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Windows 10 Anniversary Update (Windows 10, version 1607) continues our commitment to productivity, security, and privacy for all customers. Windows 10 Pro and Windows 10 Enterprise offer the functionality and safety features demanded by business and education customers around the globe. Windows 10 is the most secure Windows weve ever built. All of our Windows commercial editions can be configured to support the needs of schools, through group policies, domain join, and more. To learn more about Microsofts commitment to security and privacy in Windows 10, see more on both security and privacy. Windows 10, version 1607 offers a variety of new features and functionality, such as simplified provisioning with the Set up School PCs app or Windows Imaging and Configuration Designer (ICD), easier delivery of digital assessments with Take a Test, and faster log in performance for shared devices than ever before. These features work with all Windows for desktop editions, excluding Windows 10 Home. You can find more information about Windows 10, version 1607 on windows.com.Windows 10, version 1607 introduces two editions designed for the unique needs of K-12 institutions: Windows 10 Pro Education and Windows 10 Education. These editions provide education-specific default settings for the evolving landscape in K-12 education IT environments.
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.
CUPERTINO, CALIFORNIA Apple today introduced the new iPad with an all-screen design featuring a large 10.9-inch Liquid Retina display. The new iPad is powered by the A14 Bionic chip, which delivers even faster performance with incredible power efficiency for demanding tasks while still providing all-day battery life.1 Updated cameras include an Ultra Wide 12MP front camera located along the landscape edge of iPad for an even better video calling experience, and an updated 12MP back camera to capture sharp, vivid photos and 4K video. A USB-C port supports a wide range of accessories, Wi-Fi 6 brings even faster connections, and cellular models feature superfast 5G so users can stay connected on the go. Designed specifically for the new iPad, the all-new Magic Keyboard Folio features an incredible typing experience, a click-anywhere trackpad, and a versatile two-piece design. With iPadOS 16 and support for Apple Pencil (1st generation),2 iPad offers users more ways to be creative and productive. The new iPad is available to order starting today, with availability in stores beginning Wednesday, October 26.
For the first time on any iPad, the front-facing camera is now located along the landscape edge. Whether users are on a FaceTime call or recording a video for social media, they will always be looking right toward the camera. The landscape Ultra Wide front camera with a 12MP sensor and 122-degree field of view supports Center Stage, which automatically pans and zooms to keep users in view as they move around. The upgraded 12MP Wide back camera on iPad delivers high-resolution photos and detailed 4K video with support for 240-fps slo-mo.
Dual microphones are designed to work in unison with the cameras, capturing audio from the camera being used and minimizing distracting background noise. New landscape stereo speakers, combined with the larger display on iPad, offer a great video-viewing experience.
After founding the CD Media, Inc. publishing company in 1996, he went on to help start or grow several successful online publications, including Audioholics (as Editor-in-Chief for 12 years), Audiogurus, and AV Gadgets. In 2008, Clint founded Pro Tool Reviews followed by the landscape and outdoor power equipment-focused OPE Reviews in 2017. He also heads up the Pro Tool Innovation Awards, an annual awards program honoring innovative tools and accessories across the trades.
UltraGlass Privacy Treated Screen Protector with German-engineered technology delivers the evolution of durability and resilience in screen protection for iPhone. UltraGlass Privacy is chemically strengthened by double ion-exchange for ultra-impact protection and gives you full-screen privacy in portrait mode along with the flexibility of sharing your screen in landscape mode. The glass contains an antimicrobial agent to protect the product from microbial growth, without sacrificing touchscreen response or clarity.
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. 2b1af7f3a8
