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Bartolome, Amelita, Anna Almazan, Salina Abusali, Stanley Tam, Eric Lee, Amogh Changavi, Wendy Trinh i in. "1089. Analytical Performance of an Ultrasensitive Immunoassay for Detection of Clostridium difficile Toxins in Stool". Open Forum Infectious Diseases 5, suppl_1 (listopad 2018): S326. http://dx.doi.org/10.1093/ofid/ofy210.924.
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Abstract Background Clostridium difficile infection (CDI) is the main cause for nosocomial diarrhea. Currently available assays for the diagnosis of CDI show deficits in sensitivity, specificity, and/or turnaround time. The Singulex Clarity® C. diff toxins A/B assay, in development for the Singulex Clarity® system, was designed to provide an accurate and automated detection of C. difficile toxins A (TcdA) and B (TcdB) in stool. Here, the analytical performance of the assay is reported. Methods Limits of detection (LoD) for TcdA and TcdB in stool and buffer was determined, and a preliminary cutoff, as compared with cell cytotoxicity neutralization assay (CCNA), was established. Analytical reactivity against 38 toxigenic and nontoxigenic C. difficile strains of eight different toxinotypes was determined. Cross-reactivity against 53 other gastrointestinal pathogens and potential interference by 11 endogenous and exogenous substances were determined. Reproducibility was tested with triplicate samples (n = 85), and stability was evaluated in samples stored at room temperature, refrigerated, and frozen conditions, and subjected to three freeze-thaw cycles. Results The LoDs for TcdA and TcdB were 0.8 and 0.3 pg/mL in buffer, and 2.0 and 0.7 pg/mL in stool, respectively. Using a preliminary cutoff, the assay demonstrated 96.3% sensitivity and 96.1% specificity compared with CCNA. The Singulex Clarity® C. diff toxins A/B assay detected toxins from all tested strains and toxinotypes. No cross-reactivity or interference were detected. The repeatability was 99%, and samples for C. difficile toxin testing were stable up to 8 hours in room temperature, 1 week in 2–8°C, 6 months in −70°C, and up to three freeze–thaw cycles. Conclusion The Singulex Clarity C. diff toxins A/B assay (in development) can detect TcdA and TcdB at very low concentrations and it has high sensitivity and specificity compared with CCNA. The assay demonstrates reactivity to common C. difficile strains, does not show cross-reactivity to common gastrointestinal pathogens, is robust against common interferents, allows for toxin detection in both fresh and frozen stool samples and up to three freeze–thaw cycles, and provides results with high reproducibility. Disclosures A. Bartolome, Singulex, Inc.: Employee, Salary. A. Almazan, Singulex, Inc.: Employee, Salary. S. Abusali, Singulex, Inc.: Employee, Salary. S. Tam, Singulex, Inc.: Employee, Salary. E. Lee, Singulex, Inc.: Employee, Salary. A. Changavi, Singulex, Inc.: Employee, Salary. W. Trinh, Singulex, Inc.: Employee, Salary. K. Chau, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary. B. Noland, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary.
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Gomperts, Edward D., Shashikant Apte, Utpal Chaudhuri, Joseph M. John, Vijay Ramanan, Ri Liesner, Amy D. Shapiro, Bonnie J. Mills i Martin Lee. "IB1001, an Investigational Recombinant Factor IX, Pharmacokinetics in Pediatric Patients with Hemophilia B." Blood 120, nr 21 (16.11.2012): 2225. http://dx.doi.org/10.1182/blood.v120.21.2225.2225.
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Abstract Abstract 2225 Introduction IB1001 is a recombinant factor IX product being investigated for the treatment and prevention of bleeding in individuals with hemophilia B. Pharmacokinetics (PK) in adults (>12 years) demonstrated that IB1001 had results similar to the currently available recombinant FIX with respect to parameters such as terminal phase half-life and incremental recovery. We report the interim findings from a PK assessment in children <12 years, with severe hemophilia B (FIX <2%), >50 prior exposure days to FIX, and no history of or currently detectable inhibitor to FIX. Methods Non-randomized, open-label PK study with patients receiving 75±5 IU/kg of IB1001 following a washout period of ≥4 days from a previous FIX infusion. Factor IX levels were determined pre-infusion and at 15–30 minutes, 4–6, 24–26, and 68–72 hours post-infusion. Additional samples could be drawn at 1–3 and 10–14 hours. Calculated PK parameters were: half-life (β-phase t1/2, determined using a robust regression approach [Lee ML et al. XVIth ISTH Congress, Florence, Italy, 1997]) but generally assuming a single compartmental model because of the small number of points, maximum plasma concentration (Cmax), in vivo recovery (IVR) and AUC(0-∞) (determined by the trapezoidal rule). In addition, the AUC(0-t) and mean residence time (MRT) were calculated. Results When compared to the findings previously reported with IB1001 in adult (≥12 years of age) subjects (Martinowitz U et al. Haemophilia, 18, 2012), the results in pediatric patients demonstrate a more rapid metabolism of factor IX as is indicated by the shorter terminal half-life (mean±SD of 19.3±7.8 h versus 29.6±18.2 h in adults) and the smaller AUC0-∞ (mean±SD of 1059±264 versus 1668±598 in adults). In addition, the in vivo recovery was lower (mean±SD of 0.69±0.21) versus that seen in adults (mean±SD of 0.98±0.22). These results are similar to those reported by Berntorp et al (Haemophilia, 7, 2001) with nonacog alfa. Conclusions The pharmacokinetics of IB1001 has previously been shown to be non-inferior to nonacog alfa, another recombinant factor IX, in hemophilia B individuals >12 years of age. The current study is intended to provide information on children <12 and, particularly, <6 years of age. IB1001 is metabolized faster and has a lower recovery than the comparable findings in patients >12 years of age. Although the study is ongoing, these may represent important implications for the potential use of IB1001 in pediatric patients. Disclosures: Gomperts: Inspiration Biopharmaceuticals Inc: Consultancy. Apte:Inspiration Biopharmacauticals Inc: Research Funding. Chaudhuri:Inspiration Biopharmaceuticals Inc: Research Funding. John:Inspiration Biopharmaceuticals Inc: Research Funding. Ramanan:Inspiration Biopharmaceuticals Inc: Research Funding. Liesner:Inspiration Biopharmaceuticals Inc: Research Funding. Shapiro:Inspiration Biopharmaceuticals Inc: Honoraria, Research Funding. Mills:Inspiration Biopharmaceuticals Inc: Employment. Lee:Inspiration Biopharmaceuticals Inc: Employment.
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Karasiewicz, Kathy, Shuyang He, Mary Ng, Kristina Tess, Weifang Ling, Gunnar F. Kaufmann, Jerome B. Zeldis, Henry Ji, Robert Hariri i Xiaokui Zhang. "Preclinical Evaluation of Human Placental-Derived Allogeneic CD19 CAR-T Cells Against B Cell Malignancies". Blood 134, Supplement_1 (13.11.2019): 3222. http://dx.doi.org/10.1182/blood-2019-130782.
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Celularity, Inc. is developing a CD19 CAR-T Cell therapy using an allogeneic platform derived from postpartum human placental cells. T cells isolated from placenta/ umbilical cord blood and genetically modified to express CD19 chimeric antigen receptor (CAR), termed Placental-derived (P-) CD19 CAR T cells, are in development for the treatment of B cell malignancies. Unlike adult peripheral blood mononuclear cell (PBMC)-derived T cells, P-T cells are mostly naïve (CD45RA+) and can be readily expanded while maintaining an earlier differentiation phenotype such as greater expression of naïve/ memory markers, lower expression of effector/ exhaustion markers, allowing for greater proliferative potential of these cells ex vivo. These cells are also known to have greater immune tolerance to HLA mismatch and display impaired allogeneic activation, contributing to lower incidences of severe graft-verse-host disease (GvHD) (Barker, et. al. Blood, 2001; Chen, et al. Biology of Blood and Marrow Transplantation, 2006), making them an attractive cell population for use as an allogeneic, adoptive cell therapy. A robust process for the isolation, transduction, and expansion of placental-derived T cells to generate "off-the-shelf" allogeneic P-CD19 CAR T cells was developed. Twenty-One day expanded, non-modified P-T cells (N=3) were compared to adult PBMCs for their allo-reactivity in a Xenogeneic GvHD model in NCG mice. P-T cells did not induce xeno-GvHD whereas PBMCs did, as evidenced by significant weight loss and death of all mice (N=5) by Day 28 post infusion. Despite expanded P-T cells demonstrating lack of in vivo GvHD, current manufacture of P-CD19 CAR T cells does include a CRISPR-mediated T-cell receptor a constant (TRAC) knockout (KO) step as an additional risk-mitigation strategy to circumvent any potential GvHD stemming from expression of endogenous T cell receptor. CD19 CAR transduction using a retrovirus provided by Sorrento Therapeutics, Inc., followed by TRAC knockout with CRISPR results in both high efficiency of CD19 CAR expression (~30% CD19 Fc+) and TCR KO (>96% CD3-/ TCR a/b-). In vitro, the functional activity of P-CD19 CAR-TRAC KO T cells against CD19+ Burkitt's Lymphoma (Daudi) and Acute lymphoblastic Leukemia (NALM6) cell lines was assessed in cytotoxicity and cytokine release assays. P-CD19 CAR T cells specifically lyse CD19+ Daudi/ Nalm6 targets in both 4-hour endpoint FACS and ACEA kinetic cytotoxicity assays, and in most cases at levels equivalent to or greater than PBMC-derived CD19 CAR T cells. When P-CD19 CAR T cells were co-cultured with CD19+ Daudi/ Nalm6 target cells for 24-hours, they secreted pro-inflammatory cytokines and effector proteins in an antigen-specific manner. In vivo, the anti-tumor activity of P-CD19 CAR T cells was assessed using a disseminated lymphoma xenograft model in NSG mice. Luciferase expressing Daudi cells (3×106) were intravenously (IV) injected on Day 0, followed by IV injection of P-CD19 CAR T cells (14×106) on Day 7. Bioluminescence Imaging (BLI) and survival were used as primary study endpoints. P- CD19 CAR T cells were well tolerated and safe. P-CD19 CAR T cells significantly reduced tumor burden, and improved survival. Four weeks after treatment, the vehicle group had a 100% mortality rate, while all animals from P-CD19 CAR T-treated group (N=5) remained alive without clinical symptoms including weight loss or changes in their fur. In summary, Celularity has defined a robust process for the generation and expansion of CD19 CAR T cells from human placenta. These cells exhibit potent anti-tumor activity both in vitro and in vivo with little evidence of acute GvHD induction, highlighting their potential as an allogeneic, adoptive cell therapeutic agent. Future in vivo GvHD studies will include assessment of both CD19 CAR and TRAC KO genetically modified P-T cells. Disclosures Karasiewicz: Celgene: Equity Ownership; Celularity, Inc.: Employment, Equity Ownership, Patents & Royalties: Patent Inventor. He:Celularity Inc: Employment. Ng:Celularity, Inc.: Employment. Tess:Celularity, Inc.: Employment. Ling:Celularity Inc: Employment. Kaufmann:Sorrento Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Zeldis:Sorrento Therapeutics Inc: Employment, Equity Ownership. Ji:Celularity, Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Sorrento Therapeutics Inc: Employment, Equity Ownership, Patents & Royalties. Hariri:Celularity Inc: Employment. Zhang:Celularity Inc: Employment.
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Coyne-Beasley, Tamera, Joseph Bocchini, Alejandro Cane, Cindy Burman, Maria J. Tort i Jessica Presa. "01. Serum Bactericidal Activity Against Circulating and Reference Strains of Meningococcal Serogroup B in the United States: A Review of Meningococcal Serogroup B (MenB) Vaccines in Adolescents and Young Adults". Open Forum Infectious Diseases 8, Supplement_1 (1.11.2021): S124—S125. http://dx.doi.org/10.1093/ofid/ofab466.204.
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Abstract Background US adolescents and young adults are at particular risk of invasive meningococcal disease (IMD). In 2018, menincococcal serogroup B was responsible for 36% of IMD cases in the US overall and for 66% of cases in adolescents and young adults. This age group is at high risk of IMD during outbreaks, which result in significant response-related costs. MenB vaccine efficacy against IMD relies on its ability to provide broad protection against diverse disease-causing strains. MenB-FHbp (Trumenba) and MenB-4C (Bexsero) are MenB vaccines licensed in the US as 2-dose series with an interval of 6 mo or 1 mo, respectively, recommended in healthy adolescents and young adults. We review available data on vaccine coverage of serogroup B strains. Methods A literature review identified relevant information from peer-reviewed publications, congress presentations, and ClinicalTrials.gov. Previously presented but unpublished data from phase 2/3 studies were included. Results After 2 MenB-FHbp doses, percentages of adolescents and young adults achieving serum bactericidal activity assay using human complement (hSBA) titers ≥1:8 were 79%–99% for 4 heterologous representative test strains and 71%–97% for 10 additional strains, confirming cross-protection against a diverse strain panel (Figure 1; unpublished data). These 14 heterologous strains collectively represent ~80% of disease-causing strains in the US and Europe. In a published study with limited sample size, 44%–78% of subjects had hSBA titers ≥1:8 against strains from 4 US college outbreaks after 2 MenB-FHbp doses. After 2 MenB-4C doses, percentages of 10–25-year-olds achieving hSBA titers ≥1:5 against 3 reference strains homologous to the vaccine antigen were 82%–93% (published data); 15%–100% of adolescents achieved hSBA titers ≥1:4 against a panel of 14 strains (unpublished data). Of college students who received 2 MenB-4C doses, 53%–93% achieved hSBA titers ≥1:4 against 5 US outbreak strains (4/5 strains had antigenic similarity to MenB-4C; published data). Conclusion MenB-FHbp and MenB-4C protect against various serogroup B strains. As for the breadth of coverage provided by these vaccines, available data show that MenB-FHbp elicits robust immune responses to a wide variety of disease-causing strains prevalent in the US (Figure 2). Disclosures Tamera Coyne-Beasley, MD, MPH, Pfizer Inc and GlaxoSmithKline (Advisor or Review Panel member) Joseph Bocchini, MD, Pfizer Inc and Dynavax (Advisor or Review Panel member) Alejandro Cane, M.D., Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Maria J. Tort, PhD, Pfizer Inc (Employee, Shareholder) Jessica Presa, MD, Pfizer Inc (Employee, Shareholder)
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Lasater, Elisabeth A., An D. Do, Luciana Burton, Yijin Li, Erin Williams, Jason Oeh, Luciana Molinero i in. "Resistance of Natural Killer and T Cells to Venetoclax Allows for Combination Treatment with Cancer Immunotherapy Agents". Blood 132, Supplement 1 (29.11.2018): 1118. http://dx.doi.org/10.1182/blood-2018-99-116405.
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Abstract Introduction: Intrinsic apoptosis is regulated by the BCL-2 family of proteins, which consists of both anti-apoptotic (BCL-2, BCL-XL, MCL-1) and pro-apoptotic (BIM, BAX, BAK, BAD) proteins. Interaction between these proteins, as well as stringent regulation of their expression, mediates cell survival and can rapidly induce cell death. A shift in balance and overexpression of anti-apoptotic proteins is a hallmark of cancer. Venetoclax (ABT-199/GDC-0199) is a potent, selective small molecule BCL-2 inhibitor that has shown preclinical and clinical activity across hematologic malignancies and is approved for the treatment of chronic lymphocytic leukemia with 17p deletion as monotherapy and in combination with rituximab. Objective: To investigate the effects of BCL-2 inhibition by venetoclax on viability and function of immune-cell subsets to inform combinability with cancer immunotherapies, such as anti-PD-L1. Methods and Results: B cells, natural killer (NK) cells, CD4+ T cells, and CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from healthy donors (n=3) were exposed to increasing concentrations of venetoclax that are clinically achievable in patients, and percentage of live cells was assessed by flow-cytometry using Near-IR cell staining. B cells were more sensitive to venetoclax (IC50 of ~1nM) than CD8+ T cells (IC50 ~100nM), NK cells (IC50 ~200nM), and CD4+ T cells (IC50 ~500nM) (Figure A). CD8+ T-cell subset analysis showed that unstimulated naive, but not memory cells, were sensitive to venetoclax treatment (IC50 ~30nM and 240nM, respectively). Resistance to venetoclax frequently involves compensation by other BCL-2 family proteins (BCL-XL and MCL-1). As assessed by western blot in PBMCs isolated from healthy donors (n=6), BCL-XL expression was higher in NK cells (~8-fold) and CD4+ and CD8+ T cells (~2.5-fold) than in B cells (1X). MCL-1 protein expression was higher only in CD4+ T cells (1.8-fold) relative to B cells. To evaluate the effect of venetoclax on T-cell function, CD8+ T cells were stimulated ex vivo with CD3/CD28 beads, and cytokine production and proliferation were assessed. Venetoclax treatment with 400nM drug had minimal impact on cytokine production, including interferon gamma (IFNg), tumor necrosis factor alpha (TNFa), and IL-2, in CD8+ effector, effector memory, central memory, and naïve subsets (Figure B). CD8+ T-cell proliferation was similarly resistant to venetoclax, as subsets demonstrated an IC50 >1000nM for venetoclax. Taken together, these data suggest that survival of resting NK and T cells in not impaired by venetoclax, possibly due to increased levels of BCL-XL and MCL-1, and that T-cell activation is largely independent of BCL-2 inhibition. To evaluate dual BCL-2 inhibition and PD-L1 blockade, the syngeneic A20 murine lymphoma model that is responsive to anti-PD-L1 treatment was used. Immune-competent mice bearing A20 subcutaneous tumors were treated with clinically relevant doses of venetoclax, murine specific anti-PD-L1, or both agents. Single-agent anti-PD-L1 therapy resulted in robust tumor regression, while single-agent venetoclax had no effect. The combination of venetoclax and anti-PD-L1 resulted in efficacy comparable with single-agent anti-PD-L1 (Figure C), suggesting that BCL-2 inhibition does not impact immune-cell responses to checkpoint inhibition in vivo. These data support that venetoclax does not antagonize immune-cell function and can be combined with immunotherapy targets. Conclusions: Our data demonstrate that significant venetoclax-induced cell death at clinically relevant drug concentrations is limited to the B-cell subset and that BCL-2 inhibition is not detrimental to survival or activation of NK- or T-cell subsets. Importantly, preclinical mouse models confirm the combinability of BCL-2 and PD-L1 inhibitors. These data support the combined use of venetoclax and cancer immunotherapy agents in the treatment of patients with hematologic and solid tumor malignancies. Figure Figure. Disclosures Lasater: Genentech Inc: Employment. Do:Genentech Inc: Employment. Burton:Genentech Inc: Employment. Li:Genentech Inc: Employment. Oeh:Genentech Inc: Employment. Molinero:Genentech Inc: Employment, Equity Ownership, Patents & Royalties: Genentech Inc. Penuel:Genentech Inc: Employment. Sampath:Genentech Inc: Employment. Dail:Genentech: Employment, Equity Ownership. Belvin:CytomX Therapeutics: Equity Ownership. Sumiyoshi:Genentech Inc: Employment, Equity Ownership. Punnoose:Roche: Equity Ownership; Genentech Inc: Employment. Venstrom:Genentech Inc: Employment. Raval:Genentech Inc: Consultancy, Employment, Equity Ownership.
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He, Jie, Jose A. Bufill, Michelle K. Nahas, Kai Wang, Lauren E. Young, Kristina M. Knapp, Kristina W. Brennan i in. "Clinical Utility of Comprehensive Profiling of Genomic Alterations in Hematologic Malignancies". Blood 124, nr 21 (6.12.2014): 1072. http://dx.doi.org/10.1182/blood.v124.21.1072.1072.
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Abstract Background: The clinical utility of mutation profiling in hematologic malignancies requires robust detection of all classes of genomic alterations in a single analysis across different tumor types. We developed a novel, hybrid capture-based NGS assay (FoundationOne® Heme) designed to comprehensively assess the genomic landscape of hematologic malignancies from archived FFPE, blood and bone marrow aspirate samples, sequencing both DNA and RNA to improve sensitivity for driver fusion events. We have analyzed the genomic alterations including substitutions, indels, copy number alterations and genomic rearrangements of 795 samples with various hematolymphoid malignancies including lymphoma, leukemia and multiple myeloma to demonstrate the diagnostic, therapeutic and prognostic utility of this test in routine clinical practice. Method: Genomic profiles of 746 out of 795 (94%) consecutive samples received in a CLIA-certified laboratory (Foundation Medicine) were successfully characterized by the FoundationOne® Heme test including 527 from bone marrow aspirates, 176 FFPE samples and 92 samples derived from blood. The clinical cohort is composed of 375 multiple myeloma cases, 185 leukemia cases, 150 lymphoma cases, 75 MDS/MPN cases, and 15 unknown hematologic disorder cases (Figure A). Adaptor-ligated sequencing libraries were captured by solution hybridization using a custom bait-set targeting 405 blood cancer-related genes and 31 frequently rearranged genes by DNA-seq, and 265 frequently-rearranged genes by RNA-seq. All captured libraries were sequenced to high depth (Illumina HiSeq), averaging 498x for DNA and ~7M on-target unique pairs for RNA, to enable the sensitive and specific detection of substitutions, indels, copy number alteration and gene rearrangements. Results: 705/746 (95%) patients had at least one alteration reported as a somatic driver mutation, 68% of cases harbored at least one alteration linked to a targeted therapy or would inform enrollment in a clinical trial consistent with therapeutic relevance. These potentially actionable alterations included mutations in KRAS (14% of cases), NRAS (13%), CDKN2A (8%), DNMT3A (6%), IDH1/2 (5%), BRAF (4%) and FLT3 (3%) (Figure B). In addition, 64% of cases harbored at least one alteration that have been shown to predict outcome and have prognostic relevance, including TP53 (14% of cases), TET2 (7%), ASXL1 (7%), CDKN2B (5%), CREBBP (5%), MLL (5%) and NPM1 (3%)(Figure B). We also detected 344 genomic rearrangements in 280/746 (38%) patients. Of the 344 reported rearrangements, 166 were known fusions in various disease types and 178 were novel rearrangements involving known oncogenes and tumor suppressor genes, including a novel RCSD1-ABL2 fusion in a patient with B-cell ALL who will derive benefit from kinase inhibitor therapy as part of their anti-leukemic regimen. Genomic rearrangements (detected in 38% of cases) can lead to various functional consequences: 260 (76%) rearrangements detected in this cohort are predicted to create activating fusions; 19 (6%) rearrangements are predicted to be activating intragenic rearrangements in MLL, FLT3 and CARD11; and 60 (17%) rearrangements are likely truncating events in tumor suppressors. Conclusions: We demonstrated that hybrid capture-based targeted DNA and RNA sequencing can be used to identify all classes of genomic alterations in genes known to be therapeutic targets or prognostic predictors in a broad spectrum of hematologic malignancies. Moreover, our data suggests that the FoundationOne® Heme comprehensive genomic profiling test can alter therapeutic strategy in routine clinical practice. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures He: Foundation Medicine: Employment, Equity Ownership. Nahas:Foundation Medicine, Inc: Employment. Wang:Foundation Medicine, Inc.: Employment, Equity Ownership. Young:Foundation Medicine: Employment, Equity Ownership. Brennan:Foundation Medicine, Inc: Employment. Donahue:Foundation Medicine: Employment. Young:Foundation Medicine, Inc: Employment. Ross:Foundation Medicine, Inc.: Employment, Equity Ownership. Morosini:Foundation Medicine, Inc. : Employment, Equity Ownership. van den Brink:Foundation Medicine, Inc: Consultancy. Intlekofer:Foundation Medicine, Inc: Consultancy. Dogan:Foundation Medicine, Inc: Consultancy. Armstrong:Epizyme, Inc: Consultancy. Yelensky:Foundation Medicine, Inc.: Employment, Equity Ownership. Otto:Foundation Medicine, Inc.: Employment. Lipson:Foundation Medicine, Inc.: Employment, Equity Ownership. Stephens:Foundation Medicine, Inc.: Employment, Equity Ownership. Miller:Foundation Medicine, Inc: Employment. Levine:Foundation Medicine, Inc: Consultancy.
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Ge, Jianning, Chunhui Yang, Jing Sun, Jiao Chen, Shuyi Qiu, Wenjie Yin, Lianjun Shen, Martina Sersch, Wei Cao i Xinxin Wang. "Preclinical Results of an Allogeneic, Universal CD19/CD7-Targeting CAR-T Cell Therapy (GC502) for B Cell Malignancies". Blood 138, Supplement 1 (5.11.2021): 1722. http://dx.doi.org/10.1182/blood-2021-148500.
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Abstract Background Autologous CD19 CAR-T therapies show very promising clinical efficacy, but are limited in their applicability by several factors including cost, time to manufacture, and other factors involving patients own T-cell qualities. GC027, a CD7 targeting allogeneic, universal CAR-T (UCAR-T) currently in development for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) has demonstrated robust expansion and anti-leukemia efficacy with a manageable safety profile in an investigator-initiated trial in China. These data suggest that, a single CD7 targeting CAR-T therapy is able to generate a therapeutic window by suppressing host vs graft (HvG) rejection of UCAR-T cells by patients' own NK and T cells, and achieve efficacy in patients with T-ALL. Based on these findings we developed GC502, a CD19/CD7 dual-targeting, allogeneic CAR-T therapy for B-cell malignancies, in which the CD19 CAR moiety targets malignant cells while CD7 CAR moiety suppresses HvG in variety of preclinical models. Methods GC502 was manufactured using leukopaks from HLA-unmatched healthy donors. It contains a 4-1BB based 2 nd-generation dual targeting CAR comprising an anti-CD19 and an anti-CD7 single-chain variable fragments (scFvs). TRAC and CD7 loci were disrupted to avoid graft vs host disease and fratricide, respectively. To select the leading CAR candidate, CAR expression and functionalities of CAR constructs with different heavy-light (H-L) chain orientations of the dual CAR were analyzed via in vitro assays and mouse xenograft models, in comparing to single CD19 CAR and CD7 CAR products. To achieve optimal anti-tumor efficacy, a T-cell enhancer was included in the CAR construct. Result Gene editing and dual CAR orientation selection TRAC and CD7 double knockout efficiencies were constantly above 97% across multiple donor pan T cells. Although CD19/CD7 CAR expression levels in different H-L chain orientations were similar, in the final CAR-T product as measured by flow cytometry (FCM) analysis, significant difference was observed in their cytotoxicity and in vitro expansion under repeated antigen stimulations by CD19+ B-cell acute lymphoblastic leukemia (B-ALL) cell line Nalm6 and CD7+ T-cell line CCRF-CEM. CAR candidates mediated the strongest cytotoxicity and most durable response were selected for further optimizations. CAR construct optimizations For the leading candidates, we first assessed the dual CAR efficacy after incorporation of an enhancer. While the IL-2, TNFα and IFNγ secretion levels were comparable, enhancer addition significantly improved tumor killing and CAR-T cell expansion under repeated stimulations by either CD19+ or CD7+ target cells. Anti-leukemia response under sub-optimal CAR-T cell dosages were also greatly enhanced as assessed by both B-ALL and T-ALL mouse xenograft models. GC502 CAR functionality comparison to single CAR products with proven clinical efficacies GC502 and GC027 were compared for their CD7 CAR function to assess their anti-HvG activities. GC502 and GC027 exhibited comparable toxicities towards pan T cells and similar efficacies in a highly malignant T-ALL mouse model. The CD19 CAR functionality of GC502 were evaluated and compared to a 2 nd generation CD19 CAR product comprising a FMC63 scFv and a 4-1BB-CD3ȥ signaling domain. In a Raji based B-ALL mouse xenograft model, both products rapidly eliminated cancer cells. While CD19 CAR treated mice showed signs of relapse at 2 weeks post CAR-T infusion, GC502 treatment group maintained "leukemia free" status till the end of study (Day28). Conclusion GC502 was optimized for CD19/CD7 dual CAR functionality and in vivo durability. It demonstrated robust anti-tumor efficacy and promising potentials to suppress HvG. This report presents an example that the dual CAR design of GC502 may serve as a novel "off-the-shelf" CAR-T technology. Disclosures Ge: GracellBiotechnologies Ltd: Current Employment, Current equity holder in publicly-traded company. Yang: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Sun: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Chen: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Qiu: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Yin: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Shen: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Sersch: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Cao: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company. Wang: GracellBiotechnologies Inc: Current Employment, Current equity holder in publicly-traded company.
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Lilley, Graham, Alden Ladd, Daniel Cossette, Laura Viggiano, Gregory Hopkins, John W. Evans, Mingli Li i in. "Characterization of Lentiviral Vector Derived Anti-Bcma CAR T Cells Reveals Key Parameters for Robust Manufacturing of Cell-Based Gene Therapies for Multiple Myeloma". Blood 126, nr 23 (3.12.2015): 3243. http://dx.doi.org/10.1182/blood.v126.23.3243.3243.
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Abstract T cells engineered with chimeric antigen receptors (CAR) specific to CD19 have caused rapid and durable clinical responses in ~90% of patients with acute lymphoblastic leukemia. These data support the development of additional CAR T cell products for the treatment of other hematological malignancies. Recently, B cell maturation antigen (BCMA) expression has been proposed as a marker for identification of malignant plasma cells in patients with multiple myeloma (MM). Nearly all MM and some non-Hodgkin's lymphoma tumor cells express BCMA, while normal tissue expression is restricted to plasma cells and a subset of mature B cells. Therefore, BCMA is an attractive CAR T cell target to treat patients with MM and some B cell lymphomas. To this end, using lentiviral vector technology, we successfully generated CAR T cells specific to BCMA that exhibit potent anti-tumor activity to both multiple myeloma and Burkitt's lymphoma in animal models. Manufacture of CAR T cells for individual patient treatment requires the establishment of a robust and reproducible process - since variability in manufacturing could impact the potency of each cell product. To begin to understand the parameters of the manufacturing process that might contribute to the activity of the final product, we first tested the impact of lentiviral vector (LVV) multiplicity of infection (MOI) on CAR T cell phenotype and function. Using a broad range of MOIs (0.625 to 40) across multiple independent PBMC donors we observed no differences in population doubling or cell size throughout the ~10 day manufacturing process, irrespective of the MOI used. As expected, the number of anti-BCMA CAR expressing cells, the level of CAR expression per cell and the average vector copy number (VCN) in the cell product increased proportionally with MOI. Similarly, T cell function, as determined by an IFNg cytokine release assay in response to BCMA-expressing K562 target cells, was also correlated with the LVV MOI. Notably, increased IFNg expression was readily observable at MOIs as low as 1.25 and reached a plateau with T cells generated using an MOI of 20 or more - highlighting the sensitivity of this functional assay. Analogous data demonstrating MOI dependent in vitro killing activity were obtained using a BCMA-expressing tumor cell cytotoxicity assay. Varying the LVV MOI used during transduction simultaneously alters both the amount of anti-BCMA CAR molecules expressed per cell as well as the number of T cells in the cell product that express anti-BCMA CAR. To evaluate each variable in isolation we generated T cell products containing the same frequency of anti-BCMA CAR T cells (26 ± 4% CAR+ T cells) but different levels of anti-BCMA expression per cell by diluting T cell products made with MOIs from 5 to 40 with donor-matched untransduced cells. While these populations had markedly different levels of CAR surface expression per cell (based on anti-BCMA CAR MFI levels measured by flow cytometry) both low and high expressing anti-BCMA CAR T cell products exhibited identical levels of cytotoxicity against BCMA-expressing tumor cells. These data suggest it is the number of CAR expressing cells that is the critical driver of higher functional activity (perhaps due to the efficiency of LVV mediated anti-BCMA CAR expression per transduced cell). Finally, using this information the variability in manufacturing of anti-BCMA CAR T cells was evaluated across 11 independent normal PBMC donors. All 11 products demonstrated very similar properties with respect to cell growth (population doublings, cell volume), and VCN. Importantly, using our standard MOI we obtained a consistent and high level of anti-BCMA CAR expressing T cells that resulted in robust IFNg cytokine release when co-cultured with BCMA-expression cells. Together, our data highlight the frequency of anti-BCMA CAR T cells per cell product as a key parameter for anti-tumor activity in vitro. Moreover, these data suggest that our LVV driven T cell engineering process can reproducibly generate robust anti-BCMA CAR expressing T cell products in a donor independent manner. A phase I clinical trial to evaluate this technology as a cell-based gene therapy for MM is under development. Disclosures Lilley: bluebird bio, Inc: Employment, Equity Ownership. Ladd:bluebird bio, Inc: Employment, Equity Ownership. Cossette:bluebird bio, Inc: Employment, Equity Ownership. Viggiano:bluebird bio, Inc: Employment, Equity Ownership. Hopkins:bluebird bio, Inc: Employment, Equity Ownership. Evans:bluebird bio, Inc: Employment, Equity Ownership. Li:bluebird bio, Inc: Employment, Equity Ownership. Latimer:bluebird bio: Employment, Equity Ownership. Miller:bluebird bio: Employment, Equity Ownership. Kuczewski:bluebird bio: Employment, Equity Ownership. Bakeman:bluebird bio, Inc: Employment, Equity Ownership. MacLeod:bluebird bio, Inc: Employment, Equity Ownership. Friedman:bluebird bio: Employment, Equity Ownership. Maier:bluebird bio, Inc: Employment, Equity Ownership. Paglia:bluebird bio, Inc: Employment, Equity Ownership. Morgan:bluebird bio: Employment, Equity Ownership. Angelino:bluebird bio, Inc: Employment, Equity Ownership.
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Tran, Thai Hong, Krupa Scott, Shyun-Shyun Lee, Reshma Singh, Shawn Cogan, Jennifer Bordeaux, Hummel Jennifer i in. "Quantitative Multiplexed Immunohistochemistry Assays for Exploring CAR Modified T Cells and Checkpoint Inhibitors in Lymphoma Trials". Blood 126, nr 23 (3.12.2015): 2659. http://dx.doi.org/10.1182/blood.v126.23.2659.2659.
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Abstract Although there have been compelling advances in the cancer immunotherapy space recently in the form of chimeric antigen receptor (CAR) modified T-cells and checkpoint inhibitors, advanced tools to explore the therapeutic mechanisms of their combination are not adequately developed or widely available. To address this growing need, we developed a robust quantitative fluorescent immunohistochemistry platform using multiplex AQUA (Automated Quantitative Analysis) technology to evaluate checkpoint inhibitor expression, enumerate CAR T cells and determine the interaction between tumor cells and immune cells via novel co-localization algorithms. We explored utility of this method both in preclinical- and clinical model systems. In an immunodeficient mouse model of B-cell lymphoma, we evaluated homing of CAR T cells to malignant B-cells in primary lymphoid organs. We determined the phenotype and functional status of the CAR T cells via multiplex analyses of CD4, CD8, PD1 and FOXP3 expression. Additionally, to enable combination immunotherapies in Diffuse Large B-Cell Lymphoma (DLBCL) setting, we explored prevalence of adaptive immune resistance mechanisms in the form of PD1 and PD-L1 expression in immune- and tumor cell compartments via landmarks created by cytoplasmic and nuclear stains in both primary and secondary biopsies from DLBCL patients (n = 63). To support patient selection for CAR T trials, we quantified expression and prevalence of relevant tumor antigens that could not be scored reproducibly by traditional methods to yield objective cut points. We anticipate utilization of these quantitative multiplexed IHC methods for optimal selection of patients into upcoming novel combination immunotherapy trials Disclosures Tran: Genoptix: Employment. Scott:Genoptix: Employment. Lee:Genoptix: Employment. Singh:Novartis: Employment. Cogan:Novartis: Employment. Bordeaux:Genoptix: Employment. Jennifer:Genoptix: Employment. Lameh:Genoptix: Employment. Tribouley:Novartis: Employment. Kassim:Novartis: Employment. Tangri:Genoptix Inc., a Novartis company: Employment. Dakappagari:Genoptix Inc., a Novartis company: Employment.
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Totman, Jennifer, Dorothy Brach, Vinny Motwani, Selene Howe, Emily Deutschman, John Lampe, Thomas V. Riera i in. "Pharmacologic Inhibition of the Histone Methyltransferase SETD2 with EZM0414 As a Novel Therapeutic Strategy in Relapsed or Refractory Multiple Myeloma and Diffuse Large B-Cell Lymphoma". Blood 138, Supplement 1 (5.11.2021): 1142. http://dx.doi.org/10.1182/blood-2021-151147.
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Abstract Introduction: SETD2 is the only known histone methyltransferase (HMT) capable of catalyzing H3K36 trimethylation (H3K36me3) in vivo. It plays an important role in several biological processes including B cell development and maturation, leading to the hypothesis that SETD2 inhibition in these settings could provide anti-tumor effects. The normal process of B cell development/maturation renders B cells susceptible to genetic vulnerabilities that can result in a dysregulated epigenome and tumorigenesis, including in multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL). For example, 15%-20% of MM harbors the high risk (4;14) chromosomal translocation, resulting in high expression of the multiple myeloma SET domain (MMSET) gene. MMSET is an HMT that catalyzes H3K36me1 and H3K36me2 formation and extensive scientific work has established overexpressed MMSET as a key factor in t(4;14) myeloma pathogenesis. To the best of our knowledge MMSET has eluded drug discovery efforts, however, since t(4;14) results in high levels of the H3K36me2 substrate for SETD2, inhibiting SETD2 offers promise for targeting the underlying oncogenic mechanism driven by MMSET overexpression in t(4;14) MM patients. In addition, SETD2 loss of function mutations described to date in leukemia and DLBCL are always heterozygous, suggesting a haploinsufficient tumor suppressor role for SETD2. This observation points to a key role for SETD2 in leukemia and lymphoma biology and suggests that therapeutic potential of SETD2 inhibition may also exist in these or similar settings. EZM0414 is a first-in-class, potent, selective, orally bioavailable small molecule inhibitor of the enzymatic activity of SETD2. We explored the anti-tumor effects of SETD2 inhibition with EZM0414 in MM and DLBCL preclinical studies to validate its potential as a therapy in these tumor types. Methods: Cellular proliferation assays determined IC 50 values of EZM0414 in MM and DLBCL cell line panels. Cell line-derived xenograft preclinical models of MM and DLBCL were evaluated for tumor growth inhibition (TGI) in response to EZM0414. H3K36me3 levels were determined by western blot analysis to evaluate target engagement. Combinatorial potential of SETD2 inhibition with MM and DLBCL standard of care (SOC) agents was evaluated in 7-day cotreatment in vitro cellular assays. Results: Inhibition of SETD2 by EZM0414 results in potent anti-proliferative effects in a panel of MM and DLBCL cell lines. EZM0414 inhibited proliferation in both t(4;14) and non-t(4;14) MM cell lines, with higher anti-proliferative activity generally observed in the t(4;14) subset of MM cell lines. The median IC 50value for EZM0414 in t(4;14) cell lines was 0.24 μM as compared to 1.2 μM for non-t(4;14) MM cell lines. Additionally, inhibitory growth effects on DLBCL cell lines demonstrated a wide range of sensitivity with IC 50 values from 0.023 μM to >10 μM. EZM0414 resulted in statistically significant potent antitumor activity compared to the vehicle control in three MM and four DLBCL cell line-derived xenograft models. In the t(4;14) MM cell line-derived xenograft model, KMS-11, robust tumor growth regressions were observed at the top two doses with maximal TGI of 95%. In addition, two non-t(4;14) MM (RPMI-8226, MM.1S) and two DLBCL xenograft models (TMD8, KARPAS422) demonstrated > 75% TGI; with two additional DLBCL models (WSU-DLCL2, SU-DHL-10) exhibiting > 50% TGI in response to EZM0414. In all models tested, the antitumor effects observed correlated with reductions in intratumoral H3K36me3 levels demonstrating on-target inhibition of SETD2 methyltransferase activity in vivo. In vitro synergistic antiproliferative activity was also observed when EZM0414 was combined with certain SOC agents for MM and DLBCL. Conclusions: Targeting SETD2 with a small molecule inhibitor results in significantly reduced growth of t(4;14) MM, as well as non-t(4;14) MM and DLBCL cell lines, in both in vitro and in vivo preclinical studies. In addition, in vitro synergy was observed with EZM0414 and certain SOC agents commonly used in MM and DLBCL, supporting the combination of SETD2 inhibition with current MM and DLBCL therapies. This work provides the rationale for targeting SETD2 in B cell malignancies such as MM, especially t(4;14) MM, as well as DLBCL, and forms the basis for conducting Phase 1/1b clinical studies to evaluate the safety and activity of EZM0414 in patients with R/R MM and DLBCL. Disclosures Totman: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Brach: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Motwani: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Howe: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Deutschman: Epizyme, Inc.: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Lampe: Epizyme, Inc.: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Riera: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Tang: Epizyme, Inc.: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Eckley: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Alford: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Duncan: Epizyme, Inc.: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Farrow: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Dransfield: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Raimondi: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Thomeius: Foghorn Therapeutics: Current Employment, Current equity holder in publicly-traded company. Cosmopoulos: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company. Kutok: Epizyme, Inc.: Current Employment, Current equity holder in publicly-traded company.
Rozprawy doktorskie na temat "B. E. Robuck, Inc"
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Baker, Leuan Zumwalt. "Susan B. Anthony House graphic design program /". Online version of thesis, 1989. http://hdl.handle.net/1850/10900.
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Hsu, Yueh-yuan Ho, i 徐玥圓. "The Study of Conventional Industry: Market Develops from B to B into B to C-Reference:Gallant-Ocean International.,Inc". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/386vs3.
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碩士國立中山大學
高階經營碩士班
97
Taiwan Island has magnificent resources, one of them is fishery industry, which happens to be one of Taiwan’s major economical activities. Seafood is considered by the people general to be a health choice, primarily for its assortment, tenderness, high nutrition of values and low in both calories and cholesterols. Gallant Ocean International Inc. exports 66% of Taiwan’s total annual seafood productions, indicating its industry leading status and capacity. To the current Taiwanese seafood industry, there is only focus in seafood processing and production, and commonly lacks the knowledge and experience of marketing, branding and distribution channels. It is the aim of the study to discuss and explore the operations and influences of corporate integrated purchasing, e-commerce, organic produce channels, marketing activities and Blog marketing; based on the case study of Gallant Ocean International Inc. In the research design perspective, this study employs Gallant Ocean International Inc. as the primary research target, by adapting exploratory analysis of single case study, qualitative case study research and in-depth interviews to acquire the necessary data for research purpose. The case study intends to provide a reference business model in the domestic traditional industries for the transition and development from B to B to B to C. This study has observed that the Taiwanese traditional industries’ development of B to C possesses the following trends: 1.The establishment of “Own-Brand” has an influential effect on market development: developing own-brand is a current trend and also an assurance to quality. Transforming product to brand does not only require product being “consumer-focus”, but also needs to take into consideration of the quality and competitiveness. This is particularly important in order to attain seafood “quality”, “freshness” and “safety” being the primary considerations. 2.“Integrated marketing” has concrete results in operational effectiveness: Effective utilization of actual and E-channels in integrated marketing have concrete operational results in developing B to C retailing market. 3.Adaptation of “Blog marketing” to establish virtual communities: Blogs have become increasingly popular due to its easiness to use, with low technical barrier, free of charge provides direct of interaction between both parties. Blog, being a free community marketing channel have attracted many B to C corporate utilizing them for relationship marketing. Finally, this research will present an argument for “people being the most critical factor for domestic traditional industries in developing B to C markets.” Consequently the decision markers’ decision-making ability and adaptation of integrated marketing tools are the critical success factors for the traditional industries’ B to C markets’ development.
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Silvano, André Gonçalo Matias. "Mergers & aquisitions : buy-side advisory solution to PepsiCo, Inc. on its acquisition of Mondelez International, Inc". Master's thesis, 2019. http://hdl.handle.net/10400.14/29182.
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The aim of this dissertation is to issue a buy-side recommendation, based upon a combination of strategical drivers and valuation methodologies, to PepsiCo, Inc. on its acquisition of Mondelēz International, Inc. Within the non-cyclical markets framework, the F&B business sector stands out for its solid M&A activity. Product innovation and shifts in consumer preferences stimulate PepsiCo, Inc. to engage in a sizeable deal, being Mondelēz International, Inc. the optimal target. PepsiCo, Inc. intrinsic EV amount to USD 238,093 million, while Mondelēz International, Inc. intrinsic EV is equal to USD 86,076 million. The deal relies on a friendly approach with a purchase premium of 25% on Mondelēz International, Inc. current market value on the 24th of May 2019. This proposal generates a total purchase price of USD 93,862 million, captures synergies, net of fees, of USD 5,654 million and the sources of funds correspond to 55% of stock and 45% of cash. The transaction signals shareholder value creation and presents a potential accretion of 25.40% in 2025.objetivo desta dissertação consiste em emitir uma recomendação de compra, baseada na combinação de vetores estratégicos e metodologias de avaliação, à PepsiCo, Inc. na sua aquisição da Mondelēz International, Inc. No âmbito dos mercados não cíclicos, o sector de negócio dos alimentos e bebidas destaca-se pelo elevado número de fusões e aquisições. A inovação e as alterações das preferências dos consumidores estimulam a PepsiCo, Inc. a envolver-se num negócio de maior dimensão, sendo a Mondelēz International, Inc. o alvo ideal. O valor intrínseco da PepsiCo, Inc. é de 238.093 milhões de dólares, enquanto o da Mondelēz International, Inc. corresponde a 86.076 milhões de dólares. A transação assenta numa abordagem amigável com um prémio de 25% sobre o valor de mercado da Mondelēz International, Inc. a 24 de maio de 2019. Esta proposta gera um preço de compra de 93.862 milhões de dólares, cria sinergias no valor líquido de 5.654 milhões de dólares e projeta-se que ações e dinheiro sejam as fontes de financiamento do negócio em 55% e 45% respetivamente. A transação demonstra que existe criação de valor para os acionistas e apresenta um potencial lucro por ação de 25,40% em 2025.
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HSU, CHI-CHUN, i 許濟群. "A Study on the Venture Philanthropy Development of Social Enterprises in Taiwan A Case Study of the B Current Impact Investment Inc". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/h33ket.
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碩士中國文化大學
國際企業管理學系碩士在職專班
104
In Taiwan, the development of non-profit organizations concerning public issues or events, such as education, ecology, medicine, farming and the disadvantaged groups, has been booming. However, the social needs have exceeded the growth speed of the social resources in the recent years, so the non-profit organizations have started to face a competitive market of quite a scale. In addition to the economic recession and the changes of the government’s strategies, their developments have been facing major challenges. In order to solve these problems, each of them has seek organizational changes or opportunities for transformation for sustainable development, just as the pouring of fresh water to continue fighting for the future of Taiwan and to provide the next generations with a better environment. With the purpose to solve this predicament, social enterprises have arisen. Specific social service purposes are achieved through commercial approaches. Among them, there is a significant difference between the charity functions of the “venture philanthropy from social enterprises of independent business” and other types of social enterprises. Donations are replaced by investments, while investment structure is highly transparent. It is the integration of self-professionalism and experience with the network of contacts, establishing comprehensive entrepreneurship-investment ecology for the non-profit organizations or social enterprises. Through the development of innovative business models and investment opportunities that may change the society as well as the speeding-up of their formations and developments, the self-sufficient and sustainable operations are still in expansion. Therefore, this study aims to understand the main spirit, approach and operation model through case studies of venture philanthropy. It explores the impacts of the social enterprises, which allow seeing a clearer positioning of venture philanthropy and facilitate an easier success of the venture philanthropy, helping the development of social enterprises or related organizations and organizational entrepreneurships.
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Chung, Wang Ming, i 王明中. "From Integrated Marketing Communication Approach to Study The Marketing Model of B-to-C Application Service Provider--A Case Study of Nexus Communications International Inc". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/03650267935978073057.
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碩士元智大學
資訊傳播學系
93
The blooming of internet shopping in Taiwan, which give the opportunity for e-commerce business suppliers of providing B2C-ASP platform grow up substantially. But it also results in the highly competitive status. Based on this, lots of e-store owners start to make efforts on marketing support to promote their service. Since Integrated Marketing Communication play an important role for the evolution of marketing. Therefore, this study will use the Integrated Marketing Communication concept to study B2C-ASP marketing service model, which would provide e-commerce business supplier the optimal marketing service. This study is conducted by in-deep interview of Hyper link Internet technology company and those users of using their platform service to do e-commerce business as background to collect information and find out the current marketing development, marketing strategy and operation model of hyper link Internet technology company and e-stores’ marketing demand and operation problems to analyze and summarize together with the Integrated Marketing Communication model be transmitted into hyper link Internet technology company. Finally the Study also implements this kind of mode as experimental example to make explanation. The study uses the number of visitors to link to the e-stores, the sales amount, and the increase number of members be registered as supporting data to show the Integrated Marketing Communication is better than the original one. E-stores also put marketing service as key element for planning to run Internet business. It’s no doubt that the new integrated marketing service model will bring outstanding performance.
Książki na temat "B. E. Robuck, Inc"
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Inc, Michael B. Weisbrod, red. Metal, mud and minerals: An exhibition of Chinese works of art, December 5-19, 1989 : catalogue. New York: Michael B. Weisbrod, Inc, 1989.
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Inc, Michael B. Weisbrod, red. Religion and ritual in Chinese art: An exhibition, December 8 to 22, 1987. New York: Michael B. Weisbrod, 1987.
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Klaás, M. D. Last of the flying clippers: The Boeing B-314 story. Atglen, PA: Schiffer Pub., 1998.
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Charles B. Wood III (Firm). The literature of rock'n'roll: A special collection. Cambridge, Mass: C.B. Wood III, 1990.
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Charles B. Wood III Inc. The literature of rock 'n' roll: A special collection. Cambridge, Mass: Charles B. Wood, 1990.
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Miller, James H. Business plan for West River Transit Authority Inc. d/b/a Prairie Hills Transit: Spearfish, South Dakota. [Fargo, N.D.]: Upper Great Plains Transportation Institute, North Dakota State University, 2009.
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Kitaj, R. B. R. B. Kitaj: November-December 1985, Marlborough Fine Art (London) Ltd., March 1986 Marlborough Gallery Inc., New York. (S.1: s.n, 1985.
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Museum, Mack Trucks Historical. Mack Model B, 1953-1966: Photo archive : photographs from the Mack Trucks Historical Museum archives. Minneapolis, Minn: Iconografix, 1994.
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Sotheby's (Firm). Prints: Including the Louis B. Dailey collection of Whistler prints. New York: Sotheby's, 2003.
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Armin, B. Allen Inc. Exhibition European pottery and porcelain: 8th-26th June, 1987. London: Armin B. Allen, Inc., 1987.
Znajdź pełny tekst źródłaCzęści książek na temat "B. E. Robuck, Inc"
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Kumar, B. Rajesh. "Case 2 B. Riley Financial, Inc." W Rising Stars, 9–17. Cham: Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-50032-9_2.
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Matam, Sai, i Jagdeep Jain. "Appendix B: Setting Up Digital Toys Inc." W Pro Apache JMeter, 327–31. Berkeley, CA: Apress, 2017. http://dx.doi.org/10.1007/978-1-4842-2961-3_14.
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Lehmann, Paul V., Zhigang Liu, Noémi Becza, Alexis V. Valente, Junbo Wang i Greg A. Kirchenbaum. "Monitoring Memory B Cells by Next-Generation ImmunoSpot® Provides Insights into Humoral Immunity that Measurements of Circulating Antibodies Do Not Reveal". W Methods in Molecular Biology, 167–200. New York, NY: Springer US, 2024. http://dx.doi.org/10.1007/978-1-0716-3690-9_11.
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AbstractMemory B cells (Bmem) provide the second wall of adaptive humoral host defense upon specific antigen rechallenge when the first wall, consisting of preformed antibodies originating from a preceding antibody response, fails. This is the case, as recently experienced with SARS-CoV-2 infections and previously with seasonal influenza, when levels of neutralizing antibodies decline or when variant viruses arise that evade such. While in these instances, reinfection can occur, in both scenarios, the rapid engagement of preexisting Bmem into the recall response can still confer immune protection. Bmem are known to play a critical role in host defense, yet their assessment has not become part of the standard immune monitoring repertoire. Here we describe a new generation of B cell ELISPOT/FluoroSpot (collectively ImmunoSpot®) approaches suited to dissect, at single-cell resolution, the Bmem repertoire ex vivo, revealing its immunoglobulin class/subclass utilization, and its affinity distribution for the original, and for variant viruses/antigens. Because such comprehensive B cell ImmunoSpot® tests can be performed with minimal cell material, are scalable, and robust, they promise to be well-suited for routine immune monitoring.
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Müller, Birgit Charlotte. "The Pricing of European Non-Performing Real Estate Loan Portfolios". W Three Essays on Empirical Asset Pricing in International Equity Markets, 94–126. Wiesbaden: Springer Fachmedien Wiesbaden, 2021. http://dx.doi.org/10.1007/978-3-658-35479-4_4.
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ZusammenfassungNon-performing loans (NPL), commonly referred to as loans in arrears for at least 90 days, have continuously been characterized as the top priority of the European Central Bank (ECB) and continue to attract central attention (ECB, 2018a,b). With the outbreak of the European debt crisis, the quality of banks’ assets had deteriorated in a manner that, despite robust economic recovery and a variety of regulatory efforts, NPL still today pose a threat to bank and thrift institutions. Against this backdrop, the European regulator requires banks to develop effective strategies for reducing NPL, to set up clear governance and to operate powerful work-out structures (ECB, 2017).
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Baldota, Siddhant, C. Malathy, Arjun Chaudhary i M. Gayathri. "Robust Segmentation of Nodules in Ultrasound-B Thyroid Images Through Deep Model-Based Features". W Advances in Intelligent Systems and Computing, 35–45. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-0475-2_4.
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Arvanitakis, Konstantinos, Romanos Kalamatianos i Markos Avlonitis. "Self-Optimized Computational Method Calculating Robust b Values for Earthquake Catalogs Containing Small Number of Events". W Advances in Experimental Medicine and Biology, 291–99. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-56246-9_24.
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Aguirre Fernández Bravo, Elena, i María Dolores Guindal Pintado. "Chapter 4. Free voluntary reading as a language and knowledge enhancement tool and its impact on interpreting students’ self-perceived B language fluency". W Instrumentalising Foreign Language Pedagogy in Translator and Interpreter Training, 54–75. Amsterdam: John Benjamins Publishing Company, 2023. http://dx.doi.org/10.1075/btl.161.04fer.
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The present proposal argues that it is relevant to design, implement and test more practical strategies to help Interpreting students enhance their second active working language to meet market requirements. Within the framework of a dialogue interpreting B.A. course, a free voluntary reading (FVR) experiment was conducted, based on the extensive literature proving that self-selected reading contributes to improving second language acquisition. The aim was to explore its potential as a Language and Knowledge Enhancement tool in improving native Spanish Interpreting students’ self-perceived fluency in English, and to analyze whether introducing FVR transversally as a horizontal activity in different B.A. in TI courses can help students build more robust active core competences in this foreign language.
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"APPENDIX B:". W Murder, Inc., 267–70. Potomac Books, 2019. http://dx.doi.org/10.2307/j.ctvhrd0vs.34.
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"B. Appendix to Chapter 4". W Disaggregating China, Inc., 175–76. Cornell University Press, 2021. http://dx.doi.org/10.1515/9781501759659-012.
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"C.R. Barger & Sons, Inc. (B)". W Growing an Entrepreneurial Business, 254–61. Stanford University Press, 2020. http://dx.doi.org/10.1515/9780804777568-018.
Pełny tekst źródłaStreszczenia konferencji na temat "B. E. Robuck, Inc"
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Gu, Yu, i Xiaoping Qian. "B-Spline Based Robust Topology Optimization". W ASME 2015 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2015. http://dx.doi.org/10.1115/detc2015-46076.
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In this paper, we present an extension of the B-spline based density representation to a robust formulation of topology optimization. In our B-spline based topology optimization approach, we use separate representations for material density distribution and analysis. B-splines are used as a representation of density and the usual finite elements are used for analysis. The density undergoes a Heaviside projection to reduce the grayness in the optimized structures. To ensure minimal length control so the resulting designs are robust with respect to manufacturing imprecision, we adopt a three-structure formulation during the optimization. That is, dilated, intermediate and eroded designs are used in the optimization formulation. We give an analytical description of minimal length of features in optimized designs. Numerical examples have been implemented on three common topology optimization problems: minimal compliance, heat conduction and compliant mechanism. They demonstrate that the proposed approach is effective in generating designs with crisp black/white transition and is accurate in minimal length control.
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Clausen, B. R., M. Nakhamkin i E. C. Swensen. "Preliminary Engineering for a 50 MW Compressed Air Energy Storage Plant for Alabama Electric Cooperative, Inc." W 1986 Joint Power Generation Conference: GT Papers. American Society of Mechanical Engineers, 1986. http://dx.doi.org/10.1115/86-jpgc-gt-5.
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This paper presents preliminary engineering results for a 50 MW Compressed Air Energy Storage (CAES) plant for the Alabama Electric Cooperative, Inc. (AEC). The CAES plant would improve AEC’s power generation mix in two ways: (a) it would provide needed peaking/intermediate power (otherwise purchased) and (b) it would increase the load factor of economical baseload units. The paper presents the following: a. Comparative trade-off analysis of various conceptual arrangements with underground storage depths ranging between 1000 feet and 4000 feet. (The most economical concept is selected based on the consideration of economics of the overall plant including underground storage). b. Engineering and cost data, performance data, construction schedule and environmental data for the selected CAES plant concept. The results of this preliminary engineering effort prove that a CAES plant is a cost effective addition to AEC’s installed power generation plants.
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Hsu, Fu-Chuan, Cheng-Chang Chiu, Yu-Ting Lyu, Wen-Long Chang, Junz J. J. Wang, Yung-Yuan Liao i Steven Y. Liang. "Application of an Accuracy Enhancement Module for Precision Machine Tools by Spatial Error Compensation". W ASME 2008 International Manufacturing Science and Engineering Conference collocated with the 3rd JSME/ASME International Conference on Materials and Processing. ASMEDC, 2008. http://dx.doi.org/10.1115/msec_icmp2008-72177.
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A PC-based precision promotion module named “Precimatics” is presented in this study, which uses a spatial error compensation algorithm to modify the G/M code of coordinates of a CNC machine tool. The spatial errors of three axes machine tools were measured by two kinds of laser interferometers (Renishaw Inc. & Optodyne Inc.) According to the American standard (ASME B 5.54) and the laser vector method with sequential step diagonal path (LDDM™), the spatial errors of machine tools, such as linear position error, horizontal straightness error, vertical straightness error, and squareness error, were obtained without time consuming. A spatial error map of machine tools was created and embedded into the “Precimatics” for error compensation. The compensated results were simulated and verified by the coordinates of numerical control (NC) code. Integrating a CAD/CAM system with the “Precimatics”, the position accuracy of micro/meso machine tools (mMTs) can be improved by spatial error compensation without changing the configuration of CNC controller.
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Migliore, R. J., J. G. Field, D. S. Hillstrom i R. A. Johnson. "Gamma Scan Confirmation of Lead Pour in a Type B Cask". W ASME 2002 Pressure Vessels and Piping Conference. ASMEDC, 2002. http://dx.doi.org/10.1115/pvp2002-1626.
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Packaging Technology, Inc., a subsidiary of the French nuclear consortium Areva, has been tasked with manufacturing six RH-72B (72B) casks for the Department of Energy’s Carlsbad Operations Office. The 72B transportation cask will be used to transport remote-handled (RH) transuranic wastes to the Waste Isolation Pilot Plant (WIPP) located in New Mexico. Certification of each 72B cask includes a gamma scan of the cask lead shielded wall to verify that no significant voids form within the lead subsequent to the lead pour. Voids in the lead would be revealed as spikes in the gamma scan measurements. The radioactive isotope Iridium-192 was used as the source for the gamma scan measurements. To determine the maximum and minimum expected values for the cask gamma scan, a test fixture was required to be developed with flat plate shields that matched the maximum and minimum thicknesses of the steel-lead-steel cask wall. Design of the test fixture was a non-trivial exercise due to the influence of backscatter radiation, which if unshielded resulted in unreasonably high test fixture radiation doses. To properly shield the backscatter radiation, a collimator is required around the source. The measured dose rates using the test fixture is highly sensitive to the diameter of the collimator penetration, as a collimator penetration diameter that is too narrow results in artificially low dose rate measurements when compared to the cask measurements. To assist in the design of the collimator, the Monte Carlo N-Particle (MCNP) gamma transport code was employed. Using MCNP computer simulations, it was determined that a collimator diameter of 6 inches was sufficient to properly mimic the cask configuration.
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Grishin, Alex, i Jami J. Shah. "A Meshfree B-Spline Finite Element Formulation for Unilateral Contact Problems". W ASME 2011 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. ASMEDC, 2011. http://dx.doi.org/10.1115/detc2011-47776.
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The integrated, accurate and robust analysis of unilateral structural contact problems at all scales is a prerequisite for a comprehensive CAE process which accommodates the design of assemblies. In addition, such an integration must reduce any manual intervention to a bare minimum. The current reliance on legacy mesh-based finite element software for such analysis instead leads to excessive manual mesh construction and modification. Although the adoption of a meshfree formulation would seem to hold the answer, the current state-of-the-art in node-based formulations suffers from a lack of stability and/or consistency for such applications. This investigation demonstrates that there exists a meshfree B-Spline formulation which is consistent, stable, and demonstrates accuracy comparable to that of mesh-based approaches for simple frictionless Hertzian problems in two dimensions. Together with the Solution Structure Method (SSM) of boundary condition enforcement, it is argued that this approach may provide a more robust finite element framework within existing CAE pipelines.
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Aristokleous, Nicolas, Mohammad Iman Khozeymeh, Yannis Papaharilaou, Georgios C. Georgiou i Andreas S. Anayiotos. "CFD Challenge: Solutions Using the Commercial Finite Volume Solver, Fluent". W ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80691.
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This work is a collaborative effort between the Biomechanics and Living System Analysis Laboratory (BIOLISYS) in Cyprus and the Biomechanics Laboratory of IACM/FORTH in Greece. Both labs combine interdisciplinary skills from engineering, medicine and biology to provide solutions to clinical problems associated with cardiovascular and other diseases. For this study, numerical flow simulations were performed using: a) open source software VMTK and commercial software ICEM CFD as pre-processors, b) the finite volume based solver Fluent and c) Tecplot 360 (Amtec Inc.) for post-processing.
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Goettler, Richard W., Joseph T. Keeley i Richard A. Wagner. "Ceramic Composites Technology Development for Industrial Applications at Babcock & Wilcox". W ASME 1997 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1997. http://dx.doi.org/10.1115/imece1997-0680.
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Abstract Babcock & Wilcox (B&W) and its parent corporation, McDermott International, Inc., comprise one of the world’s largest energy engineering and service companies. Included within the spectrum of it’s businesses are: • fossil power generation systems, related environmental equipment and boiler cleaning products • design engineering, structure fabrication, and equipment for offshore oil and gas production • nuclear fuel and other nuclear propulsion components for the US Navy • industrial heat exchangers and condensers • automated work cells for material processing and inspection • design of onshore hydrocarbon processing facilities • environmental remediation services
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Liu, Xiaodong. "Filling N-Sided Holes Using Trimmed B-Spline Surfaces". W ASME 2012 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/detc2012-70735.
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Using one single trimmed B-Spline surface to fill an n-sided hole is a much desired operation in CAD, but few papers have addressed this issue. The paper presents the method of using trimmed B-Spline surfaces to fill n-sided holes based on energy minimization or variational technique. The method is efficient and robust, and takes less than one second to fill n-sided holes with high quality B-Spline surfaces under complex constraints. As the foundation of filling n-sided holes, some key issues on variational B-Spline technique are also discussed. The variational technique discussed is significantly much more efficient and powerful than previous research, and the result is very accurate to satisfy CAD systems’ high-precision requirements. We demonstrate that, without any pre-calculation, the discussed technique is efficient enough to solve a B-Spline surface with up to 20,000 control points in real time while satisfying an arbitrary combination of point and curve constraints.
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Wood, Gary, Aaron Sahm, Rick Hurt, Robert Boehm i Kenneth W. Stone. "Performance of the Southern Nevada Water Authority of Amonix’s High Concentration Multi-Junction System". W ASME 2011 5th International Conference on Energy Sustainability. ASMEDC, 2011. http://dx.doi.org/10.1115/es2011-54398.
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The Southern Nevada Water Authority contracted with Amonix, Inc. in 2008 to procure 220 kWdc of their latest generation multi-junction cell High Concentration Photovoltaic systems (HCPV). This paper discusses the performance of the six HCPV systems that started operating in mid 2009. Data sets included show: a. Daily power performance; b. Power performance compared to the specified performance; c. Effect of field shading upon the daily power performance. What is demonstrated is the system power performance has not degraded during this initial period of operation and continues to meet or exceed the specified performance levels.
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Mukundan, Harish, Kwang Hee Ko i Nicholas M. Patrikalakis. "Intersections With Validated Error Bounds for Building Interval Solid Models". W ASME 2005 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. ASMEDC, 2005. http://dx.doi.org/10.1115/detc2005-85268.
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Interval arithmetic has been considered as a step forward to counter numerical robustness problem in geometric and solid modeling. The interval arithmetic boundary representation (B-rep) scheme was developed to tackle this problem. In constructing an interval B-rep solid, robust and efficient computation of intersections between the bounding surfaces of the solid is a critical issue. To address this problem, a marching method based on a validated interval ordinary differential equation (ODE) solver was proposed, motivated by its potential for the interval B-rep model construction. In this paper, we concentrate on the issue of error control in model space using the validated ODE solver, and further explain that the validated ODE solver can be used in the construction of an interval B-rep solid model using such an error control.
Raporty organizacyjne na temat "B. E. Robuck, Inc"
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Green, Darren C. MDA B Characterization and Remediation Geospatial Materials for Portage, Inc. External Marketing. Office of Scientific and Technical Information (OSTI), lipiec 2013. http://dx.doi.org/10.2172/1088357.
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Hultgren, R. Interim report of the DOE (Department of Energy) Type B Investigation Group: Appendix C, Oral statements about the RSI (Radiation Sterilizers, Inc. ) incident. Office of Scientific and Technical Information (OSTI), lipiec 1990. http://dx.doi.org/10.2172/6016485.
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Hultgren, R. Interim report of the DOE (Department of Energy) Type B Investigation Group: Cesium-137, a systems evaluation, encapsulation to release at Radiation Sterilizers, Inc. , Decatur, Georgia. Office of Scientific and Technical Information (OSTI), lipiec 1990. http://dx.doi.org/10.2172/6016484.
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Almås, Ingvild, Orazio Attanasio, Jyotsna Jalan, Francisco Oteiza i Marcella Vigneri. Using data differently and using different data. Centre for Excellence and Development Impact and Learning (CEDIL), 2018. http://dx.doi.org/10.51744/cip8.
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The lack of adequate measures to capture relevant factors, and the prevalence of measurement error in existing ones, often constitute the main impediment to robust policy evaluation. Random assignment of a given treatment, when feasible, may allow for the identification of causal effects, given that the necessary measurements are available. Measurement challenges include: (a) adequately measuring outcomes of interest; (b) measuring factors that relate to the mechanisms of estimated impacts; and (c) conducting a robust evaluation in areas where the RCT methodology is not feasible. In this paper, we discuss three categories of related approaches to innovation in the use of data and measurements relevant for evaluation: the creation of new measures, the use of multiple measures, and the use of machine learning algorithms. We motivate the relevance of each of the categories by providing a series of detailed examples of cases where each approach has proved useful in impact evaluations. We discuss the challenges and risks involved in each strategy and conclude with an outline of promising directions for future work.
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Chauhan i Wood. L52007 Experimental Validation of Methods for Assessing Closely Spaced Corrosion Defects. Chantilly, Virginia: Pipeline Research Council International, Inc. (PRCI), marzec 2005. http://dx.doi.org/10.55274/r0011167.
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A full-scale burst test program was devised and agreed with the PRCI Materials Technical Committee Ad Hoc group. The work was undertaken over a two year period, 2003 and 2004. Due to budget constraints, only one pipe diameter and material was chosen for the test program. This was 24� (610 mm) outside diameter (OD) by 7.9 mm wall thickness, welded ERW steel linepipe of material API 5L grade B/X42. The criterion that defects separated by a distance of 6t or less will interact is over conservative. New rules for interaction, derived using non-linear finite element analyses and validated using full scale burst testing, have been derived for closely spaced metal loss interacting defects in pipelines. New, robust interaction rules for assessing corrosion metal loss defects in pipelines have been formulated for use by the pipeline industry.
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Ahmed, Qadeer, i Vishnu Renganathan. Cybersecurity and Digital Trust Issues in Connected and Automated Vehicles. 400 Commonwealth Drive, Warrendale, PA, United States: SAE International, kwiecień 2024. http://dx.doi.org/10.4271/epr2024009.
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<div class="section abstract"><div class="htmlview paragraph">Given the rapid advancements in engineering and technology, it is anticipated that connected and automated vehicles (CAVs) will soon become prominent in our daily lives. This development has a vast potential to change the socio-technical perception of public, personal, and freight transportation. The potential benefits to society include reduced driving risks due to human errors, increased mobility, and overall productivity of autonomous vehicle consumers. On the other hand, the potential risks associated with CAV deployment related to technical vulnerabilities are safety and cybersecurity issues that may arise from flawed hardware and software.</div><div class="htmlview paragraph"><b>Cybersecurity and Digital Trust Issues in Connected and Automated Vehicles</b> elaborates on these topics as unsettled cybersecurity and digital trust issues in CAVs and follows with recommendations to fill in the gaps in this evolving field. This report also highlights the importance of establishing robust cybersecurity protocols and fostering digital trust in these vehicles to ensure safe and secure deployment in our modern transportation system.</div><div class="htmlview paragraph"><a href="https://www.sae.org/publications/edge-research-reports" target="_blank">Click here to access the full SAE EDGE</a><sup>TM</sup><a href="https://www.sae.org/publications/edge-research-reports" target="_blank"> Research Report portfolio.</a></div></div>
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Hayes, Michael. Introduction of Continuous Fiber-reinforced Polymer: A New Additive Manufacturing Path for Aerospace. 400 Commonwealth Drive, Warrendale, PA, United States: SAE International, sierpień 2023. http://dx.doi.org/10.4271/epr2023019.
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<div class="section abstract"><div class="htmlview paragraph">To grow the application space of polymer additive manufacturing (AM), the industry must provide an offering with improved mechanical properties. Several entities are working towards introducing continuous fibers embedded into either a thermoplastic or thermoset resin system. This approach can enable significant improvement in mechanical properties and could be what is needed to open new and exciting applications within the aerospace industry.</div><div class="htmlview paragraph"><b>Introduction of Continuous Fiber Reinforced Polymer: A New Additive Manufacturing Path for Aerospace</b> examines a couple of unsettled issues that are beginning to come to light regarding these materials and focuses on the ability to design and provide robust structural analysis for continuous fiber reinforced polymer AM—unsung aspects that can make or break this new technology as it finds its way into the aerospace market. Without solutions to them, adoption by the aerospace industry will be limited to point design applications, thus constraining the technology to being nothing more than a specialized tool.</div><div class="htmlview paragraph"><a href="https://www.sae.org/publications/edge-research-reports" target="_blank">Click here to access the full SAE EDGE</a><sup>TM</sup><a href="https://www.sae.org/publications/edge-research-reports" target="_blank"> Research Report portfolio.</a></div></div>
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Fu. L51878 Methods for Assessing Corroded Pipeline-Review Validation and Recommendations. Chantilly, Virginia: Pipeline Research Council International, Inc. (PRCI), kwiecień 2002. http://dx.doi.org/10.55274/r0010358.
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An assessment of the remaining strength of corroded line pipe is generally accomplished using the ASME B31G method and RSTRENG methods. These methods were developed using an early fracture mechanics relationship for toughness-independent failure of pressurised pipes and were empirically calibrated against a database of around 80 full-scale burst tests for thin wall pipes, dominated by pipes of grade B and grade X52. Applications of these methods to modern higher toughness pipe materials have not been fully justified. Neither of these methods is able to assess the significance of interactions between adjacent corrosion defects. Considerable effort, funded by Pipeline Research Council International, Inc. and by various industry groups, in particular in Europe, has in recent years addressed full-scale testing, analytical and numerical investigations, and the development of improved assessment methods. This report presents the results of a comparative review of a number of existing and newly developed methods for assessing corroded pipelines and a proposed methodology for the development of integrated corrosion assessment guidelines. This study was funded by the Line Pipe Research Supervisory Committee of Pipeline Research Council International, Inc. (project No. PR-273-9803) and was carried out jointly by BG Technology (United Kingdom), Battelle Memorial Institute (United States of America) and Shell Global Solutions (the Netherlands). BG Technology was the lead contractor.
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Keshav, Dr Geetha, Dr Suwaibah Fatima Samer, Dr Salman Haroon i Dr Mohammed Abrar Hassan. TO STUDY THE CORRELATION OF BMI WITH ABO BLOOD GROUP AND CARDIOVASCULAR RISK AMONG MEDICAL STUDENTS. World Wide Journals, luty 2023. http://dx.doi.org/10.36106/ijar/2405523.
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Introduction: Advancements and increase in access to healthcare have increased the life expectancy in India from 32 years in 1947 to almost 70 years currently. Due to robust vaccination and basic health programs, most of the communicable diseases are kept under control. The disease burden is now skewed towards non-communicable diseases. It is an established fact that body mass index (BMI) is a reliable predictor of cardiovascular disease (CVD) later in life. Early prediction can decrease the disease load and enable early preventative measures. A more novel approach of connecting it with blood groups would yield profound results in predictability and subsequent management. This study was done to see correlation between BMI and known blood groups in order to predict the potential incidence of CVDs in medical students. Material and Method - A cross-sectional descriptive study was conducted in Bhaskar Medical College from September 2022 - November 2022. The sample population included 150- 1st year medical students chosen by Randomized sampling method. BMI was calculated based as weight in kilograms divided by the square of the height in meters (kg/m2). Discussion - Many studies conducted on the association of Blood groups with BMI yielded mixed and inconclusive results. On analysis of the data obtained from this study, O- positive blood group showed the highest inclination towards obesity i.e. 30 of the total participants. A-positive and B- positive blood groups were shown to have a lesser association with obesity i.e. 11 participants of the 150. These results were in accordance with a study done among female students by Shireen Javad et.al, nding blood group O to be the most prone to obesity.8 Incompatible to our results, a study conducted by Samuel Smith Isaac Okai et.al. found no signicant association between blood groups and BMI.10 Another study conducted by Christina Ravillo et.al. found that blood group O had the highest and blood group AB with lowest prevalence of obesity9. These ndings were similar to the results obtained in our study. To study the correlation of BMI with ABO blood group and Cardiovascula AIMS and OBJECTIVES Aim: - r risk among medical students. 1. Calculate and segregate the participants according to BM Objectives: - I using the standard formula provided by the WHO. 1. Determine Blood group using antisera 2. Evaluation of Lipid prole in obese individuals
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Miller. L51699 Diverless Pipeline Repair Clamp Phase III. Chantilly, Virginia: Pipeline Research Council International, Inc. (PRCI), sierpień 1993. http://dx.doi.org/10.55274/r0010218.
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Offshore oil and gas developments are underway for water depths beyond which divers can function. The economic lifelines of these projects are the pipelines which will transport the products to shore. In preparation for the day when one of these pipelines will require repair because of a leak, the Pipeline Research Committee of Pipeline Research Council International, Inc. is funding research directed at developing diverless pipeline repair capabilities. This Report summarizes the results of the third and final phase of this project. Phase III work included design, manufacture, and dry testing of 1) a one-half scale model of a 12"� repair clamp, 2) a full-scale bolt test fixture to demonstrate boltcontainment and startup under realistic misalignment of the clamp halves, and 3) a full-scale one-way cylinder for end seal activation. Engineering drawings for a 12" - 900# (324 mm, 15.3 mPa) diverless repair clamp package were also produced, and are provided with this report in Appendix B. Phase III also included a study commissioned from Oceaneering directed at defining the interfaces of the clamp package and the ROV, including suggested procedures for deployment and positioning of the clamp package on the pipeline. Issues regarding bolt make-up by the ROV were also studied in detail and limitations in bolting capability were outlined.