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Installation issues can be caused by many factors, including conflicting startup items, incorrect data in the Windows registry, and hardware conflicts. Follow the troubleshooting steps below to clear up many types of installation issues, including the following:
Important: Some of the procedures in this document initiate a User Account Control dialog that asks for your permission to continue. Read the details in the dialog to determine if you want to continue. If you choose to cancel the dialog, you cannot continue with that troubleshooting step.
To install Photoshop Elements or Premiere Elements, your system has to meet or exceed the system requirements. For the most up-to-date information on system requirements, see Photoshop Elements Tech Specs or Premiere Elements Tech Specs.
Move all personal files (for example, images, videos, or third-party plug-ins) from the Photoshop Elements, Premiere Elements, and Elements Organizer folders and their subfolders to backup folders for safe keeping.
Note: The procedures in this document are based on the default Windows interface. If your interface is customized, some procedures vary. For example, navigating to Control Panel from the Start menu could be Start > Settings > Control Panel instead of Start > Control Panel.
When uninstall is complete, close the Control Panel and return to the hard drive location where the app was originally installed. Delete these folders (if the installer did not delete them): Photoshop Elements or Premiere Elements, and Elements Organizer. (By default, they are installed under the Program Files/Adobe folder.)
Dust or dirt on a CD can interfere with an installation and prevent the CD-ROM drive from recognizing the CD. Examine the Photoshop Elements and Premiere Elements CD for dirt, dust, or fingerprints. Gently wipe the bottom of the CD from the center outward with a soft, lint-free cloth.
Verify that the CD-ROM drive can read other CDs. If it can't, examine the CD caddy or loading tray for dirt, and clean it with a lint-free cloth. If it still can't read other CDs, contact the CD-ROM drive manufacturer or the computer manufacturer.
Note: Some of these procedures require locating hidden files and hidden folders, or finding files by their full filenames, including extensions (such as, Setup.exe or Sample_filename.ini). By default, Windows Explorer doesn't show hidden files, hidden folders, and recognizable filename extensions. For help, see Show hidden files, folders, filename extensions.
Device drivers and software that loads automatically with Windows can conflict with the Elements installer and cause problems in installation. (Software that loads automatically includes screen savers and virus protection utilities.) To prevent conflicts, reinstall Photoshop Elements/Premiere Elements while Windows is in a simplified mode. In a simplified mode, nonstandard device drivers and startup software are disabled.
The security settings in Windows 7, 8, 10, and Vista sometimes prevent applications from writing to protected file locations or registry keys. Setting the installer to run as an administrator bypasses the security settings and allows it to write to the protected areas.
Create a folder at the root level of the hard drive. Make sure that the folder name has eight or fewer characters (for example, C:\PSE or C:\PRE) and doesn't include special characters, such as "#." Also, make sure that the path to where Windows is installed doesn't contain special characters.
Create a user account that has the same permissions as the account that you use when the problem occurs. If the problem doesn't recur, the original user account could be damaged. For instructions on creating a user account, see Create a new user or contact your system administrator.
Many video card manufacturers frequently update their software drivers. If you haven't recently updated the video card driver, contact the video card manufacturer for an updated driver, or download one from the manufacturer's website. (To determine the manufacturer of a video card, view the card's properties in Device Manager.) You can often determine if the video driver is outdated by changing the color depth and resolution of the video card. You can also determine if it's outdated by disabling graphics hardware acceleration.
If updating the video card driver doesn't resolve the problem, verify that all other device drivers are compatible with your version of Windows (Windows 8 or Windows 7 and Vista). Device drivers are software files that allow Windows to communicate with devices such as scanners, mouse devices, and keyboards. Contact the device manufacturer to make sure you're using the latest driver for it.
Use current antivirus software (for example, Symantec Norton Antivirus or McAfee Virus Scan) to check the system for viruses. Virus infections can damage software and cause installation errors. For more information, see the documentation for the antivirus software.
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Acute promyelocytic leukemia (APL) represents a paradigm for targeted differentiation therapy, with a minority of patients experiencing treatment failure and even early death. We here report a comprehensive single-cell analysis of 16 APL patients, uncovering cellular compositions and their impact on all-trans retinoic acid (ATRA) response in vivo and early death. We unveil a cellular differentiation hierarchy within APL blasts, rooted in leukemic stem-like cells. The oncogenic PML/RARα fusion protein exerts branch-specific regulation in the APL trajectory, including stem-like cells. APL cohort analysis establishes an association of leukemic stemness with elevated white blood cell counts and FLT3-ITD mutations. Furthermore, we construct an APL-specific stemness score, which proves effective in assessing early death risk. Finally, we show that ATRA induces differentiation of primitive blasts and patients with early death exhibit distinct stemness-associated transcriptional programs. Our work provides a thorough survey of APL cellular hierarchies, offering insights into cellular dynamics during targeted therapy.
The landscape of cancer-targeted therapies has shifted from molecular target identification to cellular heterogeneity characterization and targeting1,2. The direct targeting of molecular changes driving tumorigenesis has proven to enhance therapeutic efficacy in cancer, as exemplified by the success of molecular targeted therapy in acute promyelocytic leukemia (APL)3. APL is characterized by its driver oncogenic fusion protein (PML/RARα), which plays a crucial role in initiating APL leukemogenesis, as supported by substantial evidence, including insights from murine models4,5. Notably, two drugs, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), have already achieved remarkable therapeutic outcomes by directly targeting this oncogenic fusion protein6. We7,8,9,10,11 and others12,13 have long been focusing on molecular mechanisms to illustrate how ATRA and ATO directly target the stability of PML/RARα to reverse transcriptional deregulation, affecting the proliferation and differentiation of APL cells. It is well-established that intratumoral heterogeneity at the cellular level is a critical factor in leukemogenesis, disease progression, and therapy response14. Advances in single-cell genomics technologies have uncovered the cellular heterogeneity of chronic myeloid leukemia and lung cancer1,15, demonstrating the potential for exploring heterogeneous features to improve cancer therapy success rates. In the context of APL, it has now become imperative to explore whether leukemic cells driven by the same oncogenic driver, PML/RARα, exhibit diverse cellular states; if so, to what extent the cellular composition and transcriptional heterogeneity might impact the outcomes of targeted therapy in APL.
Furthermore, extensive investigations into the molecular mechanisms underlying effective targeted therapies in APL have primarily relied on in vitro analyses or in vivo murine models3,7,8. These studies have sought to elucidate the effectiveness of ATRA and/or ATO in reversing the aberrant transcriptional regulatory activity of PML/RARα. Additionally, functional analyses of cell behavior have showcased the efficient induction of terminal granulocyte differentiation3,7,8. However, the genuine in vivo responses of APL cells to ATRA, particularly its impact on different cellular compartments, remain ill-defined. This limitation restricts our ability to explain the effectiveness of ATRA in treating APL patients with varying prognoses.
In this work, we use the single-cell RNA sequencing (scRNA-seq) technology to comprehensively dissect the cellular heterogeneity in APL and its potential impact on ATRA therapy in vivo and early death, as outlined in Fig. 1a. We generate a single-cell transcriptome resource on the malignant APL blasts from 16 newly diagnosed APL patients. Subsequently, we conduct a series of data analyses to gain deeper insights into APL cellular heterogeneity and its association with genomic and clinical characteristics of APL patients. The resources and findings presented in this study hold significant implications in four aspects. Firstly, our resource enables the characterization of intratumoral heterogeneity with multiple branches, including a small subpopulation of APL stem-like cells at the root of the differentiation trajectories. Secondly, at the single-cell level, we show that the stemness characteristics of APL stem-like cells are determined by PML/RARα target genes and can be further enhanced in the presence of FLT3-ITD. Thirdly, deconvolution analysis conducted on a large cohort of 323 APL patients reveals a significant association of higher APL stem-like cell proportions with elevated white blood cell (WBC) counts and the presence of FLT3-ITD. We also successfully construct an APL-specific stemness score, which effectively assesses prognosis, especially the risk of early death in APL patients. Lastly, our single-cell level investigations into the in vivo effects of ATRA confirm that ATRA directly targets APL primitive blasts, leading to their differentiation and maturation.
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