Mutations of spliceosome components are common in myeloid neoplasms. One of the affected genes, PRPF8, encodes the most evolutionarily conserved spliceosomal protein. We identified either recurrent somatic PRPF8 mutations or hemizygous deletions in 15/447 and 24/450 cases, respectively. Fifty percent of PRPF8 mutant and del(17p) cases were found in AML and conveyed poor prognosis. PRPF8 defects correlated with increased myeloblasts and ring sideroblasts in cases without SF3B1 mutations. Knockdown of PRPF8 in K562 and CD34+ primary bone marrow cells increased proliferative capacity. Whole-RNA deep sequencing of primary cells from patients with PRPF8 abnormalities demonstrated consistent missplicing defects. In yeast models, homologous mutations introduced into Prp8 abrogated a block experimentally produced in the second step of the RNA splicing process, suggesting that the mutants have defects in proof-reading functions. In sum, the exploration of clinical and functional consequences suggests that PRPF8 is a novel leukemogenic gene in myeloid neoplasms with a distinct phenotype likely manifested through aberrant splicing.

We investigate the local stability and the global asymptotic stability of the difference equation , with nonnegative parameters and initial conditions such that , for all . We obtain the local stability of the equilibrium for all values of parameters and give some global asymptotic stability results for some values of the parameters. We also obtain global dynamics in the special case, where , in which case we show that such equation exhibits a global period doubling bifurcation.

Free flow speed is used as a parameter in transportation planning and capacity analysis models, as well as speed-flow diagrams. Many of these models suggest estimating free flow speed according to measurements from similar highways, which is not a practical method for use in B&H. This paper first discusses problems with using these methodologies in conditions prevailing in B&H and then presents a free flow speed evaluation model developed from a comprehensive field survey conducted on nine homogeneous sections of state and regional roads.

In recent years, HCI researchers have increased their focus on studying the power relationships between researchers and users, and developing methodologies for eliciting design ideas that are sensitive to existing epistemic hierarchies in technology design. The differential value given to expert versus lay knowledge is a central factor in these debates. We apply Artifact Analysis, developed to help designers handle the complexity of digital artifacts, as a method to explore how experts and non-experts understand and frame robots, a technology characterized by significant complexity. Our results show that both non-expert users and expert researchers have knowledge that is significant to future robot development, but they focus on different aspects of the technology - users address mediated and interaction complexity while researchers focus on internal and external complexity. We also found that robots function as boundary objects between experts and users, and suggest that one task designers can perform is to "stay on the boundary" and mediate between the different ways in which experts and non-experts frame emerging technology to develop designs that benefit from insights from both user and researcher perspectives.

Modern technology has immensely influenced popular doctrine of education and learning and they must be adjusted to the new techonlogy-supported lifestyle. Mobile devices, like tablets and smartphones, are most acceptable technological learning tools because they have many advantages over traditonal teaching tools. Main idea of mobile learning is that studens can learn at the any place with the any device. While pedagogical and didactic ideas behind may seem to be straightforward, i-textbooks present a technological challenge - from preparing content, authoring tools, managing learning units, improving processes, to compilations of learning units in i-textbooks and using them for active learningonhome computers or tablets.Except of the availability of learning, mobile learning allows the use of interactive learning materials - audio/video elements, interactive tasks, tests, quizzes, animations and interactive didactical games. In the paper we propose a new aged version of textbooks, i-textbooks, which truly base on the idea of mobile learning - using them anytime and anywhere, on all devices with higher interactive levels and are specifically designed for active learners and more complex cognitive processes of all age groups and educational levels. While the pedagogical idea behind may seem to be straightforward, i-textbooks present a technological challenge - from preparing content, authoring tools, managing learning units, improving processes, to compilations of learning units in i-textbooks and using them for active learning on home computers or tablets. In the paper, the challenges we tackled when developing i-textbooks for natural science courses in primary and secondary school are discussed and solutions (technologies, strategies, processes and products) are proposed. Special emphasize will be given to solutions for achieving device independent usage of i-textbooks which represents significant obstacle.

Abstract Background. The aim of the study was to examine on the CT basis the inter-application displacement of the positions D0.1cc, D1cc and D2cc of the brachytherapy dose applied to the bladder and rectum of the patients with inoperable cervical cancer. Patients and methods. This prospective study included 30 patients with cervical cancer who were treated by concomitant chemo-radiotherapy. HDR intracavitary brachytherapy was made by the applicators type Fletcher tandem and ovoids. For each brachytherapy application the position D0.1cc was determined of the bladder and rectum that receive a brachytherapty dose. Then, based on the X, Y, and Z axis displacement, inter-application mean X, Y, and Z axis displacements were calculated as well as their displacement vectors (R). It has been analyzed whether there is statistically significant difference in inter-application displacement of the position of the brachytherapy dose D0.1cc, D1cc and D2cc of the bladder and rectum. The ANOVA test and post-hoc analysis by Tukey method were used for testing statistical importance of differences among the groups analyzed. The difference among the groups analyzed was considered significant if p < 0.05. Results. There are significant inter-application displacements of the position of the brachytherapy dose D0,1cc, D1cc and D2cc of the bladder and rectum. Conclusions. When we calculate the cumulative brachytherapy dose by summing up D0,1cc, D1cc and D2cc of the organs at risk for all the applications, we must bear in mind their inter-application displacement, and the fact that it is less likely that the worst scenario would indeed happen