Lync Server 2. 01. Planning Tool The Lync Server 2. Planning Tool has been a long time coming for Lync aficionados. Lync Server 2. 01. Many admins who deployed Lync in the past are familiar with Microsoft's previous planning tool (for Lync 2. I'll address two key areas of the new Lync 2. Planning Tool Walkthrough Planning Tool Reporting Lync Server 2. Download content for Azure, ASP.NET, Office, SQL Server, SharePoint Server and other Microsoft technologies in e-book formats. Reference, guide, and step-by-step information are all available. All the e-books are free.Planning Tool Walkthrough One of the biggest areas where customers like to get assistance is in doing the initial planning for which server roles they'll need and how many of each role will be necessary to support their environment. The Lync Server 2. Planning Tool is great at creating a high- level blueprint of what you'll need for your conceptual deployment. As deployments get more detailed and complex (and specifically when it comes to integration with telephony), customers might find it necessary to engage a consulting service of some sort. Related: The UC Architects: Spreading the News about Lync and Exchange When you launch the Lync Server 2. Planning Tool, you'll see the welcome page, which Figure 1 shows. From here, you can jump into the question- and- answer portion of the wizard or jump directly into the Design Sites section, which allows for custom configuration of the site. Click Get Started to walk through a wizard where you answer questions about your proposed environment for Lync 2. Here are just a few of the areas (in no particular order) where the planning tool asks questions about your planned deployment: mobility Persistent Chat (formerly Group Chat) archiving high availability/disaster recovery conferencing usage remote access audio/video conferencing The planning tool wizard addresses key areas around capacity planning and profile usage scenarios. The goal is to better assist individuals who are faced with deploying Lync 2. Lync 2. 01. 3 server roles for their environments. In the Enterprise Voice questions, the planning tool asks for details about response groups and Microsoft Exchange Server Unified Messaging usage (Exchange 2. Exchange 2. 00. 7 are both treated the same in the planning tool). When you've answered all the questions, the tool generates a Visio output, as Figure 2shows. The diagram is high- level conceptual view of the Lync 2. Lync Server 2. 01. Planning Tool Reporting The Lync Server 2. Planning Tool reports section is my favorite area of the tool. After you've gone through the deployment wizard and view the site topology that you created, you can click the Edge Admin tab to get to the reports page. This is where everything comes together: The tool provides you a rich, full set of reports that makes the deployment of your Lync 2. The following are the reports the tool creates: Certificates Report - - This report shows certificate Subject Names and Subject Alternative Names you'll need for Lync server roles. Figure 4 shows an example of a DNS Report. Firewall Report - - Your Lync environment uses certain ports and protocols for the Edge server and additional roles and services such as hardware load balancers, Front End servers and Mediation servers; this report lists what you'll need to be aware of. Figure 5 shows a sample of the Firewall Report. Summary. Report - - This report produces an overview of the settings that are needed to set up your Lync 2. Edge environment, such as fully qualified domain names (FQDNs) and IP addresses. Figure 6 shows an example of the Summary Report. A nice nuance of the reporting is the editing capability. On the Edge Network Diagram tab, you have the ability to edit information such as IP addresses or FQDNs of the servers to fit your environment. Also, the DNS Report details practically all the DNS SRV and A records that you'll need in the deployment from internal and external (public) records. The end goal of the planning tool is to give customers a starting point and a reference to get going with the Lync 2. The one big piece of advice I give to all my clients is to walk through the planning tool a few times before you begin your planning process. Using the tool puts you in the right mindset for the questions you have to ask to have an effective Lync 2.
A way to measure the target platform to make sure it has sufficient resources to run the workload. For disk resources the defacto tool is SQLIO. I have some notes on how to specify requirements here (http: //blogs. How- to- Specify- SQL- Storage- Requirements- to- your- SAN- Dude. For CPU resources you may simply check the number of cores and frequency, or use an industry standard benchmark such as those available on www. The cloud presents some challenges. If we are migrating to the Infrastructure as a Service,its really easy to verify we have the correct resources by simply running tools like SQLIO or running the workload and checking the performance counters for throughput and latency. If we are migrating a database to “Windows Azure SQL Database” or SQL Azure as it is still commonly called, we are a bit more restricted. WASD doesn’t allow us to use perfmon or SQLIO, so the best benchmark we can use is something measured from the application like OPM. So what does SQLIO tell me about running SQL in the cloud ? As a test we created a four core VM in the West Europe data centre and then run a series of SQLIO tests to measure the “saturation” point for disk IO (Thanks Fintan and Stephen!). The resulting chart is below. This shows that the disk we tested scaled up to about 3. MB/Second at just over 3. The highlighted section on the chart shows the “saturation point” where increasing the outstanding IO gives no more throughout. This is essentially the limit. MB/Sec equates to almost exactly 1,0. IOPS. Quite a nice round number! Traditionally we like to keep the latency at say 3ms, but assumabley due the replication and the fact the VHD is mounted on top of a blob store we have very high write latency. At low yields, say only a few MB/Sec, it maintains 1. I ran a sample ecommerce OLTP supplied by dell on a four core VM running in Iaa. S. We can see that the number one wait statistics was indeed WRITELOG, so a primary bottleneck is the disk subsystem. Uptime Infrastructure Monitor's capacity planning tools helps you manage capacity across different platforms from 1 unified dashboard. You can see the delays from the DMV “exec requests”. So what does this mean again ? This gives us a few facts we can use when doing capacity planning for workloads moving to the cloud: Azure Iaa. S (4 core) offering currently has a max ceiling of 1,0. IOPS for a disk. How much you get in terms of MB/Sec will depend on the block size: 3. MB/Sec with an 8. K block size and 2. MB/Sec with 6. 4k block size. You won’t get beyond 2. MB/Sec or 1,0. 00 IOPS due to throttling, but maybe this will change in the future. While the max IOPS is 1,0. I was just in a session with the SQLCAT team at Sql. Bits and they recommend to consider 5. IOPS per disk for capacity planning. Different VM Sized allow you to add more disks, and therefore get more IOPS. It seems that you probably want to consider using multiple disks as a matter of course in Azure Iaa. S as the charge is not based on the number of disks Write latency will start to affect service quality moreso than it will with on premise disk subsystems which are not replicated. I would love to test the effect of both of these on IO throughput and latency. This could for example affect placement of Temp. DB. We ran the tests with geo- replication disabled. I’m just going to see if we can get more throughput or better latency by utilising more than one logical disks. Will hopefully post the results ; -)If you want to repeat these tests you can sign up for Azure Iaa. S here. http: //www. SQLIOhttp: //blogs. How- to- Specify- SQL- Storage- Requirements- to- your- SAN- Dude.
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Nursing Home Administrator. The Nursing Home Administrator Program (NHAP) sets the standards for licensing of Nursing Home Administrators (NHAs), administers a training program for NHAs, tests and issues licenses. Prospective students who searched for nursing home administrator found the articles, information, and resources on this page helpful. Nursing Home Administrator Jobs In Lincoln, NE – Monster . Nursing home administrator program However, some schools are better than others and some are more suited to one person rather than another. My Colleges and Careers recommends that each student research their school before. Admissions Process NEW ADMISSIONS PROCESS. The UNC Charlotte School of Nursing (SON) is piloting a new admission process. During this pilot program, Nursing CAS will no longer be used as a gateway for application and. Nursing Home Administrator Program Many can also use an online degree to assist them in transitioning to related careers with transferable skill sets. For example, an artist could become an architect, using knowledge learned. Find the right Nurse Administration program for you and learn what it takes to be a leader in the nursing industry. Nha state of connecticut department of public health nursing home administrator application an application will not be reviewed by professional staff of the department until all required documents have been received. 3 G/EDUC COMM/RN-PN PROGRAM SURVEYS/CONTINUING APPROVAL RN-PN PROGRAMS, 6/00; 7/10; 07/13 R4-19-203. Administrator; Qualifications and Duties A. The nursing program administrator shall hold a current Arizona registered nurse. Nursing Home Administrator Training Program and Schools. A nursing home administrator runs a facility that meets the needs of senior citizens; he or she is compassionate with residents while taking a no-nonsense approach to. Baseball - Wikipedia. Baseball. Highest governing body. World Baseball Softball Confederation. First played. 18th century England. 2017 Lenape Valley Baseball. Below are the dates, times, and contacts for the 2017 LVBA travel tryouts. 8 Year Olds (Chris Blum). Detailed Gamechanger app review, with particular emphasis on youth baseball stats. GameChanger provides free stat tracking and team management tools for baseball, softball and basketball teams. A tutorial on scorekeeping for the casual baseball fan as well as a glossary and related links. Baseball scorekeeping is the practice of recording the details of a baseball game as it unfolds. Professional baseball leagues hire official scorers to keep an. Baseball is a bat-and-ball game played between two teams of nine players each, who take turns batting and fielding. The batting team attempts to score runs by hitting. Free scorekeeping and stat software for coaches and teams. Live updates and recaps for parents and fans. Characteristics. Contact. No. Team members. Mixed gender. Yes, separate competitions. Typeteam sport, bat- and- ball. Equipment. Baseball. Baseball bat. Baseball glove. Bases. Venue. Baseball field. Presence. Country or region. North America. Olympic. How to Keep Score for a Softball/baseball Game. Have you ever been sitting on the bench of a softball or baseball game and there is someone frantically asking if. No, Demonstrated in 1. Summer Olympics. In Summer Olympic program, 1. A run is scored when a player advances around the bases and returns to home plate. Players on the batting team take turns hitting against the pitcher of the fielding team, which tries to prevent runs by getting hitters out in any of several ways. A player on the batting team who reaches a base safely can later attempt to advance to subsequent bases during teammates' turns batting, such as on a hit or by other means. The teams switch between batting and fielding whenever the fielding team records three outs. One turn batting for both teams, beginning with the visiting team, constitutes an inning. A game is composed of nine innings, and the team with the greater number of runs at the end of the game wins. Baseball has no game clock, although almost all games end in the ninth inning. Baseball evolved from older bat- and- ball games already being played in England by the mid- 1. This game was brought by immigrants to North America, where the modern version developed. By the late 1. 9th century, baseball was widely recognized as the national sport of the United States. Baseball is now popular in North America and parts of Central and South America, the Caribbean, and East Asia. In the United States and Canada, professional Major League Baseball (MLB) teams are divided into the National League (NL) and American League (AL), each with three divisions: East, West, and Central. The major league champion is determined by playoffs that culminate in the World Series. The top level of play is similarly split in Japan between the Central and Pacific Leagues and in Cuba between the West League and East League. History. Origins. The evolution of baseball from older bat- and- ball games is difficult to trace with precision. A French manuscript from 1. Baseball Before We Knew It: A Search for the Roots of the Game (2. David Block, suggests that the game originated in England; recently uncovered historical evidence supports this position. Block argues that rounders and early baseball were actually regional variants of each other, and that the game's most direct antecedents are the English games of stoolball and . It contains a rhymed description of . Rounders was also brought to the USA by Canadians of both British and Irish ancestry. The first known American reference to baseball appears in a 1. Pittsfield, Massachusetts, town bylaw prohibiting the playing of the game near the town's new meeting house. As described by Johann Gutsmuths, . These games were often referred to locally as . There were many similarities to modern baseball, and some crucial differences: five bases (or byes); first bye just 1. The rules thus facilitated the use of a smaller, harder ball than had been common. Several other rules also brought the Knickerbockers' game close to the modern one, though a ball caught on the first bounce was, again, an out and only underhand pitching was allowed. With the Knickerbocker code as the basis, the rules of modern baseball continued to evolve over the next half- century. In 1. 85. 8 in Corona, Queens. New York, at the Fashion Race Course, the first games of baseball to charge admission took place. The games, which took place between the all stars of Brooklyn, including players from the Brooklyn Atlantics, Excelsior of Brooklyn, Putnams and Eckford of Brooklyn, and the All Stars of New York (Manhattan), including players from the New York Knickerbockers, Gothams (predecessors of the San Francisco Giants), Eagles and Empire, are commonly believed to be the first all- star baseball games. Four years later, it barred participation by African Americans. As the oldest surviving major league, the National League is sometimes referred to as the . In 1. 88. 4, African American Moses Walker (and, briefly, his brother Welday) played in one of these, the American Association. Several independent African American teams succeeded as barnstormers. The pact formalized relations both between the two major leagues and between them and the National Association of Professional Base Ball Leagues, representing most of the country's minor professional leagues. During the major leagues' early decades, players on various teams occasionally attempted strikes, which routinely failed when their jobs were sufficiently threatened. In general, the strict rules of baseball contracts and the reserve clause, which bound players to their teams even when their contracts had ended, tended to keep the players in check. The Black Sox Scandal led to the formation of a new National Commission of baseball that drew the two major leagues closer together. That year also saw the founding of the Negro National League; the first significant Negro league, it would operate until 1. For part of the 1. Eastern Colored League. The Irish Catholics dominated in the late 1. By the mid- 1. 88. Irish men dominated the sport and popularized a style of play that was termed heady, daring, and spontaneous.. Ed Delahanty personified the flamboyant, exciting spectator- favorite, the Casey- at- the- bat, Irish slugger. The handsome masculine athlete who is expected to live as large as he played. Strict new regulations governing the ball's size, shape and composition along with a new rule officially banning the spitball, along with other pitches that depended on the ball being treated or roughed- up with foreign substances after the death of Ray Chapman who was hit by a pitch in August 1. World War I, resulted in a ball that traveled farther when hit. The construction of additional seating to accommodate the rising popularity of the game often had the effect of bringing the outfield fences closer in, making home runs more common. The club with which Ruth set most of his slugging records, the New York Yankees, built a reputation as the majors' premier team. Louis Cardinalsgeneral manager. Branch Rickey invested in several minor league clubs and developed the first modern . The first elections to the Baseball Hall of Fame took place in 1. In 1. 93. 9 Little League Baseball was founded in Pennsylvania. By the late 1. 94. United States. With America's entry into World War II, many professional players had left to serve in the armed forces. A large number of minor league teams disbanded as a result and the major league game seemed under threat as well. Chicago Cubs owner Philip K. Wrigley led the formation of a new professional league with women players to help keep the game in the public eye . This program soon became another important organizing body for children's baseball. The first crack in the unwritten agreement barring blacks from white- controlled professional ball occurred the previous year: Jackie Robinson was signed by the National League's Brooklyn Dodgers. Larry Doby debuted with the American League's Cleveland Indians the same year. In 1. 95. 1, two Chicago White Sox, Venezuelan- born Chico Carrasquel and black Cuban- born Minnie Mi. While the majors rebounded by the mid- 1. It was the first professional baseball union to survive more than briefly, but it remained largely ineffective for years. Louis until 1. 95. Brooklyn Dodgers and New York Giants relocated to Los Angeles and San Francisco, respectively. This coincidentally helped Roger Maris break Babe Ruth's long- standing single- season home run record, one of the most celebrated marks in baseball. With this, the first major league expansion in 6. Attendance records and the age of steroids. The players' union became bolder under the leadership of former United Steelworkers chief economist and negotiator Marvin Miller, who was elected executive director in 1. After the 1. 96. 8 season, in an effort to restore balance, the strike zone was reduced and the height of the pitcher's mound was lowered from 1. In 1. 96. 9, both the National and American leagues added two more expansion teams, the leagues were reorganized into two divisions each, and a post- season playoff system leading to the World Series was instituted. Also that same year, Curt Flood of the St. Louis Cardinals made the first serious legal challenge to the reserve clause. The major leagues' first general players' strike took place in 1. Significant work stoppages occurred again in 1. World Series for the first time in 9. Regular- season interleague play was introduced in 1. In 2. 00. 0, the National and American leagues were dissolved as legal entities. While their identities were maintained for scheduling purposes (and the designated hitter distinction), the regulations and other functions. There had long been suspicions that the dramatic increase in power hitting was fueled in large part by the abuse of illegal steroids (as well as by the dilution of pitching talent due to expansion), but the issue only began attracting significant media attention in 2. The history of baseball in Canada has remained closely linked with that of the sport in the United States. As early as 1. 87. International Association, featured teams from both countries. In 1. 97. 7, the expansion Toronto Blue Jays joined the American League. The Blue Jays won the World Series in 1. United States to do so. After the 2. 00. 4 season, Major League Baseball relocated the Expos to Washington, D. C., where the team is now known as the Nationals. In 1. 84. 7, American soldiers played what may have been the first baseball game in Mexico at Parque Los Berros in Xalapa, Veracruz. A few days after the Battle of Cerro Gordo, they used the . The Dominican Republic held its first islandwide championship tournament in 1. In Asia, South Korea (1. Taiwan (1. 99. 0), and China (2. In 2. 00. 4, Australia won a surprise silver medal at the Olympic Games. The Diversion programs are run in collaboration with the The Center for Life Skills Development and the Tucson City Prosecutor's Office. Diversion provides many first. Tucson, Arizona 85701. The Judicial Branch of Arizona, Maricopa. Employment : Home; You are here: Juvenile Probation > Probation Community Supervision: Drug Diversion The Drug Diversion Program was developed and implemented in. Pretrial Services, with the Arizona Superior Court in Pima. About Pretrial Services: Intake Program: Supervised Release. 1st Floor Tucson, Arizona 85701 Phone: (520) 724-3310 FAX: (520) 222-0536: E. The UA Diversion Program provides UA students with the opportunity to have misdemeanor charges dismissed upon completion of the program. Court and University of Arizona Diversion Programs March 8, 2014 - Posted by: ryangibsonesq. Tucson City Court This program is offered to first-time misdemeanor defendants. Arizona Drug Diversion Program - TASCHochgeladen am 1. An experienced Arizona drug crimes lawyer explains the TASC drug diversion program if you had been charges with possession or use of drugs including marijuana. The Monitored Diversion Program involves more intensive counseling. The Mental Health Diversion program is offered by the Tucson City Prosecutor’s Office. Tucson, Arizona 85701 (520) 791-4104 Victim Assistance.Degrees and Programs . This program includes courses about all levels in government, political theory, public administration and much more, which are designed to give students a well- rounded and accurate view of their nation and the world. Concordia University is one of the best Christian colleges and universities in Michigan. We are a part of the Concordia University System, and affiliated with the Lutheran Church Missouri Synod. Major in Biology Major (BA) Biology coursework at Concordia University gives students a framework of knowledge that allows them to learn and incorporate new facts and concepts as the field evolves. Biology students benefit. Concordia College in Moorhead, Minn., prepares students to influence the affairs of the world through a liberal arts education with a globally focused curriculum. Academic programs offered at Concordia University Wisconsin. Many of our alumni have chosen to share their success and help CUW further its mission through financial support. The Concordia University Texas Police Department supports Developing Christian Leaders by providing a safe and secure campus environment through professional law enforcement services, safety programs, and emergency management. See details for Concordia University School of Law in Boise, Idaho. 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It offers many advanced features for seasoned users but at the same time, with its excellent basic configuration options, is ideal for less experienced users. Norton Antivirus 2. Genomic profiling of murine mammary tumors identifies potential personalized drug targets for p. Trp. 53- null transplant tumors are counterparts for multiple expression subtypes of human breast cancer. The latest Tweets from Gene Tools support (@GeneTools). Gene Tools, LLC manufactures Morpholino antisense oligos for binding RNA and blocking processes. Gene Tools Morpholino Oligos. Advance articles; Current issue; Issue archive; Subject collections; Archive by article type; Alerts; About us. To study p53 signaling in breast cancer. Gene Tools Morpholino Oligos. Yki acts via regulation of p53 on reaper. The Trp. 53- null transplant model produces phenotypically and genomically diverse tumors that can be classified into three major subtypes/classes based on gene expression profiles: p. Basal. Ex, Claudin- low. Ex and p. 53null- Luminal. Ex (Pfefferle et al., 2. A crucial component of breast cancer comparative studies is to properly identify corresponding human- to- murine subtype counterparts. Once counterparts are determined, conserved features can be identified to highlight the candidate genetic drivers of those subtypes. For this purpose, a transcriptomic comparison between the two species was performed. To do this, we created gene signatures for each of our three previously identified Trp. Significance Analysis of Microarrays (SAM) analysis across a 3. Pfefferle et al., 2. Each signature was defined as all genes highly expressed in the class of interest with a false discovery rate (FDR) of 0%. The average of these signatures was calculated within each sample of the UNC3. Prat et al., 2. 01. Combined. 85. 5 (Harrell et al., 2. Metabric (Curtis et al., 2. As anticipated from previous human subtype associations (Pfefferle et al., 2. Basal. Ex subtype signature was highly expressed in basal- like human tumors and the Claudin- low. Ex signature was specific to the human claudin- low subtype (Fig. Huntington disease iPSCs show early molecular changes in intracellular signaling, the expression of oxidative stress proteins and the p53 pathway. Download Protocols, Publications and Useful Documents. Gene Tools publishes response to the paper 'Reverse Genetic Screening. Paste in one of these coupon codes when checking out of the Gene Tools online store to receive a complimentary T. This is a Morpholino oligo targeting zebrafish p53, reported to suppress. These synthetic oligos were conceived by James E. Summerton (Gene Tools). Gene Tools makes Morpholino antisense oligos. Morpholino oligos bind to complementary RNA and get in the way of processes; they can knock down gene expression, modify RNA splicing or inhibit miRNA activity and maturation. Morpholino oligonucleotides were ordered from Gene Tools LLC. The morpholino sequences were as follows: dnmt3 Mo1: 5. The tumor suppressor gene product p53 protects cells from transformation and. All of the p53 morpholino-injected bap28 mutants. Although the p. 53null- Luminal. Ex signature was most highly expressed in basal- like human tumors, it was also highly expressed in HER2- enriched and luminal- B tumors, indicating that these murine tumors have expression features in common with several human subtypes. Similar results were observed when we compared 9. Fig. S1) (Pfefferle et al., 2. Human counterparts of Trp. The standardized average of these gene signatures was calculated across more than 3. The D- Scores of the three Trp. Student's t- test. One explanation for the transcriptomic associations observed in Fig. A is that both the human and murine subtypes arise from similar cell types within the mammary- gland hierarchy (Visvader, 2. To address this possibility, a . B) (Prat et al., 2. Low scores indicate a tumor similarity to adult mammary stem cells (a. Ma. SCs), intermediate scores a similarity to luminal progenitor (Lum. Prog) cells, and high scores a similarity to mature luminal (Mature. Lum) cells (Prat et al., 2. The D- Score varied across the three Trp. Claudinlow. Ex subtype being the lowest, the p. Basal. Ex being intermediate, and the p. Luminal. Ex being the highest (P< 0. Fig. 1. B); even though the p. Luminal. Ex subtype had the highest D- Score among the three p. This indicates that, although the p. Luminal. Ex class is the most . S1), these results indicate that p. Basal. Ex and p. 53null- Claudinlow. Ex tumors are best considered murine counterparts for human basal- like and claudin- low subtypes, respectively. On the other hand, p. Luminal. Ex tumors uniquely contained traits of multiple human intrinsic subtypes, namely all three aggressive human subtypes (i. This finding suggests that p. Luminal. Ex tumors might be useful for studying aspects of several human subtypes. Profiling of secondary genetic aberrations highlights conserved DNA copy- number changes between human and murine Trp. In broad terms, disruption of normal Trp. Bieging et al., 2. This phenotype leads to the accumulation of both small- scale mutations (e. Specific genetic aberrations are predicted to be responsible for determining a cell's subtype fate during tumorigenesis, but identifying these specific drivers has been challenging. Here, we leveraged the power of multiple . Specifically, Illumina sequencing and microarray technologies were used to produce four datasets of varying sizes: DNA whole- genome sequencing (n=1. DNA exome sequencing (n=2. DNA copy- number microarray (n=4. Fig. For the purposes of our analyses, the DNA whole- genome and exome sequencing datasets were combined into a single dataset by reducing the whole genome samples to exome space, with all data deposited into the Sequence Read Archive (SRA). Murine Trp. 53- null tumor datasets. Sequencing and microarray technologies were used to produce four Trp. DNA copy- number microarray (n=4. The intrinsic class of each sample is displayed on the dendrogram, with colored boxes being previously identified human subtype counterparts (Pfefferle et al., 2. The hierarchical clustering location of each p. For each dataset, the number of tumors studied from each of the three murine classes highlighted by . Using this approach with our combined DNA whole- genome and exome dataset (Table S2), there were no identifiable genes that were enriched with non- silent somatic mutations within the p. Basal. Ex or p. 53null- Luminal. Ex classes, and only one gene in the p. Claudin- low. Ex class (Dchs. P=0. 0. 05) when using a two- class (class x versus all others) Fisher's exact test (Fig. We therefore focused on large- scale chromosomal rearrangements, amplifications and deletions as possible drivers of the murine Trp. An analysis of chromosome structural variants (SVs) (Table S3) identified several rearrangements that were enriched within each of the three Trp. Fisher's exact test (Fig. For instance, Mad. SVs in p. 53null- Basal. Ex tumors. Mad. 2l. Schvartzman et al., 2. Overexpression of Mad. Basal. Ex tumors (FDR 0%), might promote tumor development by further decreasing chromosome stability (Sotillo et al., 2. Although these SVs that are enriched in certain Trp. As a result, we were unable to definitively call any of these SVs drivers of these classes. Chromosome structural- variation analysis. Displayed are circos plots of the structural variants (SVs) enriched within (A) p. Basal. Ex, (B) p. Claudin- low. Ex and (C) p. Luminal. Ex tumors as determined by a two- class (class x versus all others) Fisher's exact test. The genes affected by these SVs are listed under each circos plot. The mechanism by which DNA copy- number variation leads to changes in the tumor phenotype, however, is more intuitive and more easily tested; therefore, we focused our attention on DNA amplifications and deletions as secondary genetic drivers. We were primarily interested in identifying genes in which the DNA copy- number variation was highly correlated with their gene expression, because this observation is consistent with causality. First, we identified DNA copy- number changes that were statistically enriched within each of our three Trp. SAM analysis (Fig. Interestingly, both the p. Basal. Ex (Fig. 4. A) and p. 53null- Luminal. Ex (Fig. 4. C) classes had distinct genomic regions of DNA gains and losses, whereas the p. Claudin- low. Ex (Fig. B) class was relatively copy- number neutral, having no genomic regions enriched with gains or losses; these results are consistent with human studies that have highlighted several DNA copy- number events specific to basal- like tumors but few, if any, events in claudin- low tumors (Weigman et al., 2. Specifically, p. 53null- Basal. Ex tumors were defined by both gains and losses on chromosome 8 and almost a complete loss of chromosome 1. Fig. 4. A), whereas p. Luminal. Ex tumors were defined by a DNA amplification on chromosome 6 (Fig. DNA copy- number analysis. Displayed in genomic order are the median class DNA copy- number levels for (A) p. Basal. Ex, (B) p. Claudin- low. Ex and (C) p. Luminal. Ex tumors. DNA copy- number changes enriched within each of the three Trp. SAM analysis. Genomic regions of significant gain are labeled in red and regions of significant loss are labeled in green. To narrow the list of potential genetic drivers within these subtype- enriched regions, the Pearson correlation between DNA copy number and gene expression was calculated to highlight the genes that were the most concordant with DNA gains and losses (Fig. A Pearson correlation cut- off of 0. DNA- RNA association. A number of interesting genes fell into this classification. As we previously noted (Herschkowitz et al., 2. Inpp. 4b (Pearson=0. PI3. K- AKT signaling (Agoulnik et al., 2. Basal. Ex tumors on chromosome 1. Weigman et al., 2. Cul. 4a, which is located on the p. Basal. Ex chromosome 8 amplicon, had a very high correlation with its gene expression (Pearson=0. CUL4. A is a scaffolding protein for E3 ubiquitin ligase, which helps regulate the cellular concentration of key protein substrates, including CHK1, E2. F1, ER- . Given the wide variety of cellular phenotypes that these protein substrates influence, such as proliferation and DNA repair (Jackson and Xiong, 2. CUL4. A has been proposed as a possible cancer driver and drug target (Sharma and Nag, 2. The p. 53null- Luminal. Ex tumors had a distinct amplification of chromosome 6 (Fig. Fig. 5), including Met (Pearson=0. Met, which is also spontaneously amplified in a subset of Brca. Trp. 53 (Smolen et al., 2. Xu et al., 2. 01. MAPK and PI3. K- AKT (Gastaldi et al., 2. Conserved DNA aberrations with human basal- like tumors. Pearson correlations between DNA copy number and gene expression were determined for all genes within the significant regions of gain and loss from Fig. Genes with a correlation greater than or equal to 0. The heatmap corresponds to DNA copy- number abundance. The percentage of human non- basal and human basal- like tumors affected by amplification or deletion of these genes is displayed. Human basal- like enriched events (indicated by ***) were determined using a two- class Fisher's exact test (P< 0. CL, p. 53null- Claudin- low. Ex. Given that p. Basal. Ex tumors are counterparts for the human basal- like subtype (Pfefferle et al., 2. Luminal. Ex tumors show features of all three aggressive human subtypes (i. Using a two- class (human basal- like versus human non- basal) Fisher's exact test, we identified 2. DNA copy- number gains or losses commonly enriched in human basal- like tumor genomes (P- value< 0. Met and Cul. 4a and loss of Inpp. Fig. 5). 2. 25. 0L (p. Its IP Number is 1. IP: 1. 30. 1. 02. Encoding: utf- 8.
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