Laboratory experiments as evaluating method for IT artifacts – Experimental design and use case within a Product-Service-System

According to the paradigm of Design Science Research, IT artifacts are developed and built to solve real-life problems that occur in business life. Since Design Science Research consists of two phases, it is divided in the building and the evaluation phase. The evaluation phase is considered to be highly important as it analyses the relevance and the functionality of the artifact. To evaluate if an artifact meets the users’ needs, experiments are a possible method. Based on findings in a current research project, we present an experiment design to evaluate artifacts being part of Product-Service-Systems. The design is applied in a use case and supplemented by statistical data to analyze how the artifact meets the users’ needs

Supporting Technical Customer Services with Mobile Devices: Towards an Integrated Information System Architecture

Due to increasing complexity of machines and plants, information tailored to the needs of Technical Customer Services(TCS) is a prerequisite for the execution of efficient service processes. This paper describes the conception of a supportingarchitecture incorporating an integration platform to meet the TCS’ demand for information. On the one hand, the developedarchitecture directs the integration of data from different specialized systems to cover the aforementioned information needs.On the other hand, it enables the feedback of the TCS to other corporate departments which is often neglected. The systemclasses to be integrated are presented besides options and technologies for realizing the integration platform. The articlecreates a framework for future discussions on information technology integration to support the TCS

Role of RNA-binding proteins Rbfox1l and Rbfox2 in neuronal development and behavior in zebrafish

Rbfox proteins are RNA-binding proteins that play a significant role in the alternative splicing of neuronal transcripts in the central nervous system (CNS). Rbfox proteins are required for proper brain development and function. In humans, RBFOX1 has been implicated in a variety of neurological disorders, including autism, anxiety, epilepsy, and schizophrenia. Rbfox2 is involved in cerebellar development in mammals. The zebrafish is used as a model system for studies in neurobiology given their neuroanatomical conservation with mammals, and remarkable capability to regenerate parts of their CNS. Rbfox1l (Rbfox1-like) and Rbfox2 have been identified in neurons of the adult zebrafish brain. Rbfox1l was found in a restricted population of dorsal telencephalic neurons, and Rbfox2 was found broadly throughout the brain. Both genes have been found in Purkinje cells of the cerebellum. Utilizing antibody staining on zebrafish brain tissue sections, we will analyze expression of Rbfox1l and Rbfox2 at larval stages and stages leading up to adulthood. Furthermore, we will use rbfox1l and rbfox2 mutant zebrafish (in collaboration with Ohio State University) to better understand the role of rbfox1l in behavior and determine whether rbfox2 is necessary for the regeneration of the cerebellum. Understanding the role of the Rbfox proteins in neural development, regeneration, and behavior may lead to a substantial advancement in the research field and health care

Role of RNA-binding proteins Rbfox1l and Rbfox2 in neuronal development and behavior in zebrafish

Rbfox proteins are RNA-binding proteins that play a significant role in the alternative splicing of neuronal transcripts in the central nervous system (CNS). Rbfox proteins are required for proper brain development and function. In humans, RBFOX1 has been implicated in a variety of neurological disorders, including autism, anxiety, epilepsy, and schizophrenia. Rbfox2 is involved in cerebellar development in mammals. The zebrafish is used as a model system for studies in neurobiology given their neuroanatomical conservation with mammals, and remarkable capability to regenerate parts of their CNS. Rbfox1l (Rbfox1-like) and Rbfox2 have been identified in neurons of the adult zebrafish brain. Rbfox1l was found in a restricted population of dorsal telencephalic neurons, and Rbfox2 was found broadly throughout the brain. Both genes have been found in Purkinje cells of the cerebellum. Utilizing antibody staining on zebrafish brain tissue sections, we will analyze expression of Rbfox1l and Rbfox2 at larval stages and stages leading up to adulthood. Furthermore, we will use rbfox1l and rbfox2 mutant zebrafish (in collaboration with Ohio State University) to better understand the role of rbfox1l in behavior and determine whether rbfox2 is necessary for the regeneration of the cerebellum. Understanding the role of the Rbfox proteins in neural development, regeneration, and behavior may lead to a substantial advancement in the research field and health care

Functional inhibition of acid sphingomyelinase by Fluphenazine triggers hypoxia-specific tumor cell death

Owing to lagging or insufficient neo-angiogenesis, hypoxia is a feature of most solid tumors. Hypoxic tumor regions contribute to resistance against antiproliferative chemotherapeutics, radiotherapy and immunotherapy. Targeting cells in hypoxic tumor areas is therefore an important strategy for cancer treatment. Most approaches for targeting hypoxic cells focus on the inhibition of hypoxia adaption pathways but only a limited number of compounds with the potential to specifically target hypoxic tumor regions have been identified. By using tumor spheroids in hypoxic conditions as screening system, we identified a set of compounds, including the phenothiazine antipsychotic Fluphenazine, as hits with novel mode of action. Fluphenazine functionally inhibits acid sphingomyelinase and causes cellular sphingomyelin accumulation, which induces cancer cell death specifically in hypoxic tumor spheroids. Moreover, we found that functional inhibition of acid sphingomyelinase leads to overactivation of hypoxia stress-response pathways and that hypoxia-specific cell death is mediated by the stress-responsive transcription factor ATF4. Taken together, the here presented data suggest a novel, yet unexplored mechanism in which induction of sphingolipid stress leads to the overactivation of hypoxia stress-response pathways and thereby promotes their pro-apoptotic tumor-suppressor functions to specifically kill cells in hypoxic tumor areas

Elevated APOBEC3B Correlates with Poor Outcomes for Estrogen-Receptor-Positive Breast Cancers

Recent observations connected DNA cytosine deaminase APOBEC3B to the genetic evolution of breast cancer. We addressed whether APOBEC3B is associated with breast cancer clinical outcomes. APOBEC3B messenger RNA (mRNA) levels were related in 1,491 primary breast cancers to disease-free (DFS), metastasis-free (MFS), and overall survival (OS). For independent validation, APOBEC3B mRNA expression was associated with patient outcome data in five additional cohorts (over 3,500 breast cancer cases). In univariate Cox regression analysis, increasing APOBEC3B expression as a continuous variable was associated with worse DFS, MFS, and OS (hazard ratio [HR] = 1.20, 1.21, and 1.24, respectively; all P < .001). Also, in untreated ER-positive (ER+), but not in ER−, lymph-node-negative patients, high APOBEC3B levels were associated with a poor DFS (continuous variable: HR = 1.29, P = .001; dichotomized at the median level, HR = 1.66, P = .0002). This implies that APOBEC3B is a marker of pure prognosis in ER + disease. These findings were confirmed in the analyses of five independent patient sets. In these analyses, APOBEC3B expression dichotomized at the median level was associated with adverse outcomes (METABRIC discovery and validation, 788 and 706 ER + cases, disease-specific survival (DSS), HR = 1.77 and HR = 1.77, respectively, both P < .001; Affymetrix dataset, 754 ER + cases, DFS, HR = 1.57, P = 2.46E-04; NKI295, 181 ER + cases, DFS, HR = 1.72, P = .054; and BIG 1-98, 1,219 ER + cases, breast-cancer-free interval (BCFI), HR = 1.42, P = 0.0079). APOBEC3B is a marker of pure prognosis and poor outcomes for ER + breast cancer, which strongly suggests that genetic aberrations induced by APOBEC3B contribute to breast cancer progression. Electronic supplementary material The online version of this article (doi: 10.1007/s12672-014-0196-8) contains supplementary material, which is available to authorized users

Prior knowledge based mining functional modules from Yeast PPI networks with gene ontology

<p>Abstract</p> <p>Background</p> <p>In the literature, there are fruitful algorithmic approaches for identification functional modules in protein-protein interactions (PPI) networks. Because of accumulation of large-scale interaction data on multiple organisms and non-recording interaction data in the existing PPI database, it is still emergent to design novel computational techniques that can be able to correctly and scalably analyze interaction data sets. Indeed there are a number of large scale biological data sets providing indirect evidence for protein-protein interaction relationships.</p> <p>Results</p> <p>The main aim of this paper is to present a prior knowledge based mining strategy to identify functional modules from PPI networks with the aid of Gene Ontology. Higher similarity value in Gene Ontology means that two gene products are more functionally related to each other, so it is better to group such gene products into one functional module. We study (i) to encode the functional pairs into the existing PPI networks; and (ii) to use these functional pairs as pairwise constraints to supervise the existing functional module identification algorithms. Topology-based modularity metric and complex annotation in MIPs will be used to evaluate the identified functional modules by these two approaches.</p> <p>Conclusions</p> <p>The experimental results on Yeast PPI networks and GO have shown that the prior knowledge based learning methods perform better than the existing algorithms.</p