The Price of Privacy - An Evaluation of the Economic Value of Collecting Clickstream Data

The analysis of clickstream data facilitates the understanding and prediction of customer behavior in e-commerce. Companies can leverage such data to increase revenue. For customers and website users, on the other hand, the collection of behavioral data entails privacy invasion. The objective of the paper is to shed light on the trade-off between privacy and the business value of cus- tomer information. To that end, the authors review approaches to convert clickstream data into behavioral traits, which we call clickstream features, and propose a categorization of these features according to the potential threat they pose to user privacy. The authors then examine the extent to which different categories of clickstream features facilitate predictions of online user shopping pat- terns and approximate the marginal utility of using more privacy adverse information in behavioral prediction models. Thus, the paper links the literature on user privacy to that on e-commerce analytics and takes a step toward an economic analysis of privacy costs and benefits. In par- ticular, the results of empirical experimentation with large real-world e-commerce data suggest that the inclusion of short-term customer behavior based on session-related information leads to large gains in predictive accuracy and business performance, while storing and aggregating usage behavior over longer horizons has comparably less value

Galectin-12 colocalizes with splicing factor-rich speckles and shuttles between the nucleus and cytoplasm in colon cancer cells

Several members of the glycan-binding family of galectins have been linked to colon cancer initiation and progression while the role of galectin-12 in this malignancy is largely unexplored. In previous studies we observed expression of galectin-12 in normal colon epithelium in contrast to its lack of expression in colorectal cancer tissues. In order to gain insight into its molecular function we established a genetically engineered colon cancer model cell line, which facilitates inducible and reconstituted expression of LGALS12 transgene at physiological levels in an isogenic background. Regulation of transgene expression by doxycycline was confirmed at the transcript- and protein level in a time- and dose-dependent manner for two independent clones. Reconstituted galectin-12 expression did not affect cell morphology and proliferation. Analysis of its subcellular distribution showed that galectin-12 resides in and shuttles between the nucleus and cytoplasm. More detailed analysis by double-immunofluorescence and confocal microscopy revealed colocalization of galectin-12 with splicing-factor rich nuclear speckles, hinting towards a potential role of galectin-12 in pre-mRNA splicing and processing. Therefore, the established model cell line represents a powerful tool to investigate the functional impact of galectin-12 reconstitution on colon cancer tumorigenesis

Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability

<p>Abstract</p> <p>Background</p> <p>Protein tyrosine phosphatases (PTPs) like their antagonizing protein tyrosine kinases are key regulators of signal transduction thereby assuring normal control of cellular growth and differentiation. Increasing evidence suggests that mutations in PTP genes are associated with human malignancies. For example, mutational analysis of the tyrosine phosphatase (PTP) gene superfamily uncovered genetic alterations in about 26% of colorectal tumors. Since in these studies tumors have not been stratified according to genetic instability status we hypothesized that colorectal tumors characterized by high-level of microsatellite instability (MSI-H) might show an increased frequency of frameshift mutations in those PTP genes that harbor long mononucleotide repeats in their coding region (cMNR).</p> <p>Results</p> <p>Using bioinformatic analysis we identified 16 PTP candidate genes with long cMNRs that were examined for genetic alterations in 19 MSI-H colon cell lines, 54 MSI-H colorectal cancers, and 17 MSI-H colorectal adenomas. Frameshift mutations were identified only in 6 PTP genes, of which PTPN21 show the highest mutation frequency at all in MSI-H tumors (17%).</p> <p>Conclusion</p> <p>Although about 32% of MSI-H tumors showed at least one affected PTP gene, and cMNR mutation rates in PTPN21, PTPRS, and PTPN5 are higher than the mean mutation frequency of MNRs of the same length, mutations within PTP genes do not seem to play a common role in MSI tumorigenesis, since no cMNR mutation frequency reached statistical significance and therefore, failed prediction as a Positive Selective Target Gene.</p

TGFBR2-dependent alterations of exosomal cargo and functions in DNA mismatch repair-deficient HCT116 colorectal cancer cells

Background: Colorectal cancers (CRCs) that lack DNA mismatch repair function exhibit the microsatellite unstable (MSI) phenotype and are characterized by the accumulation of frameshift mutations at short repetitive DNA sequences (microsatellites). These tumors recurrently show inactivating frameshift mutations in the tumor suppressor Transforming Growth Factor Beta Receptor Type 2 (TGFBR2) thereby abrogating downstream signaling. How altered TGFBR2 signaling affects exosome-mediated communication between MSI tumor cells and their environment has not been resolved. Here, we report on molecular alterations of exosomes shed by MSI cells and the biological response evoked in recipient cells. Methods: Exosomes were isolated and characterized by electron microscopy, nanoparticle tracking, and western blot analysis. TGFBR2-dependent effects on the cargo and functions of exosomes were studied in a MSI CRC model cell line enabling reconstituted and inducible TGFBR2 expression and signaling. Microsatellite frameshift mutations in exosomal and cellular DNA were examined by PCR-based DNA fragment analysis and exosomal protein profiles were identified by mass spectrometry. Uptake of fluorescent-labeled exosomes by hepatoma recipient cells was monitored by confocal microscopy. TGFBR2-dependent exosomal effects on secreted cytokine levels of recipient cells were analyzed by Luminex technology and ELISA. Results: Frameshift mutation patterns in microsatellite stretches of TGFBR2 and other MSI target genes were found to be reflected in the cargo of MSI CRC-derived exosomes. At the proteome level, reconstituted TGFBR2 expression and signaling uncovered two protein subsets exclusively occurring in exosomes derived from TGFBR2-deficient (14 proteins) or TGFBR2-proficient (five proteins) MSI donor cells. Uptake of these exosomes by recipient cells caused increased secretion (2–6 fold) of specific cytokines (Interleukin-4, Stem Cell Factor, Platelet-derived Growth Factor-B), depending on the TGFBR2 expression status of the tumor cell. Conclusion: Our results indicate that the coding MSI phenotype of DNA mismatch repair-deficient CRC cells is maintained in their exosomal DNA. Moreover, we uncovered that a recurrent MSI tumor driver mutation like TGFBR2 can reprogram the protein content of MSI cell-derived exosomes and in turn modulate the cytokine secretion profile of recipient cells. Apart from its diagnostic potential, these TGFBR2-dependent exosomal molecular and proteomic signatures might help to understand the signaling routes used by MSI tumors. Graphical Abstract Fricke et al. uncovered coding microsatellite instability-associated mutations of colorectal tumor driver genes like TGFBR2 in MSI tumor cellderived exosomes. Depending on the TGFBR2 expression status of their donor cells, shed exosomes show distinct proteomic signatures and promote altered cytokine secretion profiles in recipient cells

Tablets as an Option for Telemedicine—Evaluation of Diagnostic Performance and Efficiency in Intracranial Arterial Aneurysm Detection

Purpose: To evaluate a commercially available mobile device for the highly specialized task of detection of intracranial arterial aneurysm in telemedicine. Methods: Six radiologists with three different levels of experience retrospectively interpreted 60 computed tomography (CT) angiographies for the presence of intracranial arterial aneurysm, among them 30 cases with confirmed positive findings. Each radiologist reviewed the angiography datasets twice: once on a dedicated medical-grade workstation and on a commercially available mobile consumer-grade tablet with an interval of 3 months. Diagnostic performance, reading efficiency and subjective scorings including diagnostic confidence were analyzed and compared. Results: Diagnostic performance was comparable on both devices regardless of readers' experience, and no significant differences in sensitivity (66-87.5%) and specificity (79.4-87%) were found. Results obtained with tablets and medical workstations were also comparable in terms of subjective assessment across all reader groups. Conclusions: There was no significant difference between tablet and workstation readings of angiography datasets for the presence of intracranial arterial aneurysm. Sensitivity, specificity, efficiency and subjective scorings were similar with the two devices for all three reader groups. While medical workstations are 10 times more expensive, tablets allow higher mobility especially for radiologists on call

project report Promise2007

Das Projekt Promise2007 befasste sich mit der Erstellung und Auswertung einer Statistik zur Mitgliedersituation im Berufsverband Medizinischer Informatiker e.V.. Mit dem Ziel mehr über die Mitglieder und ihre derzeitige Situation zu erfahren wurde das Projekt an der Fachhochschule Hannover initiiert. Statistisch erfasst wurden Fragen zum Beschäftigungsverhältnis, zu Aus- und Weiterbildung, der beruflichen Situation und persönliche Angaben. Die Ergebnisse wurden ausgewertet und daraus wichtige Erkenntnisse für den BVMI e.V. abgeleitet, welche auf die weitere Verbandsarbeit Einfluss nehmen

Oriented Matroids -- Combinatorial Structures Underlying Loop Quantum Gravity

We analyze combinatorial structures which play a central role in determining spectral properties of the volume operator in loop quantum gravity (LQG). These structures encode geometrical information of the embedding of arbitrary valence vertices of a graph in 3-dimensional Riemannian space, and can be represented by sign strings containing relative orientations of embedded edges. We demonstrate that these signature factors are a special representation of the general mathematical concept of an oriented matroid. Moreover, we show that oriented matroids can also be used to describe the topology (connectedness) of directed graphs. Hence the mathematical methods developed for oriented matroids can be applied to the difficult combinatorics of embedded graphs underlying the construction of LQG. As a first application we revisit the analysis of [4-5], and find that enumeration of all possible sign configurations used there is equivalent to enumerating all realizable oriented matroids of rank 3, and thus can be greatly simplified. We find that for 7-valent vertices having no coplanar triples of edge tangents, the smallest non-zero eigenvalue of the volume spectrum does not grow as one increases the maximum spin \jmax at the vertex, for any orientation of the edge tangents. This indicates that, in contrast to the area operator, considering large \jmax does not necessarily imply large volume eigenvalues. In addition we give an outlook to possible starting points for rewriting the combinatorics of LQG in terms of oriented matroids.Comment: 43 pages, 26 figures, LaTeX. Version published in CQG. Typos corrected, presentation slightly extende

The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution

The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and to neoantigen-inducing translational frameshifts. Here, we develop a tool to quantify frameshift mutations in MSI colorectal and endometrial cancer. Our results show that frameshift mutation frequency is negatively correlated to the predicted immunogenicity of the resulting peptides, suggesting counterselection of cell clones with highly immunogenic frameshift peptides. This correlation is absent in tumors with Beta-2-microglobulin mutations, and HLA-A*02:01 status is related to cMS mutation patterns. Importantly, certain outlier mutations are common in MSI cancers despite being related to frameshift peptides with functionally confirmed immunogenicity, suggesting a possible driver role during MSI tumor evolution. Neoantigens resulting from shared mutations represent promising vaccine candidates for prevention of MSI cancers. DNA mismatch repair (MMR)-deficient cancers with microsatellite-instability are characterized by a high load of frameshift mutation-derived neoantigens. Here, by mapping the frameshift mutation landscape and predicting the immunogenicity of the resulting peptides, the authors show evidence of immunoediting in MMR-deficient colorectal and endometrial cancers.Peer reviewe

Photogalvanic probing of helical edge channels in two-dimensional HgTe topological insulators

We report on the observation of a circular photogalvanic current excited by terahertz laser radiation in helical edge channels of two-dimensional (2D) HgTe topological insulators (TIs). The direction of the photocurrent reverses by switching the radiation polarization from a right-handed to a left-handed one and, for fixed photon helicity, is opposite for the opposite edges. The photocurrent is detected in a wide range of gate voltages. With decreasing the Fermi level below the conduction band bottom, the current emerges, reaches a maximum, decreases, changes its sign close to the charge neutrality point (CNP), and again rises. Conductance measured over a approximate to 3 mu m distance at CNP approaches 2e(2)/ h, the value characteristic for ballistic transport in 2D TIs. The data reveal that the photocurrent is caused by photoionization of helical edge electrons to the conduction band. We discuss the microscopic model of this phenomenon and compare calculations with experimental data