A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

An Amphiphilic BODIPY‐Porphyrin Conjugate: Intense Two‐Photon Absorption and Rapid Cellular Uptake for Two‐Photon‐Induced Imaging and Photodynamic Therapy

The new amphiphilic BODPY‐porphyrin conjugate BZnPP and its precursor BZnPH were synthesised, and their linear and two‐photon photophysical properties, together with their cellular uptake and photo‐cytotoxicity, were studied. This amphiphilic conjugate consists of a hydrophobic BODIPY moiety and a hydrophilic tetra(ethylene glycol) chain bridging a cationic triphenylphosphonium group to an amphiphilic porphyrin ZnP through acetylide linkers at its meso positions. A large two‐photon absorption cross‐section (σ=1725 GM) and a high singlet oxygen quantum yield (0.52) were recorded. Intense linear‐ and two‐photon‐induced red emissions were also observed for both BZnPP and BZnPH. Further in vitro studies showed that BZnPP exhibited very efficient cellular uptake and strong photocytotoxic but weak dark cytotoxic properties towards human breast carcinoma MCF‐7 cells. In summary, the two‐photon‐induced emission and the potent photo‐cytotoxicity of BZnPP make it an efficacious dual‐purpose tumour‐imaging and photodynamic therapeutic agent in the tissue‐transparent spectral windows.     

Policy Based Mobility &; Flow Management for IPv6 Heterogeneous Wireless Networks

We propose a dynamic mobility management framework for Internet Protocol version 6 (IPv6) and policy enforcement enabled heterogenous wireless networks. Policies and policy rules are defined depending on network infrastructure facilities, service agreements and negotiation results. Each traffic is coupled with an identifiable traffic flow while the heterogenous interface flow bindings are regulated by polices. The network selection, flow distribution, handovers and mobility procedures are flexible and we propose to improve the decision making via Multiple Attributes Decision Making (MADM). Techniques considered in the framework include the IPv6 based Network Mobility (NEMO), multihoming capability, transparent vertical handovers, horizontal handovers and dynamic policy enforcement matching process to improve the Quality of Service (QoS), Quality of Experience (QoE) and ubiquitous connectivity. A experiment testbed and simulation models have been constructed to verify the mobility framework performance in a heterogeneous WiFi, WiMax and UMTS hybrid environment.     

Hierarchical B-picture mode decision in H.264/SVC

To enable robust video transmission over heterogeneous networks, the hierarchical B-picture prediction structure is employed in the state-of-the-art video coding standard H.264/SVC, aiming to produce scalable bitstreams with various frame rates. However, the exhaustive mode decision process with the hierarchical B-picture structure increases the computational complexity of H.264/SVC encoding dramatically. In this paper, a fast mode decision algorithm is proposed to speed up H.264/SVC encoding with the hierarchical B-picture structure, which is achieved by utilizing macroblock (MB) features, correlation of temporal–spatial neighboring MBs, and the discrepant characteristics of hierarchical layers. Extensive experimental results demonstrate that the proposed algorithm is able to reduce the encoding time of H.264/SVC significantly for video sequences with a wide range of resolutions, and meanwhile the video quality and compression ratio are well preserved.