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We must explicitly capture relationships and hierarchies between the multitude of system and security standards requirements. Current security requirements specification methods do not capture such structure effectively, making requirements management and traceability harder, consequently increasing costs and time to market for developing certified ICS. We propose a novel requirements repository model for ICS that uses labelled property graphs to structure and store system-specific and standards-based requirements using well-defined relationship types. Furthermore, we integrate the proposed requirements repository with design-time ICS tools to establish requirements traceability. A wind turbine case study illustrates the overall workflow in our framework. We demonstrate that a robust requirements traceability matrix is a natural consequence of using labelled property graphs. We also introduce a compatible requirements change management procedure that aids in adapting to changes in development and certification schemes. [ABSTRACT FROM AUTHOR]

Ablation of protein acyltransferase DHHC3 selectively enhanced the anti-cancer cell activities of several chemotherapeutic agents, but not kinase inhibitors. To understand why this occurs, we used comparative mass spectrometry-based palmitoyl-proteomic analysis of breast and prostate cancer cell lines, ± DHHC3 ablation, to obtain the first comprehensive lists of candidate protein substrates palmitoylated by DHHC3. Putative substrates included 22–28 antioxidant/redox-regulatory proteins, thus predicting that DHHC3 should have antioxidant functions. Consistent with this, DHHC3 ablation elevated oxidative stress. Furthermore, DHHC3 ablation, together with chemotherapeutic drug treatment, (a) elevated oxidative stress, with a greater than additive effect, and (b) enhanced the anti-growth effects of the chemotherapeutic agents. These results suggest that DHHC3 ablation enhances chemotherapeutic drug potency by disabling the antioxidant protections that contribute to drug resistance. Affirming this concept, DHHC3 ablation synergized with another anti-cancer drug, PARP inhibitor PJ-34, to decrease cell proliferation and increase oxidative stress. Hence, DHHC3 targeting can be a useful strategy for selectively enhancing potency of oxidative stress-inducing anti-cancer drugs. Also, comprehensive identification of DHHC3 substrates provides insight into other DHHC3 functions, relevant to in vivo tumor growth modulation. [ABSTRACT FROM AUTHOR]

A novel, air stable, water dispersible and efficient catalyst based on copper nanoparticles immobilized on nitrogen doped carbons derived from inorganic–organic composite [Cu(0)@NDC-Sil] has been prepared. Doping of carbons i.e. inorganic–organic (silica–starch) composite using 5-phenyl-1,2,3,4-tetrazole, a nitrogen-rich precursor imparts a variety of nitrogen functionalities even at moderate temperature and enables the generation of active sites for the immobilization of Cu(0) nanoparticles. The novel catalyst system has been well characterized by various techniques like SEM, HRTEM, STEM, TGA, CHN, EDX, ICP-AES, XRD and XPS and was found to be highly efficient for the one-pot synthesis of 1,4-disubstituted-1,2,3-triazoles via click chemistry approach with a wide range of substrate scope such as benzyl/allyl halides and alkyl bromides. Moreover, it could be easily recovered by filtration and reused without significant loss in its activity. [ABSTRACT FROM AUTHOR]

The affirmative action policy for socially and economically backward communities in employment has been a debated issue in India. In this context, this paper aims to analyze the level of inequality by distinguishing between ‘circumstance’ and ‘effort’ factors in the Roemer’s framework on equality of opportunity. We measure inequality of opportunities due to two circumstances: caste and religion. Our empirical analysis, at state-level, utilizes a recent household survey data, which provides information related to efforts as well as circumstances of workers. The paper estimated inequality in the labour market and then decomposed it to know the circumstances that cause income inequality. Our estimates indicated that inequality and inequality of opportunity is substantially higher in India. Specifically, the outcome of our analysis evidently indicated that the socially backward communities do have economically disadvantageous position in some of the Indian states. However, the degree of circumstances based on inequality varies to a great extent among the states. Therefore, we suggest that the country does not need a nation-level affirmative action policy instead a state-level policy could be more appropriate as the intensity of the problem differ significantly among the Indian states. [ABSTRACT FROM AUTHOR]

The laminin-binding integrin α6β4 plays key roles in both normal epithelial and endothelial cells and during tumor cell progression, metastasis, and angiogenesis. Previous cysteine mutagenesis studies have suggested that palmitoylation of α6β4 protein supports a few integrin-dependent functions and molecular associations. Here we took another approach and obtained strikingly different results. We used overexpression and RNAi knockdown in multiple cell types to identify protein acyl transferase DHHC3 as the enzyme responsible for integrin β4 and α6 palmitoylation. Ablation of DHHC3 markedly diminished integrin-dependent cellular cable formation on Matrigel, integrin signaling through Src, and β4 phosphorylation on key diagnostic amino acids (S1356 and 1424). However, unexpectedly, and in sharp contrast to prior α6β4 mutagenesis results, knockdown of DHHC3 accelerated the degradation of α6β4, likely due to an increase in endosomal exposure to cathepsin D. When proteolytic degradation was inhibited (by Pepstatin A), rescued α6β4 accumulated intracellularly, but was unable to reach the cell surface. DHHC3 ablation effects were strongly selective for α6β4. Cell-surface levels of ~10 other proteins (including α3β1) were not diminished, and the appearance of hundreds of other palmitoylated proteins was not altered. Results obtained here demonstrate a new substrate for the DHHC3 enzyme and provide novel opportunities for modulating α6β4 expression, distribution, and function. [ABSTRACT FROM AUTHOR]

Gastrin and its precursors promote proliferation in different gastrointestinal cells. Since mature, amidated gastrin (G-17) can induce cyclin D1, we determined whether G-17-mediated induction of cyclin D1 transcription involved Wnt signaling and CRE-binding protein (CREB) pathways. Our studies indicate that G-17 induces protein, mRNA expression and transcription of the G1- specific marker cyclin D1, in the gastric adenocarcinoma cell line AGSE (expressing the gastrin/cholecystokinin B receptor). This was associated with an increase in steady-state levels of total and nonphospho β-catenin and its nuclear translocation, indicating the activation of the Wnt-signaling pathway. In addition, G-17-mediated increase in cyclin D1 transcription was significantly attenuated by axin or dominant-negative (dn) T-cell factor 4(TCF4), suggesting crosstalk of G-17 with the Wnt-signaling pathway. Mutational analysis indicated that this effect was mediated through the cyclic AMP response element (CRE) (predominantly) and the TCF sites in the cyclin D1 promoter, which was also inhibited by dnCREB. Furthermore, G-17 stimulation resulted in increased CRE-responsive reporter activity and CREB phosphorylation, indicating an activation of CREB. Chromatin immunoprecipitation studies revealed a G-17- mediated increase in the interaction of β-catenin with cyclin D1 CRE, which was attenuated by dnTCF4 and dnCREB. These results indicate that G-17 induces cyclin D1 transcription, via the activation of β-catenin and CREB pathways. [ABSTRACT FROM AUTHOR]

Abstract. Restriction Fragment Length Polymorphism (RFLP) of several populations of Artemisia vulgaris, several species of Artemisia and several genera of family Asteraceae were obtained by Southern hybridization of DNAs digested with two enzymes Hind III and Eco0109 I and probed with a tobacco chloroplast DNA encoding for the entire rRNA operon. The hybridization revealed identical banding patterns among A. vulgaris populations. A remarkable degree of homogeneity was also observed at the inter species and inter generic levels of the family Asteraceae. Thus, chloroplast DNA encoding the rRNA is a potential probe for evolutionary studies. [ABSTRACT FROM AUTHOR]

Ablation of tetraspanin protein TSPAN12 from human MDA-MB-231 cells significantly decreased primary tumor xenograft growth, while increasing tumor apoptosis. Furthermore, TSPAN12 removal markedly enhanced tumor-endothelial interactions and increased metastasis to mouse lungs. TSPAN12 removal from human MDA-MB-231 cells also caused diminished association between FZD4 (a key canonical Wnt pathway receptor) and its co-receptor LRP5. The result likely explains substantially enhanced proteosomal degradation of β-catenin, a key effecter of canonical Wnt signaling. Consistent with disrupted canonical Wnt signaling, TSPAN12 ablation altered expression of LRP5, Naked 1 and 2, DVL2, DVL3, Axin 1, and GSKβ3 proteins. TSPAN12 ablation also altered expression of several genes regulated by β-catenin (e.g. CCNA1, CCNE2, WISP1, ID4, SFN, ME1) that may help to explain altered tumor growth and metastasis. In conclusion, these results provide the first evidence for TSPAN12 playing a role in supporting primary tumor growth and suppressing metastasis. TSPAN12 appears to function by stabilizing FZD4-LRP5 association, in support of canonical Wnt-pathway signaling, leading to enhanced β-catenin expression and function. [ABSTRACT FROM AUTHOR]