophobic pocket and, therefore, the I>T-change should affect its functional properties. Residue R374C is located in the interface between monomers and it has been previously suggested that this mutation affects dimerization. These findings explain the patient's clinical picture and severe course.

What is ‘wood’ – An anatomical re-definition

The technical definition of ‘wood’ is well accepted, but its botanical understanding remains vague. Different degrees and amounts of lignification in plants and their imprecise description, together with a conceptually doubtful life form catalog including trees, shrubs and herbs further complicate our understanding of ‘wood’. Here, we use permanent micro sections to demonstrate that the xylem and bark of terrestrial plants can vary from one tissue with a few lignified cells to an almost fully lignified tissue. This universal principle of plant growth and stabilization, accounting for all taxonomic units within vascular plants, suggests that the classical life form separation into herbs, shrubs and trees is not valid. An anatomical-based differentiation between ‘wood’, ‘woody’ and ‘woodiness’ is also only meaningful if supplemented by insight on the particular plant section and its lignified proportion. We therefore recommend utilizing the botanically more neutral term ‘stem anatomy’ instead of ‘wood anatomy’, which further implies integration of the xylem and bark of all terrestrial plants. Since dendrochronology considers shrubs, dwarf shrubs and perennial herbs in addition to trees, its semantic expansion toward ‘xylemchronology’ might be worthwhile considering.

Protein cross-linking mediated by tissue transglutaminase correlates with the maturation of extracellular matrices during lung development

At birth, the mammalian lung is still immature. The alveoli are not yet formed and the interairspace walls contain two capillary layers which are separated by an interstitial core. After alveolarization (first 2 postnatal weeks in rats) the alveolar septa mature: their capillary layers merge, the amount of connective tissue decreases, and the mature lung parenchyma is formed (second and third week). During the first 3 wk of life the role of tissue transglutaminase (tTG) was studied in rat lung by immunostaining of cryostat and paraffin sections, by Northern and Western blotting, and by a quantitative determination of gamma-glutamyl-epsilon-lysine. While enzyme activity and intracellular tTG were already present before term, the enzyme product (gamma-glutamyl-epsilon-lysine-crosslink) and extracellular tTG appeared between postnatal days 10 and 19 in the lung parenchyma. In large blood vessels and large airways, which mature earlier than the parenchyma, both the enzyme product and extracellular tTG had already appeared at the end of the first postnatal week. We conclude that tTG is expressed and externalized into the extracellular matrix of lung shortly before maturation of an organ area. Because tTG covalently and irreversibly crosslinks extracellular matrix proteins, we hypothesize that it may prevent or delay further remodeling of basement membranes and may stabilize other extracellular components, such as microfibrils.

Flux control of sulphate assimilation in Arabidopsis thaliana : adenosine 5′-phosphosulphate reductase is more susceptible than ATP sulphurylase to negative control by thiols

The effect of externally applied l-cysteine and glutathione (GSH) on ATP sulphurylase and adenosine 5′-phosphosulphate reductase (APR), two key enzymes of assimilatory sulphate reduction, was examined in Arabidopsis thaliana root cultures. Addition of increasing l-cysteine to the nutrient solution increased internal cysteine, γ-glutamylcysteine and GSH concentrations, and decreased APR mRNA, protein and extractable activity. An effect on APR could already be detected at 0.2 mm l-cysteine, whereas ATP sulphurylase was significantly affected only at 2 mm l-cysteine. APR mRNA, protein and activity were also decreased by GSH at 0.2 mm and higher concentrations. In the presence of l-buthionine-S, R-sulphoximine (BSO), an inhibitor of GSH synthesis, 0.2 mm l-cysteine had no effect on APR activity, indicating that GSH formed from cysteine was the regulating substance. Simultaneous addition of BSO and 0.5 mm GSH to the culture medium decreased APR mRNA, enzyme protein and activity. ATP sulphurylase activity was not affected by this treatment. Tracer experiments using 35SO42– in the presence of 0.5 mm l-cysteine or GSH showed that both thiols decreased sulphate uptake, APR activity and the flux of label into cysteine, GSH and protein, but had no effect on the activity of all other enzymes of assimilatory sulphate reduction and serine acetyltransferase. These results are consistent with the hypothesis that thiols regulate the flux through sulphate assimilation at the uptake and the APR step. Analysis of radioactive labelling indicates that the flux control coefficient of APR is more than 0.5 for the intracellular pathway of sulphate assimilation. This analysis also shows that the uptake of external sulphate is inhibited by GSH to a greater extent than the flux through the pathway, and that the flux control coefficient of APR for the pathway, including the transport step, is proportionately less, with a significant share of the control exerted by the transport step.

[The treatment of arterial hypertension in elderly men in Iceland].

The choice of antihypertensive therapy in elderly Icelanders is unknown. In the database of the Icelandic Heart Association 1145 men, aged 70-84 were alive in 1994. Eight hundred thirty-four came to the Heart Association Clinic, 429 of whom either had hypertension or were found to be hypertensive on examination. The prevalence of hypertension in elderly Icelandic men was therefore about 50%. One hundred fifty-seven men took drugs for hypertension. Ninety-five of them were treated with a single drug, 49 with two drugs and five with three drugs. The type of drugs was unknown concerning eight men. Diuretics and ß-blockers were dominant. Although the comparison between those two classes of drugs was uncontrolled the blood pressure was significantly lower in systole on diuretics. The most common combination was ß-blockers and diuretics, then angiotensin converting enzyme inhibitors and diuretics, finally ß-blockers and calcium blockers. It is suggested that the use of diuretics should be increased in this age group.