Univariate and bivariate truncated von Mises distributions

In this article we study the univariate and bivariate truncated von Mises distribution, as a generalization of the von Mises distribution (\cite{jupp1989}), (\cite{mardia2000directional}). This implies the addition of two or four new truncation parameters in the univariate and, bivariate cases, respectively. The results include the definition, properties of the distribution and maximum likelihood estimators for the univariate and bivariate cases. Additionally, the analysis of the bivariate case shows how the conditional distribution is a truncated von Mises distribution, whereas the marginal distribution that generalizes the distribution introduced in \cite{repe}. From the viewpoint of applications, we test the distribution with simulated data, as well as with data regarding leaf inclination angles (\cite{safari}) and dihedral angles in protein chains (\cite{prote}). This research aims to assert this probability distribution as a potential option for modelling or simulating any kind of phenomena where circular distributions are applicable.\par

Incremental lines of von Ebner in dinosaurs and the assessment of tooth replacement rates using growth line counts

Dinosaur dentine exhibits growth lines that are tens of micrometers in width. These laminations are homologous to incremental lines of von Ebner found in extant mammal and crocodilian teeth (i.e., those of amniotes). The lines likely reflect daily dentine formation, and they were used to infer tooth development and replacement rates. In general, dinosaur tooth formation rates negatively correlated with tooth size. Theropod tooth replacement rates negatively correlated with tooth size, which was due to limitations in the dentine formation rates of their odontoblasts. Derived ceratopsian and hadrosaurian dinosaurs retained relatively rapid tooth replacement rates through ontogeny. The evolution of dental batteries in hadrosaurs and ceratopsians can be explained by dentine formation constraints and rapid tooth wear. In combination with counts of shed dinosaur teeth, tooth replacement rate data can be used to assess population demographics of Mesozoic ecosystems. Finally, it is of historic importance to note that Richard Owen appears to have been the first to observe incremental lines of von Ebner in dinosaurs more than 150 years ago.

Role of transforming growth factor-α in von Hippel– Lindau (VHL)−/− clear cell renal carcinoma cell proliferation: A possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis

Mutations of the VHL tumor suppressor gene occur in patients with VHL disease and in the majority of sporadic clear cell renal carcinomas (VHL−/− RCC). Loss of VHL protein function is associated with constitutive expression of mRNAs encoding hypoxia-inducible proteins, such as vascular endothelial growth factor. Overproduction of angiogenic factors might explain why VHL−/− RCC tumors are so highly vascularized, but whether this overproduction is sufficient for oncogenesis still remains unknown. In this report, we examined the activity of transforming growth factor-α (TGF-α), another VHL-regulated growth factor. We show that TGF-α mRNA and protein are hypoxia-inducible in VHL−/− RCC cells expressing reintroduced VHL. In addition to its overexpression by VHL−/− RCC cells, TGF-α can also act as a specific growth-stimulatory factor for VHL−/− RCC cells expressing reintroduced wild-type VHL, as well as primary renal proximal tubule epithelial cells, the likely site of origin of RCC. This role is in contrast to those of other growth factors overexpressed by VHL−/− RCC cells, such as vascular endothelial growth factor and TGF-β1, which do not stimulate RCC cell proliferation. A TGF-α-specific antisense oligodeoxynucleotide blocked TGF-α production in VHL−/− RCC cells, which led to the dependence of those cells on exogenous growth factors to sustain growth in culture. Growth of VHL−/− RCC cells was also significantly reduced by a drug that specifically inhibits the epidermal growth factor receptor, the receptor through which TGF-α stimulates proliferation. These results suggest that the generation of a TGF-α autocrine loop as a consequence of VHL inactivation in renal proximal tubule epithelial cells may provide the uncontrolled growth stimulus necessary for the initiation of tumorigenesis.