Abstract: A packaging system comprising one or more multi-layer packaging pads applied to a pre-wrapped object, such as a metal coil, at high wear locations for increased abrasion resistance. The multi-layer packaging pad includes first and second plies and optionally a slip sheet. The first and second plies are disposed in an overlapping arrangement and have first and second inside slip surfaces, respectively, that face one another. The first and second plies are connected along only a sealed perimeter of the multi-layer packaging pad to provide a slip region between the first and second plies. The first and a second inside slip surfaces are formulated to slide relative to one another such that an unconstrained middle portion of the second ply is moveable relative to the first ply. Associated methods of manufacture and use are also provided.

Abstract: Provided herein are compounds, tautomers, or pharmaceutically acceptable salts thereof, having a structure of formula (I): wherein X1, Y, Z1, Z2, (R1)n, (R2)m, and ring A are as described herein. Also provided are pharmaceutical compositions comprising compounds, tautomers, or pharmaceutically acceptable salts having a structure of formula (I). Further provided are a method of inhibiting cyclin dependent kinase 19 (CDK19) a method of treating breast cancer with the disclosed compounds.

Abstract: Disclosed are methods of treating graft versus host disease (GVHD) or treating ocular graft versus host disease (oGVHD). The methods may comprise administering a therapeutically effective amount of a composition comprising CCL20 locked dimer to a subject, e.g., a subject suffering from GVHD. Also disclosed are modified CCL20LD compositions comprising an unstructured polypeptide.

Abstract: The present disclosure provides pyrimidine dione compounds of Formula I and pharmaceutical compositions thereof, for treating cancer, including solid tumors either-used alone or in combination with other anti-cancer agents.

Abstract: A brushless direct-current (BLDC) motor for a power tool includes a rotor assembly and a stator assembly including stator windings. A ratio of a motor size (Km) constant of the motor to an electrical envelope of the motor including electrical parts of the motor is greater than approximately 850 (N·m/?W)/m{circumflex over (?)}3. A ratio of a motor size (Km) constant of the motor to a magnetic envelope of the motor including stator core and windings is greater than approximately 980 (N·m/?W)/m{circumflex over (?)}3.

Abstract: A brushless direct-current (BLDC) motor for a power tool includes a rotor assembly; a stator assembly including a stator having stator teeth forming slots therebetween and stator windings wound around the stator teeth; stator terminals extending substantially parallel to the longitudinal axis from the stator assembly and being substantially aligned with centerlines of the slots of the stator assembly; and a circuit board mounted on the stator terminals adjacent the stator assembly. The circuit board includes conductive traces facilitating a one of a delta or a series connection between the stator windings. An end insulator is provided at an axial end of the stator to electrically insulate the stator from the stator windings, the end insulator including support members to support the stator terminals relative to the stator assembly. The circuit board is mounted and fastened to the support members.

Abstract: Provided herein is A compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein the various substituents are described herein.

Abstract: This disclosure provides data showing that LEFTY inhibits differentiation-promoting pathways such as BMP7/pSMAD5 in breast cancer cell lines, over and above its known role of inhibiting Nodal/pSMAD2. LEFTY competes with BMP7 to bind to its cell surface receptor BMPR2, leading to inhibition of pSMAD5. The LEFTY-BMPR2 interaction is dominant over BMP-BMPR2 in tumorigenic cells, resulting in diminished pSMAD status, whereas in non-tumorigenic cells, there is minimal LEFTY-BMPR2 interaction, increased BMP7-BMPR2 association, and elevated pSMAD. Compositions and methods for inducing or inhibiting expression and/or the activity of LEFTY and BMP proteins are described, which can be used in diagnosis and therapy of cancer and other conditions, and to promote proliferation of stem cells.

Abstract: Methods and compositions are provided for the treatment of Alzheimer's Disease (AD) by administering to a patient a therapeutically effective amount of an agent that inhibits signaling mediated by a bone morphogenetic protein type 1A receptor (BMPR-1A) or bone morphogenetic protein type 2 receptor (BMPR-2). Also provided are methods and compositions to increase the rate of neural stem cell self-renewal.

Abstract: The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Abstract: The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Abstract: Methods and compositions are provided for the treatment of Alzheimer's Disease (AD) by administering to a patient a therapeutically effective amount of an agent that inhibits signaling mediated by a bone morphogenetic protein type 1A receptor (BMPR-1A) or bone morphogenetic protein type 2 receptor (BMPR-2). Also provided are methods and compositions to increase the rate of neural stem cell self-renewal.

Abstract: The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Abstract: This disclosure provides data showing that LEFTY inhibits differentiation-promoting pathways such as BMP7/pSMAD5 in breast cancer cell lines, over and above its known role of inhibiting Nodal/pSMAD2. LEFTY competes with BMP7 to bind to its cell surface receptor BMPR2, leading to inhibition of pSMAD5. The LEFTY-BMPR2 interaction is dominant over BMP-BMPR2 in tumorigenic cells, resulting in diminished pSMAD status, whereas in non-tumorigenic cells, there is minimal LEFTY-BMPR2 interaction, increased BMP7-BMPR2 association, and elevated pSMAD. Compositions and methods for inducing or inhibiting expression and/or the activity of LEFTY and BMP proteins are described, which can be used in diagnosis and therapy of cancer and other conditions, and to promote proliferation of stem cells.

Abstract: Processes to infer stemness, cell lineage, and/or differentiation status are provided. In some instances, single cell RNA sequencing is used to infer a cell's stemness, cell lineage, and/or differentiation status. In some instances, a collection of cells is ordered based on each cell's differentiation status.

Abstract: Reagents and methods for epigenetic profiling using targeted chromatin ligation are disclosed. The method utilizes oligonucleotide adapters complexed with antibodies specific for DNA-binding proteins of interest and proximity ligation to tag fragmented chromatin with the adapters. Chromatin fragments having ligated adapters are amplified and sequenced with primers that hybridize to the adapters. This method can be used in epigenetic profiling, for example, for mapping histone modification patterns as well as transcriptional regulatory sites.

Abstract: A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Abstract: The present invention provides a biomarker, namely CDX2, and surrogate CDX2 biomarkers, the expression level of which is useful in predicting response of cancer patients to therapy with an EGFR inhibitor.

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.

Abstract: Methods and compositions are provided for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal. Aspects of the methods include inhibiting H2A deubiquitinating enzyme activity in cells, e.g. by administering an effective amount of an H2A deubiquitinating enzyme antagonist. Also provided are screens to identify therapeutics for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal.