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Gustav Fokin
Gustav Fokin

Pro Landscape 12 Serial Keygen And 30 \/\/TOP\\\\



Your mower's serial number (either XXX,XXX or XXX,XXX,XXX) can be found on the model and serial number plate mounted on your equipment. Serial number plate mounting location varies from mower to mower. If you cannot find your serial number plate, please consult your owners manual (typically on page 3) for location help.




Pro Landscape 12 Serial Keygen And 30



Breast cancer is a heterogeneous disease, affecting over 3.5 million women worldwide, yet the functional role of cis-regulatory elements including super-enhancers in different breast cancer subtypes remains poorly characterized. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. Here we apply integrated epigenomic and transcriptomic profiling to uncover super-enhancer heterogeneity between breast cancer subtypes, and provide clinically relevant biological insights towards TNBC. Using CRISPR/Cas9-mediated gene editing, we identify genes that are specifically regulated by TNBC-specific super-enhancers, including FOXC1 and MET, thereby unveiling a mechanism for specific overexpression of the key oncogenes in TNBC. We also identify ANLN as a TNBC-specific gene regulated by super-enhancer. Our studies reveal a TNBC-specific epigenomic landscape, contributing to the dysregulated oncogene expression in breast tumorigenesis.


Enhancers are noncoding regions of the genome that harbor cis-regulatory elements and promote transcription of a target gene. They are characterized by histone modifications such as acetylation of histone H3 at lysine 27 (H3K27ac) and binding of coactivators such as p3007. Super-enhancers (SEs) are large clusters of enhancers that drive specific expression programs that define cellular identity8. They have been associated with different disease states such as the enrichment of enhancer clusters in pancreatic islet cells of Type 2 diabetes individuals9. It has been shown recently that SEs also play a critical role in upregulating the expression of cancer driver genes10,11. For example, focal amplifications of SEs that drive MYC expression have been identified in multiple epithelial cancers7. In gastric cancer, reprogramming and heterogeneity of SEs are observed during tumorigenesis, underpinning TF occupancy, and disease outcome12. Recently, CD47 and ERG are shown to be upregulated by SEs in breast and prostate cancer, respectively13,14. It has also been demonstrated that in neuroblastoma, expression of PRRX1 alters the SE and mRNA landscapes toward a mesenchymal state15. Epigenomic profiling has been done in various solid tumors, including medulloblastoma16 and colon cancer17, for identifying subgroup-specific SEs. However, comprehensive catalogs of SEs in different subtypes of breast cancer, and their functional importance in tumorigenesis, are not published yet.


In this study, we aim at characterizing the SE landscape in breast cancer. To dissect the heterogeneity of SEs in TNBC and non-TNBC subtypes, we perform integrative transcriptomic and epigenomic analyses, and provide evidence that SEs play an important role in characterizing subtype-specific identity. We also identify corresponding targeting genes of TNBC-specific SEs, including FOXC1, MET, and ANLN. The critical function of TF FOXC1 in breast cancer growth and its clinical relevance has been determined18,19. Phenotypically, overexpression of FOXC1 results in increased tumor growth and migration. However, very few studies have addressed the regulatory network of FOXC1. Here, our network biology analysis defines FOXC1 as the major node in regulating the expression of invasion and metastasis signature genes. Using CRISPR/Cas9 genomic editing, we delete the FOXC1-associated SE, and find a significant reduction of FOXC1 expression, as well as impairment of spheroid and clonogenic growth, consistent with its oncogenic properties. In addition, we identify ANLN as a TNBC-specific gene regulated by SE, contributing to TNBC tumorigenicity. Taken together, our multiomic analysis has revealed breast cancer subtype-specific SE regulatory mechanisms, and we have characterized the critical function of SEs in the specific oncogenic signaling of TNBC.


Through high-throughput cis-regulatory element mapping, epigenomic dysregulation including SE heterogeneity, has emerged to play critical roles in the pathogenesis of various cancer types12,16. In breast cancer, it has been demonstrated that enhancer transcription can be used to improve the fidelity of functional enhancer identification20. However, the knowledge for subtype-dependent heterogeneity of breast cancer is lacking. Here, we collected the ChIP-seq data of 17 public breast cancer cell lines and two triple-negative (TN), immortalized breast cell lines (Supplementary Table 1), genome-widely identified and profiled the landscapes of SEs for different subtypes of breast cancer.


In summary, we have discovered distinct SE landscapes between TNBC and non-TNBC cells. Our studies highlight the functional significance of TNBC-specific SE in determining biological outcomes, and provide mechanisms by which key oncogenes specifically overexpressed in TNBC. We also demonstrate the utility of our multiomic platform in dissecting the regulatory circuits of gene expression and biology of different subtypes of breast cancer, further advocate for elucidating epigenetic dysregulation to provide insights for novel therapeutic interventions.


Because you can set page orientation on a worksheet-by-worksheet basis, you might print some worksheets in a workbook in one orientation (such as portrait orientation) and other worksheets in the same workbook in the opposite orientation (such as landscape orientation). Simply set the orientation for each worksheet as appropriate, and then Print a worksheet or workbook.


Browse our gallery to find inspiration for your next landscape project. The photos highlight a range of applications using the Luxor lighting control system, from architectural enhancements to landscape accents.


FX Luminaire is an industry-leading manufacturer of landscape and architectural lighting products with a focus on the advancement of LED Landscape Lighting technology and digital lighting control with zoning, dimming and color adjustment capabilities.


Homemade trailers are required to have a serial plate attached before the trailer can be registered and issued a license plate. To obtain a serial plate for your homemade trailer, submit the signed and notarized Form T-23 Homemade Trailer Affidavit to the County Tag Office in the county in Georgia where you live.


You must permanently attach the serial plate to your homemade trailer with rivets and have a Georgia Law Enforcement Officer complete Form T-22C (Permission for County Assigned Serial Number Plate for a Homemade Trailer) certifying that the serial plate has been attached to the trailer.


In the USA, be sure the serial number on your lens (in tiny black-on-black numbers on the bottom between A012 and MADE IN JAPAN) matches the serial number on the top of the box and on the warranty papers inside the box, and be sure your box has this six-year USA hologram sticker:


Open the top flap and you should see the bare serial number slip carefully tucked into a slot in the left flap. If it's just sitting on top of the other paperwork, that suggests someone's been in there before.


Nikon's 16-35mm f/4 VR FX (check price) is a superb lens. It is far more practical because it takes normal filters, also has VR, covers a broader zoom range, is as sharp, weighs a lot less and costs the same as this Tamron. I've been using my 16-35 VR since it came out in 2010 and love it. I don't care that it's a stop slower; for nature and architecture and landscape, get the 16-35 VR and stay safe with proven Nikon service and longevity.


If you purchase a DJI Care Refresh activation card, you need to enter your activation code and serial number of your product through DJI Care Activation page to activate your DJI Care Refresh service.


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