Hybodont sharks of the English Bathonian and Callovian (Middle Jurassic).

Recent bulk sampling and study of museum collections has revealed a high diversity of hybodont sharks from the English Bathonian, with 15 species being recognised. In addition, study of dental and skeletal material from the English Callovian has allowed the diagnosis of a new genus and species, Planohybodus peterboroughensis gen. et sp. nov., allowing the Bathonian species Hybodus grossiconus Agassiz to be referred to Planohybodus. Two additional new genera, Secarodus and Frangerodus, are erected for the Bathonian taxa Hybodus polyprion Agassiz and Strophodus lingualis Woodward, respectively. Egertonodus duffini sp. nov. is described and the diagnosis of Egertonodus based on dental material is discussed. The previously unrecorded Hybodus sp., Parvodus sp., and Lonchidion sp. are recognised but left in open nomenclature. Asteracanthus medius (Owen) is recorded in the British Bathonian for the first time, and the status of Bathonian nominal species of Asteracanthus are assessed. Bathonian hybodonts showed great diversity in trophic ecology and many of the species are specific to particular palaeoenvironments

Use of Dipeptidyl Peptidase-4 Inhibitors and the Reporting of Infections: A Disproportionality Analysis in the World Health Organization VigiBase

OBJECTIVE - Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. They inactivate incretin hormones but also have many other effects throughout the body, among which are effects on the immune system. This might result in an increased infection risk. This study assessed the association between use of DPP-4 inhibitors and the reporting of infections. RESEARCH DESIGN AND METHODS - A nested case-control was conducted using VigiBase, the World Health Organization-Adverse Drug Reactions (WHO-ADR) database. The base cohort consisted of ADRs for antidiabetic drugs (Anatomical Therapeutic Chemical code A10). Cases were defined as ADRs of infection according to the Medical Dictionary for Regulatory Activities (MedDRA) classification system. All other ADRs were considered controls. Reporting odds ratios (RORs) were calculated to estimate the strength of the association between different classes of antidiabetic drugs and the reporting of infections. RESULTS - We identified 305,415 suspected ADRs involving antidiabetic drugs in 106,469 case reports, of which 8,083 involved DPP-4 inhibitors monotherapy. Overall, the reporting of infections was higher for patients using DPP-4 inhibitors compared with users of biguanides (ROR 2.3 [95% CI 1.9-2.7]). Reporting of upper respiratory tract infections (ROR 12.3 [95% CI 8.6-17.5]) was significantly associated with use of DPP-4 inhibitors. CONCLUSIONS - This study indicates an increased reporting of infections, in particular upper respiratory tract infections, for users of DPP-4 inhibitors compared with users of other antidiabetic drugs. However, the limitations of spontaneous reporting systems (e.g., underreporting, the Weber-effect, reporting bias) should be taken into account. Therefore, further research is needed to evaluate this suspicion and the underlying mechanism

Assignment of chromosomal locations for unassigned SNPs/scaffolds based on pair-wise linkage disequilibrium estimates

<p>Abstract</p> <p>Background</p> <p>Recent developments of high-density SNP chips across a number of species require accurate genetic maps. Despite rapid advances in genome sequence assembly and availability of a number of tools for creating genetic maps, the exact genome location for a number of SNPs from these SNP chips still remains unknown. We have developed a locus ordering procedure based on linkage disequilibrium (LODE) which provides estimation of the chromosomal positions of unaligned SNPs and scaffolds. It also provides an alternative means for verification of genetic maps. We exemplified LODE in cattle.</p> <p>Results</p> <p>The utility of the LODE procedure was demonstrated using data from 1,943 bulls genotyped for 73,569 SNPs across three different SNP chips. First, the utility of the procedure was tested by analysing the masked positions of 1,500 randomly-chosen SNPs with known locations (50 from each chromosome), representing three classes of minor allele frequencies (MAF), namely >0.05, 0.01<MAF ≤ 0.05 and 0.001<MAF ≤ 0.01. The efficiency (percentage of masked SNPs that could be assigned a location) was 96.7%, 30.6% and 2.0%; with an accuracy (the percentage of SNPs assigned correctly) of 99.9%, 98.9% and 33.3% in the three classes of MAF, respectively. The average precision for placement of the SNPs was 914, 3,137 and 6,853 kb, respectively. Secondly, 4,688 of 5,314 SNPs unpositioned in the Btau4.0 assembly were positioned using the LODE procedure. Based on these results, the positions of 485 unordered scaffolds were determined. The procedure was also used to validate the genome positions of 53,068 SNPs placed on Btau4.0 bovine assembly, resulting in identification of problem areas in the assembly. Finally, the accuracy of the LODE procedure was independently validated by comparative mapping on the hg18 human assembly.</p> <p>Conclusion</p> <p>The LODE procedure described in this study is an efficient and accurate method for positioning SNPs (MAF>0.05), for validating and checking the quality of a genome assembly, and offers a means for positioning of unordered scaffolds containing SNPs. The LODE procedure will be helpful in refining genome sequence assemblies, especially those being created from next-generation sequencing where high-throughput SNP discovery and genotyping platforms are integrated components of genome analysis.</p

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients

<p>Abstract</p> <p>Background</p> <p>The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.</p> <p>Methods</p> <p>Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test <it>P </it>< 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts.</p> <p>Results</p> <p>Forty-seven markers had positive association values; including one in the <it>SEMA3A </it>promoter region (P = 1.24 × 10^-5). <it>SEMA3A </it>knockdown enhanced radiation resistance.</p> <p>Conclusions</p> <p>This study identified 47 putative radiosensitivity markers, and suggested a role for <it>SEMA3A </it>in radiosensitivity.</p

Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Traffic and Related Self-Driven Many-Particle Systems

Since the subject of traffic dynamics has captured the interest of physicists, many astonishing effects have been revealed and explained. Some of the questions now understood are the following: Why are vehicles sometimes stopped by so-called ``phantom traffic jams'', although they all like to drive fast? What are the mechanisms behind stop-and-go traffic? Why are there several different kinds of congestion, and how are they related? Why do most traffic jams occur considerably before the road capacity is reached? Can a temporary reduction of the traffic volume cause a lasting traffic jam? Under which conditions can speed limits speed up traffic? Why do pedestrians moving in opposite directions normally organize in lanes, while similar systems are ``freezing by heating''? Why do self-organizing systems tend to reach an optimal state? Why do panicking pedestrians produce dangerous deadlocks? All these questions have been answered by applying and extending methods from statistical physics and non-linear dynamics to self-driven many-particle systems. This review article on traffic introduces (i) empirically data, facts, and observations, (ii) the main approaches to pedestrian, highway, and city traffic, (iii) microscopic (particle-based), mesoscopic (gas-kinetic), and macroscopic (fluid-dynamic) models. Attention is also paid to the formulation of a micro-macro link, to aspects of universality, and to other unifying concepts like a general modelling framework for self-driven many-particle systems, including spin systems. Subjects such as the optimization of traffic flows and relations to biological or socio-economic systems such as bacterial colonies, flocks of birds, panics, and stock market dynamics are discussed as well.Comment: A shortened version of this article will appear in Reviews of Modern Physics, an extended one as a book. The 63 figures were omitted because of storage capacity. For related work see http://www.helbing.org

Parameters for the collapse of turbulence in the stratified plane Couette flow

\u3cp\u3eWe perform direct numerical simulation of the Couette flow as a model for the stable boundary layer. The flow evolution is investigated for combinations of the (bulk) Reynolds number and the imposed surface buoyancy flux. First, we establish what the similarities and differences are between applying a fixed buoyancy difference (Dirichlet) and a fixed buoyancy flux (Neumann) as boundary conditions. Moreover, two distinct parameters were recently proposed for the turbulent-to-laminar transition: the Reynolds number based on the Obukhov length and the shear capacity, a velocity-scale ratio based on the buoyancy flux maximum. We study how these parameters relate to each other and to the atmospheric boundary layer. The results show that in a weakly stratified equilibrium state, the flow statistics are virtually the same between the different types of boundary conditions. However, at stronger stratification and, more generally, in nonequilibrium conditions, the flow statistics do depend on the type of boundary condition imposed. In the case of Neumann boundary conditions, a clear sensitivity to the initial stratification strength is observed because of the existence of multiple equilibriums, while for Dirichlet boundary conditions, only one statistically steady turbulent equilibrium exists for a particular set of boundary conditions. As in previous studies, we find that when the imposed surface flux is larger than the maximum buoyancy flux, no turbulent steady state occurs. Analytical investigation and simulation data indicate that this maximum buoyancy flux converges for increasing Reynolds numbers, which suggests a possible extrapolation to the atmospheric case.\u3c/p\u3

Parameters for the collapse of turbulence in the stratified plane Couette flow

We perform direct numerical simulation of the Couette flow as a model for the stable boundary layer. The flow evolution is investigated for combinations of the (bulk) Reynolds number and the imposed surface buoyancy flux. First, we establish what the similarities and differences are between applying a fixed buoyancy difference (Dirichlet) and a fixed buoyancy flux (Neumann) as boundary conditions. Moreover, two distinct parameters were recently proposed for the turbulent-to-laminar transition: the Reynolds number based on the Obukhov length and the "shear capacity," a velocity-scale ratio based on the buoyancy flux maximum. We study how these parameters relate to each other and to the atmospheric boundary layer. The results show that in a weakly stratified equilibrium state, the flow statistics are virtually the same between the different types of boundary conditions. However, at stronger stratification and, more generally, in nonequilibrium conditions, the flow statistics do depend on the type of boundary condition imposed. In the case of Neumann boundary conditions, a clear sensitivity to the initial stratification strength is observed because of the existence of multiple equilibriums, while for Dirichlet boundary conditions, only one statistically steady turbulent equilibrium exists for a particular set of boundary conditions. As in previous studies, we find that when the imposed surface flux is larger than the maximum buoyancy flux, no turbulent steady state occurs. Analytical investigation and simulation data indicate that this maximum buoyancy flux converges for increasing Reynolds numbers, which suggests a possible extrapolation to the atmospheric case.</p

Parameters for the Collapse of Turbulence in the Stratified Plane Couette Flow

We perform direct numerical simulation of the Couette flow as a model for the stable boundary layer. The flow evolution is investigated for combinations of the (bulk) Reynolds number and the imposed surface buoyancy flux. First, we establish what the similarities and differences are between applying a fixed buoyancy difference (Dirichlet) and a fixed buoyancy flux (Neumann) as boundary conditions. Moreover, two distinct parameters were recently proposed for the turbulent-to-laminar transition: the Reynolds number based on the Obukhov length and the shear capacity, a velocity-scale ratio based on the buoyancy flux maximum. We study how these parameters relate to each other and to the atmospheric boundary layer. The results show that in a weakly stratified equilibrium state, the flow statistics are virtually the same between the different types of boundary conditions. However, at stronger stratification and, more generally, in nonequilibrium conditions, the flow statistics do depend on the type of boundary condition imposed. In the case of Neumann boundary conditions, a clear sensitivity to the initial stratification strength is observed because of the existence of multiple equilibriums, while for Dirichlet boundary conditions, only one statistically steady turbulent equilibrium exists for a particular set of boundary conditions. As in previous studies, we find that when the imposed surface flux is larger than the maximum buoyancy flux, no turbulent steady state occurs. Analytical investigation and simulation data indicate that this maximum buoyancy flux converges for increasing Reynolds numbers, which suggests a possible extrapolation to the atmospheric case