Abstract: The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the insulin-like growth factor binding protein, acid labile subunit (IGFALS) gene or the insulin-like growth factor 1 (IGF-1) gene, methods of using such double stranded RNAi agents to inhibit expression of an IGFALS gene or an IGF-1 gene, and methods of treating subjects having an IGF system-associated disorder.

Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

Abstract: Disclosed herein are heterocyclic compounds that inhibit the activity of FLT3. Also described are specific covalent inhibitors of FLT3. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the FLT3 inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of proliferative diseases or conditions, including hematological malignancies and other diseases or conditions dependent on FLT3 activity.

Abstract: A state machine management component that executes on an edge device within an industrial facility is capable of discovering state machines defined on industrial controllers and translating the state machine definitions to information models that allow the state machines to be discovered and utilized by remote client applications. The edge-level information models allow the client applications to render or consume the state machine data generated by the controller, graphically render the state machines, submit commands, or set values, to the controller as state machine commands via the edge device. The edge-level system thus allows client applications with no prior knowledge of the control-level state machines to discover, retrieve, and interact with state machines defined on the industrial controllers.

Abstract: The present invention relates to methods of use of RNAi agents, e.g., double stranded RNAi agents, targeting a Factor XII (Hageman Factor (F12) gene, for treating subjects having a contact activation pathway-associated disease, such as a thrombophilia or hereditary angioedema (HAE), methods for preventing at least one symptom in a subject having a contact activation pathway-associated disease, such as a thrombus formation or an angioedema attack, and RNAi agents targeting an F12 gene, for use in the methods of the invention.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

Abstract: A medical device such as a stent or medical balloon is functionalised prior to coating with a bioactive material, specifically by carboxylic acidification of the contact surface or surfaces of the medical device. The preferred process involves washing a stent or other medical device in a washing solution which may be sodium hydroxide, soaking in a carboxylic acid solution, rinsing in water to remove excess carboxylic acid, allowing to dry before applying a bioactive agent layer. It has been found that washing after functionalisation removes excess carboxylic acid and enhances the retention of bioactive agent on the contact surface or surfaces of the medical device leading to a more uniform and consistent layer of bioactive agent.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Kallikrein B, Plasma (Fletcher Factor) 1 (KLKB1) gene, the Factor XII (Hageman Factor (F12) gene, or the Kininogen 1 (KNG1) gene, and methods of using such RNAi agents to inhibit expression of a KLKB1 gene, an F12 gene, and/or a KNG1 gene, and methods of treating subjects having an hereditary angioedema (HAE) and/or a contact activation pathway-associated disorder.

Abstract: A fuel container having a body defining a volume for receiving fuel. The body has an inlet and optionally a vent. The inlet extends upwards as a spout and has a threaded collar which is closed by a threaded cap. A gas expansion pathway is provided between the inlet and the vent. The spout has a guide for receiving and locating a dog-leg portion of a fuel dispenser nozzle. A restriction in the throat of the spout prevents the fuel dispenser nozzle from being inserted beyond a preselected distance into the container thereby preventing backwash and spillage.

Abstract: There is disclosed a method of improving the reliability of coating an implantable medical device, such as a stent, with bioactive material in the absence of a carrier material such as a matrix or polymer layer. The method involves cleaning volatile components from the exposed surfaces of the medical device, removing carbon deposits and then applying a uniform carbon layer in a controlled environment. The deliberately applied carbon layer masks impurities of the underlying native oxide layer and leads to more uniform bioactive material coating not only a over the surfaces of a single medical device but also from device to device within a batch and between batches of devices. This improves production as well as optimising the amount and release of drug on the medical device without the need for a carrier material.

Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

Abstract: A method of modifying a surface of a medical device for implantation or disposition inside a patient is described. The medical device comprises a structure having at least one surface. The method includes the steps of: placing the medical device into a plasma chamber substantially free from contaminants and substantially sealing the plasma chamber from the atmosphere; removing at least an outermost layer of any oxide layer from the at least one surface of the structure by a plasma oxide-removal process, whilst maintaining the plasma chamber under seal from the atmosphere; and subsequently forming a new oxide layer at the least one surface of the structure by introducing at least one gas into the plasma chamber, whilst maintaining the plasma chamber under seal from the atmosphere. A medical device including a bulk material and an oxide layer disposed over at least one surface of the medical device. The oxide layer is substantially pure and free from contaminants.

Abstract: A ground penetrating radar stencil and system for using the same is provided. The stencils are reusable. The stencils are foldable, allowing for storing and transportation. A first data collection grid stencil is used to mark a grid followed by alternative target marking stencils used to mark utility line and structural support lines. Indelible stencil paint/ink is applied on and through the stencils onto the concrete surfaces to provide for a permanent, standardized and consistent marking of critical embedded infrastructure. The system allows for a uniform collecting and recording of the scanning data results for future reference and work in the same area.

Abstract: A medical device assembly including a catheter having a proximal end, a distal end, and a lumen therethrough. A medical device is disposed about a distal portion of the catheter. A removable loading tool and protector is disposed about the catheter and the medical device, and includes a body having a generally tubular configuration and having a proximal end, a distal end, an intermediate region disposed between the proximal end and the distal end, and a lumen disposed therethrough; and a proximal region having a length and extending from the proximal end of the body, the proximal region having at least one slit positioned adjacent to the proximal end of the body. The proximal region has a first inner diameter and the intermediate region has a second inner diameter, the first inner diameter of the proximal region being greater than the second inner diameter of the intermediate region.

Abstract: There is disclosed a method of improving the reliability of coating an implantable medical device, such as a stent, with bioactive material in the absence of a carrier material such as a matrix or polymer layer. The method involves cleaning volatile components from the exposed surfaces of the medical device, removing carbon deposits and then applying a uniform carbon layer in a controlled environment. The deliberately applied carbon layer masks impurities of the underlying native oxide layer and leads to more uniform bioactive material coating not only a over the surfaces of a single medical device but also from device to device within a batch and between batches of devices. This improves production as well as optimising the amount and release of drug on the medical device without the need for a carrier material.

Abstract: A medical device such as a stent or medical balloon is functionalised prior to coating with a bioactive material, specifically by carboxylic acidification of the contact surface or surfaces of the medical device. The preferred process involves washing a stent or other medical device in a washing solution which may be sodium hydroxide, soaking in a carboxylic acid solution, rinsing in water to remove excess carboxylic acid, allowing to dry before applying a bioactive agent layer. It has been found that washing after functionalisation removes excess carboxylic acid and enhances the retention of bioactive agent on the contact surface or surfaces of the medical device leading to a more uniform and consistent layer of bioactive agent.

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the TMPRSS6 gene, and methods of using such RNAi agents to inhibit expression of TMPRSS6 and methods of treating subjects having a TMPRSS6 associated disorder, e.g., an iron overload associated disorder, such as ?-thalassemia or hemochromatosis.

Abstract: A state machine management component that executes on an edge device within an industrial facility is capable of discovering state machines defined on industrial controllers and translating the state machine definitions to information models that allow the state machines to be discovered and utilized by remote client applications. The edge-level information models allow the client applications to render or consume the state machine data generated by the controller, graphically render the state machines, submit commands, or set values, to the controller as state machine commands via the edge device. The edge-level system thus allows client applications with no prior knowledge of the control-level state machines to discover, retrieve, and interact with state machines defined on the industrial controllers.

Abstract: The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the apolipoprotein C3 (APOC3) gene, and methods of using such RNAi agents to inhibit expression of APOC3 and methods of treating subjects having an APOC3 associated disorder, e.g., hypertriglyceridemia.