Abstract: The disclosure provides multimeric proteins comprising three, four, or more monomer polypeptides, each comprising a first 4-1BB-targeting moiety, an oligomerization moiety, and optionally a linker. The monomer polypeptide may further comprise one or more additional targeting moieties. The oligomerization moiety promotes the trimerization, tetramerization, or higher state of oligomerization of the monomer polypeptides. Such multimeric proteins can be used in many pharmaceutical applications, for example, as anti-cancer agents and/or immune modulators. The present disclosure also concerns methods of making the multimeric proteins described herein as well as compositions comprising such multimeric proteins. The present disclosure further relates to nucleic acid molecules encoding such multimeric proteins and methods for the generation of such multimeric proteins and nucleic acid molecules.

Abstract: A reentry guide tool includes an overshot defining a lower end and comprises a bowl and grapple. The bowl defines an interior space of the overshot, and the grapple is disposed in the bowl and is operable to engage a tubular. A tubular guide nipple has a downhole and an uphole end, the downhole end complementary to the overshot and the uphole end complementary to the reentry guide. The guide nipple is operable to connect and provide a transition between the overshot and reentry guide. The reentry guide is a tubular piece having an uphole end with a bevel. A deployment mechanism is defined on the overshot, reentry guide, or guide nipple, and is operable to connect the reentry guide to a running tool for deployment. A method of providing a transition from a first to a second tubular in a wellbore is also provided.

Abstract: A reentry guide tool includes an overshot defining a lower end and comprises a bowl and grapple. The bowl defines an interior space of the overshot, and the grapple is disposed in the bowl and is operable to engage a tubular. A tubular guide nipple has a downhole and an uphole end, the downhole end complementary to the overshot and the uphole end complementary to the reentry guide. The guide nipple is operable to connect and provide a transition between the overshot and reentry guide. The reentry guide is a tubular piece having an uphole end with a bevel. A deployment mechanism is defined on the overshot, reentry guide, or guide nipple, and is operable to connect the reentry guide to a running tool for deployment. A method of providing a transition from a first to a second tubular in a wellbore is also provided.

Abstract: The present invention relates to inhaled administration of a lipocalin mutein to a subject, wherein the administration provides for local exposure to the lipocalin mutein in the respiratory tract. The present invention also relates to inhalative administration of a lipocalin mutein to a subject, wherein the administration provides for systemic exposure to the lipocalin mutein.

Abstract: Methods and devices for liquid-liquid extraction using digital microfluidic arrays are provided. A polar droplet is transported to a separation region containing a substantially non-polar solvent, where non-polar impurities may be extracted from the polar droplet while maintaining a distinct phase separation. In a preferred embodiment, biological samples containing hormones are dried on a digital microfluidic array, lysed by a lysing solvent, dried, subsequently dissolved in a polar solvent, and further purified in a separation step in which droplets are transported through a volume of non-polar solvent. The method disclosed herein provides the distinct advantage of an automated sample preparation method that is capable of extracting hormones from low sample volumes with high precision and recovery.

Abstract: Methods and devices for liquid-liquid extraction using digital microfluidic arrays are provided. A polar droplet is transported to a separation region containing a substantially non-polar solvent, where non-polar impurities may be extracted from the polar droplet while maintaining a distinct phase separation. In a preferred embodiment, biological samples containing hormones are dried on a digital microfluidic array, lysed by a lysing solvent, dried, subsequently dissolved in a polar solvent, and further purified in a separation step in which droplets are transported through a volume of non-polar solvent. The method disclosed herein provides the distinct advantage of an automated sample preparation method that is capable of extracting hormones from low sample volumes with high precision and recovery.

Abstract: A method of extracting hormones from a biological sample using digital microfluidic arrays is provided. Biological samples containing hormones are dried on a digital microfluidic array, lysed by a lysing solvent, dried, subsequently dissolved in a polar solvent, and further purified in an extraction step in which droplets are transported through a volume of non-polar solvent. The method disclosed herein provides the distinct advantage of an automated sample preparation method that is capable of extracting hormones from low sample volumes with excellent precision and recovery.

Abstract: Methods and devices for liquid-liquid extraction using digital microfluidic arrays are provided. A polar droplet is transported to a separation region containing a substantially non-polar solvent, where non-polar impurities may be extracted from the polar droplet while maintaining a distinct phase separation. In a preferred embodiment, biological samples containing hormones are dried on a digital microfluidic array, lysed by a lysing solvent, dried, subsequently dissolved in a polar solvent, and further purified in a separation step in which droplets are transported through a volume of non-polar solvent. The method disclosed herein provides the distinct advantage of an automated sample preparation method that is capable of extracting hormones from low sample volumes with high precision and recovery.

Abstract: A method of extracting hormones from a biological sample using digital microfluidic arrays is provided. Biological samples containing hormones are dried on a digital microfluidic array, lysed by a lysing solvent, dried, subsequently dissolved in a polar solvent, and further purified in an extraction step in which droplets are transported through a volume of non-polar solvent. The method disclosed herein provides the distinct advantage of an automated sample preparation method that is capable of extracting hormones from low sample volumes with excellent precision and recovery.

Abstract: A pharmaceutical composition and a method of treating inflammation in a mammal. The method administers the therapeutic composition to the mammal. The therapeutic composition includes: a standard therapeutic dose of a COX2 inhibitor consisting of celecoxib or rofecoxib; and low dose aspirin in an amount of 70-85 mg.

Abstract: The present invention provides compositions and method of use for the prevention and treatment of vascular-related disorders such as vascular re-occlusion or restenosis post-coronary intervention with balloon angioplasty or stent procedures and diseases associated with pathological angiogenesis such as cancer, ocular or inflammatory diseases. More specifically, compositions and methods of the present invention involve the combination of the garlic-derived or related compounds and antioxidants.

Abstract: This invention pertains to methods and compositions for inhibiting endothelial cell tube formation, the initial step of tumor angiogenesis. More specifically, the present invention relates to tripeptides that show inhibition of angiogenesis-mediated processes.

Abstract: This invention pertains to methods and compositions for inhibiting endothelial cell tube formation, the initial step of tumor angiogenesis. More specifically, the present invention relates to tripeptides that show inhibition of angiogenesis-mediated processes.

Abstract: The present invention provides compositions and method of use for the prevention and treatment of vascular-related disorders such as vascular re-occlusion or restenosis post-coronary intervention with balloon angioplasty or stent procedures and diseases associated with pathological angiogenesis such as cancer, ocular or inflammatory diseases. More specifically, compositions and methods of the present invention involve the combination of the garlic-derived or related compounds and antioxidants.

Abstract: This invention relates to novel isoxazolines and isoxazoles which are useful as antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex or the vitronectin receptor, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.

Abstract: This invention relates to a method of prevention and/or treatment of thrombosis in a mammal without significantly altering bleeding time or coagulation. This invention further relates to methods of using selective inhibitors of the binding of vitronectin to the .alpha..sub.v .beta..sub.3 receptor, alone or in combination with other therapeutic agents, for the inhibition of thrombus formation and/or the treatment of thromboembolic disorders.

Abstract: This invention provides novel radiopharmaceuticals that are radiolabeled cyclic compounds containing carbocyclic or heterocyclic ring systems which act as antagonists of the platelet glycoprotein IIb/IIIa complex; to methods of using said radiopharmaceuticals as imaging agents for the diagnosis of arterial and venous thrombi; to novel reagents for the preparation of said radiopharmaceuticals; and to kits comprising said reagents.

Abstract: This invention provides novel radiopharmaceuticals that are radiolabeled cyclic compounds containing carbocyclic or heterocyclic ring systems which act as antagonists of the platelet glycoprotein IIb/IIIa complex; to methods of using said radiopharmaceuticals as imaging agents for the diagnosis of arterial and venous thrombi; to novel reagents for the preparation of said radiopharmaceuticals; and to kits comprising said reagents.

Abstract: This invention relates to novel cyclic compounds linked by a heterocyclic ring system, which are useful as antagonists of the platelet glycoprotein IIb/IIIa complex, to pharmaceutical compositions containing such cyclic compounds, and to methods of using these compounds for the inhibition of platelet aggregation.

Abstract: This invention relates to novel isoxazolines and isoxazoles which are useful as antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex or the vitronectin receptor, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.