Abstract: The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: The present invention provides compounds having a structure according to Formula I: (I) or a salt or solvate thereof, wherein R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Abstract: The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDMIA, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

Abstract: The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: Compounds are provided having a structure according to Formula (I): wherein A1, A2, A3, Y, R1, R2, R3, R4, R5, R6, m, n and p are defined herein. Further provided are pharmaceutical compositions including the compounds provided and methods of making and using the compounds and compositions as provided, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: Compounds are provided having a structure according to Formula (I): wherein A1, A2, A3, Y, R1, R2, R3, R4, R5, R6, m, n and p are defined herein. Further provided are pharmaceutical compositions including the compounds provided and methods of making and using the compounds and compositions as provided, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: The present invention relates to atom probe pulse energy. One aspect of the invention is directed toward a method that includes establishing a data relationship between pulse energy and bias energy for a target evaporation rate. In selected embodiments, establishing a data relationship can include determining an equivalent pulse fraction for a selected pulse energy and bias energy combination based on a local change in bias energy compared to a local change in pulse energy associated with the selected pulse energy and bias energy combination. Another aspect of the invention is directed toward a method that includes determining an equivalent pulse fraction for a first bias energy and pulse energy combination and/or a second bias energy and pulse energy combination based on the difference between the first bias energy and the second bias energy compared to the difference between the first pulse energy and the second pulse energy.

Abstract: An atom probe includes a specimen mount that can hold a specimen to be analyzed. A detector is spaced apart from the specimen mount. Between the detector and specimen mount Is a local electrode with an aperture. A laser is oriented to emit a laser beam toward the specimen mount at a nonzero angle with respect to the aperture plane, the aperture plane being oriented perpendicular to an ion travel path defined through the aperture between the specimen mount and detector.

Abstract: The present invention relates to atom probe data processes and associated systems. Aspects of the invention are directed toward a computing system configured to process atom probe data that includes a data set receiving component configured to receive a first three-dimensional data set. The first three-dimensional data set has a first data element structure and is based on data collected from performing an atom probe process on a portion of an atom probe specimen. The system further includes a data set constructing component configured to create a second three-dimensional data set having a second data element structure different than the first data element structure. In selected embodiments, the system can further include a Fourier Transform component configured to perform a Fourier Transform on a portion of the second three-dimensional data set.

Abstract: Aspects of the present invention are directed generally toward atom probe and three-dimensional atom probe microscopes. For example, certain aspects of the invention are directed-toward an atom probe or a three-dimensional atom probe that includes a sub-nanosecond laser to evaporate ions from a specimen under analysis and a reflectron for reflecting the ions. In further aspects of the invention, the reflectron can include a front electrode and a back electrode. At least one of the front and back electrodes can be capable of generating a curved electric field. Additionally, the front electrode and back electrodes can be configured to perform time focusing and resolve an image of a specimen.

Abstract: A laser atom probe situates a counter electrode between a specimen mount and a detector, and provides a laser having its beam aligned to illuminate the specimen through the aperture of the counter electrode. The detector, specimen mount, and/or the counter electrode may be charged to some boost voltage and then be pulsed to bring the specimen to ionization. The timing of the laser pulses may be used to determine ion departure and arrival times allowing determination of the mass-to-charge ratios of the ions, thus their identities. Automated alignment methods are described wherein the laser is automatically directed to areas of interest.

Abstract: A laser atom probe (100) situates a counter electrode between a specimen mount and a detector (106), and provides a laser (116) having its beam (122) aligned to illuminate the specimen (104) through the aperture (110) of the counter electrode (108). The detector, specimen mount (102), and then be pulsed to bring the specimen to ionization. The timing of the laser pulses may be used to determine ion departure and arrival times allowing determination of the mass-to-charge ratios of the ions, thus their identities. Automated alignment methods are described wherein the laser is automatically directed to areas of interest.

Abstract: A laser atom probe (100) situates a counter electrode between a specimen mount and a detector (106), and provides a laser (116) having its beam (122) aligned to illuminate the specimen (104) through the aperture (110) of the counter electrode (108). The detector, specimen mount (102), and/or the counter electrode may be charged to some boost voltage and then be pulsed to bring the specimen to ionization. The timing of the laser pulses may be used to determine ion departure and arrival times allowing determination of the mass-to-charge ratios of the ions, thus their identities. Automated alignment methods are described wherein the laser is automatically directed to areas of interest.

Abstract: A method for treating an atom probe electrode (120), which comprises the steps of providing an atom electrode (120) having a surface (123) and an aperture (122); and removing material (604) from the surface (123) to reduce a potential of the atom probe electrode creating a non-uniformity in an electric field (502) when the atom probe electrode is used in a atom probe device during specimen analysis.

Abstract: In an atom probe or other mass spectrometer wherein a specimen is subjected to ionizing pulses (voltage pulses, thermal pulses, etc.) which induce field evaporation of ions from the specimen, the evaporated ions are then subjected to corrective pulses which are synchronized with the ionizing pulses. These corrective pulses have a magnitude and timing sufficient to reduce the velocity distribution of the evaporated ions, thereby resulting in increased mass resolution for the atom probe/mass spectrometer. In a preferred arrangement, ionizing pulses are supplied to the specimen from a first counter electrode adjacent the specimen. The corrective pulses are then supplied from a second counter electrode which is coupled to the first via a passive or active network, with the network controlling the form (timing, amplitude, and shape) of the corrective pulses.

Abstract: The present invention relates generally to atom probes, atom probe specimens, and associated methods. For example, certain aspects are directed toward methods for analyzing a portion of a specimen that includes selecting a region of interest and moving a portion of material in a border region proximate to the region of interest so that at least a portion of the region of interest protrudes relative to at least a portion of the border region. The method further includes analyzing a portion of the region of interest. Other aspects of the invention are directed toward a method for applying photonic energy in an atom probe process by passing photonic energy through a lens system separated from a photonic device and spaced apart from the photonic device. Yet other aspects of the invention are directed toward a method for reflecting photonic energy off an outer surface of an electrode onto a specimen.

Abstract: Disclosed are methods to prepare a specimen for microanalysis, the specimens so prepared, and methods to analyze the specimens by atom probe microscopy. The specimens are prepared by embedding a specimen within an electrically conductive matrix to yield an embedded specimen; and then forming regions on the embedded specimen into shapes suitable for microanalysis by an atom probe.