The Impact of Human Asset Specificity on the Sourcing of Application Services

The question concerning the circumstances under which it is advantageous for a company to outsource certain information systems functions has been a controversial issue for the last decade. While opponents emphasize the risks of outsourcing based on the loss of strategic potentials and increased transaction costs, proponents emphasize the strategic benefits of outsourcing and high potentials of cost-savings. This paper brings together both views by examining the conditions under which both the strategic potentials as well as savings in production and transaction costs of developing and maintaining software applications can better be achieved in-house as opposed to by an external vendor. We develop a theoretical framework from three complementary theories and test it empirically based on a mail survey of 139 German companies. The results show that insourcing is more cost efficient and advantageous in creating strategic benefits through IS if the provision of application services requires a high amount of firm specific human assets. These relationships, however, are partially moderated by differences in the trustworthiness and intrinsic motivation of internal versus external IS professionals. Moreover, capital shares with an external vendor can lower the risk of high transaction costs as well the risk of loosing the strategic opportunities of an IS.

Family business: Multiple members of major phytohormone classes orchestrate plant stress responses

Low-molecular-weight compounds such as jasmonic, abscisic and salicylic acids are commonly thought to be regulators of plant stress responses. However, it is becoming clear that these molecules, often referred to as phytohormones, are only a part of bigger groups of compounds with biological activity. We propose that the concept of "hormone families" may help to better understand plant physiological responses by taking into account not only the alleged main regulators, but also their precursors, conjugates and catabolites. Novel approaches to profile potentially active compounds in plants are discussed.

Multiasset Derivatives and Joint Distributions of Asset Prices

Several of multiasset derivatives like basket options or options on the weighted maximum of assets exhibit the property that their prices determine uniquely the underlying asset distribution. Related to that the question how to retrieve this distributions from the corresponding derivatives quotes will be discussed. On the contrary, the prices of exchange options do not uniquely determine the underlying distributions of asset prices and the extent of this non-uniqueness can be characterised. The discussion is related to a geometric interpretation of multiasset derivatives as support functions of convex sets. Following this, various symmetry properties for basket, maximum and exchange options are discussed alongside with their geometric interpretations and some decomposition results for more general payoff functions.

Effects of doxorubicin cancer therapy on autophagy and the ubiquitin-proteasome system in long-term cultured adult rat cardiomyocytes

The clinical use of anthracyclines in cancer therapy is limited by dose-dependent cardiotoxicity that involves cardiomyocyte injury and death. We have tested the hypothesis that anthracyclines affect protein degradation pathways in adult cardiomyocytes. To this aim, we assessed the effects of doxorubicin (Doxo) on apoptosis, autophagy and the proteasome/ubiquitin system in long-term cultured adult rat cardiomyocytes. Accumulation of poly-ubiquitinated proteins, increase of cathepsin-D-positive lysosomes and myofibrillar degradation were observed in Doxo-treated cardiomyocytes. Chymotrypsin-like activity of the proteasome was initially increased and then inhibited by Doxo over a time-course of 48 h. Proteasome 20S proteins were down-regulated by higher doses of Doxo. The expression of MURF-1, an ubiquitin-ligase specifically targeting myofibrillar proteins, was suppressed by Doxo at all concentrations measured. Microtubule-associated protein��1 light chain 3B (LC3)-positive punctae and both LC3-I and -II proteins were induced by Doxo in a dose-dependent manner, as confirmed by using lentiviral expression of green fluorescence protein bound to LC3 and live imaging. The lysosomotropic drug chloroquine led to autophagosome accumulation, which increased with concomitant Doxo treatment indicating enhanced autophagic flux. We conclude that Doxo causes a downregulation of the protein degradation machinery of cardiomyocytes with a resulting accumulation of poly-ubiquitinated proteins and autophagosomes. Although autophagy is initially stimulated as a compensatory response to cytotoxic stress, it is followed by apoptosis and necrosis at higher doses and longer exposure times. This mechanism might contribute to the late cardiotoxicity of anthracyclines by accelerated aging of the postmitotic adult cardiomyocytes and to the susceptibility of the aging heart to anthracycline cancer therapy.

Transfection of drug-specific T-cell receptors into hybridoma cells: tools to monitor drug interaction with T-cell receptors and evaluate cross-reactivity to related compounds

In the context of drug hypersensitivity, our group has recently proposed a new model based on the structural features of drugs (pharmacological interaction with immune receptors; p-i concept) to explain their recognition by T cells. According to this concept, even chemically inert drugs can stimulate T cells because certain drugs interact in a direct way with T-cell receptors (TCR) and possibly major histocompatibility complex molecules without the need for metabolism and covalent binding to a carrier. In this study, we investigated whether mouse T-cell hybridomas transfected with drug-specific human TCR can be used as an alternative to drug-specific T-cell clones (TCC). Indeed, they behaved like TCC and, in accordance with the p-i concept, the TCR recognize their specific drugs in a direct, processing-independent, and dose-dependent way. The presence of antigen-presenting cells was a prerequisite for interleukin-2 production by the TCR-transfected cells. The analysis of cross-reactivity confirmed the fine specificity of the TCR and also showed that TCR transfectants might provide a tool to evaluate the potential of new drugs to cause hypersensitivity due to cross-reactivity. Recombining the alpha- and beta-chains of sulfanilamide- and quinolone-specific TCR abrogated drug reactivity, suggesting that both original alpha- and beta-chains were involved in drug binding. The TCR-transfected hybridoma system showed that the recognition of two important classes of drugs (sulfanilamides and quinolones) by TCR occurred according to the p-i concept and provides an interesting tool to study drug-TCR interactions and their biological consequences and to evaluate the cross-reactivity potential of new drugs of the same class.

[Treatment of hypertension in type 2 diabetes mellitus--2002 update]

Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.

Spatial Assessment of Erosion and its Impact on Soil Fertility in the Tajik Foothills

Efficient planning of soil conservation measures requires, first, to understand the impact of soil erosion on soil fertility with regard to local land cover classes; and second, to identify hot spots of soil erosion and bright spots of soil conservation in a spatially explicit manner. Soil organic carbon (SOC) is an important indicator of soil fertility. The aim of this study was to conduct a spatial assessment of erosion and its impact on SOC for specific land cover classes. Input data consisted of extensive ground truth, a digital elevation model and Landsat 7 imagery from two different seasons. Soil spectral reflectance readings were taken from soil samples in the laboratory and calibrated with results of SOC chemical analysis using regression tree modelling. The resulting model statistics for soil degradation assessments are promising (R2=0.71, RMSEV=0.32). Since the area includes rugged terrain and small agricultural plots, the decision tree models allowed mapping of land cover classes, soil erosion incidence and SOC content classes at an acceptable level of accuracy for preliminary studies. The various datasets were linked in the hot-bright spot matrix, which was developed to combine soil erosion incidence information and SOC content levels (for uniform land cover classes) in a scatter plot. The quarters of the plot show different stages of degradation, from well conserved land to hot spots of soil degradation. The approach helps to gain a better understanding of the impact of soil erosion on soil fertility and to identify hot and bright spots in a spatially explicit manner. The results show distinctly lower SOC content levels on large parts of the test areas, where annual crop cultivation was dominant in the 1990s and where cultivation has now been abandoned. On the other hand, there are strong indications that afforestations and fruit orchards established in the 1980s have been successful in conserving soil resources.

Epothilones as lead structures for the synthesis-based discovery of new chemotypes for microtubule stabilization

Epothilones are macrocyclic bacterial natural products with potent microtubule-stabilizing and antiproliferative activity. They have served as successful lead structures for the development of several clinical candidates for anticancer therapy. However, the structural diversity of this group of clinical compounds is rather limited, as their structures show little divergence from the original natural product leads. Our own research has explored the question of whether epothilones can serve as a basis for the development of new structural scaffolds, or chemotypes, for microtubule stabilization that might serve as a basis for the discovery of new generations of anticancer drugs. We have elaborated a series of epothilone-derived macrolactones whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of a conformationally constrained side chain, the removal of the C3-hydroxyl group, and the replacement of C12 with nitrogen. So far, this approach has yielded analogs 30 and 40 that are the most advanced, the most rigorously modified, structures, both of which are potent antiproliferative agents with low nanomolar activity against several human cancer cell lines in vitro. The synthesis was achieved through a macrolactone-based strategy or a high-yielding RCM reaction. The 12-aza-epothilone ("azathilone" 40) may be considered a "non-natural" natural product that still retains most of the overall structural characteristics of a true natural product but is structurally unique, because it lies outside of the general scope of Nature's biosynthetic machinery for polyketide synthesis. Like natural epothilones, both 30 and 40 promote tubulin polymerization in vitro and at the cellular level induce cell cycle arrest in mitosis. These facts indicate that cancer cell growth inhibition by these compounds is based on the same mechanistic underpinnings as those for natural epothilones. Interestingly, the 9,10-dehydro analog of 40 is significantly less active than the saturated parent compound, which is contrary to observations for natural epothilones B or D. This may point to differences in the bioactive conformations of N-acyl-12-aza-epothilones like 40 and natural epothilones. In light of their distinct structural features, combined with an epothilone-like (and taxol-like) in vitro biological profile, 30 and 40 can be considered as representative examples of new chemotypes for microtubule stabilization. As such, they may offer the same potential for pharmacological differentiation from the original epothilone leads as various newly discovered microtubule-stabilizing natural products with macrolactone structures, such as laulimalide, peloruside, or dictyostatin.

Unconventional Monetary Policy and the Great Recession: Estimating the Macroeconomic Effects of a Spread Compression at the Zero Lower Bound

We explore the macroeconomic effects of a compression in the long-term bond yield spread within the context of the Great Recession of 2007���09 via a time-varying parameter structural VAR model. We identify a ���pure��� spread shock defined as a shock that leaves the policy rate unchanged, which allows us to characterize the macroeconomic consequences of a decline in the yield spread induced by central banks��� asset purchases within an environment in which the policy rate is constrained by the effective zero lower bound. Two key findings stand out. First, compressions in the long-term yield spread exert a powerful effect on both output growth and inflation. Second, conditional on available estimates of the impact of the Federal Reserve���s and the Bank of England���s asset purchase programs on long-term yield spreads, our counterfactual simulations suggest that U.S. and U.K. unconventional monetary policy actions have averted significant risks both of deflation and of output collapses comparable to those that took place during the Great Depression.

Modeling Framework for the Establishment of the Apical-Basal Embryonic Axis in Plants

The apical-basal axis of the early plant embryo determines the body plan of the adult organism. To establish a polarized embryonic axis, plants evolved a unique mechanism that involves directional, cell-to-cell transport of the growth regulator auxin. Auxin transport relies on PIN auxin transporters 1], whose polar subcellular localization determines the flow directionality. PIN-mediated auxin transport mediates the spatial and temporal activity of the auxin response machinery 2-7] that contributes to embryo patterning processes, including establishment of the apical (shoot) and basal (root) embryo poles 8]. However, little is known of upstream mechanisms guiding the (re)polarization of auxin fluxes during embryogenesis 9]. Here, we developed a model of plant embryogenesis that correctly generates emergent cell polarities and auxin-mediated sequential initiation of apical-basal axis of plant embryo. The model relies on two precisely localized auxin sources and a feedback between auxin and the polar, subcellular PIN transporter localization. Simulations reproduced PIN polarity and auxin distribution, as well as previously unknown polarization events during early embryogenesis. The spectrum of validated model predictions suggests that our model corresponds to a minimal mechanistic framework for initiation and orientation of the apical-basal axis to guide both embryonic and postembryonic plant development.

Umstrukturierung von kollektiven Kapitalanlagen

The issuance of the Swiss Federal Act on Collective Investment Schemes (CISA) in the year 2007 and the revision thereof in 2013 expanded the possibilities for restructuring of collective investment schemes and simplified the procedures. For instance, in article 95 the CISA contains a provision that deals in a non-conclusive way with the restructuring of open-ended collective investment schemes. As a novelty regulation, this provision allows for mergers not only of contractual funds but also of investment companies with variable capital (SICAV). Additionally, the transformation of an open-ended collective investment into another CISA legal form was also included into the catalogue of possible restructuring processes. Further, a SICAV still maintains the possibility for asset transfer according to article 69 ff. of the Federal Act on Merger, Demerger, Transformation and Transfer of Assets (MerA). However, not all open questions have been clarified. As long as the CISA does not contain restructuring provisions, as is the case with closed-ended collective investment schemes, generally the MerA and/or the Swiss Code of Obligations (CO) apply. The interplay of diverse, partly overlapping legislative bases leads to the emergence of unwanted gaps. Moreover, the partial revision of the CISA was not completely implemented at the ordinance level. Among others, the following issues have not been conclusively or clearly regulated: the permitted combinations of mergers, the merger procedure of the SICAV, the permitted restructurings, the transformation procedure as well as the application scope of the asset transfer for collective investment schemes according to the relevant merger regulations. Although these questions will be clarified in the following article through a systematic and teleological analysis of the relevant regulations, it is to be hoped that the gaps will be closed within the next CISA revision in order to guarantee comprehensive legal certainty.

Social Inequality in Political Participation: The Dark Sides of Individualisation

Has the participatory gap between social groups widened over the past decades? And if so, how can it be explained? Based on a re-analysis of 94 electoral surveys in eight Western European countries between 1956 and 2009, this article shows that the difference in national election turnout between the half of the population with the lowest level of education and the half with the highest has increased. It shows that individualisation ��� the decline of social integration and social control ��� is a major cause of this trend. In their electoral choices, citizens with fewer resources ��� in terms of education ��� rely more heavily on cues and social control of the social groups to which they belong. Once the ties to these groups loosen, these cues and mobilising norms are no longer as strong as they once were, resulting in an increasing abstention of the lower classes on Election Day. In contrast, citizens with abundant resources rely much less on cues and social control, and the process of individualisation impacts on their participatory behaviour to a much lesser extent. The article demonstrates this effect based on a re-analysis of five cumulative waves of the European Social Survey.