Transcriptional Regulation of the Human Hepatic Lipase Gene: Relation to Glucose and Lipid Metabolism

Hepatic Lipase (HL; EC 3.1.1.3) is an extracellular glycoprotein with phospholipase A1 and triacylglycerol hydrolase activity. The human HL protein is encoded by the LIPC gene on chromosome 15q21. Most of this protein is synthesized in the parenchymal cells of the liver and secreted into the space of Disse where it binds to heparin sulfate proteoglycans. Some synthesis of HL was also observed in macrophages. The HL protein is also present in the steroidogenic adrenal glands, ovaries and, in small amounts, in the testes. By using heparin, HL protein is displaced from its binding site. Human HL protein is a homodimer, the monomer has a molecular weight of 65 kDa. In the metabolism of plasma lipoproteins HL plays an important role; it mediates the conversion of high density lipoprotein subfraction 2 (HDL2) to high density lipoprotein subfraction 3 (HDL3), the conversion of intermediate density lipoprotein (IDL) to low density l

On the Effectiveness of Unit Tests in Test-driven Development

Background: Writing unit tests is one of the primary activities in test-driven development. Yet, the existing reviews report few evidence supporting or refuting the effect of this development approach on test case quality. Lack of ability and skills of developers to produce sufficiently good test cases are also reported as limitations of applying test-driven development in industrial practice. Objective: We investigate the impact of test-driven development on the effectiveness of unit test cases compared to an incremental test last development in an industrial context. Method: We conducted an experiment in an industrial setting with 24 professionals. Professionals followed the two development approaches to implement the tasks. We measure unit test effectiveness in terms of mutation score. We also measure branch and method coverage of test suites to compare our results with the literature. Results: In terms of mutation score, we have found that the test cases written for a test-driven development task have a higher defect detection ability than test cases written for an incremental test-last development task. Subjects wrote test cases that cover more branches on a test-driven development task compared to the other task. However, test cases written for an incremental test-last development task cover more methods than those written for the second task. Conclusion: Our findings are different from previous studies conducted at academic settings. Professionals were able to perform more effective unit testing with test-driven development. Furthermore, we observe that the coverage measure preferred in academic studies reveal different aspects of a development approach. Our results need to be validated in larger industrial contexts.Istanbul Technical University Scientific Research Projects (MGA-2017-40712), and the Academy of Finland (Decision No. 278354)

Defining Domain-Specific Modeling Languages to Automate Product Derivation: Collected Experiences

Abstract. Domain-Specific Modeling offers a language-based approach to raise the level of abstraction in order to speed up development work and set variation space already at specification and design phase. In this paper we identify approaches that are applied for defining languages that enable automated variant derivation. This categorization is based on analyzing over 20 industrial cases of DSM language definition.

Prototyping the Semantics of a DSL using ASF+SDF: Link to Formal Verification of DSL Models

A formal definition of the semantics of a domain-specific language (DSL) is a key prerequisite for the verification of the correctness of models specified using such a DSL and of transformations applied to these models. For this reason, we implemented a prototype of the semantics of a DSL for the specification of systems consisting of concurrent, communicating objects. Using this prototype, models specified in the DSL can be transformed to labeled transition systems (LTS). This approach of transforming models to LTSs allows us to apply existing tools for visualization and verification to models with little or no further effort. The prototype is implemented using the ASF+SDF Meta-Environment, an IDE for the algebraic specification language ASF+SDF, which offers efficient execution of the transformation as well as the ability to read models and produce LTSs without any additional pre or post processing.Comment: In Proceedings AMMSE 2011, arXiv:1106.596

Fermi Surface Properties of Low Concentration Cex_{x}La1−x_{1-x}B6_{6}: dHvA

The de Haas-van Alphen effect is used to study angular dependent extremal areas of the Fermi Surfaces (FS) and effective masses of Ce$_{x}$La$_{1-x}$B$_{6}$ alloys for $x$ between 0 and 0.05. The FS of these alloys was previously observed to be spin polarized at low Ce concentration ($x$ = 0.05). This work gives the details of the initial development of the topology and spin polarization of the FS from that of unpolarized metallic LaB$_{6}$ to that of spin polarized heavy Fermion CeB$_{6}$ .Comment: 7 pages, 9 figures, submitted to PR

Heavy quasiparticles in the ferromagnetic superconductor ZrZn2

We report a study of the de Haas-van Alphen effect in the normal state of the ferromagnetic superconductor ZrZn2. Our results are generally consistent with an LMTO band structure calculation which predicts four exchange-split Fermi surface sheets. Quasiparticle effective masses are enhanced by a factor of about 4.9 implying a strong coupling to magnetic excitations or phonons. Our measurements provide insight in to the mechanism for superconductivity and unusual thermodynamic properties of ZrZn2.Comment: 5 pages, 2 figures (one color

The epigenetic regulators CBP and p300 facilitate leukemogenesis and represent therapeutic targets in acute myeloid leukemia.

Growing evidence links abnormal epigenetic control to the development of hematological malignancies. Accordingly, inhibition of epigenetic regulators is emerging as a promising therapeutic strategy. The acetylation status of lysine residues in histone tails is one of a number of epigenetic post-translational modifications that alter DNA-templated processes, such as transcription, to facilitate malignant transformation. Although histone deacetylases are already being clinically targeted, the role of histone lysine acetyltransferases (KAT) in malignancy is less well characterized. We chose to study this question in the context of acute myeloid leukemia (AML), where, using in vitro and in vivo genetic ablation and knockdown experiments in murine models, we demonstrate a role for the epigenetic regulators CBP and p300 in the induction and maintenance of AML. Furthermore, using selective small molecule inhibitors of their lysine acetyltransferase activity, we validate CBP/p300 as therapeutic targets in vitro across a wide range of human AML subtypes. We proceed to show that growth retardation occurs through the induction of transcriptional changes that induce apoptosis and cell-cycle arrest in leukemia cells and finally demonstrate the efficacy of the KAT inhibitors in decreasing clonogenic growth of primary AML patient samples. Taken together, these data suggest that CBP/p300 are promising therapeutic targets across multiple subtypes in AML.Funding in the Huntly laboratory comes from Cancer Research UK, Leukemia Lymphoma Research, the Kay Kendal Leukemia Fund, the Leukemia lymphoma Society of America, the Wellcome Trust, The Medical Research Council and an NIHR Cambridge Biomedical Research Centre grant. Patient samples were processed in the Cambridge Blood and Stem Cell Biobank.This is the author accepted manuscript. The final version is available via NPG at http://dx.doi.org/10.1038/onc.2015.9