Relating software requirements and architectures using problem frames

Problem frames provide a means of analyzing and decomposing problems. They emphasise the world outside of the computer, helping the developer to focus on the problem domain, instead of drifting into inventing solutions. However, even modestly complex problems can force us into detailed consideration of the architecture of the solution. This is counter to the intention of the problem frames approach, which is to delay consideration of the solution space until a good understanding of the problem is gained. We therefore extend problem frames, allowing architectural structures, services and artifacts to be considered as part of the problem domain. Through a case study, we show how this extension enhances the applicability of problem frames in permitting an architecture-based approach to software development. We conclude that, through our extension, the applicability of problem frames is extended to include domains with existing architectural support

MCAM/MUC18/CD146 as a multifaceted warning marker of melanoma progression in liquid biopsy

Human malignant melanoma shows a high rate of mortality after metastasization, and its incidence is continuously rising worldwide. Several studies have suggested that MCAM/MUC18/CD146 plays an important role in the progression of this malignant disease. MCAM/MUC18/CD146 is a typical single-spanning transmembrane glycoprotein, existing as two membrane isoforms, long and short, and an additional soluble form, sCD146. We previously documented that molecular MCAM/MUC18/CD146 expression is strongly associated with disease progression. Recently, we showed that MCAM/MUC18/CD146 and ABCB5 can serve as melanoma-specific-targets in the selection of highly primitive circulating melanoma cells, and constitute putative proteins associated with disease spreading progression. Here, we analyzed CD146 molecular expression at onset or at disease recurrence in an enlarged melanoma case series. For some patients, we also performed the time courses of molecular monitoring. Moreover, we explored the role of soluble CD146 in different cohorts of melanoma patients at onset or disease progression, rather than in clinical remission, undergoing immune therapy or free from any clinical treatment. We showed that MCAM/MUC18/CD146 can be considered as: (1) a membrane antigen suitable for identification and enrichment in melanoma liquid biopsy; (2) a highly effective molecular "warning " marker for minimal residual disease monitoring; and (3) a soluble protein index of inflammation and putative response to therapeutic treatments

Haploidentical, unmanipulated,G-CSF primed bona marrow transplantation for patients with high risk hematological malignancies

Eighty patients with high-risk hematologic malignancies underwent unmanipulated, G-CSF–primed BM transplantation from an haploidentical family donor. Patients were transplanted in first or second complete remission (CR, standard-risk: n =45) or in > second CR or active disease (high-risk: n =35). The same regimen for GVHD prophylaxis was used in all cases. The cumulative incidence (CI) of neutrophil engraftment was 93% 0.1%. The 100-day CIs for II-IV and III-IV grade of acute GVHD were 24% 0.2% and 5% 0.6%, respectively. The 2-year CI of extensive chronic GVHD was 6% 0.1%. The 1-year CI of treatment-related mortality was 36% 0.3%. After a median follow-up of 18 months, 36 of 80 (45%) patients are alive in CR. The 3-year probability of overall and disease-free survival for standard-risk and high-risk patients was 54% 8% and 33% 9% and 44% 8% and 30% 9%, respectively. In multivariate analysis, disease-free survival was significantly better for patients who had standard-risk disease and received transplantations after 2007. We conclude that unmanipulated, G-CSF–primed BM transplantation from haploidentical family donor provides very encouraging results in terms of engraftment rate, incidence of GVHD and survival and represents a feasible, valid alternative for patients with high-risk malignant hematologic diseases, lacking an HLA identical sibling and in need to be urgently transplanted

The Usability of E-learning Platforms in Higher Education: A Systematic Mapping Study

The use of e-learning in higher education has increased significantly in recent years, which has led to several studies being conducted to investigate the usability of the platforms that support it. A variety of different usability evaluation methods and attributes have been used, and it has therefore become important to start reviewing this work in a systematic way to determine how the field has developed in the last 15 years. This paper describes a systematic mapping study that performed searches on five electronic libraries to identify usability issues and methods that have been used to evaluate e-learning platforms. Sixty-one papers were selected and analysed, with the majority of studies using a simple research design reliant on questionnaires. The usability attributes measured were mostly related to effectiveness, satisfaction, efficiency, and perceived ease of use. Furthermore, several research gaps have been identified and recommendations have been made for further work in the area of the usability of online learning

Automatic synthesis of parallel algorithms

Solving combinatorial optimization problems can often lead to runtime growing exponentially as a function of the input size. But important real-world problems, industrial applications, and academic research challenges, may demand exact optimal solutions. In such situations, parallel processing can reduce the runtime from days or months, typical when one workstation is used, to a few minutes or even seconds. Partners of the CEC-sponsored SCOOP Project (Solving Combinatorial Optimization Problems in Parallel) contributed, on invitation, to this book; much attention was paid to competent coverage of the topic and the style of writing. Readers will include students, scientists, engineers, and professionals interested in the design and implementation of parallel algorithms for solving combinatorial optimization problems

Software engineering as the design theoretic transformation of software problems

Rogers characterises engineering as: ... the practice of organising the design and construction of any artifice which transforms the physical world around us to meet some recognised need. When the artifice is software, a key challenge is learn how to recon- cile the formal world of the computing machine and its software with the non-formal physical world around it. In this paper, we describe an approach that brings both non-formal and formal aspects of software en- gineering together within a single theoretical framework, which sees soft- ware engineering practice as recordable and re-playable design theoretic transformations of software problems. The framework permits the iden- tification and clarification of software requirements, the representation of the problem world into which the software solution will be delivered, and the construction of adequacy arguments for stake-holders. Designs are recordable and re-playable through our adaptation of tactics, a (now standard) form of programming language used in transformational proof theoretic presentations. This brings to our system many other benefits of such approaches, including the ability to abstract from a captured design, and to combine programmatically captured designs. This paper provides an example-driven presentation of our framework

ALL1 gene alterations in acute leukemia: Biological and clinical aspects

BACKGROUND AND OBJECTIVE: The ALL1 gene, also referred to as MLL, HRX or Htrx1, is interrupted in the vast majority of translocations involving the chromosome band 11q23. Alterations in this gene are reported in approximately 5-10% of acute leukemias (AL) and characterize different leukemic subtypes such as infant (< 12 months of age) AL, topoisomerase II inhibitors-related (TR) AL and a small subset of de novo AML and ALL. Distinguishing features of ALL1 alterations include the striking heterogeneity of its recombinations, i.e., more than 30 chromosome partners have been described in ALL1 rearrangements, and the lack of association with a definite lineage. The objective of this article is to review the biological and structural properties of ALL1 gene and its various fusion proteins, and to discuss the clinical relevance of these lesions with special emphasis on their role in molecular diagnosis and monitoring of minimal residual disease. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes data published by the authors in this field, articles and abstracts published in journals covered by the Science Citation Index and Medline, as well as some more recent personal unpublished observations. STATE OF THE ART: The ALL1 gene spans approximately 90 kb of DNA in length, and consists of 36 exons, ranging in size from 65 bp to 4249 bp. ALL1 codifies for a major transcript of approximately or equal to 15 kb. It encodes a protein of more than 3910 amino acids, containing three regions sharing sequence homology with the Drosophila trithorax gene. These homologies suggest that ALL1 is a transcription factor controlling development and/or differentiation of human cells. To date, twelve ALL1 partner genes have been characterized which are involved in the following translocations: t(4;11), t(9;11), t(6;11), t(11;19), t(1;11) t(10;11), t(11;16), t(11;17) and t(X;11). Since all these genes do not share relevant homologies among each other, their putative role in ALL1 activation still remains to be clarified. The analysis of ALL1 breakpoint cluster region (bcr) shows that several DNA motifs implicated in illegitimate recombination events are located within the bcr. Thus, mapping of breakpoints in the different subtypes of ALL1 +ve leukemia may help in understanding the events leading to translocations in human ALs. In this respect, data on ALL1 breakpoint localization suggest that similar pathogenetic mechanisms may underlie infant and TR AL and that these events might differ from those occurring in de novo AL. The availability of this molecular marker provides a new tool for diagnostic purposes and characterization of ALs and for monitoring of minimal residual disease. To date, the prognostic value of ALL1 rearrangements has been clearly demonstrated for infant ALs only, whereas the clinical relevance of ALL1 rearrangements in the other leukemic subtypes needs further evaluation by future prospective studies on a larger number of patients homogeneously treated. As concerning studies on minimal residual disease, data on PCR monitoring of the ALL1/AF4 fusion transcript, resulting from the t(4;11) translocation, show the clinical relevance of this molecular test in predicting outcome and, as a consequence, in designing individual post-remission therapies. PERSPECTIVES: It is expected that future studies will provide more detailed information regarding either the normal ALL1 function and/or the leukemogenic effect of ALL1 alterations, together with a better definition of the prognostic relevance of the hybrid proteins formed by this gene at diagnosis and during remission of diseas

Monitoring of KI and WU polyomaviruses in hematopoietic stem cell transplant patients

Primary infection with KIPyV and WUPyV polyomaviruses occurs early in childhood followed by lifelong persistence in the body. Polyomavirus reactivation can occur in the presence of impaired immunity as in hematological malignancies or during immunosuppresssion induced by medications. In this study, reactivation of KIPyV and WUPyV was monitored by conventional PCR in plasma samples of 26 stem cell transplant patients and in 26 related bone marrow donors. Plasma samples from transplant patients were collected immediately after the end of conditioning regimen and up to 270 days after transplant. All plasma samples from transplant patients were negative for KIPyV and WUPyV DNA. Instead, KIPyV DNA was detected in two bone marrow donors. There was no evidence of KIPyV transmission from the donor to the recipient. The data suggest that detection of KIPyV in plasma is sporadic and that KPIyV and WUPyV do not affect the post-transplant clinical course. However, further studies on a larger sample size and more sensitive PCR methods are needed to confirm these observations