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In this manuscript, we report the surprising findings that ATO inhibits and induces Pin1 degradation and suppresses cancer cell growth via noncovalently binding to the Pin1 active site, as corraborated by nuclear magnetic resonance (NMR) and co-crystal structure. ATO, at clinically relevant and safe doses, ablates Pin1 to inactivate multiple oncoproteins and activate many tumor suppressors and global microRNAs, as well as inhibit triple-negative breast cancer (TNBC) tumor growth. Disrupting the ability of Pin1 to bind to ATO results in ATO resistance in vitro and in vivo. Moreover, the anticancer effects of ATO are potently amplified by co-treatment with ATRA, which induces aquaporin-9 (AQP9) to increase cellular ATO uptake, in addition to directly inhibiting and degrading Pin1. Consequently, ATO and ATRA work cooperatively to ablate Pin1, thereby blocking multiple oncogenic pathways and eliminating TICs and their drug resistance in TNBC in human cells and in animal models including patient-derived orthotopic xenografts (PDOXs). This ATO-ATRA cooperative phenotype closely resembles Pin1 CRISPR KO, which is also substantiated by comprehensive analyses of protein and microRNA expression. Thus, Pin1 is a novel drug target for ATO, and synergistic targeting of Pin1 by ATO and ATRA offers an attractive approach to block multiple cancer-driving pathways and eliminate TICs, which are the two major sources of drug resistance in current cancer therapy.
We thank Nathanael Gray, Tony Hunter, Michael Eck, and Ellen Weisberg for their expert advice, and the members of Lu/Zhou laboratory for constructive discussion. S.K. is a fellowship recipient of the Japan Society for the Promotion of Science and the Uehara memorial foundation; Y.-M.L. is a fellowship recipient of the Taiwan Science Foundation, and X. L. is sponsored in part by the P.R.C. National and Fujian Provincial Key Clinical Specialty Discipline Construction Program. ATO and Pin1 co-crystal structure was determined at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines (NIGMS P41 GM103403). The work is supported by NIH grants R01CA167677 to K.P.L. and R01CA205153 to K.P.L. and X.Z.Z.
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Download SolidWorks 2022 SP1 full version program free setup for Windows. Dassault Systems SolidWorks 2022 full premium for Windows provides the breadth of tools to tackle the most complex problems and the depth to finish critical detail work. New features help you improve your product development process to get your innovative products into production faster.
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SCAPS (a Solar Cell Capacitance Simulator) is a one dimensional solar cell simulation programme developed at the Department of Electronics and Information Systems (ELIS) of the University of Gent, Belgium. Several researchers have contributed to it's development: Alex Niemegeers, Marc Burgelman, Koen Decock, Stefaan Degrave, Johan Verschraegen. The was originally programme is developed for cell structures of the CuInSe2 and the CdTe family. Recent developments make the programme now also applicable to crystalline solar cells (Si and GaAs family) and amorphous cells (a-Si and micromorphous Si) The most recent version, SCAPS 3.8, may 2020, includes: up to 7 semiconductor layers
almost all parameters can be graded (i.e. dependent on the ocal composition or on the depth in the cell): Eg, chi;, epsilon;, NC, NV, vthn, vthp, µn, µp, NA, ND, all traps (defects) Nt
recombination mechanisms: band-to-band (direct), Auger, SRH-type defect levels: in bulk or at interface; their charge state and recombination is accounted for defect levels, charge type: no charge (idealisation), monovalent (single donor, acceptor), divalent (double donor, double acceptor, amphoteric), multivalent (user defined) defect levels, energetic distributions: single level, uniform, Gauss, tail, or combinations
defect levels, optical property: direct excitation with light possible (impurity photovoltaic effect, IPV)
meta-stable defects: transitions between acceptor and donor configurations for known meta-stable defects in CIGS: the V_Se and the In_Cu defect; also custom set meta-stable transitions implemented.
contacts: work function or flat-band; optical property (reflection of transmission filter) filter
tunneling: intra-band tunneling (within a conduction band or within a valence band); tunneling to and from interface states
generation: either from internal calculation or from user suppied G(x) file
illumination: a variety of standard and other spectra included (AM0, AM1.5D, AM1.5G, AM1.5Gedition2, monochromatic, white,...)
illumination: from either the p-side or the n-side; spectrum cut-off and attenuation
working point for calculations: voltage, frequency, temperature
the programme calculates energy bands, concentrations and currents at a given working point, J-V characteristics, ac characteristics (C and G as function of V and/or f ), spectral response (also with bias light or voltage)
batch calculations possible; presentation of results and settings as a function of batchparameters
loading and saving of all settings; startup of SCAPS in a personalised configuration; a script language including a free user function
very intuitive user interface
a script language facility to run SCAPS from a "script file"; all internal variables can be accessed and plotted via the script.
a built-in curve fitting facility
a panel for the interpretation of admittance measurements
grading of all parameters can be set from file; more analytic "grading laws" implemented
new analytic models for the spectrum, the generation and the optical absorption coefficient
script support for the simulation of tandem cells
A description of the programme, and the algorithms it uses, is found in the literature:
It is is freely available to the PV research community (universities and research institutes, companies), however... You should comply with some basic conditions: don't sell, don't distribute further, refer when you publish results obtained with SCAPS
You should send us an e-mail request: your name, full name and address of your university/institution/company with laboratory/department, and, if applicable, the name of your promoter/supervisor
Send your request to: Marc BurgelmanSCAPS historySCAPS 3.3.10: MB. 26-11-2021: New update, but no new installation and no new new version number. Script command set layer.add_default also works for new problem (when no layer is present already). SCAPS 3.3.10: MB. 20-8-2021: New update, but no new installation and no new new version number. One little bug in the representation of one IPV rec/gen graph. SCAPS 3.3.10: MB. 10-4-2021: New update, new installation and new version number. Script support for simulating tandem cells. Detailed description in a new Chapter (Ch. 11) of the SCAPS users Manual. SCAPS 3.3.09: MB. 19-12-2020: New update, new installation and new version number. The number of scriptvaiables mindex, mvalue and mvector has been increased from 6 to 26: the letter m now can be any letter out of (a, b, c, ..., z), instead of only (x, y, z,u, v,w) in SCAPS = save scriptvectors.asSCAPSgenerationfile xy filename and set generation.from_scriptvectors xy (see Manual)... and finally (!) a new verion number and installation package. SCAPS 3.3.07: MB. 25-12-2019: New update (including new .uir file!), but no new installation and no new version number. Relaxing of requirements for SCAPS input files (absorption, generation, grading, filter, IPV cross sections): SCAPS eliminates double input points, orders the file data properly, and forces extrapolated R and T data in the range [0,1]... but the warning for possibly erroneous input files is not given anymore. SCAPS 3.3.07: MB. 17-2-2019: New update, new installation but no new version number. A few new script commands. Better interpretation of complicated filenames (multiple dots, multiple spaces) in the script. A bug in representing interpolated alpha(lambda) when set "from model". Note: At 21-2-2019 there was a new version (.exe and .gui file), but no new installation and no new version number, that corrected a bug in the version of 17-2-2019. Only on 13-5-2019 this new version (thus 21-2-2019, without the bug) was included in a new installation package. SCAPS 3.3.07: MB. 18-1-2019: New update, but no new installation and no new version number. Small bug manifesting itself (sometimes) in tunnel simulations. SCAPS 3.3.07: MB. 7-11-2018: New update, but no new installation and no new version number. A bug in setting the capture cross sections of metastable transitions in the batch and the script. Improvement of output layout with Show buttons if a user runs SCAPS with a Run Time Engine of Labwindows/CVI (National Instruments) that is more recent then the version used in the development of SCAPS. SCAPS 3.3.07: MB. 6-10-2018: New update, but no new installation and no new version number. A (small) further precaution against (user introduced...) inconsistency in definition files. SCAPS 3.3.07: MB. 4-5-2018: New update, but no new installation and no new version number. A few more script commands (extract, save scriptvectors.asSCAPS...file, vectorscale and vectoroffset). User Manual updated. SCAPS 3.3.07: MB. 26-1-2018: New update, new installation and new version number. Two more grading laws: gaussian and complementary error function functions; these are relevant for grading of densities (shallow acceptors NA, shallow donors ND, defects Nt) by in-diffusion of impurities. Extension of the models for optical absorption: see a detailed Application Note. User Manual updated. SCAPS 3.3.06: MB. 17-10-2017: New update, new installation and new version number. Mott-Schottky analysis (Napparent(x) from C-V) improved to cover also layers with graded epsilon, or depletion layer extending over more than one layer, with different epsilons. More script commands. A (very) few bugs. See a detailed Application Note. User Manual update coming soon (but after holiday :-) ). SCAPS 3.3.05: MB. 24-8-2017: New update, but no new installation and no new version number. Spectral response SR (in A/W) added as an option to QE output. A bug in setting the generation attenuation from script. Improvements in the AS-analysis. SCAPS 3.3.05: MB. 30-12-2016: New update, new installation and new version number. New illumination facilities: spectrum from analytical models (including black body), generation profiles from analytical models, e.g. EBIC-like beams, see Application Note. SCAPS 3.3.04: MB. 9-10-2016: New update, new installation and new version number. Updating of screen during batch execution and/or script execution can be suppressed (gain of speed, though not too much...). Some new script commands. Units bug with number of photons for QE calculation, when set from script.. See manual. SCAPS 3.3.03: MB. 14-2-2016: New update, new installation and new version number. Grading files can now be shared over several adjacent layers. Simultaneous batch parameters are treated as one group of variables in the curve fitter, thus constituting only one curve fitting variable. See manual. SCAPS 3.3.02: MB. 2-10-2015: New update, but no new installation and no new version number. New script variables (points/decade and total points for C-f measurement; Mott-Schottky parameters and recalculate mesh parameters). Bug in reading Mott-Schottky parameters from def file. Button to reset all numerical parameters to default. See manual. SCAPS 3.3.02: MB. 6-7-2015: New update, new installation and new version number. A few bugs(sign of QE in an np structure; user interface cosmetics). Measurements can be weighted for total Chi-square calculation in the curve fitter. New script commands (listoffilenames; median; get Pi, Jideal,…; save generation as SCAPS generation file, …; a scalar Jtot next to the vector Jtot(x); … see manual). More precise numerical integration in G_cumulated, R_cumulated (see manual).. SCAPS 3.3.01: MB. 2-3-2015: New update, new installation and new version number. Graphical view of all graded parameters; facility to split a layer, conserving total thickness and grading proifile; new script commands for removing, adding, duplicating and splitting, and renaming a layer; for renaming an interface; for removing, adding and duplicating bulk and interface defects. SCAPS 3.3.00: MB. 19-2-2015: New update, but no new installation and no new version number. Flat band calculation also done when a problem is loaded from the command line, or from AllScaps, or from file. A refinement in the mesh generator. A bug in reading position-dependent grading from a file, for the 2nd... layer. SCAPS 3.3.00: MB. 6-9-2014: New update, but no new installation and no new version number. Adding columns with radiative and Auger recombination constants to the "Show Grading" output table; Adding checks for internally inconsistent .def files, that can occur when a user has manually edited existing .def files (this practice is strongly disadvised!). SCAPS 3.3.00: MB. 25-8-2014: New update, but no new installation and no new version number. Fixing of a minor bug in the flat band calculation, if there were charged deep defects, with energy defined "below EC." On demand: thickness range extended from 1 nm to 0.01 nm and from 10 cm to 100 cm; facility to display in another unit than micrometer (e.g. nm). SCAPS 3.3.00: MB. 18-5-2014: New update, new installation and new version number. Fixing of a few minor bugs in output files and graphs. User reference of the cell enabled: voltage applied to the left or to the right contact, current labeled positive when entering or leaving a specified contact. SCAPS 3.2.01: MB. 6-3-2014: New update and new installation; no new version number. Energy band calculation can now be saved and shown also when no I-V... simulation was done. The Save button on the Cell Definition Panel will save the cell definition with all the current changes, even when these changes are not yet confirmed with the OK button. SCAPS 3.2.01: MB. 15-11-2013: New update and new installation; no new version number. A minor bug in plotting G(x) profiles, when some data equalled zero; and in loading defects from a materials file. 4-12-2013: Bug fixed: apparent doping when CV was calculated from V0 (ordering of points). SCAPS 3.2.01: MB. 3-9-2013: New installation and update; no new version number. All parameters can now be graded from a file input. SCAPS 3.2.01: MB. 24-10-2012: New installation and update; no new version number. Minor bug with visibility of ND(x) and NA(x) options in layerpanel. SCAPS 3.2.01: MB. 24-10-2012: New installation and update; no new version number. Minor bug with visibility of ND(x) and NA(x) options in layerpanel. SCAPS 3.2.01: MB. 8-8-2012: New installation and update; no new version number. More options for loading/saving materials. SCAPS checks for unfound files in a problem before running, and allows to browse for existing files. SCAPS 3.2.01: KD&MB. 25-6-2012: New installation. A bug with tunneling (introduced with version 3.2.00) is fixed. Material files can be saved. Tunnel mechanism SCAPS 3.2.00: KD&MB. 2-5-2012: New update, no new installation. The complete initial state work point can now be saved and loaded form a file, and can be used as a batch patameter. SCAPS 3.2.00: KD&MB. 26-4-2012: New installation. Metastable defect states implemented. Some user interface improvements, e.g. normalised QEplots, better looking of the user interface (we hope).SCAPS 3.1.02: MB&KD. 15-10-2011: New installation. Built-in curve fitting facility. Panel to interpret admittance measurements (C(f)). A plot legend and selection facility. 041b061a72