Abstract: Disclosed herein are heterocyclic compounds that inhibit the binding of menin and MLL or MLL fusion proteins. Also described are specific irreversible inhibitors of menin-MLL interaction. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the menin-MLL irreversible inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, leukemia and other diseases or conditions dependent on menin-MLL interaction.

Abstract: Disclosed herein are heterocyclic compounds, for example, according to the following formula and analogs thereof: 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: Fiber optic terminals, tools and methods for adjusting a split ratio of a fiber optic terminal are disclosed. In one embodiment, a tool for adjusting a split ratio of a fiber optic terminal includes an axle for insertion into a port of the fiber optic terminal, and a terminal engagement body disposed about the axle. The terminal engagement body includes a terminal engagement feature for engaging an alignment feature within the fiber optic terminal, wherein the axle is free to rotate with respect to the terminal engagement body, and a set-point indicator. The tool further includes an end piece coupled to the axle, and a plurality of set-point markers, wherein rotation of the end piece causes rotation of the axle and an alignment between one set-point marker of the plurality of set-point markers with the set-point indicator indicates the split ratio of the fiber optic terminal.

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: The technologies described herein are generally directed to configuring carrier aggregation zones based on transmission information in a fifth generation (5G) network or other next generation networks. For example, a method described herein can include identifying, by carrier aggregation equipment including a processor, carrier transmission information corresponding to a first carrier signal and a second carrier signal. The method can further include analyzing, by the carrier aggregation equipment, the carrier transmission information to determine first overlap zone information representative of a first carrier overlap zone for the first carrier signal and the second carrier signal. Further, based on the first overlap zone information, the method includes facilitating configuring transmission parameter information representative of a transmission parameter applicable to transmission of the first carrier signal, to enable carrier aggregation by network equipment within the first carrier overlap zone.

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.

Abstract: A vascular intervention device delivery system includes a catheter with a proximal end attached to a handle, and a distal carrier segment for mounting a vascular intervention device thereon. A retractable sheath is movable from a first position covering the distal carrier segment to a second position retracted proximally uncovering the distal carrier segment. A pull is attached to the retractable sheath and extends proximally from the retractable sheath toward the handle. A majority of the length of the pull has a cross sectional shape with a concave side that faces the longitudinal axis and is opposite to a convex side that faces away from the longitudinal axis. The cross sectional shape has a width that is greater than a thickness.

Abstract: Techniques for remotely executing a secondary-device driver for generating commands for a secondary device are described herein. For instance, a secondary device (or “appliance”) may reside within an environment, along with a device to which the secondary device communicatively couples. The device may be configured to send control signals to the secondary device for causing the secondary device to perform certain operations. For instance, a user in the environment may provide, to the device, a request that the secondary device perform a certain operation. The device, which may lack some or all of a device driver associated with the secondary device, may then work with a remote service that executes the device driver for the purpose of receiving a command from the device driver and sending the command along to the secondary device. Upon receiving the command, the secondary device may perform the operation.