Abstract: The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations.

Abstract: A digital phase-locked loop includes a digital loop filter, a digitally controllable oscillator (DCO), and an injection-locked calibration-free time-to-digital converter (TDC) having a ring oscillator connected to the DCO via an input buffer that converts a sinusoidal DCO signal to a differential square wave signal provided to the ring oscillator such that ring oscillator frequency matches DCO frequency. A spur cancellation loop between the TDC and digital loop filter generates a spur cancellation signal based on an estimate of a spurious tone amplitude and phase. The spur cancellation signal is subtracted from TDC output signals prior to input to the digital loop filter. The spur cancellation loop may include a gradient descent strategy, or a feedforward strategy having a high-pass filter, integer delay chain, adaptive fractional delay, and signal averaging logic to cancel multiple internal and external spurs having frequencies that are not related to the reference clock frequency.

Abstract: The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of treating a proliferative disorder characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering an ATRA-related compound. The invention also features methods of treating proliferative disorders, autoimmune diseases, and addiction conditions (e.g., diseases, disorders, and conditions characterized by elevated Pin1 marker levels) by administering an ATRA-related compound in combination with another therapeutic compound.

Abstract: An analog-to-digital converter may convert an analog signal into digital codes representative of the changing level of the analog signal. An analog high pass filter may receive and continuously differentiate the analog signal. A voltage controlled oscillator may receive the differentiated analog signal and continuously generates an output that is an integral of the differentiated analog signal in the phase domain. A time-to-digital converter may sample the output of the voltage controlled oscillator and convert each sample into a digital code representative of the current phase of the sampled output of the voltage controlled oscillator.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations.

Abstract: Biomarkers and driver mutations for diagnosis and prognosis of Pin 1-associated diseases are disclosed. In one embodiment, the methods for diagnosis of Pin 1-associated diseases may include detecting the level of Pin1 to stage abnormal cell growth, such as breast or prostate cancer. In another embodiment, the methods include evaluating the efficacy of a treatment of abnormal cell growth, such as cancer, by monitoring the levels of Pin1. In another embodiment, the methods include using driver mutations to determine the pharmacogenetics of abnormal cell growth, such as cancer. In the present disclosure, elevated active monomeric Pin1 levels may be detected by Pin1 biomarkers, which may include Pin1 Q33K or E100D driver mutations, Pin1 protein or transcript overexpression, dephosphorylation of Pin1 on Ser71, dephosphorylation of S16, phosphorylation of S65, phosphorylation of S138, deacetylation of Pin1 on K13 and deacetylation of K46, and/or desumoylation of Pin1 on K6 and desumolation of K63, among others.

Abstract: The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of identifying the same. The invention also provides methods of treating a condition selected from the group consisting of a proliferative disorder, an autoimmune disease, and an addiction condition characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating proliferative disorders, autoimmune diseases, and addiction conditions (e.g., diseases, disorders, and conditions characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with another therapeutic compound. The invention also features a co-crystal including Pin1 and a retinoic acid compound.

Abstract: A digital phase-locked loop includes a digital loop filter, a digitally controllable oscillator (DCO), and an injection-locked calibration-free time-to-digital converter (TDC) having a ring oscillator connected to the DCO via an input buffer that converts a sinusoidal DCO signal to a differential square wave signal provided to the ring oscillator such that ring oscillator frequency matches DCO frequency. A spur cancellation loop between the TDC and digital loop filter generates a spur cancellation signal based on an estimate of a spurious tone amplitude and phase. The spur cancellation signal is subtracted from TDC output signals prior to input to the digital loop filter. The spur cancellation loop may include a gradient descent strategy, or a feedforward strategy having a high-pass filter, integer delay chain, adaptive fractional delay, and signal averaging logic to cancel multiple internal and external spurs having frequencies that are not related to the reference clock frequency.

Abstract: The present invention provides an improved file system format for an optical disc to help prevent illegal copying of multimedia content, where certain non-readable data record is placed into increased measured length of a multimedia data block; disc made pursuant to present format allows normal playback with very low level noise that would not affect the user enjoyment of viewing/listening the movie or music content on the multimedia disc.

Abstract: The method adapted for a disc burner for sensing/computing the maximum allowable capacity of a disc for overburn purpose where an accurate capacity of the disc based on the outermost-edge wobble signal is obtained, resulting in more data written on the disc with an amount of the data smaller than the physically-recordable maximum capacity of the disc and decreasing the failure rate of data overburning.

Abstract: A solar cell is provided. The substrate of the solar cell has heavily-doped regions and lightly-doped regions. The anode and the cathode are disposed on the back surface of the substrate, and thus the amount of incident light on the front surface of the substrate is increased. The anode and the cathode are in contact with the heavily doped regions to form selective emitter structure, and thus the contact resistance is reduced. The lightly-doped regions, which are not in contact with the anode and the cathode, have lower saturation current, and thus recombination of hole-electron pairs is reduced, and absorption of infrared light is increased.

Abstract: A solar cell includes a doped layer disposed on a first surface of a semiconductor substrate, a doped polysilicon layer disposed in a first region of a second surface of the semiconductor substrate, a doped area disposed in a second region of the second surface, and an insulating layer covering the doped polysilicon layer and the doped area. The insulating layer has openings exposing portions of the doped polysilicon layer and the doped layer, and the doped polysilicon layer and doped layer are respectively connected to a first electrode and a second electrode through the openings. The semiconductor substrate and the doped layer have a first doping type. One of the doped polysilicon layer and the doping area has a second doping type, and the other one of the doped polysilicon layer and the doping area has the first doping type which is opposite to the second doping type.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: A solar cell includes a doped layer disposed on a first surface of a semiconductor substrate, a doped polysilicon layer disposed in a first region of a second surface of the semiconductor substrate, a doped area disposed in a second region of the second surface, and an insulating layer covering the doped polysilicon layer and the doped area. The insulating layer has openings exposing portions of the doped polysilicon layer and the doped layer, and the doped polysilicon layer and doped layer are respectively connected to a first electrode and a second electrode through the openings. The semiconductor substrate and the doped layer have a first doping type. One of the doped polysilicon layer and the doping area has a second doping type, and the other one of the doped polysilicon layer and the doping area has the first doping type which is opposite to the second doping type.

Abstract: A solar cell is provided. The substrate of the solar cell has heavily-doped regions and lightly-doped regions. The anode and the cathode are disposed on the back surface of the substrate, and thus the amount of incident light on the front surface of the substrate is increased. The anode and the cathode are in contact with the heavily doped regions to form selective emitter structure, and thus the contact resistance is reduced. The lightly-doped regions, which are not in contact with the anode and the cathode, have lower saturation current, and thus recombination of hole-electron pairs is reduced, and absorption of infrared light is increased.

Abstract: The method adapted for a disc burner for sensing/computing the maximum allowable capacity of a disc for overburn purpose where an accurate capacity of the disc based on the outermost-edge wobble signal is obtained, resulting in more data written on the disc with an amount of the data smaller than the physically-recordable maximum capacity of the disc and decreasing the failure rate of data overburning.

Abstract: A solar cell includes a doped layer disposed on a first surface of a semiconductor substrate, a doped polysilicon layer disposed in a first region of a second surface of the semiconductor substrate, a doped area disposed in a second region of the second surface, and an insulating layer covering the doped polysilicon layer and the doped area. The insulating layer has openings exposing portions of the doped polysilicon layer and the doped layer, and the doped polysilicon layer and doped layer are respectively connected to a first electrode and a second electrode through the openings. The semiconductor substrate and the doped layer have a first doping type. One of the doped polysilicon layer and the doping area has a second doping type, and the other one of the doped polysilicon layer and the doping area has the first doping type which is opposite to the second doping type.

Abstract: The invention features methods of treating a proliferative disorder characterized by elevated Pin1 marker levels and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating proliferative disorders (e.g., proliferative disorders characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with another anti-proliferative compound. Finally, the invention also features methods including high-throughput screens for discovering and validating Pin1 inhibitors.