12 research outputs found
Internet Marketing for Profit Organizations: A framework for the implementation of strategic internet marketing
Merged with duplicate record 10026.1/828 on 13.03.2017 by CS (TIS)The development of the Internet has significantly changed the face of established markets
and operation approaches across a tremendous spectrum of different industries. Within
the competitive environment of those industries, the opportunities and risks derived from
the new platform are so ubiquitous that unused opportunities quickly translate into
potential risks. Those opportunities and risks demand for a structured approach how to
implement a sustainable Internet marketing strategy that targets clear business objectives.
Marketing and strategic management theory describes very clear structural principles
towards their operational implementation. Based on those principles an extensive
literature review has been conducted which confirms the result from representative
statistics that demonstrate the lack of a comprehensive framework for strategic Internet
marketing. The distinct result of this research is such a comprehensive framework which
has been directly derived from the illustrated principles of strategic management and
Internet marketing. All major components of this generic framework are designed,
evaluated in dedicated surveys and validated in extensive case studies.
The main achievements of the research are:
• A comprehensive review of the current state-of-the-art Internet marketing
strategies
• Conceptual specification of a strategic Internet marketing framework with generic
applicability to profit organizations
• Demonstration of the practical feasibility of the proposed framework at the
implementation level (via several examples like the SIMTF and SIMPF)
• Confirmation of the applicability of the framework based upon a survey of potential
beneficiaries
• Validation of the effectiveness of the approach via case study scenarios
Changing the understanding of a former technical discipline, the thesis describes how
Internet marketing becomes a precise strategic instrument for profit organizations. The
new structured, complete and self-similar framework facilitates sales organizations to
significantly increase the effectiveness and efficiency of their marketing operations.
Furthermore, the framework ensures a high level of transparency about the impact and
benefit of individual activities. The new model explicitly answers concerns and problems
raised and documented in existing research and accommodate for the current limitations
of strategic Internet marketing. The framework allows evaluating existing as well as future
Internet marketing tactics and provides a reference model for all other definitions of
objectives, KPI and work packages. Finally this thesis also matures the subject matter of
Internet marketing as a discipline of independent scientific research providing an
underlying structure for subsequent studies.Darmstadt Node of the CSCAN Network
at University of Applied Sciences, Darmstad
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
Metabolic Signature of Electrosurgical Liver Dissection
<div><p>Background and Aims</p><p>High frequency electrosurgery has a key role in the broadening application of liver surgery. Its molecular signature, <i>i.e.</i> the metabolites evolving from electrocauterization which may inhibit hepatic wound healing, have not been systematically studied.</p><p>Methods</p><p>Human liver samples were thus obtained during surgery before and after electrosurgical dissection and subjected to a two-stage metabolomic screening experiment (discovery sample: N = 18, replication sample: N = 20) using gas chromatography/mass spectrometry.</p><p>Results</p><p>In a set of 208 chemically defined metabolites, electrosurgical dissection lead to a distinct metabolic signature resulting in a separation in the first two dimensions of a principal components analysis. Six metabolites including glycolic acid, azelaic acid, 2-n-pentylfuran, dihydroactinidiolide, 2-butenal and n-pentanal were consistently increased after electrosurgery meeting the discovery (p<2.0×10<sup>−4</sup>) and the replication thresholds (p<3.5×10<sup>−3</sup>). Azelaic acid, a lipid peroxidation product from the fragmentation of abundant sn-2 linoleoyl residues, was most abundant and increased 8.1-fold after electrosurgical liver dissection (p<sub>replication</sub> = 1.6×10<sup>−4</sup>). The corresponding phospholipid hexadecyl azelaoyl glycerophosphocholine inhibited wound healing and tissue remodelling in scratch- and proliferation assays of hepatic stellate cells and cholangiocytes, and caused apoptosis dose-dependently <i>in vitro</i>, which may explain in part the tissue damage due to electrosurgery.</p><p>Conclusion</p><p>Hepatic electrosurgery generates a metabolic signature with characteristic lipid peroxidation products. Among these, azelaic acid shows a dose-dependent toxicity in liver cells and inhibits wound healing. These observations potentially pave the way for pharmacological intervention prior liver surgery to modify the metabolic response and prevent postoperative complications.</p></div
Metabolites identified as consistently increased after ES in liver samples.
<p>The results of the screening stage are noted with the decadic logarithm of the peak area in the GC/MS denoted as Log10(I), the fold increase after ES and the p-value obtained from the analysis of variance including the patient as covariate denoted as PAOV. For the replication series, results of the paired t-test are denoted as Pt-test. Nominal p-values are given for all analyses.</p
Incubated cells with HAzPC.
<p>Incubation of cells with HAzPC at 5 µM in a wound healing scratch assay demonstrated that closure of the scratch occurs more rapidly in the absence of HAzPC (upper panels A and B) than with HAzPC treatment (lower panels C and D).</p
Overview of the patients used for metabolic screening of the effects of ES on human liver.
<p>In all cases, paired samples with and without electrosurgical coagulation were obtained. For the discovery stage, two to three independent pairs of samples from each patient and in the replication stage exactly one pair of samples were obtained. The range of the numeric parameters is given in square brackets.</p
Log10 concentrations for each of the six replicated metabolites before (denoted with open symbols) and after ES (denoted with filled symbols).
<p>The paired samples are each connected with a line and pairs are coloured differently for better visualization.</p
Principal components analysis of the samples of the discovery stage.
<p>The first two principal components are plotted. Samples before and after ES are marked with open and filled circles, respectively.</p
HAzPC dose-dependently increased apoptosis as reflected by an increase of Trypan Blue inclusion in CFSC-2G (A) and MMNK-1 (B) cells.
<p>Cell morphology suggesting apoptosis was confirmed by a dose-dependent increase of cleaved caspase and pro-apoptotic protein bax in both cell lines. The decrease of protein expression including that of cleaved caspase 3 (C) and bax at 5mcrmol of HAzPC in Western Blots likely reflects cell demise.</p