Main transport challenges in South Eastern Europe, after enlargement

This paper looks at the main challenges that are facing the Transport sector in the countries of S. E. Europe after enlargement. First, it looks at the challenge of setting a common Transport policy and points as priority areas the questions of: frontier crossings, road transport quotas, working hours (road transport), restructuring of railways, promotion of Rail Freight “Freeways”, new financing schemes through Public Private Partnerships, and other issues. Then it looks at the factors that will determine the future transport outlook of the area in both qualitative and quantitative terms and it finds that there is a web of factors and issues that will play a role, such as for example the socio-political climate and preferences, the advent of New Technologies, and the degree of development of the Trans-European Networks. The paper looks at the “challenges” facing the inter-urban and urban transport separately. As regards the first it concludes that a) higher integration of the transport provider into the whole transport and logistics chain, and b) closer co-operation and “integration” with the customer, will be the main ones, while for urban transport the main challenge will be improvement of urban traffic management systems and, inevitably, demand management measures, as well as implementation and operation of a whole new series of technologies and systems of urban ICT that will form the Integrated Urban ICT environment of the future

Geometric Multicut

We study the following separation problem: Given a collection of colored objects in the plane, compute a shortest “fence” F, i.e., a union of curves of minimum total length, that separates every two objects of different colors. Two objects are separated if F contains a simple closed curve that has one object in the interior and the other in the exterior. We refer to the problem as GEOMETRIC k-CUT, where k is the number of different colors, as it can be seen as a geometric analogue to the well-studied multicut problem on graphs. We first give an O(n4log3n)-time algorithm that computes an optimal fence for the case where the input consists of polygons of two colors and n corners in total. We then show that the problem is NP-hard for the case of three colors. Finally, we give a (2−4/3k)-approximation algorithm

Estimation in high dimensions: a geometric perspective

This tutorial provides an exposition of a flexible geometric framework for high dimensional estimation problems with constraints. The tutorial develops geometric intuition about high dimensional sets, justifies it with some results of asymptotic convex geometry, and demonstrates connections between geometric results and estimation problems. The theory is illustrated with applications to sparse recovery, matrix completion, quantization, linear and logistic regression and generalized linear models.Comment: 56 pages, 9 figures. Multiple minor change

The regulation of denitrification in P. denitrificans

Bacterial respiration generates the energy required for bacterial growth. Respiration is not only limited to oxygen but could be fuelled with nitrate in anaerobic environments. Upon signal reception bacteria adjust their respiratory pathway in short time by effectively regulating respiratory gene expression and subsequently engineering the complete removal of nitrite, nitric oxide and nitrous oxide from the cytoplasm. Comparison of anaerobic and aerobic gene expression data in continuous cultures of Paracoccus denitrificans revealed a majority of highly expressed genes were co-regulated by CPR/FNR type transcriptional regulators. Motif analysis of the upstream region showed similar patterns recognizable by FNR. P. denitrificans expresses three FNR type regulators that could potentially compete for cognate site binding. Three mutant strains of fnrP, nnrR and narR were used to investigate the transcriptional expression of genes involved in respiration. It was demonstrated that the transcriptional factor FnrP positively regulated the transcription of nar, nor and nap and repressed the expression of nos operon. NnrR positively regulated the nir and nor operons and inhibited the expression of the nar and nos operons, in the latter case due to substrate unavailability. Finally, NarR positively enhanced the expression of the nar operon during the initial stage of anaerobicity. Additionally the expression of the nir and nos operons was repressed in the ΔnarR strain suggesting that NarR may compete for the promoter binding sites and possibly repress the expression of those genes. Additionally, sub-optimal pH inhibited growth and repressed the expression of nirS, norB and nosZ resulting in detectable nitrous oxide emissions. Therefore, the transcription factors FnrP, NnrR and NarR compete for the binding sites upstream of the denitrification operons in a way that optimizes the metabolic rates of denitrification and subsequently eliminates the accumulation of toxic denitrification intermediates. Therefore a new model of regulation of denitrification in P. denitrificans is proposed and discussed

Defining IT "Business Value" Under Conditions of Economic Uncertainty

Investment in Information Technology (IT) has typically been justified as playing a crucial role in assisting business and other Organisations in conducting their business in a more efficient and effective way. The implied "value" that results from such investments is known as "IT business value" and its definition and measurement under conditions of economic austerity and uncertainty is the main subject of this paper. The question is why, under such conditions, many Organisations fail to realize the positive impacts expected from IT investment, which by itself is then rather scarce and difficult to attain. To answer this question we concentrate in this paper on the issues of IT business value measurement and more specifically we attempt to answer the research question of how best to define the "business value" of IT and what factors may affect it. The paper first puts forward the main definitions used for both "IT" and "Business value" in the literature. It then goes on to present and critically examine the most prominent of the existing methodologies for measuring "IT Business value" again by resorting to a relevant literature search. Then, we examine the special influencing factors that are at work in times of economic austerity and uncertainty and puts forward a framework for analyzing IT Business value under conditions of economic austerity. This framework is presented in terms of its elements and a description of their main characteristics and measures (metrics). Finally, before the conclusions, a list of the critical success factors for IT investment is presented which is based on a previous published work of the author

The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer

Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches

Future Perspectives in HLA Typing Technologies

A wide range of malignant and nonmalignant diseases require hematopoietic stem cell transplantation (HSCT) as last resort therapeutic approach. Graft versus host disease (GVHD), which is one of the major causes of transplant-related mortality, is minimized whenever increased matching of human leukocyte antigens (HLAs) between donor and recipient is present. Suitable donor selection is determined with the utilization of HLA typing. HLAs are highly polymorphic glycoproteins encoded by a region of genes known as the major histocompatibility complex (MHC). Their biological function is to present antigenic peptides to T lymphocytes. However, they also play important role in HSCT acceptance/rejection. During the previous years, various techniques have been acquired in order to better characterize the HLA profile of transplant donors and recipients. This effort is particularly challenging due to MHC size, but most importantly due to high sequence variability in specific regions of the respective genetic loci, between individuals. Initially, HLA typing was performed using serological typing, hybridization techniques, and restriction fragment length polymorphism (RFLP) approaches. Later on, polymerase chain reaction (PCR) based techniques and direct sequencing (dideoxy-based Sanger sequencing) capillary electrophoretic analyses arose. Nowadays, 2nd and 3rd generation sequencing (NGS) technologies show great potential in effectively identifying these polymorphic regions

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

Clinical validation of an algorithm for rapid and accurate automated segmentation of intracoronary optical coherence tomography images

Objectives: The analysis of intracoronary optical coherence tomography (OCT) images is based on manual identification of the lumen contours and relevant structures. However, manual image segmentation is a cumbersome and time-consuming process, subject to significant intra- and inter-observer variability. This study aims to present and validate a fully-automated method for segmentation of intracoronary OCT images. Methods: We studied 20 coronary arteries (mean length = 39.7 ± 10.0 mm) from 20 patients who underwent a clinically-indicated cardiac catheterization. The OCT images (n = 1812) were segmented manually, as well as with a fully-automated approach. A semi-automated variation of the fully-automated algorithm was also applied. Using certain lumen size and lumen shape characteristics, the fully- and semi-automated segmentation algorithms were validated over manual segmentation, which was considered as the gold standard. Results: Linear regression and Bland–Altman analysis demonstrated that both the fully-automated and semiautomated segmentation had a very high agreement with the manual segmentation, with the semi-automated approach being slightly more accurate than the fully-automated method. The fully-automated and semiautomated OCT segmentation reduced the analysis time by more than 97% and 86%, respectively, compared to manual segmentation. Conclusions: In the current work we validated a fully-automated OCT segmentation algorithm, as well as a semiautomated variation of it in an extensive “real-life” dataset of OCT images. The study showed that our algorithm can perform rapid and reliable segmentation of OCT images

Linking healthcare and societal resilience during the Covid-19 pandemic

Coronavirus disease 2019 (Covid-19) has highlighted the link between public healthcare and the broader context of operational response to complex crises. Data are needed to support the work of the emergency services and enhance governance. This study develops a Europe-wide analysis of perceptions, needs and priorities of the public affected by the Covid-19 emergency. An online multilingual survey was conducted from mid-May until mid-July 2020. The questionnaire investigates perceptions of public healthcare, emergency management and societal resilience. In total, N = 3029 valid answers were collected. They were analysed both as a whole and focusing on the most represented countries (Italy, Romania, Spain and the United Kingdom). Our findings highlight some perceived weaknesses in emergency management that are associated with the underlying vulnerability of the global interconnected society and public healthcare systems. The spreading of the epidemic in Italy represented a ‘tipping point’ for perceiving Covid-19 as an ‘emergency’ in the surveyed countries. The respondents uniformly suggested a preference for gradually restarting activities. We observed a tendency to ignore the cascading effects of Covid-19 and possible concurrence of threats. Our study highlights the need for practices designed to address the next phases of the Covid-19 crisis and prepare for future systemic shocks. Cascading effects that could compromise operational capacity need to be considered more carefully. We make the case for the reinforcement of cross-border coordination of public health initiatives, for standardization in business continuity management, and for dealing with the recovery at the European level