Abstract: A method useful for regulating cytokine production by a hematopoietic cell by regulating an MEKK/JNKK-contingent signal transduction pathway in such a cell is disclosed. Methods of identifying compounds capable of specifically regulating an MEKK/JNKK-contingent signal transduction pathway in hematopoietic cells, a kit for identifying cytokine regulators, methods to treat diseases involving cytokine production, and cells useful in such methods are also set forth.

Abstract: A method useful for regulating cytokine production by a hematopoietic cell by regulating an MEKK/JNKK-contingent signal transduction pathway in such a cell is disclosed. Methods of identifying compounds capable of specifically regulating an MEKK/JNKK-contingent signal transduction pathway in hematopoietic cells, a kit for identifying cytokine regulators, methods to treat diseases involving cytokine production, and cells useful in such methods are also set forth.

Abstract: Isolated nucleic acid molecules encoding human MEKK proteins, and isolated MEKK proteins, are provided. The invention further provides anti sense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a human MEKK transgene. The invention further provides human MEKK fusion proteins and anti-human MEKK antibodies. Methods of using the human MEKK proteins and nucleic acid molecules of the invention are also disclosed, including methods for detecting human MEKK activity in a biological sample, methods of modulating human MEKK activity in a cell, and methods for identifying agents that modulate the activity of human MEKK.

Abstract: The present invention relates to isolated MEKK1 proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to use such proteins to regulate apoptosis. The invention provides active fragments of MEKK1 proteins that are generated upon cleavage of MEKK1 with a caspase protease. These active fragments are capable of stimulating apoptosis. Moreover, the invention provides protease-resistant forms of MEKK1 proteins, that are resistant to cleavage by caspase proteases and that are capable of inhibiting apoptosis. Still further, the invention provides methods for generating an active fragment of MEKK1, methods of identifying modulators of the apoptotic activity of an active fragment of MEKK1 and methods of identifying modulators of caspase-mediated cleavage of MEKK1.

Abstract: The present invention relates to methods useful for identifying compounds capable of specifically controlling CD40 regulation of JNK or p38 activity useful for inhibiting immunoglobulin heavy chain class switching, cytokine production and activation of cells involved in an inflammatory response. The present invention also includes kits to perform such assays and methods to control disease related to such responses.

Abstract: The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to use such proteins to regulate signal transduction in a cell. The present invention also includes therapeutic compositions comprising such proteins or nucleic acid molecules that encode such proteins and their use to treat animals having medical disorders including cancer, inflammation, neurological disorders, autoimmune diseases, allergic reactions, and hormone-related diseases. When MEKK is expressed, it phosphorylates and activates MKKs 1-4 (also referred to as MEK-1, MEK-2 and JNKK1 and JNKK2).

Abstract: Isolated nucleic acid molecules encoding human MEKK proteins, and isolated MEKK proteins, are provided. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and nonhuman transgenic animals carrying a human MEKK transgene. The invention further provides human MEKK fusion proteins and anti-human MEKK antibodies. Methods of using the human MEKK proteins and nucleic acid molecules of the invention are also disclosed, including methods for detecting human MEKK activity in a biological sample, methods of modulating human MEKK activity in a cell, and methods for identifying agents that modulate the activity of human MEKK.

Abstract: An applicator/remover mechanism automatically applies and/or removes a clip, such as the so-called Safelok clip. Each clip applicator/remover mechanism preferably includes a workarm which is pivotable transversely towards and away from the longitudinal centerline of the rail, a clip applicator tool mounted on the workarm, and a clip retractor tool mounted on the workarm. The clip retractor tool includes first and second retractor arms pivotably mounted on a housing, each arm having downwardly-extending fingers to engage the side of a rail clip. The arms have intermeshing teeth which cause the second retractor arm to pivot upon pivoting of the first retractor arm to selectively pinch and release the rail clip. The resulting mechanism is capable of both applying and removing clips rapidly and efficiently while accommodating variations in position and orientation of the rail and/or the clips.

Abstract: The present invention relates to methods useful for identifying compounds capable of specifically controlling CD40 regulation of JNK or p38 activity useful for inhibiting immunoglobulin heavy chain class switching, cytokine production and activation of cells involved in an inflammatory response. The present invention also includes kits to perform such assays and methods to control disease related to such responses.

Abstract: The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to use such proteins to regulate signal transduction in a cell. The present invention also includes therapeutic compositions comprising such proteins or nucleic acid molecules that encode such proteins and their use to treat animals having medical disorders including cancer, inflammation, neurological disorders, autoimmune diseases, allergic reactions, and hormone-related diseases. When MEKK is expressed, it phosphorylates and activates MEKs including MEK-1, MEK-2 and JEK.

Abstract: A side loading refuse collection vehicle has a lift arm extendible and rotatable relative to the vehicle, the lift arm carrying grabber apparatus at an end for grasping a refuse container which may be lifted and dumped into the top of the body of the vehicle. The lift arm which is guided to move in a path so as to grasp the container, raise it, dump it and return it to its initial position, is driven toward and away from the vehicle by a first hydraulic drive cylinder and lifted and lowered by a second hydraulic drive cylinder. The first hydraulic drive cylinder has a drive rod on which a locking bolt is secured and may be captured in a receptacle of a keeper when the rod is in the fully retracted position to lock the arm against inadvertent and undesirable extension outwardly away from the vehicle. The keeper is pivotally mounted and moved by the output rod of a pneumatic cylinder to permit the bolt to be released from the receptacle when the hydraulic drive is activated.

Abstract: The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to use such proteins to regulate signal transduction in a cell. The present invention also includes therapeutic compositions comprising such proteins or nucleic acid molecules that encode such proteins and their use to treat animals having medical disorders including cancer, inflammation, neurological disorders, autoimmune diseases, allergic reactions, and hormone-related diseases. When MEKK is expressed, it phosphorylates and activates MEKs including MEK-1, MEK-2 and JEK.

Abstract: A method useful for regulating cytokine production by a hematopoietic cell by regulating an MEKK/JNKK-contingent signal transduction pathway in such a cell is disclosed. Methods of identifying compounds capable of specifically regulating an MEKK/JNKK-contingent signal transduction pathway in hematopoietic cells, a kit for identifying cytokine regulators, methods to treat diseases involving cytokine production, and cells useful in such methods are also set forth.

Abstract: The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to use such proteins to regulate signal transduction in a cell. The present invention also includes therapeutic compositions comprising such proteins or nucleic acid molecules that encode such proteins and their use to treat animals having medical disorders including cancer, inflammation, neurological disorders, autoimmune diseases, allergic reactions, and hormone-related diseases. When MEKK is expressed, it phosphorylates and activates MEKs including MEK-1, MEK-2 and JEK.

Abstract: The present invention relates to methods useful for identifying compounds capable of specifically regulating actin polymerization, stress fiber formation or focal adhesion assembly by regulating G.sub..alpha.12 and/or G.sub..alpha.13 activity in cells involved in inflammatory responses, immune responses, allergic responses and neuronal responses, kits to perform such assays and methods to control disease related to such responses.

Abstract: A machine is capable of automatically applying and removing transversely applied rail clips such as the so-called Safelok-type clip. The machine preferably includes a workhead on which is disposed one or more applicator/remover mechanisms, each of which is capable of automatically applying and/or removing a clip. Each clip applicator/remover mechanism preferably includes a workarm which is pivotable transversely towards and away from the longitudinal centerline of the rail, a clip applicator tool mounted on the workarm, and a clip retractor tool mounted on the workarm. The resulting mechanism is capable of both applying and removing clips rapidly and efficiently while accommodating variations in position and orientation of the rail and/or the clips.

Abstract: A rail saw has a power head which includes a two cycle engine which does not require premixing of gasoline and lubricating oil. Instead, undiluted gasoline is stored in the engine's fuel tank, and lubricating oil is supplied to the engine's fuel supply system downstream of the fuel tank by a mechanical metering pump which delivers a designated, preferably adjustable, quantity of oil to the fuel supply system per engine revolution. In the case of a power head formed by converting a chain saw power head to a rail saw power head, the oil supply system may comprise the lubricating oil system originally designed to lubricate the chain saw's chain. Also disclosed is a preferred method of converting a chain saw power head requiring the storage of a premixed gasoline/lubricating oil mixture in its fuel tank to a rail saw power head whose fuel tank stores gasoline only.

Abstract: The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods useful for identifying compounds capable of specifically regulating signal transduction in cells expressing MEKK protein.

Abstract: The isolated nucleic acid sequence for MEKK, the MEKK amino acid sequence and protein, antibodies to MEKK, and methods for using such sequences, proteins and antibodies are described. The amino acid sequence of MEKK (MEK kinase), was elucidated from a cDNA sequence encoding a protein of 672 amino acid residues (73 kilodaltons). When MEKK is expressed, it phosphorylates and activates MEK. Phosphorylation and activation of MEK by MEKK is independent of Raf, a growth factor regulated protein kinase that also phosphorylates MEK. Thus, MEKK and Raf converge at MEK in the protein kinase network mediating the activation of MAPKs by hormones, growth factors, and neurotransmitters.