Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas

Cutaneous melanoma (CM) is the most aggressive form of skin cancer, and its worldwide incidence is rapidly increasing. Early stages can be successfully treated by surgery, but once metastasis has occurred, the prognosis is poor. However, some 5–10% of thick (≥2 mm) melanomas do not follow this scenario and run an unpredictable course. Little is known about the factors that contribute to metastasis in some patient with thick melanomas and the lack thereof in thick melanoma patients who never develop metastatic disease. We were therefore interested to study differential gene expression and pathway analysis and compare non-metastatic and metastatic thick melanomas. We found that the TNF-like weak inducer of apoptosis (TWEAK) pathway was upregulated in thick non-metastasizing melanomas. MAP3K14 (NIK1), BIRC2 (cIAP1), RIPK1, CASP7, CASP8, and TNF play an important role in inhibiting proliferation and invasion of tumor cells via the activation of the non-canonical NF-κB signaling pathway. In particular, this pathway sensitizes melanoma cells to TNF-alpha and activates the apoptosis module of the TWEAK pathway in thick non-metastasizing melanomas. Hence, our study suggests a potential role of the TWEAK pathway in inhibiting thick melanoma from metastasis. Exploitation of these genes and the pathway they control may open future therapeutic avenues.     

The expansion of Google Scholar versus Web of Science: a longitudinal study

Web of Science (WoS) and Google Scholar (GS) are prominent citation services with distinct indexing mechanisms. Comprehensive knowledge about the growth patterns of these two citation services is lacking. We analyzed the development of citation counts in WoS and GS for two classic articles and 56 articles from diverse research fields, making a distinction between retroactive growth (i.e., the relative difference between citation counts up to mid-2005 measured in mid-2005 and citation counts up to mid-2005 measured in April 2013) and actual growth (i.e., the relative difference between citation counts up to mid-2005 measured in April 2013 and citation counts up to April 2013 measured in April 2013). One of the classic articles was used for a citation-by-citation analysis. Results showed that GS has substantially grown in a retroactive manner (median of 170 % across articles), especially for articles that initially had low citations counts in GS as compared to WoS. Retroactive growth of WoS was small, with a median of 2 % across articles. Actual growth percentages were moderately higher for GS than for WoS (medians of 54 vs. 41 %). The citation-by-citation analysis showed that the percentage of citations being unique in WoS was lower for more recent citations (6.8 % for citations from 1995 and later vs. 41 % for citations from before 1995), whereas the opposite was noted for GS (57 vs. 33 %). It is concluded that, since its inception, GS has shown substantial expansion, and that the majority of recent works indexed in WoS are now also retrievable via GS. A discussion is provided on quantity versus quality of citations, threats for WoS, weaknesses of GS, and implications for literature research and research evaluation.     

Analysis of cultured neuronal networks using intraburst firing characteristics

It is an open question whether neuronal networks, cultured on multielectrode arrays, retain any capability to usefully process information (learning and memory). A necessary prerequisite for learning is that stimulation can induce lasting changes in the network. To observe these changes, one needs a method to describe the network in sufficient detail, while stable in normal circumstances. We analyzed the spontaneous bursting activity that is encountered in dissociated cultures of rat neocortical cells. Burst profiles (BPs) were made by estimating the instantaneous array-wide firing frequency. The shape of the BPs was found to be stable on a time scale of hours. Spatiotemporal detail is provided by analyzing the instantaneous firing frequency per electrode. The resulting phase profiles (PPs) were estimated by aligning BPs to their peak spiking rate over a period of 15 min. The PPs reveal a stable spatiotemporal pattern of activity during bursts over a period of several hours, making them useful for plasticity and learning studies. We also show that PPs can be used to estimate conditional firing probabilities. Doing so, yields an approach in which network bursting behavior and functional connectivity can be studied.     

Nephrotoxicity of cephaloridine in newborn rabbits: role of the renal anionic transport system

The nephrotoxicity of cephaloridine, cefazolin and mercuric chloride was studied in rabbits of various ages. Cephaloridine produced dose-related elevations in serum urea nitrogen, creatinine and renal tubular necrosis in adult and 30-day-old rabbits, only slight changes at 15 days of age and no effect in 5-day-old rabbits. Cefazolin also produced dose-related nephrotoxicity in adult rabbits but no effect in 15-day-old rabbits. Mercuric chloride administration resulted in similar nephrotoxicity in 5-, 15- and 30-day-old rabbits and adults. The development of susceptibility to cephaloridine nephrotoxicity paralleled the maturation of the renal anionic transport system as determined by the accumulation of p-aminohippurate by renal cortical slices in vitro. Substrate stimulation of the anionic transport system by p-aminohippurate or penicillin increased the nephrotoxicity of cephaloridine in between rabbits. The authors concluded that the lack of cephaloridine nephrotoxicity in newborn rabbits is due to the incomplete development of the renal anionic transport system.     

Locative and Directional Prepositions in Conceptual Spaces: The Role of Polar Convexity

We approach the semantics of prepositions from the perspective of conceptual spaces. Focusing on purely spatial locative and directional prepositions, we analyze both types of prepositions in terms of polar coordinates instead of Cartesian coordinates. This makes it possible to demonstrate that the property of convexity holds quite generally in the domain of prepositions of location and direction, supporting the important role that this property plays in conceptual spaces.     

Psychological constructs in driving automation: a consensus model and critical comment on construct proliferation

As automation in vehicles becomes more prevalent, the call for understanding the behaviour of the driver while driving an automated vehicle becomes more salient. Although a variety of driver behaviour models exist, and various psychological constructs have been said to be influenced by automation, an empirically testable psychological model of automated driving has yet to be developed. Building upon Stanton and Young's model of driving automation, this article presents an updated model of interrelated psychological constructs. The proposed model was created based upon a systematic literature search of driving automation papers and a subsequent quantification of the number of reported links between a selected set of psychological constructs. A secondary aim of this article is to reach consensus in the use of psychological constructs regarding driving automation. Henceforth special attention is paid to resolving the issue of construct proliferation.     

A multi-criteria decision analysis framework for evaluating point-of-use water treatment alternatives

Despite significant progress on meeting global water targets, the lack of access to safe drinking water remains a significant problem in today’s world. Statistics from health agencies indicate that waterborne diseases are among the leading causes of health-related mortalities, particularly in developing nations. This paper examines the performance and applicability of various point-of-use (POU) water treatment alternatives, namely (i) solar disinfection; (ii) boiling of water; (iii) chlorination; (iv) disinfection–flocculation with a natural coagulant (powdered Moringa seeds); (v) filtration with ceramic pots; and (vi) biosand filtration. We evaluated the efficacy of each alternative using a set of criteria based on environmental sustainability, technological performance, financial viability, and social acceptability. We also integrated several multi-criteria decision analysis (MCDA) approaches to determine the most suitable water treatment method for a given community. The analytic hierarchy process (AHP) was implemented to elicit various preference structures and to generate the weights for the criteria. Subsequent ranking of the POU alternatives was then performed using the technique for order preference by similarity to ideal solutions (TOPSIS) method. Sensitivity analysis and visualization charts were developed to evaluate the impact of changes in preference ratings of each alternative with respect to the criteria. A case study was implemented in a rural area in the Philippines to determine the optimal POU alternatives given variations in AHP and TOPSIS input data. The resulting MCDA framework is flexible and can accommodate the inclusion of other alternatives and criteria, and it can also be generalized for other regions and applications.     

High quality TbMnO3 films deposited on YAlO3

High quality thin films of TbMnO₃ were grown by pulsed laser deposition on orthorhombicYAlO₃ (1 0 0). The interface and surface roughness of a 55 nm thick film were probed by X-ray reflectometry and atomic force microscopy, yielding a roughness of 1 nm. X-ray diffraction revealed untwinned films and a small mosaic spread of 0.04° and 0.2° for out-of-plane and in-plane reflections, respectively. This high degree of epitaxy was also confirmed by Rutherford backscattering spectrometry. Using polarized neutron diffraction we could identify a magnetic structure with the propagation vector (0 0.27 0), identical to the bulk magnetic structure of TbMnO₃.