Lawrence Livermore National Security, LLC

University of California

Other

The United States of America as Represented by the Department of Energy

The American University in Cairo

The Regents of California

Rodney L Balhorn

Sally Joan Denardo

Gerald Louis Denardo

Joe H Satcher, Jr

Olgica Bakajin

Stephen M Lane

Mehdi Balooch

Saleem H Zaidi

Joseph W Tringe

Christopher B Darrow

Wigbert J Siekhaus

Thomas R Huser

Christopher W Hollars

Hassan Azzazy

Christopher H Barry

Reem Al-Olaby

Robert J Tench

Michael J Allen

Sally J Denardo

Gerald L Denardo

This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Selective high-affinity polydentate ligands and methods of making such

The invention pertains to ligands that bind to CD81 and that inhibit or blockattachment to CD81, compositions and methods for preventing, inhibiting or treating infection byand ligands that target abinding site on CD81 and methods of making and using them. A series of ligand binding sites on the large extracellular loop of the open conformation of CD81 have been identified. Several important sites were located in regions identified by mutational studies to be the site ofbinding. Ligands that recognize these sites were identified. Linking together two or three ligands that bind with low or moderate affinities to different structurally unique sites on a target protein were used to generate small molecule ligand conjugates that exhibit very high affinities to their CD81 targets. Hybrid ligand molecules were also designed using fragment-based drug design methods to generate analogs of the ligands that bind more tightly to the protein than the parent compounds. Identification and design of groups of compounds that bind to CD81 for use as therapeutics for treating patients infected byand pathogens that interact with CD81. By binding to CD81, these molecules can block 1)attachment and entry into cells (infection), especially hepatocytes; 2) block or inhibit inflammatory responses caused by, and 3) block or inhibit the induction of other pathologies associated withinfection.

Ligands that targetsporozoite binding sites on CD81 and therapeutic methods using them

This invention provides polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each binds different regions on the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

A method of fabricating a nanoporous membrane filter having a uniform array of nanopores etch-formed in a thin film structure (e.g. (100)-oriented single crystal silicon) having a predetermined thickness, by (a) using interferometric lithography to create an etch pattern comprising a plurality array of unit patterns having a predetermined width/diameter, (b) using the etch pattern to etch frustum-shaped cavities or pits in the thin film structure such that the dimension of the frustum floors of the cavities are substantially equal to a desired pore size based on the predetermined thickness of the thin film structure and the predetermined width/diameter of the unit patterns, and (c) removing the frustum floors at a boundary plane of the thin film structure to expose, open, and thereby create the nanopores substantially having the desired pore size.

Method of fabricating a scalable nanoporous membrane filter

Selective high affinity polydentate ligands and methods of making such

A method and apparatus with the sensitivity to detect and identify single target molecules through the localization of dual, fluorescently labeled probe molecules. This can be accomplished through specific attachment of the taget to a surface or in a two-dimensional (2D) flowing fluid sheet having approximate dimensions of 0.5 &#x3bc;m&#xd7;100 &#x3bc;m&#xd7;100 &#x3bc;m. A device using these methods would have 10&#x2013;10greater throughput than previous one-dimensional (1D) micro-stream devices having 1 &#x3bc;minterrogation volumes and would for the first time allow immuno- and DNA assays at ultra-low (femtomolar) concentrations to be performed in short time periods (&#x2dc;10 minutes). The use of novel labels (such as metal or semiconductor nanoparticles) may be incorporated to further extend the sensitivity possibly into the attomolar range.

High-throughput, dual probe biological assays based on single molecule detection

Microscopic beads or other structures are attached to nucleic acids (DNA) using a terminal transferase. The transferase adds labeled dideoxy nucleotide bases to the ends of linear strands of DNA. The labels, such as the antigens digoxigenin and biotin, bind to the antibody compounds or other appropriate complementary ligands, which are bound to the microscopic beads or other support structures. The method does not require the synthesis of a synthetic oligonucleotide probe. The method can be used to tag or label DNA even when the DNA has an unknown sequence, has blunt ends, or is a very large fragment (e.g., >500 kilobase pairs).

DNA attachment to support structures

Instrumentation and techniques to image small objects, such as but not limited to individual human chromosomes, with nanometer resolution, to cut-off identified parts of such objects, to move around and manipulate such cut-off parts on the substrate on which they are being imaged to predetermined locations on the substrate, and to remove the cut-off parts from the substrate. This is accomplished using an atomic force microscope (AFM) and by modification of the conventional cantilever stylus assembly of an AFM, such that plural cantilevers are used with either sharp-tips or knife-edges thereon. In addition, the invention can be utilized for measuring hardness of materials.

Imaging, cutting, and collecting instrument and method

The control of fungus is a serious problem in the hatching of fish. Sodium dichromate, potassium dichromate and chromium trioxide are effective fungicides for the inhibition of fungal growth on fish eggs and young fry during hatching.

Fish egg fungicide

Growing community of inventors

Livermore, CA, United States of America

Rodney L Balhorn