THE STRATEGIC IMPORTANCE OF AFTER-SALES SERVICES FOR THE INSURANCE OF GROWTH IN CUSTOMER-VALUE-ORIENTED MANAGEMENT: AN OBSERVATION OF SMALL- AND MEDIUM-SIZED INDUSTRIAL GOODS MANUFACTURERS

Small and medium-sized companies in the investment goods industry find themselves more and more often confronted with radical changes in the conditions of their business environments. The access to one dimensional growth just by selling physical products is becoming increasingly limited. Traditional means are suffering of a constant loss of effectiveness. But even though it has been shown that there are enormous chances in the area of after-sales services in this industry, small- and medium-sized industrial goods manufacturers obtain only about 25% of their turnover with services, due to an insufficient strategic involvement of this topic. On the basis of a long term perspective and against the background of the discussions on stakeholder integration, strategic business segments and the customer-lifetime-value, this paper focuses on the different possibilities of accessing new market potentials by combining and analyzing the implications of different strategic perspectives on after-sales-services and their effects on the customer-lifetime-value.After-Sales Services; Investment goods industry; Capital goods; Strategic marketing; Strategic business segment.

The Role of Ets Factors in Tumor Angiogenesis

Angiogenesis is a critical component of tumor growth. A number of growth factors, including VEGF, FGF, and HGF, have been implicated as angiogenic growth factors that promote tumor angiogenesis in different types of cancer. Ets-1 is the prototypic member of the Ets transcription factor family. Ets-1 is known to be a downstream mediator of angiogenic growth factors. Expression of Ets-1 in a variety of different tumors is associated with increased angiogenesis. A role for other selected members of the Ets transcription factor family has also been shown to be important for the development of tumor angiogenesis. Because Ets factors also express a number of other important genes involved in cell growth, they contribute not only to tumor growth, but to disease progression. Targeting Ets factors in mouse tumor models through the use of dominant-negative Ets proteins or membrane permeable peptides directed at competitively inhibiting the DNA binding domain has now demonstrated the therapeutic potential of inhibiting selected Ets transcription factors to limit tumor growth and disease progression

Fluorescent quantification of melanin

Melanin quantification is reportedly performed by absorption spectroscopy, commonly at 405 nm. Here, we propose the implementation of fluorescence spectroscopy for melanin assessment. In a typical in vitro assay to assess melanin production in response to an external stimulus, absorption spectroscopy clearly overvalues melanin content. This method is also incapable of distinguishing non-melanotic/amelanotic control cells from those that are actually capable of performing melanogenesis. Therefore, fluorescence spectroscopy is the best method for melanin quantification as it proved to be highly specific and accurate, detecting even small variations in the synthesis of melanin. This method can also be applied to the quantification of melanin in more complex biological matrices like zebrafish embryos and human hair.This work was supported by the Portuguese Foundation for Science and Technology (FCT) through the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145- FEDER-006684) and BioTecNorte Operation (NORTE-01-0145- FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. The authors would like to thank to the hair donor volunteers and to Marisa Passos, Ana Sofia Teixeira, and In^es Pinto for technical assistance regarding the collection of zebrafish embryos. The author Teresa Matam a would also like to acknowledge her postdoctoral fellowship funded by FCT (SFRH/BPD/ 102153/2014)

Gene expression analysis of embryonic stem cells expressing VE-cadherin (CD144) during endothelial differentiation

Background: Endothelial differentiation occurs during normal vascular development in the developing embryo. This process is recapitulated in the adult when endothelial progenitor cells are generated in the bone marrow and can contribute to vascular repair or angiogenesis at sites of vascular injury or ischemia. The molecular mechanisms of endothelial differentiation remain incompletely understood. Novel approaches are needed to identify the factors that regulate endothelial differentiation. Methods: Mouse embryonic stem (ES) cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2+ cells, that were CD41 positive at 3.5 days. A separate population of VEGF-R2+ stem cells expressing the endothelial-specific marker CD144 (VE-cadherin) was also identified at this same time point. Channels lined by VE-cadherin positive cells developed within the embryoid bodies (EBs) formed by differentiating ES cells. VE-cadherin and CD41 expressing cells differentiate in close proximity to each other within the EBs, supporting the concept of a common origin for cells of hematopoietic and endothelial lineages. Results: Microarray analysis of \u3e45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2+, CD41+, and CD144+ and VEGF-R2-, CD41-, and CD144-. All microarray experiments were performed in duplicate using RNA obtained from independent experiments, for each subset of cells. Expression profiling confirmed the role of several genes involved in hematopoiesis, and identified several putative genes involved in endothelial differentiation. Conclusion: The isolation of CD144+ cells during ES cell differentiation from embryoid bodies provides an excellent model system and method for identifying genes that are expressed during endothelial differentiation and that are distinct from hematopoiesis

Epithelium-Specific ETS (ESE)-1 upregulated GP73 expression in hepatocellular carcinoma cells

Background: Golgi protein-73 (GP73) is a Golgi transmembrane glycoprotein elevated in numerous liver diseases. Clinically, GP73 is strongly elevated in the serum of HCC patients and is thus regarded as a novel potential biomarker for HCC. However, the mechanism leading to GP73 dysregulation in liver diseases remains unknown. Results: This study determined that epithelium-specific ETS (ESE)-1, an epithelium-specific transcription factor, and GP73 expressions were induced by IL-1β stimulation in vitro, and both were triggered during liver inflammation in vivo. In hepatocellular carcinoma cells, the overexpression of ESE-1 induced GP73 expression, whereas its knock-down did the opposite. Mechanistically, ESE-1 activated GP73 expression by directly binding to its promoter. Conclusions: Our findings supported a novel paradigm for ESE-1 as a transcriptional mediator of GP73. This study provided a possible mechanism for GP73 upregulation in liver diseases. Electronic supplementary material The online version of this article (doi:10.1186/2045-3701-4-76) contains supplementary material, which is available to authorized users

Bioinformatic identification and characterization of human endothelial cell-restricted genes

<p>Abstract</p> <p>Background</p> <p>In this study, we used a systematic bioinformatics analysis approach to elucidate genes that exhibit an endothelial cell (EC) restricted expression pattern, and began to define their regulation, tissue distribution, and potential biological role.</p> <p>Results</p> <p>Using a high throughput microarray platform, a primary set of 1,191 transcripts that are enriched in different primary ECs compared to non-ECs was identified (LCB >3, FDR <2%). Further refinement of this initial subset of transcripts, using published data, yielded 152 transcripts (representing 109 genes) with different degrees of EC-specificity. Several interesting patterns emerged among these genes: some were expressed in all ECs and several were restricted to microvascular ECs. Pathway analysis and gene ontology demonstrated that several of the identified genes are known to be involved in vasculature development, angiogenesis, and endothelial function (P < 0.01). These genes are enriched in cardiovascular diseases, hemorrhage and ischemia gene sets (P < 0.001). Most of the identified genes are ubiquitously expressed in many different tissues. Analysis of the proximal promoter revealed the enrichment of conserved binding sites for 26 different transcription factors and analysis of the untranslated regions suggests that a subset of the EC-restricted genes are targets of 15 microRNAs. While many of the identified genes are known for their regulatory role in ECs, we have also identified several novel EC-restricted genes, the function of which have yet to be fully defined.</p> <p>Conclusion</p> <p>The study provides an initial catalogue of EC-restricted genes most of which are ubiquitously expressed in different endothelial cells.</p

Immune Sensitization in the Skin Is Enhanced by Antigen-Independent Effects of IgE

AbstractContact sensitivity responses require both effective immune sensitization following cutaneous exposure to chemical haptens and antigen-specific elicitation of inflammation upon subsequent hapten challenge. We report that antigen-independent effects of IgE antibodies can promote immune sensitization to haptens in the skin. Contact sensitivity was markedly impaired in IgE−/− mice but was restored by either transfer of sensitized cells from wild-type mice or administration of hapten-irrelevant IgE before sensitization. Moreover, IgE−/− mice exhibited impairment in the reduction of dendritic cell numbers in the epidermis after hapten exposure. Monomeric IgE has been reported to influence mast cell function. We observed diminished contact sensitivity in mice lacking FcϵRI or mast cells, and mRNA for several mast cell-associated genes was reduced in IgE−/− versus wild-type skin after hapten exposure. We speculate that levels of IgE normally present in mice favor immune sensitization via antigen-independent but FcϵRI-dependent effects on mast cells