Graphpad Prism 6 Crack Mac Screen
Asela Buchheit
Prism 7 requires a minimum display height of 540 pixels.Prism Windows 6 and Prism 5 (starting with 5.03) run in a screen as small as 800 x 576. Earlier releases of Prism 5 required a larger screen, so update to the latest.
Prism 5.03 and 5.0c will run on netbooks with at least 576 pixels of vertical resolution (Prism 5.02 and 5.0b require 600 pixels). But, working on a small screen can be difficult. There are a couple of things you can do to free up space in Prism. You can hide the Prism Navigator tree and use buttons at the bottom of the Prism window to move around in your file, and you can hide the button toolbar and use Prism's menus.
In some cases, the best way to ask for technical support is to send screen shots that show what went wrong or what is confusing. Or perhaps a video showing a series of steps. That can also be helpful when showing colleagues or family how to accomplish something on a computer, or to share part of a page.
Tool built into MacOS
The screenshot toolbar on your Mac allows taking screenshots or recording a video of the entire screen or a portion of it so we can use them to reproduce the issues.
The recommended minimum display resolution for comfortable work in Prism is 1280x1024. However, unlike in previous versions, there is no restriction for the latest version of Prism to launch using screen resolutions below this recommended value. Prism will still launch, but it is possible that some of the dialogs will not quite fit the screen, or will appear with the controls at the bottom of the dialogs overlapped by the macOS Dock panel (assuming its default size and position).
This overlap issue happens when the effective resolution of the display is lower than what the dialog requires to fit on the screen. The result is that the dialog occupies the entire vertical space of the display, not accounting for the space required by the Dock panel. The result is that these two components overlap each other.
To make the Dock panel smaller or to move it to the left or right side of the screen, open System Preferences. Select "Dock" from the list of icons, and then adjust the size of the Dock or select the positioning from the subsequent menu.
If you use earlier vrsions of Prism, here are some things to try, in order:
- On Windows 95, 98, or ME (but the choice is not available on XP, NT or 2000), reduce the graphics acceleration. Click "Start.. Settings.. Control panel.. System.. Performance.. Graphics". Change the acceleration to a lower setting. Reboot your system.
- Experiment with the optional settings, if any, on your display driver ("Start.. Settings.. Control panel.. Display.."). One Prism user found that Prism always crashed when he tried to view a graph gallery. The problem was resolved, at least on that machine, by increasing the number of colors displayed on the screen.
- Install an updated or different video driver, available free on the Microsoft or computer manufacturer's web site.
- Try an updated or different printer driver.
- If you have a Matrox video driver, consider moving the graphics adaptor card to a different slot. The support forum at matrox.com mentioned to someone who had page fault problems: "... Make sure there is nothing in the first PCI slot beneath the AGP."
- If all else fails, try a different video card altogether. This has worked for two Prism users.
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The multiplexed cancer cell line screening platform PRISM demonstrated its utility in testing hundreds of cell lines in a single run, possessing the potential to speed up anti-cancer drug discovery, validation and optimization. Here we described the development and implementation of a next-generation PRISM platform combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated gene editing, cell line DNA barcoding and next-generation sequencing to enable genetic and/or pharmacological assessment of target addiction in hundreds of cell lines simultaneously. Both compound and CRISPR-knockout PRISM screens well recapitulated the results from individual assays and showed high consistency with a public database.
Human cancer cell lines serve as a powerful tool for defining the mechanism of cancer growth and metastasis, as well as for developing therapeutic interventions to attack cancer vulnerabilities. More than 1000 cancer cell lines from various tumor types have been established in the past decades and are widely used by the cancer research community1. However, these cancer cell lines, which are passaged for many years in culture dishes, may no longer fully recapitulate their original genetic and/or epigenetic characteristics owing to clonal selection2,3. It is not rare that scientific findings from one laboratory cannot be reproduced by other researchers using different strains of the same cell line that underwent genomic evolution. As such, a better approach to faithfully capture cancer vulnerability specific to a tissue lineage or genetic background is to assess the response to inactivation of a candidate disease-driving protein across a large number of cell lines covering common and distinctive genetic characteristics. This practice is usually impractical in small laboratories with limited resources, thus calling for the need for a reliable platform that allows the screening of hundreds of cell lines in a high-throughput manner.
In order to enable the rapid validation of the therapeutic value of a given target of interest across a large panel of human cancer cell lines using both CRISPR and pharmacological perturbations, we developed BMS (Bristol Myers Squibb)-PRISM platform combining CRISPR/Cas9-mediated gene editing capability and DNA-barcoding multiplexing technique. We carried out a focused run with epidermal growth factor receptor (EGFR) and a full library run with KRAS as proof-of-principle studies. Both compound and CRISPR-knockout PRISM screens well recapitulated the results from individual assays and showed high consistency with public database.
Solid tumor cell lines were individually infected with Cas9 and 26-bp barcode and tested for CRISPR editing efficiency before archived into BMS-PRISM library. These engineered cell lines were then subpooled and banked according to cancer indications for convenient handling. A full or focused collection of cell lines can be used for the compound as well as CRISPR/Cas9 knockout screening to evaluate drug response or gene essentiality in a single run. Relative cell line abundance after various treatments can be determined by PCR amplification of barcodes and next-generation sequencing.
KRAS mutations are found in nearly one-third of all human malignancies worldwide, among which KRAS G12C is highly smoking related and can now be selectively targeted by covalent inhibitors, such as AMG-510, which is currently under clinical investigation11,12. Since both KRAS dependency and AMG-510 specificity are well defined, we picked KRAS as one of our targets to validate the BMS-PRISM platform. Out of the total 17 KRAS G12C mutant cell lines in the current BMS-PRISM collection, most showed decent AMG-510 sensitivity in the PRISM compound screen, while 61 cell lines with non-G12C KRAS mutations did not respond to AMG-510 treatment (Fig. 3a, b). In comparison, most cell lines with either G12C or non-G12C KRAS mutations showed great depletion in the KRAS CRISPR knockout screen. In order to further demonstrate the reproducibility of the PRISM platform, we chose four KRAS-G12C, four KRAS non-G12C mutant, and three KRAS wild-type cell lines for individual validation of their response to AMG-510 treatment or KRAS CRISPR knockout. As shown in Fig. 3d, KRAS wild-type cell lines did not respond to AMG-510 or KRAS knockout, while non-G12C KRAS mutant cells only responded to KRAS knockout but not to AMG-510. Interestingly, among the group of G12C cell lines, SW1573 showed very little response to either AMG-510 or KRAS knockout, which was consistent with earlier reports that some of the KRAS mutant cells do not show KRAS dependency under conventional two-dimensional (2-D) cell culture conditions13,14. Notably, LU99 cells responded well to KRAS knockout in both the individual assay and the PRISM screen but only showed a mild response to AMG-510 treatment. It is possible that this cell line harbors a certain resistance mechanism to the compound but still maintains KRAS dependency. In contrast, SW837, another G12C cell line, showed KRAS dependency to both AMG-510 and KRAS knockout in the individual culture conditions but not in the mixed PRISM culture condition. This is likely owing to the aforementioned non-cell-autonomous paracrine effect in the mixed cell culture that may compensate for the KRAS dependency in supporting cell proliferation. This effect should be investigated further particularly when gene dependency relies heavily on culture conditions (e.g., 2-D vs three-dimensional (3-D) cell culture). Nevertheless, most of the 17 KRAS G12C mutant cell lines showed their consistent response to AMG-510 and KRAS CRISPR PRISM screen (Supplementary Fig. 5a). Finally, our KRAS CRISPR PRISM screen result correlated well with what has been reported at DepMap portal (Fig. 3e). KRAS mutant cancer cell lines were relatively more sensitive to KRAS genetic knockout. Overall, the KRAS screen further demonstrated the utility of the BMS-PRISM platform in evaluating the response of multiple cell lines in a single mixture to compound treatment or genetic manipulation, with the cell lines responding to AMG-510 or KRAS knockout as expected based on their KRAS mutation status.
a Pie chart showed the coverage of BMS-PRISM library composition. Total 368 cell lines were included in the current study. b Cell line response to Kras G12C inhibitor AMG-510 in PRISM screen. Cell lines were divided into three groups: KRAS G12C mutant (17 lines), KRAS other mutant (non-G12C, 61 lines), and KRAS wild-type (290 lines). c Cell line response to KRAS CRISPR knockout in PRISM screen (plotted with average of two sgRNAs). Cell lines were divided into three groups: KRAS G12C mutant (17 lines), KRAS other mutant (non-G12C, 61 lines), and KRAS wild-type (290 lines). Error bars represent standard error of the mean. d Validation of cell line response to KRAS perturbation in individual and PRISM assays (left, AMG-510 treatment; right, KRAS CRISPR knockout). KRAS G12C mutant (red circles); KRAS non-G12C mutant (green squares); KRAS wild-type (blue triangles). e Correlation analysis of KRAS CRISPR PRISM assay vs DepMap CRISPR gene effect score (CERES, 242 cell lines). KRAS mutant (red circles); KRAS wild-type (green squares).
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