The human papillomavirus type 18 E6 oncoprotein induces Vascular Endothelial Growth Factor 121 (VEGF121) transcription from the promoter through a p53-independent mechanism

Altered angiogenic response is associated with high-grade cervical dysplasia and with invasive squamous carcinoma of the cervix. Vascular Endothelial Growth Factor (VEGF) is one of the most potent inducers of angiogenesis and is up-regulated in carcinoma of the cervix. Infection by high-risk human papillomavirus and persistent expression of viral oncogene E6 are etiologically linked to the development of cervical cancer. E6 is able to immortalize cells and induce malignant transformation by inactivating p53. In cervical cancer, regulation of VEGF expression is poorly described. Thus, we investigated whether E6 oncoprotein could regulate VEGF expression in HPV18-positive cervical cancer-derived HeLa cells harboring a wild-type p53. The alternative splicing of vegf mRNA renders three major isoforms of 121, 165 and 189 amino-acids in humans. We have designed isoform specific real time QRT-PCR assays to quantitate vegf transcripts and VEGF121 was the predominant isoform. Silencing HPV18 E6 mRNA with specific siRNA reduced VEGF121 expression by at least 50% whereas silencing of p53 did not alter its expression. Treatment with cycloheximide did not inhibit E6-induced VEGF121 expression. Collectively, these results suggest that HPV18 E6 oncoprotein contributes to tumor angiogenesis by inducing VEGF transcription from the promoter in a p53-independent manner

Large-scale automated analysis of vehicle interactions and collisions

Road collisions are a worldwide pandemic that can be addressed through the improvement of existing tools for safety analysis. A refined probabilistic framework is presented for the analysis of road-user interactions. In particular, the identification of potential collision points is used to estimate collision probabilities, and their spatial distribution can be visualized. A probabilistic time to collision is introduced, and interactions are grouped into four categories: head-on, rear-end, side, and parallel. The framework is applied to a large data set of video recordings collected in Kentucky that contains more than 300 severe interactions and collisions. The results demonstrate the usefulness of the approach for studying road-user behavior and mechanisms that may lead to collisions

Effect of several saponin containing plant extracts on rumen fermentation in vitro, Tetrahymena pyriformis and sheep erythrocytes

Among the nutritional solutions developed since in-feed antibiotics were banned by the European Union in 2006, extracts from plants with high saponin content have shown the capacity to modulate rumen fermentation. Most previous studies have focused on the effects of Yucca schidigera and Quillaja saponaria. This study was designed to evaluate i) the effects of extracts obtained from 11 saponin-containing plants and monensin on rumen fermentation patterns in vitro at 417 and 2.0 mg/L, respectively, and ii) the capacity of hemolytic test and inhibition of Tetrahymena pyriformis to model the effect of saponin-containing plant extracts on rumen protozoa. Plants belonging to 8 different families were investigated to evaluate a high diversity of saponin compounds. Total gas and methane productions were numerically lower with extract of Saponaria officinalis compared to control (-3.0 and -9.0%, respectively). The effect was more pronounced with monensin (-25.5 and -31.7%, p<0.05, respectively). Ammonia (NH3) and protozoa patterns varied among the extracts during in vitro incubations, e.g. from -22.6% (p<0.05) for Y. schidigera extract to -50.7% (p<0.05) for Primula veris extract, with respect to the protozoa number. Extracts from Primula veris, Chenopodium quinoa and Gypsophila paniculata mitigated significantly NH3 production by more than 26% (p<0.05) which, in our experimental conditions, was better than the results obtained with monensin and extracts from Y. schidigera and Q. saponaria. Statistically significant positive correlations were found between hemolytic capacity and inhibition of T. pyriformis (Pearson coefficient = 0.55, p<0.05) and between protozoa number and NH3 concentration during in vitro rumen incubation (Pearson coefficient = 0.56, p<0.05). Neither hemolytic capacity, nor inhibition of T. pyriformis, nor the content in total saponins estimated by gravimetric method was correlated to the inhibition of rumen protozoa. These parameters did not model the effect of extracts from different saponin containing plants on rumen protozoa number. However, the results suggest that by-products containing saponins from food (C. quinoa) and horticultural (G. paniculata) industries could be investigated as feed additives to improve nitrogen utilization by ruminants

The opposite of Dante's hell? The transfer of ideas for social housing at international congresses in the 1850s–1860s

With the advent of industrialization, the question of developing adequate housing for the emergent working classes became more pressing than before. Moreover, the problem of unhygienic houses in industrial cities did not stop at the borders of a particular nation-state; sometimes literally as pandemic diseases spread out 'transnationally'. It is not a coincidence that in the nineteenth century the number of international congresses on hygiene and social topics expanded substantially. However, the historiography about social policy in general and social housing in particular, has often focused on individual cases because of the different pace of industrial and urban development and is thus dominated by national perspectives. In this paper, I elaborate on transnational exchange processes and local adaptations and transformations. I focus on the transfer of the housing model of SOMCO in Mulhouse, (a French house building association) during social international congresses. I examine whether cross-national networking enabled and facilitated the implementation of ideas on the local scale. I will elaborate on the transmission and the local adaptation of the Mulhouse-model in Belgium. Convergences, divergences, and different factors that influenced the local transformations (personal choice, political situation, socioeconomic circumstances) will be taken into accoun

From Physical to Virtual: Widening the Perspective on Multi-Agent Environments

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-23850-0_9Since more than a decade, the environment is seen as a key element when analyzing, developing or deploying Multi-Agent Systems (MAS) applications. Especially, for the development of multi-agent platforms it has become a key concept, similarly to many application in the area of location-based, distributed systems. An emerging, prominent application area for MAS is related to Virtual Environments. The underlying technology has evolved in a way, that these applications have grown out of science fiction novels till research papers and even real applications. Even more, current technologies enable MAS to be key components of such virtual environments. In this paper, we widen the concept of the environment of a MAS to encompass new and mixed physical, virtual, simulated, etc. forms of environments. We analyze currently most interesting application domains based on three dimensions: the way different "realities" are mixed via the environment, the underlying natures of agents, the possible forms and sophistication of interactions. In addition to this characterization, we discuss how this widened concept of possible environments influences the support it can give for developing applications in the respective domains.Carrascosa Casamayor, C.; Klugl, F.; Ricci, A.; Boissier, O. (2015). From Physical to Virtual: Widening the Perspective on Multi-Agent Environments. En Agent Environments for Multi-Agent Systems IV. 4th International Workshop, E4MAS 2014 - 10 Years Later, Paris, France, May 6, 2014. 133-146. https://doi.org/10.1007/978-3-319-23850-0_9S133146Aggarwal, J.K., Ryoo, M.S.: Human activity analysis: a review. ACM Comput. Surv. 43(3), 16:1–16:43 (2011)Argente, E., Boissier, O., Carrascosa, C., Fornara, N., McBurney, P., Noriega, P., Ricci, A., Sabater-Mir, J., et al.: The role of the environment in agreement technologies. AI Rev. 39(1), 21–38 (2013)Barreteau, O., et al.: Our companion modelling approach. J. Artif. Soc. Soc. Simul. 6(1), 1–6 (2003)Boissier, O., Bordini, R.H., Hübner, J.F., Ricci, A., Santi, A.: Multi-agent oriented programming with jacamo. Sci. Comput. Program. 78(6), 747–761 (2013)Burdea, G., Coiffet, P.: Virtual Reality Technology. Wiley, New York (2003)Castelfranchi, C., Pezzullo, G., Tummolini, L.: Behavioral implicit communication (BIC): communicating with smart environments via our practical behavior and its traces. Int. J. Ambient Comput. Intell. 2(1), 1–12 (2010)Castelfranchi, C., Piunti, M., Ricci, A., Tummolini, L.: AMI systems as agent-based mirror worlds: bridging humans and agents through stigmergy. In: Bosse, T. (ed.) Agents and Ambient Intelligence, Ambient Intelligence and Smart Environments, pp. 17–31. IOS Press, Amsterdam (2012)Ferber, J.: Multi-Agent Systems: An Introduction to Distributed Artificial Intelligence. Addison Wesley Longman, Harlow (1999)Gelernter, D.: Mirror Worlds - or the Day Software Puts the Universe in a Shoebox: How it Will Happen and What it Will Mean. Oxford University Press, New York (1992)Gibson, W.: Neuromancer. Ace, New York (1984)Klügl, F., Fehler, M., Herrler, R.: About the role of the environment in multi-agent simulations. In: Weyns, D., Van Parunak, H.D., Michel, F. (eds.) E4MAS 2004. LNCS (LNAI), vol. 3374, pp. 127–149. Springer, Heidelberg (2005)Krueger, M.: Artificial Reality II. Addison-Wesley, New York (1991)Luck, M., Aylett, R.: Applying artificial intelligence to virtual reality: intelligent virtual environments. Appl. Artif. Intell. 14(1), 3–32 (2000)Dorigo, M., Floreano, D., Gambardella, L.M., et al.: Swarmanoid: a novel concept for the study of heterogeneous robotic swarms. IEEE Robot. Autom. Mag. 20(4), 60–71 (2013)Milgram, P., Kishino, A.F.: Taxonomy of mixed reality visual displays. IEICE Trans. Inf. Syst. E77–D(12), 1321–1329 (1994)Olsson, T., Salo, M.: Online user survey on current mobile augmented reality applications. In: Proceedings of the 2011 10th IEEE International Symposium on Mixed and Augmented Reality, ISMAR 2011, pp. 75–84. IEEE Computer Society, Washington, DC, USA (2011)Saunier, J., Balbo, F., Pinson, S.: A formal model of communication and context awareness in multiagent systems. J. Logic Lang. Inform. 23(2), 219–247 (2014)Stephenson, N.: Snow Crash. Bantam Books, New York (1992)Tummolini, L., Castelfranchi, C.: Trace signals: the meanings of stigmergy. In: Weyns, D., Van Parunak, H.D., Michel, F. (eds.) E4MAS 2006. LNCS (LNAI), vol. 4389, pp. 141–156. 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Analysis of pedestrian-vehicle traffic conflicts in street designs with elements of shared space

This paper investigates changes in pedestrian-vehicle traffic conflicts in urban streets redesigned according to the principles of shared space, using a recently developed Pedestrian-Vehicle Conflicts Analysis (PVCA) method. In a first step, the PVCA method is revised to more accurately reflect the features of shared space: this includes the definition of a systematic process for identifying conflict occurrences on one hand, and the full quantification of the conflict severity grading process on the other. Then, the refined PVCA method is applied to a case study in London, using video data from periods before and after the redevelopment of the Exhibition Road site from a conventional dual carriageway to a modern design with some elements of shared space. The results of the comparative analysis carried out indicate a general decrease in traffic conflict rates as a result of the redesign, but also highlight specific issues that may require additional analysis

Event-related alpha suppression in response to facial motion

This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al

Apoptotic HPV Positive Cancer Cells Exhibit Transforming Properties

Previous studies have shown that DNA can be transferred from dying engineered cells to neighboring cells through the phagocytosis of apoptotic bodies, which leads to cellular transformation. Here, we provide evidence of an uptake of apoptotic-derived cervical cancer cells by human mesenchymal cells. Interestingly, HeLa (HPV 18+) or Ca Ski (HPV16+) cells, harboring integrated high-risk HPV DNA but not C-33 A cells (HPV-), were able to transform the recipient cells. Human primary fibroblasts engulfed the apoptotic bodies effectively within 30 minutes after co-cultivation. This mechanism is active and involves the actin cytoskeleton. In situ hybridization of transformed fibroblasts revealed the presence of HPV DNA in the nucleus of a subset of phagocytosing cells. These cells expressed the HPV16/18 E6 gene, which contributes to the disruption of the p53/p21 pathway, and the cells exhibited a tumorigenic phenotype, including an increased proliferation rate, polyploidy and anchorage independence growth. Such horizontal transfer of viral oncogenes to surrounding cells that lack receptors for HPV could facilitate the persistence of the virus, the main risk factor for cervical cancer development. This process might contribute to HPV-associated disease progression in vivo

Estrogenic Plant Extracts Reverse Weight Gain and Fat Accumulation without Causing Mammary Gland or Uterine Proliferation

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women

Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization

Ciliopathies are a large group of clinically and genetically heterogeneous disorders caused by defects in primary cilia. Here we identified mutations in TRAF3IP1 (TNF Receptor-Associated Factor Interacting Protein 1) in eight patients from five families with nephronophthisis (NPH) and retinal degeneration, two of the most common manifestations of ciliopathies. TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis. The identified mutations result in mild ciliary defects in patients but also reveal an unexpected role of IFT54 as a negative regulator of microtubule stability via MAP4 (microtubule-associated protein 4). Microtubule defects are associated with altered epithelialization/polarity in renal cells and with pronephric cysts and microphthalmia in zebrafish embryos. Our findings highlight the regulation of cytoplasmic microtubule dynamics as a role of the IFT54 protein beyond the cilium, contributing to the development of NPH-related ciliopathies