Komplex molekuláris genetikai vizsgálati algoritmus myeloproliferativ neoplasiák diagnosztikájában

Introduction: Mutations in Janus kinase 2, calreticulin and thrombopoietin receptor genes have been identified in the genetic background of Philadelphia chromosome negative, "classic" myeloproliferative neoplasms. Aim: The aim of the authors was to identify driver mutations in a large myeloproliferative cohort of 949 patients. Method: A complex array of molecular techniques (qualitative and quantitative allele-specific polymerase chain reactions, fragment analyzes, high resolution melting and Sanger sequencing) was applied. Results: All 354 patients with polycythemia vera carried Janus kinase 2 mutations (V617F 98.6%, exon 12: 1.4%). In essential thrombocythemia (n = 468), the frequency of V617F was 61.3% (n = 287), that of calreticulin 25.2% (n = 118), and that of thrombopoietin receptor mutations 2.1% (n = 10), while 11.3% (n = 53) were triple-negative. Similar distribution was observed in primary myelofibrosis (n = 127): 58.3% (n = 74) V617F, 23.6% (n = 30) calreticulin, 6.3% (n = 8) thrombopoietin receptor mutation positive and 11.8% (n = 15) triple-negative. Conclusions: The recent discovery of calreticulin gene mutations led to definite molecular diagnostics in around 90% of clonal myeloproliferative cases. Orv. Hetil., 2014, 155(52), 2074-2081

XTraQue: traceability for product line systems

Product line engineering has been increasingly used to support the development and deployment of software systems that share a common set of features and are developed based on the reuse of core assets. The large number and heterogeneity of documents generated during the development of product line systems may cause difficulties to identify common and variable aspects among applications, and to reuse core assets that are available under the product line. In this paper, we present a traceability approach for product line systems. Traceability has been recognised as an important task in in software system development. Traceability relations can improve the quality of the product being developed and reduce development time and cost. We present a rule-based approach to support automatic generation of traceability relations between feature-based object-oriented documents. The traceability rules used in our work are classified into two groups namely (a) direct rules, which support the creation of traceability relations that do not depend on the existence of other relations, and (b) indirect rules, which require the existence of previously generated relations. The documents are represented in XML and the rules are represented in an extension of XQuery. A prototype tool called XTraQue has been implemented. This tool, together with a mobile phone product line case study, has been used to demonstrate and evaluate our work in various experiments. The results of these experiments are encouraging and comparable with other approaches that support automatic generation of traceability relations

Pushouts in software architecture design

A classical approach to program derivation is to progressively extend a simple specification and then incrementally refine it to an implementation. We claim this approach is hard or impractical when reverse engineering legacy software architectures. We present a case study that shows optimizations and pushouts--in addition to refinements and extensions--are essential for practical stepwise development of complex software architectures.NSF CCF 0724979NSF CNS 0509338NSF CCF 0917167NSF DGE-1110007FCT SFRH/BD/47800/2008FCT UTAustin/CA/0056/200

Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations

Somatic insertions/deletions in the calreticulin gene have recently been discovered to be causative alterations in myeloproliferative neoplasms. A combination of qualitative and quantitative allele-specific polymerase chain reaction, fragment-sizing, high resolution melting and Sanger-sequencing was applied for the detection of three driver mutations (in Janus kinase 2, calreticulin and myeloproliferative leukemia virus oncogene genes) in 289 cases of essential thrombocythemia and 99 cases of primary myelofibrosis. In essential thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%) myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple-negative (11%) cases were identified, while in primary myelofibrosis 56 (57%) Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were identified. Patients positive for the calreticulin mutation were younger and had higher platelet counts compared to Janus kinase 2 mutation-positive counterparts. Calreticulin mutation-positive patients with essential thrombocythemia showed a lower risk of developing venous thrombosis, but no difference in overall survival. Calreticulin mutation-positive patients with primary myelofibrosis had a better overall survival compared to that of the Janus kinase 2 mutation-positive (P=0.04) or triple-negative cases (P=0.01). Type 2 calreticulin mutation occurred more frequently in essential thrombocythemia than in primary myelofibrosis (P=0.049). In essential thrombocythemia, the calreticulin mutational load was higher than the Janus kinase 2 mutational load (P<0.001), and increased gradually in advanced stages. Calreticulin mutational load influenced blood counts even at the time point of diagnosis in essential thrombocythemia. We confirm that calreticulin mutation is associated with distinct clinical characteristics and explored relationships between mutation type, load and clinical outcome

Successful treatment of a primary uterine B-cell lymphoma with rituximab-CHOP immunochemotherapy

We report the case of a 26 year old patient with a primary, Ann Arbor stage IE, diffuse large B-cell lymphoma of the uterine corpus. The patient was admitted to our hospital because of a one year history of vaginal contact bleeding. Final diagnosis was based on the histological and immunohistochemical evaluation of a specimen obtained by fractionated cervical and uterine curettage. Further staging has not revealed any other localization of the disease. Antilymphoma treatment was started with CHOP combined with rituximab and resulted complete remission. This is the first reported case of an uterine lymphoma treated by rituximab-based immunochemotherapy

Tag relatedness in image folksonomies

Folksonomies - networks of users, resources, and tags allow users to easily retrieve, organize and browse web contents. However, their advantages are still limited mainly due to the noisiness of user provided tags. To overcome this issue, we propose an approach for characterizing related tags in folksonomies: we use tag co-occurrence statistics and Laplacian score based feature selection in order to create empirical co-occurrence probability distribution for each tag; then we identify related tags on the basis of the dissimilarity between their distributions. For this purpose, we introduce variant of the Jensen-Shannon Divergence, which is more robust to statistical noise. We experimentally evaluate our approach using WordNet and compare it to a common tag-relatedness approach based on the cosine similarity. The results show the effectiveness of our approach and its advantage over the competing method

A Bioorthogonal Double Fluorogenic Probe to Visualize Protein–DNA Interaction

Two sets of bioorthogonally applicable, double fluorogenic probes, capable of sensing DNA–protein interactions, were prepared by installing an azide or tetrazine motif onto structurally fluorogenic, DNA sensitive frames. Installation of these bioorthogonal functions onto DNA intercalating dyes furnished these scaffolds with reactivity based fluorogenicity, rendering these probes double-fluorogenic, AND-type logic switches that require the simultaneous occurrence of a bioorthogonal reaction and interaction with DNA to trigger high intensity fluorescence. The probes were evaluated for double fluorogenic behavior in the presence/absence of DNA and a complementary bioorthogonal function. Our studies revealed that azide and tetrazine appending thiazole orange frames show remarkable double fluorogenic features. One of these probes, a membrane permeable tetrazine modified thiazole orange derivative was further tested in live cell labeling studies. Cells expressing bioorthogonalized DNA-binding proteins showed intensive fluorescence characteristics of the localization of the proteins upon treatment with our double fluorogenic probe. On the contrary, labeling similarly bioorthogonalized cytosolic proteins did not result in the appearance of the fluorescence signal. These studies suggest that such double-fluorogenic probes are indeed capable of sensing DNA–protein interactions in cells