1,720,962 research outputs found
Vps28 is involved in the intracellular trafficking of AWD, the Drosophila homolog of NMe1/2
Full text linkThe Awd (abnormal wing discs) gene is the Drosophila homolog of human NME1 and NME2 metastasis suppressor genes. These genes play a key role in tumor progression. Extensive studies revealed that intracellular NME1/2 protein levels could be related to either favorable or poor prognosis depending on tissue context. More recently, extracellular activities of NME1/2 proteins have also been reported, including a tumor- promoting function. We used Drosophila as a genetic model to investigate the mechanism controlling intra- and extracellular levels of NME1/2. We examined the role of several components of the ESCRT (endosomal sorting complex required for transport) complex in controlling Awd trafficking. We show that the Vps28 component of the ESCRT−I complex is required for maintenance of normal intracellular level of Awd in larval adipocytes. We already showed that blocking of Shibire (Shi)/Dynamin function strongly- lowers Awd intracellular level. To further investigate this down regulative effect, we analyzed the distribution of endosomal markers in wild type and Shi-defective adipocytes. Our results suggest that Awd does not enter CD63-positive endosomes. Interestingly, we found that in fat body cells, Awd partly- colocalizes with the ESCRT accessory component ALiX, the ALG-2 (apoptosis-linked gene 2)-interacting protein X. Moreover, we show that the intracellular levels of both proteins are downregulated by blocking the function of the Dynamin encoded by the shibire gene
Development of a wear model for the prediction of wheel and rail profile evolution in railway systems
No full textThe prediction of the wear at the wheel–rail interface is a fundamental problem in the railway field, mainly correlated to the planning of maintenance interventions, vehicle stability and the possibility of researching specific strategies for the wheel and rail profile optimization. In this work the Authors present a model specifically developed for the evaluation of the wheel and rail profile evolution due to wear, whose layout is made up of two mutually interactive but separate units: a vehicle model for the dynamic analysis and a model for the wear estimation. The first one is made up of two parts that interact online during the dynamic simulations: a 3D multibody model of the railway vehicle implemented in Simpack Rail (a commercial software for the analysis of multibody systems) and an innovative 3D global contact model (developed by the Authors in previous works) for the detection of the contact points between wheel and rail and for the calculation of the forces in the contact patches (implemented in C/C++ environment). The wear model, implemented in the Matlab environment, is mainly based on experimental relationships found in literature between the removed material and the energy dissipated by friction at the contact. It starts from the outputs of the dynamic simulations (position of contact points, contact forces and global creepages) and calculates the pressures inside the contact patches through a local contact model (FASTSIM algorithm); then the material removed due to wear is evaluated and the worn profiles of wheel and rail are obtained. This approach allows the evaluation of both the quantity of removed material and its distribution along the wheel and rail profiles in order to analyze the development of the profiles shape during their lifetime.
The whole model is based on a discrete process: each discrete step consists in one dynamic simulation and one profile update by means of the wear model while, within the discrete step, the profiles are supposed to be constant. The choice of an appropriate step is fundamental in terms of precision and computational load. Moreover the different time scales characterizing the wheel and rail wear evolution require the development of a suitable strategy for the profile update: the strategy proposed by the Authors is based both on the total distance traveled by the considered vehicle and on the total tonnage burden on the track. The entire model has been developed and validated in collaboration with Trenitalia S.p.A. and Rete Ferroviaria Italiana (RFI), which have provided the technical documentation and the experimental results relating to some tests performed with the vehicle DMU Aln 501 Minuetto on the Aosta-Pre Saint Didier line
Development and validation of a wear model for the analysis of the wheel profile evolution in railway vehicles
No full textThe numerical wheel wear prediction in railway applications is of great importance for different aspects, such as the safety against vehicle instability and derailment, the planning of wheelset maintenance interventions and the design of an optimal wheel profile from the wear point of view. For these reasons, this paper presents a complete model aimed at the evaluation of the wheel wear and the wheel profile evolution by means of dynamic simulations, organised in two parts which interact with each other mutually: a vehicle's dynamic model and a model for the wear estimation. The first is a 3D multibody model of a railway vehicle implemented in SIMPACKTM, a commercial software for the analysis of mechanical systems, where the wheel–rail interaction is entrusted to a C/C++user routine external to SIMPACK, in which the global contact model is implemented. In this regard, the research on the contact points between the wheel and the rail is based on an innovative algorithm developed by the authors in previous works, while normal and tangential forces in the contact patches are calculated according to Hertz's theory and Kalker's global theory, respectively. Due to the numerical efficiency of the global contact model, the multibody vehicle and the contact model interact directly online during the dynamic simulations.
The second is the wear model, written in the MATLAB® environment, mainly based on an experimental relationship between the frictional power developed at the wheel–rail interface and the amount of material removed by wear. Starting from a few outputs of the multibody simulations (position of contact points, contact forces and rigid creepages), it evaluates the local variables, such as the contact pressures and local creepages, using a local contact model (Kalker's FASTSIM algorithm). These data are then passed to another subsystem which evaluates, by means of the considered experimental relationship, both the material to be removed and its distribution along the wheel profile, obtaining the correspondent worn wheel geometry.
The wheel wear evolution is reproduced by dividing the overall chosen mileage to be simulated in discrete spatial steps: at each step, the dynamic simulations are performed by means of the 3D multibody model keeping the wheel profile constant, while the wheel geometry is updated through the wear model only at the end of the discrete step. Thus, the two parts of the whole model work alternately until the completion of the whole established mileage. Clearly, the choice of an appropriate step length is one of the most important aspects of the procedure and it directly affects the result accuracy and the required computational time to complete the analysis.
The whole model has been validated using experimental data relative to tests performed with the ALn 501 ‘Minuetto’ vehicle in service on the Aosta–Pre Saint Didier track; this work has been carried out thanks to a collaboration with Trenitalia S.p.A and Rete Ferroviaria Italiana, which have provided the necessary technical data and experimental results
Comparative expression profiling of wild type Drosophila Malpighian tubules and von Hippel-Lindau haploinsufficient mutant
Full text linkThe von-Hippel Lindau (VHL) disease is a hereditary genetic disorder that predisposes to the onset of several highly vascularized benign and malignant tumors, developing with elevate frequency in the central nervous system and kidneys. The most-aggressive VHL tumor is ccRCC, the clear-cell renal cell carcinoma, affecting the kidney. VHL disease etiology can be attributed to the inheritance of a VHL loss-of-function allele, typically a deletion (Gnarra et al., 1994; Herman et al., 1994); this facilitates the somatic inactivation of the other allele (through amorphic mutations or gene silencing through promoter methylation), leading to the onset of the tumorous phenotype (Latif et al., 1993). This reveals the haploinsufficient behavior of the VHL gene.
The high vascularization of VHL tumors can be explained considering that human VHL protein is the substrate-binding subunit of an E3 ubiquitin ligase (Lonergan et al., 1998; Iwai et al., 1999; Kamura et al., 1999) involved in the poly-ubiquitination of HIF-1α transcription factor. This post-translational modification leads HIF-1α to proteosomal degradation (Maxwell et al., 1999). Loss of VHL function causes the stabilization of HIF-1α, triggering cellular response and adaptation to hypoxic conditions (expression of genes involved in glycolysis, angiogenesis and erythropoiesis) (Bader and Hsu, 2012). While this represents the canonical function of VHL, other HIF-1α-independent function of VHL have been identified, thanks to the contribution of model organisms (Hsu, 2012). Indeed, VHL gene function is conserved and also Drosophila has a VHL homolog, the dVHL gene (Adryan et al., 2000; Aso et al., 2000). dVHL is involved in the development of Drosophila vascular system (Adryan et al., 2000; Hsouna et al., 2010) and in morphogenesis of follicular epithelium of the egg chamber (Duchi et al., 2010). Interestingly, some VHL functions are mediated by Awd, an endocytic mediator whose human orthologs are NME1/2 metastasis suppressors (Rosengard et al., 1989). Awd is broadly required during Drosophila development since it is involved in epithelial morphogenesis (Nallamothu et al., 2008; Woolworth et al., 2009; Ignesti et al., 2014) and required for maintaining genomic stability (Romani et al., 2017). Moreover, Awd is also present into the extracellular fluids of Drosophila larvae (Romani et al., 2016, 2018).
In Drosophila, two pairs of monolayered epithelial Malpighian tubules, each composed of 100-150 cells, absolve to osmoregulation and excretion functions (Denholm and Skaer, 2009). Transcriptomic analysis of Malpighian tubules revealed that among genes that are here enriched there are homologs of human genes implicated into renal pathologies (Wang et al., 2004). This justifies the use of Drosophila Malpighian tubules as model system to gain insights into pathophysiology of human kidneys (Dow and Romero, 2010; Miller et al., 2013).
The dVHL1.1 allele is a loss of function mutation of the dVHL locus (Duchi et al., 2010; Hsouna et al., 2010). dVHL1.1/+ flies mimic the genetic condition of VHL patients. We carried out a genome-wide gene expression profiling of whole Malpighian tubules dissected from Drosophila females both heterozygous for the dVHL1.1 mutation and with two wild type copies of the dVHL gene. The comparison of differentially expressed genes in the two genetic backgrounds potentially allows to identify genes that are sensible to dVHL functional copy number. Quality control assessments of the data were performed and results obtained from the differential expression analysis were confirmed by qRT-PCR. With this approach we aimed to provide a well-controlled dataset for a better understanding of the VHL disease. Indeed, even if further molecular and functional characterization are needed, human homologs of the differentially expressed genes, if existing, could have a role in the somatic inactivation of the wild type copy of VHL and/or into the very first phase of cancer onset
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
