Добірка наукової літератури з теми "William R. Compton Company"

This study highlights that the British had long experiences in the Malay Peninsula before Francis Light’s acquisition and development of Penang, due to the central role of Malayan ports such as Kedah, Takuapa, Langkasuka, Terengganu, Palembang, Siak, and Malacca in global trade between China and India. Under the influence of Islam, Malacca (and, to a lesser extent, Kedah) became a Muslim Sultanate and reached its peak in this trading network, which attracted European traders (and subsequent colonialism), initially from Portugal and Spain, and later France, the Netherlands, and Britain. After the East India Company attained hegemony in India, it was strongly placed to extend its power from its presidencies in Calcutta, Bombay, and Madras. The EIC’s main focus was Bengal, where the Company founded the Fort William College as its headquarters in Calcutta. As trade with China became more important, the Malay Peninsula commensurately became a more attractive destination for investment due to its closer proximity to the Chinese sea lanes, and closer access to the Indo-Malay hinterlands and their products. In 1784, the EIC sent Kinloch to Aceh but he was unsuccessful in negotiating to establish a factory there. Nevertheless, they succeeded in establishing a foothold in Malaya with Francis Light’s embassy to Riau, Kedah, and Penang. Kedah also became prosperous under the Muslim Sultanates. Many Chinese and Indian merchants were settled there, benefitting from the trade in jungle products like camphor, betelnut, bird nests, situated near the Kedah River, was identified as a strategic location. Sultan Muhammad Jiwa Zainal Abidin Muazzam Shah II of Kedah (r. 1710-1778) at that time was facing many internal as well as external conflicts. His son Sultan Abdullah Mukarram Shah (r. 1778-1797) also suffered the same fate. As a result of internal crisis and dynastic intrigues, he agreed to lease Penang to the EIC in exchange for military assistance in 1785. In July 1786, Francis Light sailed from Calcutta and reached Penang in August, and thus Penang became an EIC stronghold.

Abstract Introduction: Salvage chemotherapy followed by high dose therapy with carmustine, etoposide, cytarabine, and melphalan (BEAM) with ASCT is standard treatment for patients with chemosensitive, relapsed/refractory (r/r) NHL. Patients with inadequate response to salvage chemotherapy portend a worse prognosis. We present a phase I dose-escalation trial of venetoclax combined with BEAM conditioning followed by ASCT for the treatment of r/r or high-risk NHL. An expansion cohort of 10 patients was added at the highest tolerated dose. Venetoclax is an oral BCL-2 inhibitor that has significant single-agent and combination activity in r/r NHL. Preclinical observations showed that venetoclax potentiates the cytotoxicity of chemotherapy, increases synergistic cell kill, and can overcome chemoresistance even in highly aggressive lymphomas. In this trial, we aim to test the safety of the combination of venetoclax plus BEAM followed by ASCT. We hypothesize that venetoclax will help overcome the chemoresistance of these tumors and decrease post-ASCT relapse. Methods: This is an open-label, single-center, phase I trial (NCT03583424) with a dose expansion cohort of venetoclax in combination with BEAM and ASCT for patients with r/r or high-risk NHL. Venetoclax is given for 10 days, starting at D-10 before ASCT, in three dosing cohorts (400, 800, 1200 mg) using a quick ramp-up schedule. There were no dose limiting toxicities; therefore an expansion cohort of 10 additional patients accrued at the 1200 mg dose. Eligible participants include adult, fit patients with B and T-cell NHL refractory after upfront induction therapy, in partial remission or progressed after salvage, requiring ≥ 3 lines of therapy, relapsed within 1 year of induction, or at a high risk of relapse after ASCT (in first complete or partial remission). Patients with small lymphocytic lymphomas, with primary, or uncontrolled secondary, CNS lymphoma patients are excluded. Primary outcome is safety and determination of maximal tolerated dose (MTD). Adverse events (AEs) were recorded using CTCAE v 4.1 between days -10 to -6 then the Bearman scale was used from day -6 until engraftment. Results: Dose-escalation proceeded with no DLT and 19 patients were accrued across three cohorts. Baseline characteristics and safety data for all three cohorts are presented in Table 1. The majority were male (79%) and had stage IV disease (79%). The media age was 61. No unusual toxicities were encountered beyond what is expected with BEAM. No serious AEs were observed between days -10 to -6 that was related to treatment. No tumor lysis syndrome or other toxicities attributable to venetoclax were observed. Engraftment was as expected. Post-transplant, on the Bearman scale, there were no grade 3 toxicities, 5 grade 2, and 8 grade 1 toxicities. In cohort 3, 1 patient died prior to engraftment from fulminant sepsis. At 100 days post-transplant, 63% were in CR and 11% had stable disease. Fourty-seven percent remained in CR at 1 year post transplant (Table 2). After a median follow-up of 654 (range 335-957) days, median progression-free survival (PFS) was 398 days and median overall survival (OS) was not reached (Figure 1). Six patients went on to receive CD19 chimeric antigen receptor T-cell (CAR-T) therapy. Data of response according to BCL2 expression by IHC is presented in Table 3 for the 12 patients who had available data. Median PFS was superior in BCL2 positive group (p=0.04; figure 1C) Discussion: The addition of venetoclax to BEAM appears to be safe and well-tolerated in a typical, elderly population with high-risk disease and produced promising results. While CD19 CAR-T are a consideration, many patients may not have access to these therapies. Venetoclax in combination with BEAM can represent an option for patients with relapsed and refractory NHL. Figure 1 Figure 1. Disclosures Brammer: Celgene: Research Funding; Seattle Genetics: Speakers Bureau; Kymera Therapeutics: Consultancy. Maddocks: Celgene: Divested equity in a private or publicly-traded company in the past 24 months; Karyopharm: Divested equity in a private or publicly-traded company in the past 24 months; Beigene: Divested equity in a private or publicly-traded company in the past 24 months; ADC Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Morphosys: Divested equity in a private or publicly-traded company in the past 24 months; KITE: Divested equity in a private or publicly-traded company in the past 24 months; Pharmacyclics: Divested equity in a private or publicly-traded company in the past 24 months; BMS: Divested equity in a private or publicly-traded company in the past 24 months; Merck: Divested equity in a private or publicly-traded company in the past 24 months; Novatis: Divested equity in a private or publicly-traded company in the past 24 months; Janssen: Divested equity in a private or publicly-traded company in the past 24 months; Seattle Genetics: Divested equity in a private or publicly-traded company in the past 24 months. Saad: Kadmon: Research Funding; Amgen: Research Funding; careDx: Consultancy; Incyte Pharmaceuticals: Consultancy; Magenta Therapeutics: Consultancy; OrcaBio: Research Funding. Jaglowski: Novartis: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy; Takeda: Consultancy. William: Guidepoint Global: Consultancy; Dova Pharmaceuticals: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy; Incyte: Research Funding. OffLabel Disclosure: Venetoclax is a BCL2 inhibitor approved for treatment of hematological malignancies (AML and CLL).

Abstract Chapter 16 bisects Bob’s story: it’s roughly the halfway point in his life, and also the start of a downward trajectory in his business. By 1970, Bob was a “star”—he’d received Billboard’s Trendsetter Award, was in Vogue magazine, the Moog was on the popular Muppets TV show, and Bob and Switched-On Bach won Grammy Awards that year. But everyone else made money from the Moog except for R. A. Moog—the company was a victim of its own success, with rising sales but diminishing profits. Bob hired another engineer, Jim Scott. While Bob resisted the idea of a small synth, Bill Hemsath, on a lark, built a miniature synth he named the “Min A” that would take the company into the future. Two investors, William Waytena and Vernon Siegel, made a tentative deal to rescue the company, but then withdrew their offer. The Moog’s fourth child, Matthew, was born.

Abstract By the time Vaux had reached his 34th birthday, in 1858, he could regard himself as well along the road to success. He had authored an important book on domestic architecture, designed a major bank building, and won the competition to design the nation’s largest municipal park. Undoubtedly buoyed by these achievements, Vaux sought and obtained entry into New York club life. As an early member of the Down Town Association (founded in December 1859), he often dined at its Exchange Place clubhouse, a building he may have taken charge ofremodeling in 1860.1 As one of the original 300 members of the Athenaeum Club, Vaux must have attended the opening of the organization’s quarters, a commodious building on Fifth Avenue near 16th Street, “fitted up with every convenience requisite for the comfort of its members.”2 In addition to dining and socializing, the Athenaeum, whose executive committee included art biographer Henry T. Tuckerman, endeavored to provide its members with high-caliber programs, such as the evening that Vaux and Jervis McEntee spent listening to a lecture by expatriate artist William Page.3 But most of all, Vaux valued his membership in the prestigious Century Association, a select circle of artists and men of letters to which Vaux was admitted in 1859.4 Over the course of his lifetime, he was to pass many stimulating and pleasurable hours there, including a gala Twelfth Night celebration when, lounging on a Turkish rug, he joined fellow Centurians in “smoking, drinking, laughing, or suddenly singing a note on a horn.” 5 At the Century, Vaux could enjoy the company of such artist friends as Jervis McEntee, Frederic Edwin Church, R. Sanford Gifford, Eastman Johnson, and George Henry Hall, one of whose pictures hung in Vaux’s home.6 These men shared Vaux’s Romantic esthetic philosophy, as well as his hope that someday Ame:rica would come to value its painters, sculptors, and architects as it did its practical men of business and industry.