Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library.

Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z' > 0.7). The screening resulted in the identification of two novel noscapine derivatives as inhibitors of MDA cell growth with IC50 values of 5 µM and 1.5 µM, respectively. Both hit molecules have a five-fold and seventeen-fold higher potency, compared with that of lead compound noscapine (IC50 26 µM). The identified active derivatives retain the tubulin-binding ability of noscapine. Further testing of both hit molecules, alongside the natural product against additional cancer cell lines (HepG2, HeLa and PC3 cells) confirmed our initial findings. Both molecules have improved anti-proliferative properties when compared to the initial natural product, noscapine.

Impact of value congruence on work-family conflicts: the mediating role of work-related support.

Based on past research regarding the relationship between person-environment fit and work-family conflict (WFC), we examined the mediating effects of perceived organization/supervisor support on the relationship between person-organization/supervisor value congruence and WFC. A structural equation model was used to test three hypotheses using data collected from 637 workers in Taiwan. Person-organization value congruence regarding role boundaries was found to be positively correlated with employee perception of organizational support, resulting in reduced WFC. Person-supervisor value congruence regarding role boundaries also increased employee perception of organizational support, mediated by perceived supervisor support. Research and managerial implications are discussed.

Assessing potential effects of daily cross-domain usage of information and communication technologies.

A within-person diary research design with 39 full-time workers was used to examine the effects of daily cross-domain usage of information and communication technologies (ICTs) on job-related performance and stress in both workplace and home domains. Segmentation preference effects on links between cross-domain ICT usage and both job performance and job stress were also analyzed. A positive association was found for the first relationship in mixed home-workplace contexts, and a negative association for the second in home contexts only. A stronger segmentation preference effect on the negative relationship between cross-domain ICT usage and job stress was found for integrators (employees who integrate work and home domains) compared to separators (employees who separate work/non-work activities). Our findings suggest that daily cross-domain ICT usage can enhance job performance and reduce job stress, with a moderating effect of segmentation preference on the link between cross-domain ICT usage and job stress.

Mathematical model for bone mineralization.

Defective bone mineralization has serious clinical manifestations, including deformities and fractures, but the regulation of this extracellular process is not fully understood. We have developed a mathematical model consisting of ordinary differential equations that describe collagen maturation, production and degradation of inhibitors, and mineral nucleation and growth. We examined the roles of individual processes in generating normal and abnormal mineralization patterns characterized using two outcome measures: mineralization lag time and degree of mineralization. Model parameters describing the formation of hydroxyapatite mineral on the nucleating centers most potently affected the degree of mineralization, while the parameters describing inhibitor homeostasis most effectively changed the mineralization lag time. Of interest, a parameter describing the rate of matrix maturation emerged as being capable of counter-intuitively increasing both the mineralization lag time and the degree of mineralization. We validated the accuracy of model predictions using known diseases of bone mineralization such as osteogenesis imperfecta and X-linked hypophosphatemia. The model successfully describes the highly nonlinear mineralization dynamics, which includes an initial lag phase when osteoid is present but no mineralization is evident, then fast primary mineralization, followed by secondary mineralization characterized by a continuous slow increase in bone mineral content. The developed model can potentially predict the function for a mutated protein based on the histology of pathologic bone samples from mineralization disorders of unknown etiology.

Fast, progressive loading of binary-encoded declarative-3D Web content.

Until recently, a major drawback of declarative-3D approaches for the Web was the encoding of scene-graph-related structured data along with a text-based description of unstructured vertex data. Loading times were long, and 3D Web content wasn't available until the full page had completely loaded. To overcome this limitation requires external mesh data containers that are referenced in the scene description. In particular, sequential image geometry containers and explicit binary containers align well with GPU buffer structures, thus enabling fast decoding and GPU uploads. Furthermore, progressive binary geometry enables simple, yet highly progressive transmission of arbitrary mesh data on the Web.