Abstract: Small molecule ER? biomodulators that kill therapy-resistant ERa positive breast, ovarian, and endometrial cancer cells are disclosed. In one embodiment, the small molecule biomodulator has increased therapeutic utility because of an increased ability to kill therapy-resistant cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen, and fulvestrant/ICI). The small molecule biomodulators not only inhibit proliferation of the cancer cells but kills them, which prevents reactivation of tumors years later. Compounds of the invention, such as ErSO-DFP, are effective for treating ERa positive cancers such as breast cancer, ovarian cancer, uterine cancer, cervical carcinoma, endometrial cancer, and the like.

Abstract: Systems, apparatuses, and methods are provided for transporting a reticle chamber (pod) for processing. In one example, a system for transporting the pod is disclosed. The system may include a moving apparatus, abase coupled to the moving apparatus, and a gripping ring extending from the base. In some aspects, the gripping ring grips a flange extending from the pod. The moving apparatus moves the base in response to the gripping ring gripping the flange.

Abstract: An article of footwear includes an upper and a sole coupled to the upper. The article of footwear includes an inflation system. The inflation system includes an inflatable bladder, a pump in fluid communication with the bladder, and a control circuitry operatively linked to the pump. The pump adjusts the air pressure of the inflatable bladder. The control circuitry receives a command signal from a remote device, and upon receipt of the command signal, the control circuitry transmits an actuation signal to the pump to adjust the air pressure of the inflatable bladder.

Abstract: The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors.

Abstract: An article of footwear includes an upper and a sole coupled to the upper. The article of footwear includes an inflation system. The inflation system includes an inflatable bladder, a pump in fluid communication with the bladder, and a control circuitry operatively linked to the pump. The pump adjusts the air pressure of the inflatable bladder. The control circuitry receives a command signal from a remote device, and upon receipt of the command signal, the control circuitry transmits an actuation signal to the pump to adjust the air pressure of the inflatable bladder.

Abstract: The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors.

Abstract: Midsoles, and articles of footwear having such midsoles, with a distal surface profile based, in whole or in part, on a pressure map of pressures exerted on the bottom of a human foot when in contact with the ground are provided. The pressure map may be a measurement of the pressures exerted on the bottom of a human foot during, for example, standing, walking, or running (e.g., a natural gait). The distal surface profile of a midsole and an article of footwear may be defined, at least in part, by a plurality of cushioning projections extending from the midsole and having predetermined height profiles based on a pressure map. Methods of making midsoles and articles of footwear including a distal surface profile based, in whole or in part, on a pressure map are also provided.

Abstract: The blood-brain barrier penetrant procaspase-3-activating drug, PAC-1, has been identified as an effective approach to inducing immune stimulatory destruction of cancer cells. PAC-1 induces cleavage of MLH1 in cancer cells, and studies show that inactivation of MLH1 leads to increased mutational burden and neoantigen presentation by major histocompatibility complex (MHC) products. Herein is described a mechanistic-based strategy to bring the power of immunotherapy in an effective fashion for treatment of cancer.

Abstract: A sole for an article of footwear includes a continuous dispensed component forming a first layer and a second layer. The first layer is disposed directly on top of the second layer. The continuous dispensed component forms a medial sidewall and a lateral sidewall. The first layer includes a starting point where the continuous dispensed component is first dispensed. The continuous dispensed component continuously transitions from the first layer to the second layer at the starting point.

Abstract: A sole for an article of footwear includes a continuous dispensed component forming a first layer and a second layer. The first layer is disposed directly on top of the second layer. The continuous dispensed component forms a medial sidewall and a lateral sidewall. The first layer includes a starting point where the continuous dispensed component is first dispensed. The continuous dispensed component continuously transitions from the first layer to the second layer at the starting point.

Abstract: An article of footwear includes an upper and a sole coupled to the upper. The article of footwear includes an inflation system. The inflation system includes an inflatable bladder, a pump in fluid communication with the bladder, and a control circuitry operatively linked to the pump. The pump adjusts the air pressure of the inflatable bladder. The control circuitry receives a command signal from a remote device, and upon receipt of the command signal, the control circuitry transmits an actuation signal to the pump to adjust the air pressure of the inflatable bladder.

Abstract: The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors.

Abstract: A sole for an article of footwear includes a continuous dispensed component forming a first layer and a second layer. The first layer is disposed directly on top of the second layer. The continuous dispensed component forms a medial sidewall and a lateral sidewall. The first layer includes a starting point where the continuous dispensed component is first dispensed. The continuous dispensed component continuously transitions from the first layer to the second layer at the starting point.

Abstract: Midsoles, and articles of footwear having such midsoles, with a distal surface profile based, in whole or in part, on a pressure map of pressures exerted on the bottom of a human foot when in contact with the ground are provided. The pressure map may be a measurement of the pressures exerted on the bottom of a human foot during, for example, standing, walking, or running (e.g., a natural gait). The distal surface profile of a midsole and an article of footwear may be defined, at least in part, by a plurality of cushioning projections extending from the midsole and having predetermined height profiles based on a pressure map. Methods of making midsoles and articles of footwear including a distal surface profile based, in whole or in part, on a pressure map are also provided.