Abstract: Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.

Abstract: Systems and methods for the quantitative automated analysis of pathology samples identify groups of spatially-associated similar cells. Cells may be identified as belonging to a group on the basis of spatial location and biomarkers. In some embodiments the biomarkers are multicolour fluorescence in situ hybridization (FISH) signals. Characteristics of the cells in a group may be combined to provide quantitative FISH results that may compensate for variations and artefacts such as thin sectioning that can result in the loss of information due to damage. In heterogeneous tissue samples, grouping cells can permit quantitative results regarding pathological cells to be extracted despite the presences of infiltrating non pathological cells.

Abstract: Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.

Abstract: Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.

Abstract: Agents that reduce the amount of IGFBP-2 and/or IGFBP-5 and that are known to be useful in the treatment of cancer result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. In overcoming this, the present invention provides a combination of therapeutic agents that is useful in the treatment of cancer. The combination includes an agent that reduces the amount of IGFBP-2 and/or IGFBP-5 and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells. In some embodiments of the invention, the agent that reduces IGFBP-2 and/or IGFBP-5 is a bispecific antisense species. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.

Abstract: This invention provides compound having a structure of Formula I or Formula II Uses of such compounds for treatment of various indications, including prostate cancer as well as methods of treatment involving such compounds are also provided.

Abstract: Methods for determining a point-of-gaze (POG) of a user in three dimensions are disclosed. In particular embodiments, the methods involve: presenting a three-dimensional scene to both eyes of the user; capturing image data including both eyes of the user; estimating first and second line-of-sight (LOS) vectors in a three-dimensional coordinate system for the user's first and second eyes based on the image data; and determining the POG in the three-dimensional coordinate system using the first and second LOS vectors.

Abstract: Methods and apparatus for separating, concentrating and/or detecting molecules based on differences in binding affinity to a probe are provided. The molecules may be differentially modified. The molecules may be differentially methylated nucleic acids. The methods can be used in fields such as epigenetics or oncology to selectively concentrate or detect the presence of specific biomolecules or differentially modified biomolecules, to provide diagnostics for disorders such as fetal genetic disorders, to detect biomarkers in cancer, organ failure, disease states, infection or the like.

Abstract: Embodiments presented herein relate to various polymers. Some of the polymer embodiments are heparin binding polymers. Some embodiments of the heparin binding polymers can be employed to bind to heparin for methods such as separating, purifying, removing, and/or isolating heparin and heparin like molecules.

Abstract: The invention relates to, in part, secreted proteins of bacterial pathogens and methods for their use. More specifically, the invention provides in part several new common secreted proteins for A/E pathogens. In some embodiments of the invention, these polypeptides and nucleic acid molecules encoding these polypeptides, or portions thereof, are useful as vaccines, diagnostics, or drug screening tools for A/E pathogenic infections, or as reagents.

Abstract: The present invention provides methods of detecting mutations in a Gnaq gene in a melanocytic neoplasm for diagnostic and prognostic purposes. The invention further provides methods of treating such melanocytic neoplasm by modulating the activity of the mutated Gnaq gene.

Abstract: Therapeutic agents which target heat shock protein (hsp) 27 in vivo are used to provide treatment to individuals, particularly human individuals, suffering from prostate cancer and other cancers that overexpress hsp27. A therapeutic agent, for example an antisense oligonucleotide or RNAi nucleotide inhibitor with sequence specificity for hsp27 mRNA, for example human hsp27 mRNA, is administered to an individual suffering from prostate cancer or some other cancer expressing elevated levels of hsp 27 in a therapeutically effective amount. The therapeutic agent is suitably formulated into a pharmaceutical composition which includes a pharmaceutically acceptable carrier, and packaged in dosage unit form. A preferred dosage unit form is an injectable dosage unit form.

Abstract: This document relates to methods and materials for detecting mutations that can be linked to dementia. For example, methods and materials for detecting one or more mutations within PGRN nucleic acid are provided. This document also provides methods and materials for detecting the level of progranulin expression. In addition, this document relates to methods and materials for treating mammals having a neurodegenerative disorder (e.g., dementia). For example, methods and materials for increasing PGRN polypeptide levels in mammals are provided, as are methods and materials for identifying agents that can be used to increase PGRN polypeptide levels in mammals.

Abstract: Methods and apparatus for moving and concentrating particles apply an alternating driving field and an alternating field that alters mobility of the particles. The driving field and mobility-varying field are correlated with one another. The methods and apparatus may be used to concentrate DNA or RNA in a medium, for example. Methods and apparatus for extracting particles from one medium into another involve applying an alternating driving field that causes net drift of the particles from the first medium into the second medium but no net drift of the particles in the second medium.

Abstract: Systems and methods are provided for predicting a circadian state of an individual. The methods comprise: providing a model representative of the response of the circadian state to light stimulus, the model comprising at least one model variable representative of a probability distribution function (PDF) of a phase offset of the circadian state of the individual; and using the model to estimate an updated PDF of the phase offset, wherein using the model to estimate the updated PDF of the phase offset comprises performing a Bayesian estimation process commencing with an initial PDF of the phase offset and iterating toward the updated PDF of the phase offset.

Abstract: Particles may be injected into a matrix for concentration by scodaphoresis using a quadrupole injection field. Particles may be injected from two or more sample chambers simultaneously. Particle injection may be performed simultaneously with performing scodaphoresis. In some embodiments the particles are concentrated into a well containing fluid. The well can extend out of a plane of the matrix. Altering the relative phases of components of a scodaphoresis field permits concentration of selected particles and exclusion of other particles. Scodaphoresis methods may be applied to DNA, other bio-molecules and other particles.

Abstract: A gaseous-fuelled internal combustion engine and a method of engine operation improve combustion stability and reducing emissions of NOx, PM, and unburned hydrocarbons. The method comprises fuelling an internal combustion engine with hydrogen and natural gas, which can be directly injected into the combustion chamber together or introduced separately. Of the total gaseous fuel delivered to the engine, at least 5% by volume at standard temperature and pressure is hydrogen. For at least one engine operating condition, the ratio of fuel rail pressure to peak in-cylinder pressure is at least 1.5:1. A fuel injection valve introduces the gaseous fuel mixture directly into the combustion chamber. Two separate fuel injection valves could also introduce the methane and hydrogen separately. An electronic controller controls timing for operating the fuel injection valve(s). The engine has a preferred compression ratio of at least 14:1.

Abstract: Agents that reduce the amount of IGFBP-2 and/or IGFBP-5 and that are known to be useful in the treatment of cancer result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. In overcoming this, the present invention provides a combination of therapeutic agents that is useful in the treatment of cancer. The combination includes an agent that reduces the amount of IGFBP-2 and/or IGFBP-5 and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells. In some embodiments of the invention, the agent that reduces IGFBP-2 and/or IGFBP-5 is a bispecific antisense species. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.

Abstract: Administration of antisense oligodeoxynucleotides (ODN) targeted against the testosterone-repressed prostate message-2 (TRPM-2) gene can reduce the amount of TRPM-2 in renal cell cancer (RCC) cells and other cancer cells, and as a result enhance chemosensitivity of these cells to chemotherapy agents and radiation. Thus, for example, the sensitivity of renal cell cancer cells to a chemotherapeutic agent can be increased by exposing renal cell cancer cells to a chemotherapeutic agent and an agent which reduces the amount of TRPM-2 in the renal cell cancer cells. This provides an improved method for treatment of renal cell cancer, which is generally resistant to treatment with known chemotherapy agents.

Abstract: Methods for determining a point-of-gaze (POG) of a user in three dimensions are disclosed. In particular embodiments, the methods involve: presenting a three-dimensional scene to both eyes of the user; capturing image data including both eyes of the user; estimating first and second line-of-sight (LOS) vectors in a three-dimensional coordinate system for the user's first and second eyes based on the image data; and determining the POG in the three-dimensional coordinate system using the first and second LOS vectors.