Roundabout accident prediction model: random-parameter negative binomial approach

Roundabouts have been used widely on all road classes in the United Kingdom because they are considered safer than other types of intersections in general. The objective of this study was to examine geometric and traffic characteristics and their influences on the number of accidents. Data from each of 70 roundabouts (with 284 approaches) included all recorded vehicle accidents as well as geometric and traffic characteristics for the entire roundabout, within circulatory lanes, and at roundabout approaches. Resulting estimates were compared with those from random-parameter and fixed-parameter negative binomial count data models. The random-parameter results provided better goodness of fit than the fixed-parameter results, and more variables were found to be significant. Significant variables that influenced the number of accidents were total approach traffic, truck percentage, entry width, inscribed circle diameter, number of lanes, and presence of traffic signals

In Utero Diagnosis of Niemann-Pick Type C in the Absence of Family History

Niemann-Pick type C (NPC) disease is a recessive disorder that results in unesterified cholesterol accumulating in the lysosomal and late endosomal system. It is caused by mutations in NPC1 or NPC2 genes and leads to systemic and neurodegenerative symptoms. Few cases of prenatal presentation of NPC have been reported and only two cases in the absence of previous family history, indicating the diagnosis is particularly difficult in such a situation. We report a prenatal diagnosis of NPC in a couple without family history. An ultrasound screening at 22 weeks of gestation (WG) detected fetal ascites and hepatomegaly, which were still present at 25, 27, and 29 WG, and a splenomegaly progressively appeared. No placentomegaly or other signs of hydrops fetalis were observed. The diagnostic of NPC was prenatally confirmed by a filipin test and NPC1 sequencing and multiplex ligation-dependent probe amplification assay which revealed a maternal missense mutation (c.2608T>C; p.Ser870Pro) and a paternal deletion of exons 5 to 25. This additional prenatal case of NPC suggests that even in the absence of family history, fetal ascites associated with splenomegaly but no hydrops should nonetheless arouse suspicion concerning this disease as a possible diagnosis

Biodiversity, Species Protection, and Animal Welfare Under International Law

The chapter explores the influence of the concept of animal welfare on international biodiversity law. A close examination of the recent evolution of this branch of international law shows that animal welfare has an ambivalent place in biodiversity-related agreements. Indeed, while welfare is only a faint consideration in the development of international regimes dealing with biodiversity as a whole, the concept has become an essential element for agreements dealing with the conservation of specific endangered species. Despite its role in these agreements, the place of animal welfare in international biodiversity law highlights that this corpus of rules is currently insufficient to be an effective tool for the protection of wildlife welfare. The last section of this study suggests that the adoption of international rules aiming at ensuring the protection of wild animals’ welfare could serve the double purpose of strengthening the conservation purpose of biodiversity regimes while also filling the welfare gap of international biodiversity law

Overexpression of Partner of Numb Induces Asymmetric Distribution of the PI4P 5-Kinase Skittles in Mitotic Sensory Organ Precursor Cells in Drosophila

Unequal segregation of cell fate determinants at mitosis is a conserved mechanism whereby cell fate diversity can be generated during development. In Drosophila, each sensory organ precursor cell (SOP) divides asymmetrically to produce an anterior pIIb and a posterior pIIa cell. The Par6-aPKC complex localizes at the posterior pole of dividing SOPs and directs the actin-dependent localization of the cell fate determinants Numb, Partner of Numb (Pon) and Neuralized at the opposite pole. The plasma membrane lipid phosphatidylinositol (4,5)-bisphosphate (PIP2) regulates the plasma membrane localization and activity of various proteins, including several actin regulators, thereby modulating actin-based processes. Here, we have examined the distribution of PIP2 and of the PIP2-producing kinase Skittles (Sktl) in mitotic SOPs. Our analysis indicates that both Sktl and PIP2 reporters are uniformly distributed in mitotic SOPs. In the course of this study, we have observed that overexpression of full-length Pon or its localization domain (LD) fused to the Red Fluorescent Protein (RFP::PonLD) results in asymmetric distribution of Sktl and PIP2 reporters in dividing SOPs. Our observation that Pon overexpression alters polar protein distribution is relevant because RFP::PonLD is often used as a polarity marker in dividing progenitors

Identification of a novel Drosophila gene, beltless, using injectable embryonic and adult RNA interference (RNAi)

BACKGROUND: RNA interference (RNAi) is a process triggered by a double-stranded RNA that leads to targeted down-regulation/silencing of gene expression and can be used for functional genomics; i.e. loss-of-function studies. Here we report on the use of RNAi in the identification of a developmentally important novel Drosophila (fruit fly) gene (corresponding to a putative gene CG5652/GM06434), that we named beltless based on an embryonic loss-of-function phenotype. RESULTS: Beltless mRNA is expressed in all developmental stages except in 0–6 h embryos. In situ RT-PCR localized beltless mRNA in the ventral cord and brain of late stage embryos and in the nervous system, ovaries, and the accessory glands of adult flies. RNAi was induced by injection of short (22 bp) beltless double-stranded RNAs into embryos or into adult flies. Embryonic RNAi altered cuticular phenotypes ranging from partially-formed to missing denticle belts (thus beltless) of the abdominal segments A2–A4. Embryonic beltless RNAi was lethal. Adult RNAi resulted in the shrinkage of the ovaries by half and reduced the number of eggs laid. We also examined Df(1)RK4 flies in which deletion removes 16 genes, including beltless. In some embryos, we observed cuticular abnormalities similar to our findings with beltless RNAi. After differentiating Df(1)RK4 embryos into those with visible denticle belts and those missing denticle belts, we assayed the presence of beltless mRNA; no beltless mRNA was detectable in embryos with missing denticle belts. CONCLUSIONS: We have identified a developmentally important novel Drosophila gene, beltless, which has been characterized in loss-of-function studies using RNA interference. The putative beltless protein shares homologies with the C. elegans nose resistant to fluoxetine (NRF) NRF-6 gene, as well as with several uncharacterized C. elegans and Drosophila melanogaster genes, some with prominent acyltransferase domains. Future studies should elucidate the role and mechanism of action of beltless during Drosophila development and in adults, including in the adult nervous system

Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma

Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule-induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs

Enhanced deformation of limestone and sandstone in the presence of high pCO2 fluids

International audienceGeological repositories subject to the injection of large amounts of anthropogenic carbon dioxide will undergo chemical and mechanical instabilities for which there are currently little experimental data. This study reports on experiments where low and high pCO2 (8~MPa) aqueous fluids where injected into natural rock samples. The experiments were performed in flow-through triaxial cells, where the vertical and confining stresses, temperature, and pressure and composition of the fluid were separately controlled and monitored. The axial vertical strains of two limestones and one sandstone were continuously measured during separate experiments for several months, with a strain rate resolution of 10^-11 s-1. Fluids exiting the triaxial cells where continuously collected and their compositions analysed. The high pCO2 fluids induced an increase in strain rates of the limestones by up to a factor of 5, compared to the low pCO2 fluids. Injection of high pCO2 fluids into the sandstone resulted in deformation rates one order of magnitude smaller than the limestones. The creep accelerating effect of high pCO2 fluids with respect to the limestones was mainly due to the acidification of the injected fluids, resulting in a significant increase in solubility and reaction kinetics of calcite. Compared to the limestones, the much weaker response of the sandstone was due to the much lower solubility and reactivity of quartz in high pCO2 fluids. In general, all samples showed a positive correlation between fluid flow rate and strain rate. X-ray tomography results revealed significant increases in porosity at the inlet portion of each core; the porosity increases were dependent on the original lithological structure and composition. The overall deformation of the samples is interpreted in terms of simultaneous dissolution reactions in pore spaces and intergranular pressure solution creep

Nucleoporin98-96 Function Is Required for Transit Amplification Divisions in the Germ Line of Drosophila melanogaster

Production of specialized cells from precursors depends on a tightly regulated sequence of proliferation and differentiation steps. In the gonad of Drosophila melanogaster, the daughters of germ line stem cells (GSC) go through precisely four rounds of transit amplification divisions to produce clusters of 16 interconnected germ line cells before entering a stereotypic differentiation cascade. Here we show that animals harbouring a transposon insertion in the center of the complex nucleoporin98-96 (nup98-96) locus had severe defects in the early steps of this developmental program, ultimately leading to germ cell loss and sterility. A phenotypic analysis indicated that flies carrying the transposon insertion, designated nup98-962288, had dramatically reduced numbers of germ line cells. In contrast to controls, mutant testes contained many solitary germ line cells that had committed to differentiation as well as abnormally small clusters of two, four or eight differentiating germ line cells. This indicates that mutant GSCs rather differentiated than self-renewed, and that these GSCs and their daughters initiated the differentiation cascade after zero, or less than four rounds of amplification divisions. This phenotype remained unaffected by hyper-activation of signalling pathways that normally result in excessive proliferation of GSCs and their daughters. Expression of wildtype nup98-96 specifically in the germ line cells of mutant animals fully restored development of the GSC lineage, demonstrating that the effect of the mutation is cell-autonomous. Nucleoporins are the structural components of the nucleopore and have also been implicated in transcriptional regulation of specific target genes. The nuclear envelopes of germ cells and general nucleocytoplasmic transport in nup98-96 mutant animals appeared normal, leading us to propose that Drosophila nup98-96 mediates the transport or transcription of targets required for the developmental timing between amplification and differentiation