Abstract: The disclosure presents a formwork system which utilizes Fiber Reinforced Polymer (FRP) panels to create modular segments to form and reinforce concrete subgrade structures. The segments may be rearranged and bonded together to conform to intended dimensions of many subgrade structures. The segments are manufactured by cast molding, bonding or vacuum forming. The segments may include integrated FRP stanchions to prevent deflection of the panels during concrete placement. The stanchions also may be used for positioning structural steel or FRP rebar. FRP bars are permanently bonded to the interior sides of the panels inside the segments. In use, the assembled segments are filled with concrete. After the concrete is cured, the segments remain in place and function as external protection and reinforcement for the cured concrete.

Abstract: The disclosure presents a composite concrete structure formwork which comprises stay in place fiberglass profiles and reinforcement to form various building and shelter structures. The structures include an interior container maintained at a set distance within an exterior container to form a void. The void is filled with wet concrete which is allowed to cure. All of the components in a preferred embodiment are formed of a fiberglass material.

Abstract: The disclosure presents a reconfigurable composite floor formwork which defined by a plurality of interlocking fiberglass panels formed into profiles which may be moved and adapted to provide a concrete form for a floor or ceiling. All of the components in a preferred embodiment are formed of a fiberglass material.

Abstract: Provided herein are bifunctional compounds with a moiety or domain that is a binder of the ubiquitin receptor RPN13 and another moiety or domain that is a binder of a target protein DOT1L to induce degradation of DOT1L. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, such as cancers). Provided also are methods of inducing the degradation of DOT1L by administering a bifunctional compound or composition described herein, wherein one domain of the bifunctional compound is a binder of the ubiquitin receptor RPN13 and another domain of the compound is a binder of the target protein DOT1L in a subject.

Abstract: The presently disclosed subject matter relates to the administration of a KMT2D inhibitor for the treatment of a cancer. The present invention is based on the discovery that upon PI3K inhibition, KMT2D activity is upregulated, resulting in an increase in the expression of genes involved in breast cancer cell proliferation and tumor growth. Accordingly, the present invention provides methods for treating a subject that has cancer by administering a therapeutically effective amount of an KMT2D inhibitor.

Abstract: This invention is based on the discovery that inhibiting more than one pathway in senescent cells leading to apoptosis has a profound effect: namely, increasing the potency or the cell specificity of the therapy. Combining a Bcl inhibitor with an Mcl 1 inhibitor increases the ability of the Bcl inhibitor to remove senescent cells from the site of an adverse condition synergistically. This increases the types of senescent cells that can be targeted, broadens the therapeutic range, and allows the user to tailor a particular combination of agents by adjusting the molar ratio for the patient being treated. Suitable indications for treatment may include any condition thought to be mediated at least in part by senescent cells, such as ophthalmic conditions, pulmonary conditions, and atherosclerosis.

Abstract: Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety that is a binder of a target protein DOT1L to induce degradation of DOT1L. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, such as cancers). Provided also are methods of inducing the degradation of DOT1L by administering a bifunctional compound or composition described herein, wherein one component of the bifunctional compound is a binder of an E3 ubiquitin ligase (e.g., lenalidomide, thalidomide) and another component of the compound is a binder of the target protein DOT1L in a subject.

Abstract: Disclosed are methods for inhibiting proliferation of or inducing apoptosis in certain leukemia cells or both. The methods comprise contacting a leukemia cell exhibiting an NPM1 mutation with a pharmacologic inhibitor of interaction between MLL and menin. More broadly, disclosed are methods for treating a susceptible leukemia using pharmacologic inhibition of Menin-MLL interaction. Also disclosed are methods for treating such leukemias using inhibition of Menin-MLL interaction in combination with DOT1L inhibition.

Abstract: This invention is based on the discovery that many lung diseases associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The severity of age-related conditions typically correlates with the abundance of senescent cells: thus, clearing senescent cells can help abrogate the condition: providing symptomatic relief, and potentially inhibiting disease progression. In accordance with this invention, a family of Bcl protein inhibitors has been developed for the treatment of lung diseases. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable pulmonary diseases.

Abstract: Disclosed are: (i) methods for identifying leukemia patients who (or leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication but who are nonetheless susceptible to treatment with DOT1L inhibitors; and (ii) methods for treating leukemia patients who (or inhibiting proliferation or inducing apoptosis of leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication with DOT1L inhibitors. The patients identified as susceptible and the patients (or cells) treated exhibit elevated expression of a IIOX cluster gene or of a HOX cluster-associated gene. Elevated expression of such genes can be measured, e.g.

Abstract: This invention is based on the discovery that many lung diseases associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The severity of age-related conditions typically correlates with the abundance of senescent cells: thus, clearing senescent cells can help abrogate the condition: providing symptomatic relief, and potentially inhibiting disease progression. In accordance with this invention, a family of Bcl protein inhibitors has been developed for the treatment of lung diseases. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable pulmonary diseases.

Abstract: Described herein are antifungal peptoids, the development and characterization of the antifungal peptoids, methods of making the antifungal peptoids, and methods of using the antifungal peptoids. In some embodiments, the antifungal peptoids may be administered to a subject infected with or at risk of being infected with pathogenic fungi including, for example Cryptococcus spp. In some embodiments, the Cryptococcus spp. may include C. neoformans or C. gattii or both.

Abstract: An electrosurgical controller and related methods. At least some of the illustrative embodiments are methods including: placing a distal end of an electrosurgical wand in operational relationship with biological tissue; delivering energy to an active electrode of the electrosurgical wand. During delivering energy, the method may comprise: measuring a value indicative of flow of the energy to the active electrode; summing, over a first predetermined window of time, to create a first value indicative of energy provided to the active electrode; summing, over a second predetermined window of time, to create a second value indicative of energy provided to the active electrode. The method may further comprise: ceasing delivering energy responsive to the first value meeting or exceeding a predetermined value; and ceasing delivering energy responsive to the second value meeting or exceeding a threshold value.

Abstract: Disclosed are methods for inhibiting proliferation of or inducing apoptosis in certain leukemia cells or both. The methods comprise contacting a leukemia cell exhibiting an NPM1 mutation with a pharmacologic inhibitor of interaction between MLL and menin. More broadly, disclosed are methods for treating a susceptible leukemia using pharmacologic inhibition of Menin-MLL interaction. Also disclosed are methods for treating such leukemias using inhibition of Menin-MLL interaction in combination with DOT1L inhibition.

Abstract: An electrosurgical controller and related methods. At least some of the illustrative embodiments are methods including: placing a distal end of an electrosurgical wand in operational relationship with biological tissue; delivering energy to an active electrode of the electrosurgical wand. During delivering energy, the method may comprise: measuring a value indicative of flow of the energy to the active electrode; summing, over a first predetermined window of time, to create a first value indicative of energy provided to the active electrode; summing, over a second predetermined window of time, to create a second value indicative of energy provided to the active electrode. The method may further comprise: ceasing delivering energy responsive to the first value meeting or exceeding a predetermined value; and ceasing delivering energy responsive to the second value meeting or exceeding a threshold value.

Abstract: Disclosed are: (i) methods for identifying leukemia patients who (or leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication but who are nonetheless susceptible to treatment with DOT1L inhibitors; and (ii) methods for treating leukemia patients who (or inhibiting proliferation or inducing apoptosis of leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication with DOT1L inhibitors. The patients identified as susceptible and the patients (or cells) treated exhibit elevated expression of a HOX cluster gene or of a HOX cluster-associated gene. Elevated expression of such genes can be measured, e.g.

Abstract: The presently disclosed subject matter relates to the administration of a KMT2D inhibitor for the treatment of a cancer. The present invention is based on the discovery that upon PI3K inhibition, KMT2D activity is upregulated, resulting in an increase in the expression of genes involved in breast cancer cell proliferation and tumor growth. Accordingly, the present invention provides methods for treating a subject that has cancer by administering a therapeutically effective amount of an KMT2D inhibitor.

Abstract: The present invention relates to a method of treating a warm-blooded animal, especially a human, having Mixed Lineage Leukemia (MLL rearranged ALL) comprising administering to said animal a therapeutically effective amount of a staurosporine derivative, especially PKC412 or a pharmaceutically acceptable salt thereof, alone or in combination with further therapeutic measures, for example, those defined herein; to the use of a staurosporine derivative for the preparation of a medicament for the treatment of MLL rearranged ALL; and to a commercial package comprising a staurosporine derivative together with instructions for its use in the treatment of MLL rearranged ALL.

Abstract: The present invention relates to a method of treating a warm-blooded animal, especially a human, having Mixed Lineage Leukemia (MLL rearranged ALL) comprising administering to said animal a therapeutically effective amount of a staurosporine derivative, especially PKC412 or a pharmaceutically acceptable salt thereof, alone or in combination with further therapeutic measures, for example, those defined herein; to the use of a staurosporine derivative for the preparation of a medicament for the treatment of MLL rearranged ALL; and to a commercial package comprising a staurosporine derivative together with instructions for its use in the treatment of MLL rearranged ALL.

Abstract: Electrosurgical systems and methods are described herein, the system including an electrosurgical probe with an active electrode disposed near the probe distal end, a system with a power supply for delivery of voltage to the active electrode and a controller that receives and processes a signal from a current sensor and a temperature sensor. The current sensor measures the current output of the power supply and the temperature sensor is adjacent an electrically conductive fluid located at a target site. The controller may be programmed to operate in a low voltage mode that limits the power supply to a low voltage output so as to determine whether the current output from the current sensor is within a current output range. This range is defined by predetermined upper and lower limits that are modified by at least one measured value.