K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder

The human fibroblast growth factor receptor 3 (FGFR3) gene is frequently mutated in superficial urothelial cell carcinoma (UCC). To test the functional significance of FGFR3 activating mutations as a ‘driver’ of UCC, we targeted the expression of mutated Fgfr3 to the murine urothelium using Cre-loxP recombination driven by the uroplakin II promoter. The introduction of the Fgfr3 mutations resulted in no obvious effect on tumorigenesis up to 18 months of age. Furthermore, even when the Fgfr3 mutations were introduced together with K-Ras or β-catenin (Ctnnb1) activating mutations, no urothelial dysplasia or UCC was observed. Interestingly, however, owing to a sporadic ectopic Cre recombinase expression in the skin and lung of these mice, Fgfr3 mutation caused papilloma and promoted lung tumorigenesis in cooperation with K-Ras and β-catenin activation, respectively. These results indicate that activation of FGFR3 can cooperate with other mutations to drive tumorigenesis in a context-dependent manner, and support the hypothesis that activation of FGFR3 signaling contributes to human cancer

More-than-human participation: Design for sustainable smart city futures

In this forum we highlight innovative thought, design, and research in the area of interaction design and sustainability, illustrating the diversity of approaches across HCI communities. — Roy Bendor, Edito

Remarks on the naturality of quantization

Hamiltonian quantization of an integral compact symplectic manifold M depends on a choice of compatible almost complex structure J. For open sets U in the set of compatible almost complex structures and small enough values of Planck's constant, the Hilbert spaces of the quantization form a bundle over U with a natural connection. In this paper we examine the dependence of the Hilbert spaces on the choice of J, by computing the semi-classical limit of the curvature of this connection. We also show that parallel transport provides a link between the action of the group Symp(M) of symplectomorphisms of M and the Schrodinger equation.Comment: 20 page

Utilizing Multimedia Case Studies to Teach the Professional Side of Project Management

This research was conducted to evaluate the effectiveness of using a LITEE multimedia case study to teaching concepts in engineering courses. The LITEE Superstar case study was implemented in an engineering Project Management course. Numerous surveys regarding student expectations, outcomes, and attitudes were collected and results are presented herein. Overall, the study provided evidence that the students felt that the LITEE case study added value to the course via the different methods of teaching material, aided in the understanding of the project selection process, and ultimately helped them be successful in their course project which was conducted for a real rural Missouri city. The data was unable to be tracked on a per student basis; this yields areas for future research to track individual student improvement and attitudes. This research provides evidence that using multimedia case studies, such as the case studies published by LITEE, are effective and well received by engineering students in their coursework

How technology can impact customer-facing train crew experiences?

Customer-facing train crew have to follow strict procedures to guarantee that trains are safe and run on time. They are also responsible for revenue protection and customer care. Human factors and ergonomics research are instrumental to understand the safety-critical aspects and improve work. We bring user experience research and personas to describe how train crew perceive their routines and how new technology may impact them. We conducted seven hours of interviews and 30 hours of shadowing observations with train crew (n = 22) to provide an understanding of who are they and to define their experiences. We present crew’s current routines and created two personas to represent them. One is slightly reluctant to adopt the proposed technology, whereas the other is more accepting. Results indicate how such technology may affect crew work ergonomics and experiences, and suggest which valuable aspects should be maintained, for example the positive interactions with passengers

Surface matters: Limitations of CALIPSO V3 aerosol typing in coastal regions

In the CALIPSO data analysis, surface type (land/ocean) is used to augment the aerosol characterization. However, this surface-dependent aerosol typing prohibits a correct classification of marine aerosol over land that is advected from ocean to land. This might result in a systematic overestimation of the particle extinction coefficient and of the aerosol optical thickness (AOT) of up to a factor of 3.5 over land in coastal areas. We present a long-term comparison of CALIPSO and ground-based lidar observations of the aerosol conditions in the coastal environment of southern South America (Punta Arenas, Chile, 53° S), performed in December 2009–April 2010. Punta Arenas is almost entirely influenced by marine particles throughout the year, indicated by a rather low AOT of 0.02–0.04. However, we found an unexpectedly high fraction of continental aerosol in the aerosol types inferred by means of CALIOP observations and, correspondingly, too high values of particle extinction. Similar features of the CALIOP data analysis are presented for four other coastal areas around the world. Since CALIOP data serve as important input for global climate models, the influence of this systematic error was estimated by means of simplified radiative-transfer calculations

Do cladistic and morphometric data capture common patterns of morphological disparity?

The distinctly non-random diversity of organismal form manifests itself in discrete clusters of taxa that share a common body plan. As a result, analyses of disparity require a scalable comparative framework. The difficulties of applying geometric morphometrics to disparity analyses of groups with vastly divergent body plans are overcome partly by the use of cladistic characters. Character-based disparity analyses have become increasingly popular, but it is not clear how they are affected by character coding strategies or revisions of primary homology statements. Indeed, whether cladistic and morphometric data capture similar patterns of morphological variation remains a moot point. To address this issue, we employ both cladistic and geometric morphometric data in an exploratory study of disparity focussing on caecilian amphibians. Our results show no impact on relative intertaxon distances when different coding strategies for cladistic characters were used or when revised concepts of homology were considered. In all instances, we found no statistically significant difference between pairwise Euclidean and Procrustes distances, although the strength of the correlation among distance matrices varied. This suggests that cladistic and geometric morphometric data appear to summarize morphological variation in comparable ways. Our results support the use of cladistic data for characterizing organismal disparity

Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

The skull evolution of oviraptorosaurian dinosaurs: the role of niche-partitioning in diversification

Oviraptorosaurs are bird-like theropod dinosaurs that thrived in the final pre-extinction ecosystems during the latest Cretaceous, and the beaked, toothless skulls of derived species are regarded as some of the most peculiar among dinosaurs. Their aberrant morphologies are hypothesized to have been caused by rapid evolution triggered by an ecological/biological driver, but little is known about how their skull shapes and functional abilities diversified. Here, we use quantitative techniques to study oviraptorosaur skull form and mandibular function. We demonstrate that the snout is particularly variable, that mandibular and upper/lower beak form are significantly correlated with phylogeny, and that there is a strong and significant correlation between mandibular function and mandible/lower beak shape, suggesting a form-function association. The form-function relationship and phylogenetic signals, along with a moderate allometric signal in lower beak form, indicate that similar mechanisms governed beak shape in oviraptorosaurs and extant birds. The two derived oviraptorosaur clades, oviraptorids and caenagnathids, are significantly separated in morphospace and functional space, indicating that they partitioned niches. Oviraptorids coexisting in the same ecosystem are also widely spread in morphological and functional space, suggesting that they finely partitioned feeding niches, whereas caenagnathids exhibit extreme disparity in beak size. The diversity of skull form and function was likely key to the diversification and evolutionary success of oviraptorosaurs in the latest Cretaceous. [Abstract copyright: © 2019 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2019 European Society For Evolutionary Biology.

The function of the alula in avian flight

The alula is a small structure located at the joint between the hand-wing and arm-wing of birds and is known to be used in slow flight with high angles of attack such as landing. It is assumed to function similarly to a leading-edge slat that increases lift and delays stall. However, in spite of its universal presence in flying birds and the wide acceptance of stall delay as its main function, how the alula delays the stall and aids the flight of birds remains unclear. Here, we investigated the function of alula on the aerodynamic performance of avian wings based on data from flight tasks and wind-tunnel experiments. With the alula, the birds performed steeper descending flights with greater changes in body orientation. Force measurements revealed that the alula increases the lift and often delays the stall. Digital particle image velocimetry showed that these effects are caused by the streamwise vortex, formed at the tip of the alula, that induces strong downwash and suppresses the flow separation over the wing surface. This is the first experimental evidence that the alula functions as a vortex generator that increases the lift force and enhances manoeuvrability in flights at high angles of attack.open1