Supporting requirement analysis through requirement rationale capture and traceability

Manufacturers of complex engineering systems are increasingly recognising the importance of identifying, understanding and satisfying stakeholders’ needs in order to produce high-quality products. The analysis of these needs into a formal requirement specification is a time consuming and complex process for which little support is offered to design engineers. This can result in requirements being poorly documented and with little or no traceability to their origins. This dissertation reports an investigation to understand the process of requirement analysis and develop computational support for this important phase of the engineering design process. The key argument of this research is that the existing practice of requirement analysis can be improved by providing better support for requirement rationale capture and enabling greater requirement traceability. The research consisted of three main phases. In the first phase, literature related to the requirement analysis was reviewed and led to the creation of a requirement analysis model. In the second phase, the practices of a global engineering organisation were investigated using document analysis as well as interviews with and shadowing of company engineers. The research found that requirement analysis lacks support for requirement rationale capture and traceability. On the basis of this result, a workflow for requirement analysis was proposed. The workflow involves the use of the Decision Rationale editor tool to capture requirement rationale and enable requirement traceability. In the third phase, four studies were undertaken to validate the workflow. These studies investigated: 1) application of the workflow to requirements generated through reverse-engineering a low-complexity consumer product; 2) requirements extracted from documents produced by a graduate engineering team during a twelve-week project; 3) the requirement analysis process undertaken by two graduate engineering teams during twelve-week projects; and 4) requirements for a new aircraft engine development programme. The studies showed that the proposed workflow is feasible, practical, and scalable when applied to engineering projects. Requirement rationales were classified into categories, namely product design and use, pre-existing rationale, and project management. In order to fully support requirement traceability, it was found that it is important to make traceable four types of requirement transformations: newly introduced, copied, updated, and deleted requirements. The research demonstrated that the proposed workflow is a successful proof-of-concept and can lead to improved quality of requirement documentation and requirement traceability.Open Acces

HSP90 inhibitors stimulate DNAJB4 protein expression through a mechanism involving N6-methyladenosine.

Small-molecule inhibitors for the 90-kDa heat shock protein (HSP90) have been extensively exploited in preclinical studies for the therapeutic interventions of human diseases accompanied with proteotoxic stress. By using an unbiased quantitative proteomic method, we uncover that treatment with three HSP90 inhibitors results in elevated expression of a large number of heat shock proteins. We also demonstrate that the HSP90 inhibitor-mediated increase in expression of DNAJB4 protein occurs partly through an epitranscriptomic mechanism, and is substantially modulated by the writer, eraser, and reader proteins of N6-methyladenosine (m6A). Furthermore, exposure to ganetespib leads to elevated modification levels at m6A motif sites in the 5'-UTR of DNAJB4 mRNA, and the methylation at adenosine 114 site in the 5'-UTR promotes the translation of the reporter gene mRNA. This m6A-mediated mechanism is also at play upon heat shock treatment. Cumulatively, we unveil that HSP90 inhibitors stimulate the translation of DNAJB4 through an epitranscriptomic mechanism

Autoimmune-induced preferential depletion of myelin-associated glycoprotein (MAG) is genetically regulated in relapsing EAE (B6 × SJL) F1 mice

<p>Abstract</p> <p>Background</p> <p>Experimental autoimmune encephalomyelitis (EAE) is commonly used to investigate mechanisms of autoimmune-mediated damage to oligodendrocytes, myelin, and axons in multiple sclerosis (MS). Four distinct autoimmune mechanisms with subsequently distinct patterns of demyelination have been recognized in acute MS lesions. EAE correlates for those distinct patterns of MS lesions are unknown. An excessive loss of myelin-associated glycoprotein (MAG), as a result of distal oligodendrogliopathy, is found exclusively in the subtype III lesion. We sought to answer if types of demyelination in acute lesions during onset and relapse of EAE can replicate the specific patterns observed in MS acute lesions.</p> <p>Methods</p> <p>In parental H-2^b(C57BL/6, B6) and hybrid H-2^b/s[(B6 × SJL) F1] EAE mice, we examined spinal cord levels of MOG, MAG, and myelin basic protein (MBP), and compared to levels of axonal neurofilament (NF160) to assess axonal function, and levels of PARPp85 as an indicator of irreversible apoptosis.</p> <p>Results</p> <p>During disease onset, levels of MOG significantly dropped in both strains, although more profoundly in H-2^b/smice. Levels of MOG recovered in relapsing mice of both strains. Regulation of MAG was dissimilar to MOG. Modest loss of MAG was found at disease onset in both strains of mice. Unexpectedly, in relapsing H-2^b/smice, a major depletion of MAG and NF160, accompanied with sharp elevation of PARPp85 levels, was measured. PARPp85 immunoreactivity was observed in cytoplasm and nuclei of some MBP containing cells.</p> <p>Conclusion</p> <p>Taken together, our results show genetically controlled distinct patterns of MOG and MAG depletion, in MOG_35–55induced EAE in H-2^band H-2^b/smice. The data also suggest distinctive immune regulation of acute lesions that develop in relapsing compared to disease onset. A profound depletion of MAG, concomitant with marked depletion of axonal NF160, and sharp elevation of PARPp85 levels, occurred exclusively in relapsing H-2^b/smice. Our findings suggest concurrence of sharp decrease of MAG levels, axonal dysfunction and irreversible apoptosis with severe relapsing disease in H-2^b/smice. We propose that MOG-induced EAE in H-2^b/smice may prove as a useful model in studying mechanisms, which govern autoimmune-induced preferential loss of MAG, and its impact on oligodendroglial pathology.</p

Clinical Effects of Shenqi Fuzheng Injection in the Neoadjuvant Chemotherapy for Local Advanced Breast Cancer and the Effects on T-lymphocyte Subsets

ObjectiveTo evaluate clinical effects of Shenqi Fuzheng Injection in the neoadjuvant chemotherapy for local advanced breast cancer and the effects on T-lymphocyte subsets.MethodsDuring the period from 2000 to 2005, 126 patients with local advanced breast cancer were treated with the neoadjuvant chemotherapy. They were randomly divided into the following two groups: a control group of 61 cases treated by chemotherapy alone and a study group of 65 cases treated by chemotherapy plus Shenqi Fuzheng Injection. All the cases of both groups were given the CEF (CTX 500 mg/m2, d1, 8; EPI 40 mg/m2, d1, 8; and 5-Fu 500 mg/m2, d1,8) regimen. The clinical effects, the effects on T-lymphocyte subgroup and NK cells, and the toxic side effects were observed.ResultsAll the patients completed two cycles of the chemotherapy, and the efficacy and the toxic side effects were evaluated. For the primary tumor in the breast, the total effective rate was 69.2% (45/65) in the study group and 49.2% (30/61) in the control group with a statistically significant difference in the intergroup comparison (χ 2=5.251, P=0.022, < 0.05). There was no progression of the disease in both the groups, and there were no grade IV toxic side effects in the two groups. The major toxic responses were myelosuppression and gastrointestinal reaction, which were milder in the study group than the control group, and with a shorter recovery course in the former than the latter. Besides, an obvious rise of the T-lymphocyte subgroup and NK cells was found in the study group after the neoadjuvant chemotherapy, with a very significant difference from the controls (P < 0.01).ConclusionShenqi Fuzheng Injection can improve and regulate immune function of the patients with local advanced breast cancer given the neoadjuvant chemotherapy, and therefore it can enhance the curative effect and reduce the side effect as well

Experimental and theoretical evidence for the promotional effect of acid sites on the diffusion of alkenes through small‐pore zeolites

The diffusion of saturated and unsaturated hydrocarbons is of fundamental importance for many zeolite-catalyzed processes. Transport of small alkenes in the confined zeolite pores can become hindered, resulting in a significant impact on the ultimate product selectivity and separation. Herein, intracrystalline light olefin/paraffin diffusion through the 8-ring windows of zeolite SAPO-34 is characterized by a complementary set of first-principle molecular dynamics simulations, PFG-NMR experiments, and pulse-response temporal analysis of products measurements, yielding information at different length and time scales. Our results clearly show a promotional effect of the presence of Bronsted acid sites on the diffusion rate of ethene and propene, whereas transport of alkanes is found to be insensitive to the presence of acid sites. The enhanced diffusivity of unsaturated hydrocarbons is ascribed to the formation of favorable pi-H interactions with acid protons, as confirmed by IR spectroscopy measurements. The acid site distribution is proven to be an important design parameter for optimizing product distributions and separations

LABEL: Pediatric brain extraction using learning-based meta-algorithm

Magnetic resonance imaging of pediatric brain provides valuable information for early brain development studies. Automated brain extraction is challenging due to the small brain size and dynamic change of tissue contrast in the developing brains. In this paper, we propose a novel Learning Algorithm for Brain Extraction and Labeling (LABEL) specially for the pediatric MR brain images. The idea is to perform multiple complementary brain extractions on a given testing image by using a meta-algorithm, including BET and BSE, where the parameters of each run of the meta-algorithm are effectively learned from the training data. Also, the representative subjects are selected as exemplars and used to guide brain extraction of new subjects in different age groups. We further develop a level-set based fusion method to combine multiple brain extractions together with a closed smooth surface for obtaining the final extraction. The proposed method has been extensively evaluated in subjects of three representative age groups, such as neonate (less than 2 months), infant (1–2 years), and child (5–18 years). Experimental results show that, with 45 subjects for training (15 neonates, 15 infant, and 15 children), the proposed method can produce more accurate brain extraction results on 246 testing subjects (75 neonates, 126 infants, and 45 children), i.e., at average Jaccard Index of 0.953, compared to those by BET (0.918), BSE (0.902), ROBEX (0.901), GCUT (0.856), and other fusion methods such as Majority Voting (0.919) and STAPLE (0.941). Along with the largely-improved computational efficiency, the proposed method demonstrates its ability of automated brain extraction for pediatric MR images in a large age range