Melanocytes Affect Nodal Expression and Signaling in Melanoma Cells: A Lesson from Pediatric Large Congenital Melanocytic Nevi

Expression of Nodal, a Transforming Growth Factor-beta (TGF-β) related growth factor, is associated with aggressive melanoma. Nodal expression in adult dysplastic nevi may predict the development of aggressive melanoma in some patients. A subset of pediatric patients diagnosed with giant or large congenital melanocytic nevi (LCMN) has shown increased risk for development of melanoma. Here, we investigate whether Nodal expression can help identify the rare cases of LCMN that develop melanoma and shed light on why the majority of these patients do not. Immunohistochemistry (IHC) staining results show varying degree of Nodal expression in pediatric dysplastic nevi and LCMN. Moreover, median scores from Nodal IHC expression analysis were not significantly different between these two groups. Additionally, none of the LCMN patients in this study developed melanoma, regardless of Nodal IHC levels. Co-culture experiments revealed reduced tumor growth and lower levels of Nodal and its signaling molecules P-SMAD2 and P-ERK1/2 when melanoma cells were grown in vivo or in vitro with normal melanocytes. The same was observed in melanoma cells cultured with melanocyte conditioned media containing pigmented melanocyte derived melanosomes (MDM). Since MDM contain molecules capable of inactivating radical oxygen species, to investigate potential anti-oxidant effect of MDM on Nodal expression and signaling in melanoma, melanoma cells were treated with either N-acetyl-l-cysteine (NAC), a component of the anti-oxidant glutathione or synthetic melanin, which in addition to providing pigmentation can also exert free radical scavenging activity. Melanoma cells treated with NAC or synthetic melanin showed reduced levels of Nodal, P-SMAD2 and P-ERK1/2 compared to untreated melanoma cells. Thus, the potential role for Nodal in melanoma development in LCMN is less evident than in adult dysplastic nevi possibly due to melanocyte cross-talk in LCMN capable of offsetting or delaying the pro-melanoma effects of Nodal via anti-oxidant effects of MDM.     

The effect of the temporal resolution of NDVI data on season onset dates and trends across Canadian broadleaf forests

Satellite remote sensing has the potential to contribute to plant phenology monitoring at spatial and temporal scales relevant for regional and global scale studies. Historically, temporal composites of satellite data, ranging from 8 days to 16 days, have been used as a starting point for satellite-derived phenology data sets. In this study we assess how the temporal resolution of such composites affects the estimation of the start of season (SOS) by: 1) calibrating a relationship between satellite derived SOS with in situ leaf unfolding (LU) of trembling aspen (Populus tremuloides) across Canada and 2) quantifying the sensitivity of calibrated satellite SOS estimates and trends, over Canadian broadleaf forests, to the temporal resolution of NDVI data. SOS estimates and trends derived from daily NDVI data were compared to SOS estimates and trends derived from multiday NDVI composites that retain the exact date of the maximum NDVI value or that assume the midpoint of the multiday interval as the observation date. In situ observations of LU dates were acquired from the PlantWatch Canada network. A new Canadian database of cloud and snow screened daily 1-km resolution National Oceanic and Atmospheric Administration advanced very high resolution radiometer surface reflectance images was used as input satellite data. The mean absolute errors of SOS dates with respect to in situ LU dates ranged between 13 and 40 days. SOS estimates from NDVI composites that retain the exact date of the maximum NDVI value had smaller errors (~ 13 to 20 days). The sensitivity analysis reinforced these findings: SOS estimates from NDVI composites that use the exact date had smaller absolute deviations from the LU date (0 to − 5 days) than the SOS estimates from NDVI composites that use the midpoint (− 2 to − 27 days). The SOS trends between 1985 and 2007 were not sensitive to the temporal resolution or compositing methods. However, SOS trends at individual ecozones showed significant differences with the SOS trends from daily NDVI data (Taiga plains and the Pacific maritime zones). Overall, our results suggest that satellite based estimates of vegetation green-up dates should preferably use sub-sampled NDVI composites that include the exact observation date of the maximum NDVI to minimize errors in both, SOS estimates and SOS trend analyses. For trend analyses alone, any of the compositing methods could be used, preferably with composite intervals of less than 28 days. This is an important finding, as it suggests that existing long-term 10-day or 15-day NDVI composites could be used for SOS trend analyses over broadleaf forests in Canada or similar areas. Future studies will take advantage of the growing in situ phenology networks to improve the validation of satellite derived green-up dates.     

Microfluidics enables small-scale tissue-based drug metabolism studies with scarce human tissue

Early information on the metabolism and toxicity properties of new drug candidates is crucial for selecting the right candidates for further development. Preclinical trials rely on cell-based in vitro tests and animal studies to characterize the in vivo behavior of drug candidates, although neither are ideal predictors of drug behavior in humans. Improving in vitro systems for preclinical studies both from a technological and biological model standpoint thus remains a major challenge. This article describes how microfluidics can be exploited to come closer to this goal in combination with precision-cut liver slices (PCLS) as an improved organomimetic system. Recently, we developed a novel microfluidic-based system incorporating a microchamber for slice perifusion to perform drug metabolism studies with mammalian PCLS under continuous flow. In the present study, the viability and metabolism of human PCLS were assessed by the measurement of the leakage of liver-specific enzymes and metabolism of four different substrates: lidocaine, 7-hydroxycoumarin, 7-ethoxycoumarin, and testosterone. All experiments were verified with well plates, an excellent benchmark for these experiments. Clearly, however, human tissue is not readily available, and it is worth considering how to perform a maximum number of informative experiments with small amounts of material. In one approach, the microfluidic system was coupled to an HPLC system to allow on-line monitoring and immediate detection of unstable metabolites, something that is generally not possible with conventional well-plate systems. This novel microfluidic system also enables the in vitro measurement of interorgan interactions by connecting microchambers containing different organ slices in series for sequential perfusion. This versatile experimental system has the potential to yield more information about the metabolic profiles of new drug candidates in human and animal tissues in an early stage of development compared with well plates alone.     

Datenschutzrechtliche Einwilligung zur Werbung: Opt-out ausreichend?

Zusammenfassung  Das Interesse der Unternehmen, an personenbezogene Daten zu gelangen und diese für Werbezwecke zu verwerten, ist gro?. An die Einholung von Einwilligungen zur Verarbeitung solcher Daten stellte die Rechtsprechung daher hohe Anforderungen. Die herrschende Meinung ging bislang davon aus, dass Einwilligungen in Werbema?nahmen, die mittels Opt-out-Verfahren erlangt wurden, unwirksam sind. Bereits im vergangenen Jahr hatte das Oberlandesgericht München erneut darüber zu entscheiden, ob eine Opt-out-Klausel den datenschutzrechtlichen Anforderungen nach § 4a BDSG entspricht — und bejahte überraschenderweise die Wirksamkeit der Einwilligung.     

The analysis of embodied communicative feedback in multimodal corpora: a prerequisite for behavior simulation

Communicative feedback refers to unobtrusive (usually short) vocal or bodily expressions whereby a recipient of information can inform a contributor of information about whether he/she is able and willing to communicate, perceive the information, and understand the information. This paper provides a theory for embodied communicative feedback, describing the different dimensions and features involved. It also provides a corpus analysis part, describing a first data coding and analysis method geared to find the features postulated by the theory. The corpus analysis part describes different methods and statistical procedures and discusses their applicability and the possible insights gained with these methods.     

Enhancing information systems management with natural language processing techniques

Natural language and databases are core components of information systems. They are related to each other because they share the same purpose: the conceptualization aspects of the real world in order to deal with them in some way. Natural language processing (NLP) techniques may substantially enhance most phases of the information system lifecycle, starting with requirements analysis, specification and validation, and going up to conflict resolution, result processing and presentation. Furthermore, natural language based query languages and user interfaces facilitate the access to information for anyone and allow for new paradigms in the usage of computerized services. This paper investigates the use of NLP techniques in the design phase of information systems. Then, it reports on data base querying and information retrieval enhanced with NLP.     

Realization of RGB colors from top‐emitting white OLED by electron beam patterning

We demonstrate the realization of red, green, and blue colors from top‐emitting white organic light‐emitting diode (OLED) for display applications. In our approach, red, green, and blue colors are realized by microcavity‐based mode selection from the spectrum of a white OLED. For the tuning of individual microcavities, the OLED hole transport layer is patterned by an electron beam process.     

Unified model for assessing checkpointing protocols at extreme‐scale

In this paper, we present a unified model for several well‐known checkpoint/restart protocols. The proposed model is generic enough to encompass both extremes of the checkpoint/restart space, from coordinated approaches to a variety of uncoordinated checkpoint strategies (with message logging). We identify a set of crucial parameters, instantiate them, and compare the expected efficiency of the fault tolerant protocols, for a given application/platform pair. We then propose a detailed analysis of several scenarios, including some of the most powerful currently available high performance computing platforms, as well as anticipated Exascale designs. The results of this analytical comparison are corroborated by a comprehensive set of simulations. Altogether, they outline comparative behaviors of checkpoint strategies at very large scale, thereby providing insight that is hardly accessible to direct experimentation. Copyright © 2013 John Wiley & Sons, Ltd.