Abstract: This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol, High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Abstract: This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunctions; thus, there is also utility for small organic compound ligands and can raise LDL levels.

Abstract: This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Abstract: This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: An electrode support structure comprises a guide body having at its distal end a flexible spline leg. The spline leg is flexed to define an arcuate shape to facilitate intimate contact against tissue. An electrode element is carried by the spline leg for movement along its axis. The structure includes a control element coupled to the electrode element. The control element remotely imparts force to move the electrode element along the axis of the spline leg. Therefore, in use, the physician can cause the electrode element to travel along a path that the spline leg defines, without otherwise changing the location of the guide body.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: Systems and associated methods position arrays of multiple emitters of ablating energy in straight or curvilinear positions in contact with tissue to form elongated lesion patterns. The elongated lesion patterns can continuous or interrupted, depending upon the orientation of the energy emitters.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: Devices for insertion into an atrial appendage of stasis reducing components such as mesh members, chemical bonding agents or expandable anchors are disclosed.

Abstract: Systems and associated methods position arrays of multiple emitters of ablating energy in straight or curvilinear positions in contact with tissue to form elongated lesion patterns. The elongated lesion patterns can continuous or interrupted, depending upon the orientation of the energy emitters.

Abstract: Systems and methods supply ablation energy to an electrode in contact with tissue to form a tissue-electrode interface. The system and methods sense, simultaneously with ablation, at least two tissue temperature conditions using at least two tissue temperature sensing elements which are held within a carrier that is substantially isolated from thermal conductive contact with the electrode. The carrier holds the tissue temperature sensing elements in a spaced apart relationship in thermal conductive contact with tissue at different depths beneath the tissue-electrode interface. The systems and methods control the supply of ablation energy to the electrode based, at least in part, upon temperatures sensed by the tissue temperature sensing elements.

Abstract: Systems and associated methods position arrays of multiple emitters of ablating energy in straight or curvilinear positions in contact with tissue to form elongated lesion patterns. The elongated lesion patterns can continuous or interrupted, depending upon the orientation of the energy emitters.

Abstract: Systems and associated methods for ablating body tissue employ an electrode for contacting tissue to form a tissue-electrode interface. The electrode is adapted to be connected to a source of ablation energy to conduct ablation energy for transmission by the electrode into tissue at the tissue-electrode interface. The systems and methods also include an element to cool the electrode. The systems and methods hold a tissue temperature sensing element in a carrier in thermal conductive contact with tissue beneath the tissue-electrode interface. The systems and methods include a controller that is coupled to the tissue temperature sensing element to control either the supply of ablation energy, or the rate at which the electrode is cooled, or both based, at least in part, upon temperature sensed by the temperature sensing element.

Abstract: Systems and methods for ablating body tissue use an ablation element for contacting tissue to form a tissue interface. The ablation element is adapted to be connected to a source of ablation energy to conduct ablation energy for transmission by the ablation element into tissue at the tissue interface. The systems and methods include a tissue temperature sensing element held in a carrier in thermal conductive contact with tissue beneath the tissue interface. A mechanism attached to the carrier selectively advances the carrier relative to the ablation element to different depths beneath the tissue interface. A controller is coupled to the mechanism and to the tissue temperature sensing element to control advancement of the carrier beneath the tissue interface based, at least in part, upon tissue temperatures sensed by the sensing element beneath the tissue interface. Preferably, the controller controls the mechanism to locate the sensing element at the depth where the hottest sensed tissue temperature exists.

Abstract: A sleeve assembly for use in the transition region of a catheter between a relatively stiff catheter body and a less stiff distal catheter region mediates the difference in stiffness between these two catheter regions.