Synthesis of CuII-RuII-CuII trinuclear complexes via redox reaction of copperI across thiosemicarbazones coordinated to rutheniumII.

Pyridine-2-carbaldehyde thiosemicarbazones [C5H4N1-C(H)N2-N3H-C(S)-N4HR, R = H, L1H2; CH3, L2H2-Me; CH2CH3, L3H2-Et] with Ru(PPh3)3Cl2 have formed mononuclear RuII precursors for the generation of trinuclear complexes. The reaction of 2 mol each of L1H2, L2H2-Me, or L3H2-Et with Ru(PPh3)3Cl2 in the presence of Et3N has yielded mononuclear complexes [Ru(N3,S-L1H)2(PPh3)2] (1), [Ru(N3,S-L2H-Me)2(PPh3)2] (2), and [Ru(N3,S-L3H)2(PPh3)2] (3). The addition of 2 equiv of copperI chloride solution to complex 1 in acetonitrile has formed a novel trinuclear complex, (Ph3P)2RuII(L1)2CuII2Cl2 (4), in which the pendant amino group (-N4H2) loses one hydrogen along with the oxidation of CuI to CuII. In this complex, RuII is bonded to two P, two S, and two N3 atoms, while each CuII is coordinated to N1, N2, N4, and Cl atoms. Reaction with copper(I) bromide yielded a similar trinuclear complex, (Ph3P)2Ru(L1)2CuII2Br2 (5). From precursors 2 and 3, analogous complexes (Ph3P)2RuII(L2-Me)2CuII2Cl2 (6), (Ph3P)2RuII(L2-Me)2CuII2Br2 (7), (Ph3P)2RuII(L3-Et)2CuII2Cl2 (8), and (Ph3P)2RuII(L3-Et)2CuII2Br2 (9) have been synthesized. These complexes have been characterized using analytical, spectroscopic, and electrochemical techniques. Single-crystal X-ray crystallography has been carried out for precursor 2 and all of the trinuclear complexes, 4-9. X-band electron spin resonance and UV-vis spectra have confirmed the presence of CuII. The cyclic voltammetry studies support the RuII/RuIII redox behavior of this metal in trinuclear complexes.

The physiology analysis system: an integrated approach for warehousing, management and analysis of time-series physiology data.

The physiology analysis system (PAS) was developed as a resource to support the efficient warehousing, management, and analysis of physiology data, particularly, continuous time-series data that may be extensive, of variable quality, and distributed across many files. The PAS incorporates time-series data collected by many types of data-acquisition devices, and it is designed to free users from data management burdens. This Web-based system allows both discrete (attribute) and time-series (ordered) data to be manipulated, visualized, and analyzed via a client's Web browser. All processes occur on a server, so that the client does not have to download data or any application programs, and the PAS is independent of the client's computer operating system. The PAS contains a library of functions, written in different computer languages that the client can add to and use to perform specific data operations. Functions from the library are sequentially inserted into a function chain-based logical structure to construct sophisticated data operators from simple function building blocks, affording ad hoc query and analysis of time-series data. These features support advanced mining of physiology data.

Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays.

A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and array-based serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations.

Onto-Tools: an ensemble of web-accessible, ontology-based tools for the functional design and interpretation of high-throughput gene expression experiments.

The Onto-Tools suite is composed of an annotation database and five seamlessly integrated web-accessible data mining tools: Onto-Express (OE), Onto-Compare (OC), Onto-Design (OD), Onto-Translate (OT) and Onto-Miner (OM). OM is a new tool that provides a unified access point and an application programming interface for most annotations available. Our database has been enhanced with more than 120 new commercial microarrays and annotations for Rattus norvegicus, Drosophila melanogaster and Carnorhabditis elegans. The Onto-Tools have been redesigned to provide better biological insight, improved performance and user convenience. The new features implemented in OE include support for gene names, LocusLink IDs and Gene Ontology (GO) IDs, ability to specify fold changes for the input genes, links to the KEGG pathway database and detailed output files. OC allows comparisons of the functional bias of more than 170 commercial microarrays. The latest version of OD allows the user to specify keywords if the exact GO term is not known as well as providing more details than the previous version. OE, OC and OD now have an integrated GO browser that allows the user to customize the level of abstraction for each GO category. The Onto-Tools are available online at http://vortex.cs.wayne.edu/Projects.html.