Scottish Leaving Certificate Examination
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PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects
International Journal of Molecular Sciences Review PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects Rosalin Mishra , Hima Patel, Samar Alanazi , Mary Kate Kilroy and Joan T. Garrett * Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA; [email protected] (R.M.); [email protected] (H.P.); [email protected] (S.A.); [email protected] (M.K.K.) * Correspondence: [email protected]; Tel.: +1-513-558-0741; Fax: +1-513-558-4372 Abstract: The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted. Keywords: cancer; PIK3CA; resistance; PI3K inhibitors Citation: Mishra, R.; Patel, H.; Alanazi, S.; Kilroy, M.K.; Garrett, J.T. -
The General Stud Book : Containing Pedigrees of Race Horses, &C
^--v ''*4# ^^^j^ r- "^. Digitized by tine Internet Arciiive in 2009 witii funding from Lyrasis IVIembers and Sloan Foundation http://www.archive.org/details/generalstudbookc02fair THE GENERAL STUD BOOK VOL. II. : THE deiterol STUD BOOK, CONTAINING PEDIGREES OF RACE HORSES, &C. &-C. From the earliest Accounts to the Year 1831. inclusice. ITS FOUR VOLUMES. VOL. II. Brussels PRINTED FOR MELINE, CANS A.ND C"., EOILEVARD DE WATERLOO, Zi. M DCCC XXXIX. MR V. un:ve PREFACE TO THE FIRST EDITION. To assist in the detection of spurious and the correction of inaccu- rate pedigrees, is one of the purposes of the present publication, in which respect the first Volume has been of acknowledged utility. The two together, it is hoped, will form a comprehensive and tole- rably correct Register of Pedigrees. It will be observed that some of the Mares which appeared in the last Supplement (whereof this is a republication and continua- tion) stand as they did there, i. e. without any additions to their produce since 1813 or 1814. — It has been ascertained that several of them were about that time sold by public auction, and as all attempts to trace them have failed, the probability is that they have either been converted to some other use, or been sent abroad. If any proof were wanting of the superiority of the English breed of horses over that of every other country, it might be found in the avidity with which they are sought by Foreigners. The exportation of them to Russia, France, Germany, etc. for the last five years has been so considerable, as to render it an object of some importance in a commercial point of view. -
A Report to the President U.S
A Report to the President U.S. Department of the Interior 2017-2021 REPORT TO THE PRESIDENT 2017-2021 U.S. Department of the Interior JANUARY 15, 2021 Report to the President Report to the President U.S. DEPARTMENT OF THE INTERIOR LETTER TO THE PRESIDENT The Department of the Interior (Department) has focused on improving the ways we serve the American public, while moving forward with your policy priorities. In doing so, the Department has made incredible progress furthering conservation stewardship, expanding opportunities to hunt and fish on public lands, improving core administrative functions, creating a common-sense regulatory regime, and enhancing our Nation’s energy independence. On behalf of the more than 65,000 Secretary David L. Bernhardt dedicated employees who work diligently across our Nation to accomplish important missions in service to the American people, I am pleased to present the Department’s Summary of Actions Report for 2017- 2021. This report highlights the Department’s major and historic achievements toward fulfilling your vision on behalf of all Americans. David L. Bernhardt Secretary of the Interior Page 1 Report to the President PURPOSE AND INTRODUCTION Secretary Bernhardt and First Lady Melania Trump at Grand Teton National Park From the beginning days of the Trump-Pence Administration, President Donald J. Trump gave clear direction to the Department of the Interior (Department, DOI, or Interior). He set priorities and ambitious goals, challenging Federal agencies through Governmentwide Executive orders, Presidential memoranda, and other actions to deliver better results for the American people. Interior has worked relentlessly to implement the President’s agenda for the betterment of our society and economy. -
Wine.Kittlehouse Wine List 8.10
! The Story of the Wine Cellar at Crabtree’s Kittle House Restaurant and Inn The year was 1988 and John Crabtree’s idea was to create one of the greatest restaurant wine lists in the world. Grounded in the belief that great winemakers make great wine, we set out to learn who the world’s greatest winemakers were - the talented people making the most compelling and delicious wines of their type, creating the greatest expressions of a special place, the grapes that grow there and that winemaker’s vision of how that wine should taste. When we started our wine journey, the Kittle House wine list had about 150 selections and the wine cellar held a few thousand bottles and took up a small fraction of the space compared to what it is today. Both the list and the cellar grew very fast. We invited winemakers to the Kittle House for winemaker dinners and travelled to meet them on their estates and in their vineyards. We started in California with the wines from legendary producers like Robert Mondavi, Caymus, Groth and Dunn and from the new guard like Marcassin, Peter Michael, Bryant, Colgin and Turley. We then went to France and procured wines from the big boys in Bordeaux and Burgundy – Lafite, Latour, Margaux, Mouton, DRC, Coche-Dury, Leflaive, Dujac and Drouhin. Then we moved on to the Rhone Valley, the Loire, Alsace, Champagne and the rest of France, then on to Italy, Spain, Germany, Austria, Australia, New Zealand and the Pacific Northwest. So many great winemakers, so many great wines! In each place we would ask those great winemakers who, besides them, were making the best wines in the region. -
REPRESENTATIONS of MIND by David Lindeman a Dissertation
REPRESENTATIONS OF MIND by David Lindeman A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July 2019 © 2019 David Lindeman All Rights Reserved ABSTRACT After defending the view that we can read off the metaphysics of the things we talk about from the form and interpretation of the language we use to talk about things, I develop and defend an account of the form and interpretation of propositional attitude reports (and some closely related constructions) and then read off the metaphysics of propositional attitudes. Views on the metaphysics of speech acts, propositions, and propositionally articulated thoughts also fall out of the account. The result is a tightly knit sets of views which I think together solve a number of outstanding philosophical problems. Given the centrality and importance of the attitudes and reports thereof to our making sense of ourselves and others as minded beings, not to mention their centrality to many domains of philosophy, the hope is that this makes a contribution to our self- understanding. It should also be a contribution to cognitive science. Committee: Steven Gross (advisor), Justin Bledin, Robert Matthews, Michael Williams, Michael McCloskey ii ACKNOWLEDGEMENTS This is a progress report, extracted from an enormous, spatiotemporally distributed and disorganized corpus, spread over countless documents, handwritten and typed, alongside barely legible notes sprawling up and down the margins of hundreds of books and articles with different physical embodiments. It is, in fact, a work in progress. Like most longish works, it was composed over a longish period of time – by various time- slices, not all of whom agree with one another. -
Nick Susa Epic Mythomemology – the Iliad Book 1: Achilles Was Fighting
Nick Susa Epic Mythomemology – The Iliad Book 1: Achilles was fighting alongside Agamemnon, the King of Argos, during the Trojan war. After winning a battle each was given a war prize, a woman. Achilles was given Briseis, and Agamemnon was given Chryseis. However, the father of Chryseis, Chryses, who was also a priest of Apollo, wasn’t ready to part with his daughter and came with a ransom for his daughter for King Agamemnon. Agamemnon refused the ransom in favor of keeping Chryseis and threatened the priest. Horrified and upset the priest (Chryses) calls upon Apollo and asks him to put a plague upon the Achaean armies, one of which Agamemnon leads. For nine days the armies were struck with a plague, on the tenth Achilles called a meeting to find the reason for the plague. Calchas, a prophet and follower of Apollo, being protected by Achilles, explains that Agamemnon refusing the ransom was the reason for the plague and he must return the girl and make a sacrifice of one hundred cows to Apollo in order to end the plague. Agamemnon decides to appease Apollo, but only if he can take away Achilles war prize, Briseis. Achilles doesn’t believe that Agamemnon should gain Briseis, so the two begin to argue. Achilles decides that he and his men shall not fight in the war because of Agamemnon’s actions. After Agamemnon takes Briseis away, Achilles cries and prays to his mother, Thetis, asking her to have Zeus grant the Achaean armies many loses. Zeus was not around to be asked though, but after twelve days, he returns and promises to Thetis that he will grant the Trojans many victories and the Achaeans many losses. -
Monique Jannette Artist, Paralympian, and Former Civil Rights Lawyer
Texas Disability History Collection, University of Texas at Arlington Monique Jannette Artist, Paralympian, and former Civil Rights Lawyer Interview conducted by Mark Harris In 2016 in Dallas, Texas Disability Studies Minor Special Collections and Archives University of Texas at Arlington Copyright © 2016 by University of Texas at Arlington Libraries Biography Monique Jannette was born September 23, 1962 and graduated from Warren Travis White High School in Dallas, Texas, earned a Bachelor’s of Arts degree in Geology from the University of Texas at Arlington in 1987, and her Law Degree from Southern Methodist University in 1992. While in middle school and high school, she became interested in science and competitive diving. Jannette exceled at diving and traveled throughout the United States and other countries with diving teams. She earned a full scholarship to Southern Methodist University (SMU), but due to an accident shortly after graduation from high school in 1980, she became paraplegic. Starting in 1981, Jannette attended the University of Texas at Arlington (UTA), where she studied geology and participated in adaptive track and field under the direction of Jim Hayes. While attending UTA, she was selected to the 1988 U.S. Paralympic Track and Field team, and Table Tennis team in Seoul, South Korea. In 1992 she was selected again to compete with the U.S. Paralympic Team in Barcelona, Spain. Upon graduating from UTA, Jannette went back to SMU to study law. During her time there she collaborated with architects to make SMU more accessible to people with disabilities. After graduating law school, she and a partner began to practice civil rights law, helping the communities and business in and around the Dallas area. -
CORONATION of QUEEN ELIZABETH II 2Nd June,1953 Article by : Avni Sethi,Grade 7, SNS Faridabad
CORONATION OF QUEEN ELIZABETH II 2nd June,1953 Article by : Avni Sethi,Grade 7, SNS Faridabad DESIGN: ABHISHEK PODDAR JUNE 2021 The Coronation Ceremony Queen Elizebeth II By Avni Sethi, Grade 7, SNS Faridabad Thecoronationceremony,anoccasionforpageantry and celebration, but it is also a solemn religious ceremony,hasremainedessentiallythesameovera thousandyears.Forthelast900years,theceremony hastakenplaceatWestminsterAbbey,London.The service is conducted by the Archbishop of Canterbury;whosetaskthishasalmostalwaysbeen sincetheNormanConquestin1066. A coronation is a ceremony marking the formal investitureofamonarchwithregalpower.In1937, the11-year-oldPrincessElizabethhadwatchedher father, King George VI, crowned in the elaborate ceremonyand16yearslateron2June1953,herown officialcoronationwastotakeplace. v o l a t i l e U n c e r t a i n C o m p l e x A m b i g u o u s J U N E 2 0 2 1 Her motivation was clear, nothing must stand between her crowning and her people's right to participate. QueenElizabethIIwascrownedon2June,1953in Coronations have been held at Westminster Westminster Abbey. Her Majesty was the thirty- Abbey for 900 years and The Coronation of ninth Sovereign to be crowned at Westminster Queen Elizabeth II was to follow suit. But the Abbey. Coronationof1953wasground-breakinginits ownright‒thefirstevertobetelevised,itwas QueenElizabethIIisthesixthQueentohavebeen watchedby27millionpeopleintheUKalone crowned in Westminster Abbey in her own right. andmillionsmoreaudiencesaroundtheworld. ThefirstwasQueenMaryI,whowascrownedon1 October,1553.TheQueensucceededtotheThrone -
One Is at War One Is at Peace
Towns 30 Miles Apart Meet Race Crisis ONE IS AT WAR ONE IS AT PEACE THE 100 GAUDY YEARS AT SARATOGA . ,4 now it's Pepsi-for those who think young You see it everywhere—people on the go are going for Pepsi. Light, bracing Pepsi-Cola matches your modern activities with a sparkling-clean taste that's never too sugary or sweet. And nothing drenches your thirst better than a cold, inviting Pepsi. So think young— say "Pepsi, please!" How Allstate Life Insurance with the Sears Idea helps a man do right by his family Here is good, down-to-earth value that makes solid protection easier to afford. Let an Allstate Agent show you the amount and kind of protection you can get for as little as *2.50 a week. If you're a young family man with big plans for the future— for a cost averaging as little as $2.50 a week. but a tight budget right now—you'll be pleased to see what What makes this possible? It's because Allstate brings you you can do with a small amount of money at Allstate. high-quality life insurance without fancy price tags . clearly With Allstate Life Insurance, you can help make sure your described and carefully designed to give you the particular kind wife will have the money she needs to keep the family going, of protection you want. And you buy only what you want. This should anything happen to you. Or you can help build a sub- is the Sears Idea in life insurance. -
Baby Girl Names Registered in 2012
Page 1 of 49 Baby Girl Names Registered in 2012 # Baby Girl Names # Baby Girl Names # Baby Girl Names 1 Aadhira 1 Abbey-Gail 1 Adaeze 3 Aadhya 1 Abbi 2 Adah 1 Aadya 1 Abbie 1 Adaira 1 Aahliah 11 Abbigail 1 Adaisa 1 Aahna 1 Abbigaile 1 Adalayde 1 Aaira 2 Abbigale 3 Adalee 1 Aaiza 1 Abbigayle 1 Adaleigh 1 Aalaa 1 Abbilene 2 Adalia 1 Aaleah 1 Abbrianna 1 Adalie 1 Aaleya 20 Abby 1 Adalina 1 Aalia 8 Abbygail 1 Adalind 1 Aaliah 1 Abbygail-Claire 2 Adaline 33 Aaliyah 1 Abbygaile 8 Adalyn 1 Aaliyah-Faith 3 Abbygale 1 Adalyne 1 Aaliyah-noor 1 Abbygayle 10 Adalynn 1 Aamina 1 Abby-lynn 1 Adanaya 1 Aaminah 1 Abebaye 2 Adara 1 Aaneya 2 Abeeha 1 Adau 1 Aangi 1 Abeer 2 Adaya 1 Aaniya 2 Abeera 1 Adayah 2 Aanya 1 Abegail 1 Addaline 3 Aaralyn 1 Abella 1 Addalyn 2 Aaria 1 Abem 1 Addalynn 3 Aarna 1 Abeni 1 Addeline 1 Aarohi 2 Abheri 1 Addelynn 1 Aarolyn 1 Abida 3 Addie 1 Aarvi 1 Abidaille 1 Addie-Mae 2 Aarya 1 Abigael 3 Addilyn 1 Aaryana 159 Abigail 2 Addilynn 1 Aasha 1 Abigaile 1 Addi-Lynne 2 Aashi 3 Abigale 78 Addison 1 Aashka 1 Abigayl 13 Addisyn 1 Aashna 2 Abigayle 1 Addley 1 Aasiyah 1 Abijot 1 Addy 1 Aauriah 1 Abilleh 9 Addyson 1 Aavya 1 Abinoor 1 Adedamisola 1 Aayah 2 Abrianna 1 Adeena 1 Aayana 2 Abrielle 1 Adela 1 Aayat 2 Abuk 1 Adelade 2 Aayla 1 Abyan 1 Adelae 1 Aayushi 3 Abygail 14 Adelaide 1 Ababya 2 Abygale 1 Adelaide-Lucille 1 Abagail 1 Acacia 2 Adelaine 1 Abagayle 1 Acasia 17 Adele 1 Abaigael 2 Acelyn 1 Adeleah 1 Abba 1 Achan 1 Adelee 1 Abbagail 2 Achol 1 Adeleigh 1 Abbegail 1 Achsa 1 Adeleine 12 Abbey 11 Ada 2 Adelia Page 2 of 49 Baby Girl -
News-LEADER Arkansas’S Heritage While Leading Through the 21St Century Wednesday, Nov
THE NASHVILLE HH HH Preserving SouthwestNews-LEADER Arkansas’s Heritage While Leading Through the 21st Century Wednesday, Nov. 6, 2019 u Vol. 17, Issue 19 u 28 pages, 3 sections u 75¢ Leader ‘Two revolutions’ Board Well-known columnist describes www.swarkansasnews.com political, demographic changes Arkansans have lived through OPINION 4A By Louie Graves State officials News-Leader staff note decline The current generation of Arkansans has lived through in freshmen two revolutions, the Nash- at colleges. ville Rotary Club was told last Wednesday, Oct. 30. The speaker was Rex Nel- son, himself an Arkansan of Veterans Day many facets. He is senior editor and columnist for the Arkansas observance Democrat-Gazette, radio voice of set Monday Ouachita Baptist Tigers football, and the policy and communi- The annual Veter- Rex Nelson cations director for a former ans Day ceremony in governor. Howard County will take drive through other area cities The revolutions, he said, place Monday at the to see the difference in down- were: (1) A political revolution courthouse on North towns. that saw the state’s representa- Main Street, in front of “We have become two states tion in Washington, D.C., and in the county’s memorial within a state,” he said, and he Little Rock rotate almost com- to soldiers, sailors and predicted that the 2020 census pletely from Democratic to Re- airmen who have died in would show that as many as 50 publican; and (2) A revolution in the nation’s wars. of the state’s 75 counties would demographics -- where popula- The ceremony tradi- show a population decline. -
The State of the Animals: 2001 More Than a Slap on the Wrist
Overview: The State of Animals in 2001 Paul G. Irwin he blizzard of commentary tors have taken part in a fascinating, environments; and change their inter- marking the turn of the millen- sometimes frustrating, dialogue that actions with other animals, evolving Tnium is slowly coming to an end. seeks to balance the needs of the nat- from exploitation and harm to Assessments of the past century (and, ural world with those of the world’s respect and compassion. more ambitiously, the past millenni- most dominant species—and in the Based upon that mission, The HSUS um) have ranged from the self-con- process create a truly humane society. almost fifty years after its founding gratulatory to the condemnatory. The strains created by unrestrained in 1954, “has sought to respond cre- Written from political, technological, development and accelerating harm atively and realistically to new chal- cultural, environmental, and other to the natural world make it impera- lenges and opportunities to protect perspectives, some of these commen- tive that the new century’s under- animals” (HSUS 1991), primarily taries have provided the public with standing of the word “humane” incor- through legislative, investigative, and thoughtful, uplifting analyses. At porate the insight that our human educational means. least one commentary has concluded fate is linked inextricably to that of It is only coincidentally that the that a major issue facing the United all nonhuman animals and that we choice has been made to view the States and the world is the place and all have a duty to promote active, animal condition through thoughtful plight of animals in the twenty-first steady, thorough notions of justice analysis of the past half century—the century, positing that the last few and fair treatment to animals and life span of The HSUS—rather than of decades of the twentieth century saw nonhuman nature.