Abstract: The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo.

Abstract: The present invention relates to nanoparticles. In particular, the present invention provides nanoparticles for clinical (e.g., targeted therapeutic), diagnostic (e.g., imaging), and research applications in the field of cardiology. For example, in some embodiments, the present invention provides a method of treating (e.g., ablating) cardiac tissue, comprising: a) contacting an animal with a nanoparticle comprising a matrix, a toxic (e.g., ablative) agent (e.g., sonosensitizer, chemotherapeutic agent (e.g., doxorubicin or cisplatin), or photosensitizer), and a cardiac targeting moiety; and b) administering an activator of the toxic agent (e.g., light, chemical (e.g., pharmaceutical agent) or ultrasound) to at least a portion of the cardiac tissue (e.g., heart) of the animal to activate the toxic agent.

Abstract: Disintegrin variants that bind specifically to one or more of ?5?1 and ?v integrins, such as ?v?1, ?v?3, ?v?5, ?v?6 and ?v?8, but with reduced binding activity to ?IIb?3, are described. Also described are uses of the disintegrin variants for the treatment or prevention of a disease associated with an ?v integrin or an ?5?1 integrin.

Abstract: A method for treating an infection comprises administering a peptide in synergistic combination with an antibiotic, wherein the peptide comprises an amino acid sequence with a formula selected from the group consisting of: Bn1-Z;??(a) Bn1-Z-Bn2; and??(b) Z-Bn1??(c) wherein B is a basic amino acid residue; n1 and n2 are 1 to 6; and Z is a sequence of from about 7 to about 24 amino acid residues, said sequence having an average hydrophobicity value of at least 0.3 on the Liu-Deber scale.

Abstract: The present invention is directed to novel non-invasive diagnostic tools/compounds to image cancers, especially, melanoma, including metastatic melanoma in vivo. The present compounds exhibit enhanced uptake in cancerous cells and tissue and decreased renal uptake in kidney, evidencing favorable pharmacokinetics of compounds of the present invention. The compounds according to the present invention represent an advance in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention are also useful for initiating therapy for melanoma as well as monitor patients' response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma/metastatic melanoma. Compounds according to the present invention may be used as diagnostic tools for a number of conditions and diseases states as well as therapeutic agents for treating such conditions and disease states.

Abstract: The present invention relates to a novel protein secretion factor, a vector including a nucleic acid sequence encoding the protein secretion factor, and a transformed cell into which the vector is introduced. The invention also relates to a method of producing a target protein using the transformed cell including the vector.

Abstract: Disclosed are knottin peptides containing non-natural amino acids so that they can be formed by chemical conjugation into two or more knottin monomers. The knottin monomers comprise a non-natural amino acid such as an aminooxy residue within the polypeptide sequence. The exemplified dimers were produced by oxime formation between two aldehyde groups present on a polyether linker and an aminooxy functional group that was site-specifically incorporated the knottin. Knottins variants based on EETI (Ecballium elaterium trypsin inhibitor) and AgRP (Agouti-related protein) were engineered to contain integrin-binding loops. These dimers were shown to have increased binding strength to integrins on U87MG tumor cells, achieving significant increases in inhibition of cell adhesion and proliferation. Also disclosed are knottin monomers comprising an aminooxy residue; these may be conjugated to molecules such as doxorubicin.

Abstract: This invention relates to a pharmaceutical composition for parenteral or oral administration containing a radioactive compound which can be used diagnostically or therapeutically. The composition comprises a micro-emulsion constituted by a dispersion of vesicles or microsponges of a fatty acid based component in an aqueous or other pharmacologically acceptable carrier in which nitrous oxide is dissolved, the fatty acid based component comprising at least one long chain fatty acid based substance selected from the group consisting of free fatty acids and derivatives of free fatty acids, and the radioactive compound.

Abstract: The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, which have a decreased potential for abuse of hydrocodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

Abstract: The present invention relates to the cosmetic and/or nutraceutical use of an extract of the Lythrum salicaria plant and/or of gallic acid and/or one of the gallic acid derivatives, in particular vescalagin and/or castalagin. Provided is a cosmetic care process comprising the application, preferably topically, of the Lythrum salicaria extract according to the invention and/or of gallic acid and/or of one of the gallic acid derivatives, in particular vescalagin and/or castalagin, more preferentially castalagin, or of a cosmetic composition comprising it, for maintaining and/or increasing collagen expression in the skin and/or the mucous membranes, for increasing the firmness of the skin and/or of the mucous membranes and/or maintaining and/or increasing lipolysis in skin adipocytes for inducing a slimming effect onto the skin and/or decreasing, preventing and/or treating the unaesthetic manifestations of cellulite, for example the orange peel appearance of the skin and/or the jodhpur thigh appearance.

Abstract: Disclosed is a compound of formula (I): wherein L, R1-R5, A, B, M, and n are as defined in the specification, as well as a method of preparing the compound. Also disclosed are a method of blood-pool imaging in a mammal and a method of imaging a lymph node in a mammal, comprising use of the compound.

Abstract: Urea-based photosensitizers, which target prostate-specific membrane antigen (PSMA) for imaging and targeted therapy of PSMA-expressing tumors and cancers are disclosed.

Abstract: Embodiments of the invention provide shaped masses comprising one or more drugs such as proteins or polypeptides and methods for forming such shaped masses. One embodiment provides a shaped mass comprising a drug such as a protein or polypeptide having a biological activity in the body of a mammal. The shaped mass is formed by compression of a precursor material comprising the drug wherein an amount of biologically active drug in the mass is a preserved above a minimum level. Drugs which may be incorporated into the shaped mass may include one or more glucose regulating proteins such as insulin, incretins; and immunoglobulins such as TNF-inhibiting antibodies or interleukin neutralizing antibodies. Embodiments of the shaped mass may be incorporated into a tissue penetrating member which is inserted into the intestinal wall allowing for the oral delivery of proteins and peptides which would otherwise be degraded in the intestinal tract.

Abstract: The present invention relates to a composition and a combination comprising at least one first drug and at least one protein-binding prodrug, wherein the proteinbinding prodrug comprises a protein-binding group, a second drug, and a linker that can be cleaved hydrolytically, enzymatically, or in a pH-dependent manner in the body, as well as to a kit and a pharmaceutical composition comprising said composition or combination.

Abstract: The present invention relates to a peptide for preventing or treating inflammatory diseases and a use thereof. According to the novel dimeric or trimeric peptide according to the present invention, it is possible to not only exhibit an excellent therapeutic effect through anti-inflammatory action but also have a very small-sized peptide, thereby minimizing side effects due to the administration of external substances. Therefore, it is expected that the peptide can be used as an active substance that can replace existing therapeutic agents for inflammatory diseases.

Abstract: Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences, such as truncated LyP-1 peptides, that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

Abstract: An assay that informs precision-based intrapleural fibrinolytic therapy (IPFT) is disclosed. Provided is a simple assay based on measurement of the Fibrinolytic Potential (FP)—total fibrinolytic activity in pleural fluid when plasminogen activator inhibitors (PAIs) are neutralized and endogenous plasminogen (PLG) is activated. The assay is used to determine FP in baseline pleural fluids of patients undergoing IPFT with agents such as tPA or scuPA to determine the dose and dose intervals for the particular patient. Pleural fluids are also collected after IPFT to confirm that intrapleural fibrinolysis is inhibited and endogenous PLG accumulates in the pleural fluid. Inhibition of intrapleural fibrinolysis in combination with its increase after supplementation of pleural fluid with a plasminogen activator indicates whether or not the subject should be treated with more or higher doses of an IPFT drug.

Abstract: The present invention relates to a complex prepared by conjugating indocyanine green to mannosyl serum albumin in order to overcome shortcomings such as low light stability and low in vivo stability of indocyanine green that is a fluorescent dye reagent that is used during surgical operations, a preparation method thereof, an optical imaging probe comprising the same, and a kit comprising the probe.

Abstract: This document provides polypeptide inhibitors of Smad3 polypeptide activities. For example, methods and materials for using polypeptides (e.g., polypeptides designed to include both a cell penetrating amino acid sequence and an amino acid segment of a SH3 domain of a SNX9 polypeptide) to inhibit one or more Smad3 polypeptide activities are provided. This document also provides methods and materials for using RNA interference to treat a disease (e.g., a fibrotic disease) in a mammal (e.g., a human).

Abstract: A flow-through sampling apparatus for sampling a bulk solid mixture includes a main body forming an opening. A screen is located in the opening and forms a plurality of sample zones within the main body. The apparatus further includes a first slide door that is movable above the screen so as to close one side of the opening. Further, the apparatus includes a second slide door that is movable below the screen so as to close the other side of the opening.

Abstract: A compound includes at least one targeting peptide coupled to a detectable moiety. The targeting peptide binds to EDB-FN or EDA-FN and includes at least one of amino acid sequence selected from the group consisting of SEQ ID NOs: 1-30.

Abstract: The present invention relates to an immunostimulatory nanocomplex. The immunostimulatory nanocomplex comprises polyglutamic acid (PGA), a first positively charged substance, a second positively charged substance and a dengue viral protein for holding the dengue viral protein inside. The immunostimulatory nanocomplex is characterized by having a nonuniformally and positively charge distribution along a radial direction thereof. The nonuniformally and positively charge distribution comprises a first electrically charged portion having substantially electrical neutrality, a second electrically charged portion surrounding the first electrically charged portion, and a third electrically charged portion surrounding the second electrically charged portion.

Abstract: PEGylated diaspirin-crosslinked hemoglobin conjugates having high oxygen affinity are described which have enhanced nitrite reductase activity to deliver oxygen, carbon monoxide, nitric oxide or mixtures thereof to tissues to treat various diseases and conditions.

Abstract: Some aspects of this invention are based on the recognition that reversible protein multimers in which monomeric proteins are conjugated to a carrier molecule via chelation complex bonds are stable under physiological conditions and can be dissociated in a controlled manner under physiological, nontoxic conditions. Accordingly, such protein multimers are useful for a variety of in vitro, ex vivo, and in vivo application for research, diagnostics, and therapy. Some aspect of this invention provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized.

Abstract: Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair damaged tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to an ischemia-associated molecule; and (b) an activator domain that that detectably modulates the activity of a cellular network.

Abstract: Provided herein is a construct comprising, in combination: an EphA3, EphA2 and/or EphB2 binding ligand; and at least one effector molecule. In some embodiments, the at least one effector molecule comprises a therapeutic agent, a nanoparticle, a detectable group, a lipid, or a liposome. In some embodiments, the construct is a fusion protein and/or a covalent conjugate. Further provided is a construct comprising in combination: a ligand that binds to EphA2, EphA3 and/or EphB2; a ligand that binds to IL-13R?2; and at least one effector molecule. Also provided are methods of use thereof for treating cancer.

Abstract: A peptide that can be used as an imaging probe for GLP-1R is provided. In an embodiment, a polypeptide is represented by the following formula (3); (Sequence ID No. 3) Xaa1-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg- Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser- Ser-Gly-Ala-Pro-Pro-Pro-Ser (3) where Xaa1 represents an aspartic acid in which a —Y—X? group binds to an ?-amino group, X? includes a chelating site and a radioactive metal nuclide chelated by the chelating site, the chelating site being diethylenetriaminepentaacetic dianhydride (DTPA) or 1,4,7-triazacyclononnane-N,N?,N?-triacetic acid (NOTA), and Y represents a linker including a group selected from the group consisting of —CH2—(C6H4)—, —NH—C(?S)—, —NH—(CH2)5—C(?O)—, and a combination thereof.

Abstract: There is provided a positron-emitting radionuclide labelled peptide for non-invasive PET imaging of the Urokinase-type Plasminogen Activator Receptor (uPAR) in humans. More specifically the invention relates to human uPAR PET imaging of any solid cancer disease for diagnosis, staging, treatment monitoring and especially as an imaging biomarker for predicting prognosis, progression and recurrence.

Abstract: A high drug loading system is described comprising of at least one anticancer drug; at least one peptide; and at least one nucleic acid.

Abstract: Short bioactive sequences derived from the 2nd loop of the 7-transmembranal receptor of endothelial differentiation gene 3 (EDG3) useful in stimulation of angiogenesis, and peptide conjugates comprising a permeability enhancing moiety, are provided. Also provided are pharmaceutical compositions comprising the peptides and methods of use in conditions were insufficient blood-supply occurs, or which are associated with endothelia dysfunction such as peripheral vascular diseases, coronary artery diseases, cerebrovascular diseases, diabetes and delayed wound healing, pulmonary disease, eye diseases and pathological condition related to severe infection.

Abstract: The present invention relates to probes for use in the detection, imaging, diagnosis, targeting, treatment, etc. of cancers expressing the gastrin releasing peptide receptor (GRPR). For example, such probes may be molecules conjugated to detectable labels which are preferably moieties suitable for detection by gamma imaging and SPECT or by positron emission tomography (PET) or magnetic resonance imaging (MRI) or fluorescence spectroscopy or optical imaging methods.

Abstract: The present disclosure relates to a method and a pharmaceutical composition for hair growth. The pharmaceutical composition includes a hair growth peptide (HGP) which includes all or part of the amino acid sequence SEQ ID No: 1. The method includes administering a hair growth peptide (HGP) which includes all or part of the amino acid sequence SEQ ID No: 1 to an interest.

Abstract: Disclosed are hypoallergenic variants of Phl p 5, the major allergen from Phleum pratense, and the uses thereof in the treatment of allergic diseases.

Abstract: The present invention relates to a polypeptide binding to human serum albumin and comprising or consisting of an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDY(X1)(X2)(X3)(X4)(X5) (X6)D(X7)SFHKGEKFQIL(X8)(X9)(X10)(X11)(X12)G(X13)(X14)W(X15)(X16)RSLTTG(X17)(X18)G(X19)IPSNYVAPVDSIQ (SEQ ID NO: 1), wherein (X1) is A, V, I, L, M, G, P, S, T, N, Q, C, R, H, K, D or E; (X2) is R, H, K, A, V, I, L, M, G, P, S, T, N, Q or C; (X3) is R, H, K, S, T, N, Q, C, F, Y, W, A, V, I, L, M, G or P; (X4) is S, T, N, Q, C, A, V, I, L, M, G, P, R, H, K, F, Y, W, D or E; (X5) is S, T, N, Q, C, D, E, F, Y, W, A, V, I, L, M, G, P, R, H or K; (X6) is F, Y, W, A, V, I, L, M, G, P, R, H, K, S, T, N, Q or C; (X7) is A, V, I, L, M, G, P, R, H or K; (X8) is S, T, N, Q, C, D or E; (X9) is S, T, N, Q, C, D, E, A, V, I, L, M, G, P, F, Y or W; (X10) is A, V, I, L, M, G or P; (X11) is F, Y, W, R, H or K; (X12) is S, T, N, Q, C, F, Y or W; (X13) is F, Y, W, R, H, K, S, T, N, Q, C, D, E, A, V, I, L, M, G or P; (X14) is

Abstract: The invention provides compositions useful as molecular probes. In particular, the invention provides activatable cell penetrating peptides comprising a fluorescence donor and a fluorescence acceptor. Exemplary fluorescence donors and fluorescence acceptors include compounds derived from cyanine. Also provided are ratiometric, multispectral, and excitation lifetime imaging methods for detecting the molecular probes provided herein.

Abstract: Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A-X-B-C)-M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.

Abstract: The present disclosure generally relates to the use of des-aspartate-angiotensin I and/or its derivatives in medicine. In particular, the present invention relates to the use of des-aspartate-angiotensin I and/or its derivatives for the treatment and/or prophylaxis of inflammatory diseases or pathologies, for inducing anti-inflammatory actions and/or reducing inflammation, and/or for treatment of inflammation-related conditions.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of Erythropoietic Protoporphyria. In particular, the present invention relates to a method for increasing the amount of functional FECH in a erythroid cell carrying the hypomorphic allele IVS3 48C/T (rs2272783) in trans to a deleterious mutation in the FECH gene comprising the step of consisting of bringing the erythroid cell into contact with at least one antisense oligonucleotide (ASO) comprising the sequence as set forth by SEQ ID NO: 2 (5? gcagcctgagaaatgtttt 3?) to prevent splicing of the cryptic exon inserted into the mutant IVS3 48C/T (rs2272783) FECH mRNA.

Abstract: In one aspect the present invention is directed to mutant NGAL proteins that have the ability to bind to siderophores, such as enterochelin, and to chelate and transport iron, and that are excreted in the urine. Such NGAL mutants, and complexes thereof with siderophores, can be used to clear excess iron from the body, for example in the treatment of iron overload. The NGAL mutants of the invention also have antibacterial activity and can be used in the treatment of bacterial infections, such as those of the urinary tract.

Abstract: The present invention provides a nano/micro bubble system for drug delivery comprising a gas core, a plurality of surfactants and an active ingredient. The surfactants surround the gas core and form a double-layer structure having an inner layer and outer layer. The active ingredient is embedded in a gap formed between the inner layer and the outer layer of the double-layer structure and comprises a nucleic acid, a peptide or a protein.

Abstract: Observations regarding the role of MUC1 in promoting the nuclear accumulation of EGFR led us to propose the development of peptides to block nuclear accumulation of EGFR as a means to block breast cancer progression. One exemplary peptide, the ENLS1 peptide, promotes cell death in breast cancer cell lines. Studies in the MMTV-pyMT mouse model of breast cancer demonstrate significant anti-tumor activity.

Abstract: Disclosed are knottin peptides containing non-natural amino acids so that they can be formed by chemical conjugation into two or more knottin monomers. The knottin monomers comprise a non-natural amino acid such as an aminooxy residue within the polypeptide sequence. The exemplified dimers were produced by oxime formation between two aldehyde groups present on a polyether linker and an aminooxy functional group that was site-specifically incorporated the knottin. Knottins variants based on EETI (Ecballium elaterium trypsin inhibitor) and AgRP (Agouti-related protein) were engineered to contain integrin-binding loops. These dimers were shown to have increased binding strength to integrins on U87MG tumor cells, achieving significant increases in inhibition of cell adhesion and proliferation. Also disclosed are knottin monomers comprising an aminooxy residue; these may be conjugated to molecules such as doxorubicin.

Abstract: Disclosed are antibody drug conjugates (ADC) that include highly potent toxic agents with specific antibodies to target tumors. Also disclosed are related antibodies, polypeptides, nucleic acids, host cells, compositions, and uses.

Abstract: The present invention relates to imaging agent compositions comprising radiolabelled c-Met binding peptides suitable for positron emission tomography (PET) imaging in vivo. The c-Met binding peptides are labelled with the radioisotope 18F. Also disclosed are pharmaceutical compositions, methods of preparation of the agents and compositions, plus methods of in vivo imaging using the compositions, especially for use in the management of cancer.

Abstract: This invention relates is a label-free, enzyme-free, aptamer-free method for simultaneously measuring adenosine, and its intracellular metabolites, e.g., AMP, ADP and ATP, using high pressure liquid chromatography coupled to electrochemical detector (HPLC-ECD).

Abstract: The present invention is directed to novel non-invasive diagnostic tools/compounds to image cancers, especially, melanoma, including metastatic melanoma in vivo. The present compounds exhibit enhanced uptake in cancerous cells and tissue, suggesting favorable selective activity of compounds according to the present invention, which can be used as effective therapeutic agents against melanoma, including metastatic melanoma. The compounds according to the present invention represent an advance in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention are useful to initiate therapy for melanoma as well as monitor patients' response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma/metastatic melanoma. Compounds according to the present invention may be used as diagnostic and therapeutic tools for a number of conditions and diseases states, especially melanoma.

Abstract: The invention provides a method of treating a tumor or other lesion comprising introducing a solution comprising one or more radioactive isotopes directly into said tumor or other lesion in a mammal to effect in situ precipitation of a radioactive precipitate in the tumor or other lesion.

Abstract: The invention provides dendrimers, conjugates thereof, and methods of using dendrimer conjugates. In one embodiment, the invention provides novel polymeric dendrimers as a new class of fluorescent labels. The labels can include multiple fluorescent dye molecules conjugated to a single polymeric backbone or core, such as a dendrimer. The dendrimers can have regular or irregular branched polymeric network structures that allow for the chemical attachment of multiple dye molecules, multiple color dyes, and/or multiple functional groups, in a combinatorial fashion. The fluorescent dendritic nanoprobes (FDNs) thus provide a new class of fluorescent reporters for fluorescence microscopy and imaging.

Abstract: The performance of traditional speech recognition systems (as applied to information extraction or translation) decreases significantly with, larger domain size, scarce training data as well as under noisy environmental conditions. This invention mitigates these problems through the introduction of a novel predictive feature extraction method which combines linguistic and statistical information for representation of information embedded in a noisy source language. The predictive features are combined with text classifiers to map the noisy text to one of the semantically or functionally similar groups. The features used by the classifier can be syntactic, semantic, and statistical.

Abstract: Screening and diagnostic reagents, kits and methods for primary and or metastatic stomach or esophageal cancer are disclosed. Compositions for and methods of imaging and treating primary and/or metastatic stomach or esophageal cancer are disclosed. Vaccines compositions and methods of for treating and preventing primary and/or metastatic stomach for esophageal cancer are disclosed.